Reliability and comparison of gain values with occurrence of saccades in the EyeSeeCam video head impulse test (vHIT).

PubMed

Korsager, Leise Elisabeth Hviid; Schmidt, Jesper Hvass; Faber, Christian; Wanscher, Jens Højberg

2016-12-01

The vHIT (video head impulse test) investigates the vestibular function in two ways: a VOR (vestibulo-ocular reflex) gain value and a head impulse diagram. From the diagram covert and overt saccades can be detected. Evaluation of the vestibular function based on vHIT depends on both parameters. There is a lack of knowledge regarding the reliability of the two parameters. The objective was to investigate the reliability of vHIT by comparing gain values between examiners on the same subjects, and to see how differences affected the occurrence of saccades. 25 subjects who had undergone cochlear implant (CI) surgery. Subjects were tested using the vHIT by two of four different examiners. Two judges interpreted the occurrence of saccades in the diagram. VOR gain values and the occurrence of saccades in the diagram. Differences in gain values between examiners varied from 0.2 to 0.58 with an average of 0.14 (95 % CI 0.12-0.16) on the right ear and 0.17 (95 % CI 0.15-0.19) on the left ear. Occurrences of saccades in the same patient were reproduced in 93 % of the cases by all examiners. Kappa's coefficient on the occurrence of saccades was 0.83. Interclass correlation coefficient (ICC) of the gain values between examiners ranged from 0.62 to 0.70. Differences in gain values amongst examiners did not seem to affect the occurrence of saccades in the same patient. The occurrence of saccades, therefore, seems to be more reliable than the gain value in the evaluation of the vestibular function. Interpretation of vHIT results should, therefore, first depend on the occurrence of saccades and second on the gain value.

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.

Health information technology capacity at federally qualified health centers: a mechanism for improving quality of care

PubMed Central

2013-01-01

Background The adoption of health information technology has been recommended as a viable mechanism for improving quality of care and patient health outcomes. However, the capacity of health information technology (i.e., availability and use of multiple and advanced functionalities), particularly in federally qualified health centers (FQHCs) on improving quality of care is not well understood. We examined associations between health information technology (HIT) capacity at FQHCs and quality of care, measured by the receipt of discharge summary, frequency of patients receiving reminders/notifications for preventive care/follow-up care, and timely appointment for specialty care. Methods The analyses used 2009 data from the National Survey of Federally Qualified Health Centers. The study included 776 of the FQHCs that participated in the survey. We examined the extent of HIT use and tested the hypothesis that level of HIT capacity is associated with quality of care. Multivariable logistic regressions, reporting unadjusted and adjusted odds ratios, were used to examine whether ‘FQHCs’ HIT capacity’ is associated with the outcome measures. Results The results showed a positive association between health information technology capacity and quality of care. FQHCs with higher HIT capacity were significantly more likely to have improved quality of care, measured by the receipt of discharge summaries (OR=1.43; CI=1.01, 2.40), the use of a patient notification system for preventive and follow-up care (OR=1.74; CI=1.23, 2.45), and timely appointment for specialty care (OR=1.77; CI=1.24, 2.53). Conclusions Our findings highlight the promise of HIT in improving quality of care, particularly for vulnerable populations who seek care at FQHCs. The results also show that FQHCs may not be maximizing the benefits of HIT. Efforts to implement HIT must include strategies that facilitate the implementation of comprehensive and advanced functionalities, as well as promote meaningful use of these systems. Further examination of the role of health information systems in clinical decision-making and improvements in patient outcomes are needed to better understand the benefits of HIT in improving overall quality of care. PMID:23363660

Health information technology capacity at federally qualified health centers: a mechanism for improving quality of care.

PubMed

Frimpong, Jemima A; Jackson, Bradford E; Stewart, LaShonda M; Singh, Karan P; Rivers, Patrick A; Bae, Sejong

2013-01-31

The adoption of health information technology has been recommended as a viable mechanism for improving quality of care and patient health outcomes. However, the capacity of health information technology (i.e., availability and use of multiple and advanced functionalities), particularly in federally qualified health centers (FQHCs) on improving quality of care is not well understood. We examined associations between health information technology (HIT) capacity at FQHCs and quality of care, measured by the receipt of discharge summary, frequency of patients receiving reminders/notifications for preventive care/follow-up care, and timely appointment for specialty care. The analyses used 2009 data from the National Survey of Federally Qualified Health Centers. The study included 776 of the FQHCs that participated in the survey. We examined the extent of HIT use and tested the hypothesis that level of HIT capacity is associated with quality of care. Multivariable logistic regressions, reporting unadjusted and adjusted odds ratios, were used to examine whether 'FQHCs' HIT capacity' is associated with the outcome measures. The results showed a positive association between health information technology capacity and quality of care. FQHCs with higher HIT capacity were significantly more likely to have improved quality of care, measured by the receipt of discharge summaries (OR=1.43; CI=1.01, 2.40), the use of a patient notification system for preventive and follow-up care (OR=1.74; CI=1.23, 2.45), and timely appointment for specialty care (OR=1.77; CI=1.24, 2.53). Our findings highlight the promise of HIT in improving quality of care, particularly for vulnerable populations who seek care at FQHCs. The results also show that FQHCs may not be maximizing the benefits of HIT. Efforts to implement HIT must include strategies that facilitate the implementation of comprehensive and advanced functionalities, as well as promote meaningful use of these systems. Further examination of the role of health information systems in clinical decision-making and improvements in patient outcomes are needed to better understand the benefits of HIT in improving overall quality of care.

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.

NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds

PubMed Central

Yu, Jun-lan; Chen, Tian-tian; Zhou, Chen; Lian, Fu-lin; Tang, Xu-long; Wen, Yi; Shen, Jing-kang; Xu, Ye-chun; Xiong, Bing; Zhang, Nai-xia

2016-01-01

Aim: Fragment-based lead discovery (FBLD) is a complementary approach in drug research and development. In this study, we established an NMR-based FBLD platform that was used to screen novel scaffolds targeting human bromodomain of BRD4, and investigated the binding interactions between hit compounds and the target protein. Methods: 1D NMR techniques were primarily used to generate the fragment library and to screen compounds. The inhibitory activity of hits on the first bromodomain of BRD4 [BRD4(I)] was examined using fluorescence anisotropy binding assay. 2D NMR and X-ray crystallography were applied to characterize the binding interactions between hit compounds and the target protein. Results: An NMR-based fragment library containing 539 compounds was established, which were clustered into 56 groups (8–10 compounds in each group). Eight hits with new scaffolds were found to inhibit BRD4(I). Four out of the 8 hits (compounds 1, 2, 8 and 9) had IC50 values of 100–260 μmol/L, demonstrating their potential for further BRD4-targeted hit-to-lead optimization. Analysis of the binding interactions revealed that compounds 1 and 2 shared a common quinazolin core structure and bound to BRD4(I) in a non-acetylated lysine mimetic mode. Conclusion: An NMR-based platform for FBLD was established and used in discovery of BRD4-targeted compounds. Four potential hit-to-lead optimization candidates have been found, two of them bound to BRD4(I) in a non-acetylated lysine mimetic mode, being selective BRD4(I) inhibitors. PMID:27238211

Forms of non-suicidal self-injury as a function of trait aggression.

PubMed

Kleiman, Evan M; Ammerman, Brooke A; Kulper, Daniel A; Uyeji, Lauren L; Jenkins, Abigail L; McCloskey, Michael S

2015-05-01

To date, the considerable body of research on predictors of non-suicidal self-injury (NSSI) has conceptualized NSSI as a unitary construct despite the fact that NSSI can exist in many forms (e.g., hitting, cutting, burning). The goal of the present study is to examine differential prediction of forms of NSSI. Specifically, we examined trait aggression as a predictor of more aggressive forms of NSSI (i.e., hitting). We hypothesized that higher trait aggression would differentiate those who engaged in hitting forms of NSSI from those who did not, whereas other factors (i.e., emotion regulation and trait anger) would serve as a non-specific predictor of NSSI. We also hypothesized that higher trait aggression would be related to lifetime frequency of hitting NSSI, but not other forms of NSSI, whereas emotion regulation and anger would act as predictors of other forms of NSSI. To test these hypotheses, a large sample of young adults completed measures of trait aggression, trait anger, emotion regulation, and NSSI behaviors. Results were generally in line with our hypotheses. Higher levels of trait aggression differentiated those who engaged in hitting NSSI from those who did not and was also associated with greater frequency of hitting NSSI. These results imply that different factors predict different forms of NSSI and that NSSI may be best examined as a multi-faceted construct. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship Between Health Service Use and Health Information Technology Use Among Older Adults: Analysis of the US National Health Interview Survey

PubMed Central

2011-01-01

Background Older adults are the most frequent and heaviest users of health services in the United States; however, previous research on older adults’ use of health information technology (HIT) has not examined the possible association of HIT use among older adults with their use of health services. Objective This study examined the relationship between US older adults’ use of health services and their use of the Internet for health-related activities, controlling for socioeconomic characteristics and aging-related limitations in sensory and cognitive function. It also examined gender differences in the pattern of association between the types of health services used and HIT use. Methods The data for this study were drawn from the 2009 US National Health Interview Survey (NHIS), which was the first nationally representative household survey to collect data on HIT (Internet) use. First, the rates of lifetime and 12-month HIT use among sample adults (n = 27,731) by age group (18-29 to 85 and over) were analyzed. Second, bivariate analysis of sociodemographic characteristics, health status, and health service use by HIT use status among those aged 65 or older (n = 5294) was conducted. Finally, multivariate binary logistic regression analysis was used to test the study hypotheses with 12-month HIT use as the dependent variable and 12-month health service uses among the age group 65 or older as possible correlates. Results The rates of HIT use were significantly lower among the age groups 65 or older compared with the younger age groups, although the age group 55 to 64 was not different from those younger. The rates of HIT use decreased from 32.2% in the age group 65 to 74 to 14.5% in the age group 75 to 84 and 4.9% in the 85 and older age group. For both genders, having seen or talked to a general practitioner increased the odds of HIT use. However, having seen or talked to a medical specialist, eye doctor, or physical therapist/occupational therapist (PT/OT) were significantly associated with HIT use only for older women, while having seen or talked to a mental health professional only marginally increased the odds of HIT use only for older men. Having visited or talked to a chiropractor and having had overnight hospitalization, surgery, and/or homecare services were not associated with the odds of HIT use for either gender. Conclusions Older-adult users of general health services were more likely to use HIT than nonusers of general health services, while older-adult users of specialized health services were not different from nonusers of specialized health services in their odds of HIT use. The findings have implications for narrowing the age-related and socioeconomic status-related gaps in HIT use. The access gaps among racial/ethnic minority older adults and poorly educated and/or low-income older adults are especially striking and call for concerted efforts to facilitate Internet access and HIT use among these disadvantaged older adults. PMID:21752784

Relationship between health service use and health information technology use among older adults: analysis of the US National Health Interview Survey.

PubMed

Choi, Namkee

2011-04-20

Older adults are the most frequent and heaviest users of health services in the United States; however, previous research on older adults' use of health information technology (HIT) has not examined the possible association of HIT use among older adults with their use of health services. This study examined the relationship between US older adults' use of health services and their use of the Internet for health-related activities, controlling for socioeconomic characteristics and aging-related limitations in sensory and cognitive function. It also examined gender differences in the pattern of association between the types of health services used and HIT use. The data for this study were drawn from the 2009 US National Health Interview Survey (NHIS), which was the first nationally representative household survey to collect data on HIT (Internet) use. First, the rates of lifetime and 12-month HIT use among sample adults (n = 27,731) by age group (18-29 to 85 and over) were analyzed. Second, bivariate analysis of sociodemographic characteristics, health status, and health service use by HIT use status among those aged 65 or older (n = 5294) was conducted. Finally, multivariate binary logistic regression analysis was used to test the study hypotheses with 12-month HIT use as the dependent variable and 12-month health service uses among the age group 65 or older as possible correlates. The rates of HIT use were significantly lower among the age groups 65 or older compared with the younger age groups, although the age group 55 to 64 was not different from those younger. The rates of HIT use decreased from 32.2% in the age group 65 to 74 to 14.5% in the age group 75 to 84 and 4.9% in the 85 and older age group. For both genders, having seen or talked to a general practitioner increased the odds of HIT use. However, having seen or talked to a medical specialist, eye doctor, or physical therapist/occupational therapist (PT/OT) were significantly associated with HIT use only for older women, while having seen or talked to a mental health professional only marginally increased the odds of HIT use only for older men. Having visited or talked to a chiropractor and having had overnight hospitalization, surgery, and/or homecare services were not associated with the odds of HIT use for either gender. Older-adult users of general health services were more likely to use HIT than nonusers of general health services, while older-adult users of specialized health services were not different from nonusers of specialized health services in their odds of HIT use. The findings have implications for narrowing the age-related and socioeconomic status-related gaps in HIT use. The access gaps among racial/ethnic minority older adults and poorly educated and/or low-income older adults are especially striking and call for concerted efforts to facilitate Internet access and HIT use among these disadvantaged older adults.

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.

Developing a Health Information Technology Systems Matrix: A Qualitative Participatory Approach

PubMed Central

Chavez, Margeaux; Nazi, Kim M; Antinori, Nicole

2016-01-01

Background The US Department of Veterans Affairs (VA) has developed various health information technology (HIT) resources to provide accessible veteran-centered health care. Currently, the VA is undergoing a major reorganization of VA HIT to develop a fully integrated system to meet consumer needs. Although extensive system documentation exists for various VA HIT systems, a more centralized and integrated perspective with clear documentation is needed in order to support effective analysis, strategy, planning, and use. Such a tool would enable a novel view of what is currently available and support identifying and effectively capturing the consumer’s vision for the future. Objective The objective of this study was to develop the VA HIT Systems Matrix, a novel tool designed to describe the existing VA HIT system and identify consumers’ vision for the future of an integrated VA HIT system. Methods This study utilized an expert panel and veteran informant focus groups with self-administered surveys. The study employed participatory research methods to define the current system and understand how stakeholders and veterans envision the future of VA HIT and interface design (eg, look, feel, and function). Directed content analysis was used to analyze focus group data. Results The HIT Systems Matrix was developed with input from 47 veterans, an informal caregiver, and an expert panel to provide a descriptive inventory of existing and emerging VA HIT in four worksheets: (1) access and function, (2) benefits and barriers, (3) system preferences, and (4) tasks. Within each worksheet is a two-axis inventory. The VA’s existing and emerging HIT platforms (eg, My HealtheVet, Mobile Health, VetLink Kiosks, Telehealth), My HealtheVet features (eg, Blue Button, secure messaging, appointment reminders, prescription refill, vet library, spotlight, vitals tracker), and non-VA platforms (eg, phone/mobile phone, texting, non-VA mobile apps, non-VA mobile electronic devices, non-VA websites) are organized by row. Columns are titled with thematic and functional domains (eg, access, function, benefits, barriers, authentication, delegation, user tasks). Cells for each sheet include descriptions and details that reflect factors relevant to domains and the topic of each worksheet. Conclusions This study provides documentation of the current VA HIT system and efforts for consumers’ vision of an integrated system redesign. The HIT Systems Matrix provides a consumer preference blueprint to inform the current VA HIT system and the vision for future development to integrate electronic resources within VA and beyond with non-VA resources. The data presented in the HIT Systems Matrix are relevant for VA administrators and developers as well as other large health care organizations seeking to document and organize their consumer-facing HIT resources. PMID:27713112

Developing a Health Information Technology Systems Matrix: A Qualitative Participatory Approach.

PubMed

Haun, Jolie N; Chavez, Margeaux; Nazi, Kim M; Antinori, Nicole

2016-10-06

The US Department of Veterans Affairs (VA) has developed various health information technology (HIT) resources to provide accessible veteran-centered health care. Currently, the VA is undergoing a major reorganization of VA HIT to develop a fully integrated system to meet consumer needs. Although extensive system documentation exists for various VA HIT systems, a more centralized and integrated perspective with clear documentation is needed in order to support effective analysis, strategy, planning, and use. Such a tool would enable a novel view of what is currently available and support identifying and effectively capturing the consumer's vision for the future. The objective of this study was to develop the VA HIT Systems Matrix, a novel tool designed to describe the existing VA HIT system and identify consumers' vision for the future of an integrated VA HIT system. This study utilized an expert panel and veteran informant focus groups with self-administered surveys. The study employed participatory research methods to define the current system and understand how stakeholders and veterans envision the future of VA HIT and interface design (eg, look, feel, and function). Directed content analysis was used to analyze focus group data. The HIT Systems Matrix was developed with input from 47 veterans, an informal caregiver, and an expert panel to provide a descriptive inventory of existing and emerging VA HIT in four worksheets: (1) access and function, (2) benefits and barriers, (3) system preferences, and (4) tasks. Within each worksheet is a two-axis inventory. The VA's existing and emerging HIT platforms (eg, My HealtheVet, Mobile Health, VetLink Kiosks, Telehealth), My HealtheVet features (eg, Blue Button, secure messaging, appointment reminders, prescription refill, vet library, spotlight, vitals tracker), and non-VA platforms (eg, phone/mobile phone, texting, non-VA mobile apps, non-VA mobile electronic devices, non-VA websites) are organized by row. Columns are titled with thematic and functional domains (eg, access, function, benefits, barriers, authentication, delegation, user tasks). Cells for each sheet include descriptions and details that reflect factors relevant to domains and the topic of each worksheet. This study provides documentation of the current VA HIT system and efforts for consumers' vision of an integrated system redesign. The HIT Systems Matrix provides a consumer preference blueprint to inform the current VA HIT system and the vision for future development to integrate electronic resources within VA and beyond with non-VA resources. The data presented in the HIT Systems Matrix are relevant for VA administrators and developers as well as other large health care organizations seeking to document and organize their consumer-facing HIT resources.

Preparing Tutors to Hit the Ground Running: Lessons from New Tutors' Experiences

ERIC Educational Resources Information Center

Calma, Angelito

2013-01-01

Tutor development is an essential part of academic staff development, yet is comparatively under-researched. This article examines what tutors value as most and least important in a program. Using data from more than 300 participants in three years, and using the dimensions or worth, merit and success as an analytical framework, the article…

Practical Secondary Education: Planning for Cost-Effectiveness in Less Developed Countries.

ERIC Educational Resources Information Center

Chisman, Dennis

Public pressure for expansion of secondary and higher education has forced governments of several developing countries to urgently seek ways to meet this demand. Many of these countries have been hard hit by debt and high world interest rates. At their 1984 conference, Commonwealth Ministers of Education requested the Secretariat to examine ways…

Acute intraoperative heparin-induced thrombocytopenia (HIT) and thrombosis during coronary artery bypass grafting: Two case reports providing evidence for the role of preoperative LMWH in triggering sensitization.

PubMed

Khoury, M; Pitsis, A; Poumpouridou-Kioura, H; Soufla, G; Kanthou, C; Matoula, N; Angelidis, A; Melissari, E

2016-10-01

Systemic anticoagulation is necessary during cardiac surgery. To date, the only well established anticoagulation protocol involves the use of heparin. However, heparin can cause heparin-induced thrombocytopenia (HIT) a potentially life threatening immune-mediated thromboembolic syndrome. Until now, devastating consequences of HIT syndrome in patients undergoing heart surgery have been described, but only postoperatively. Here we report the development of HIT syndrome during cardiac revascularization by intra-operative heparin administration in two patients previously exposed to LMWH. We report on two patients who developed rapid and profound intravascular coagulation with severe thrombocytopenia (platelet count decreased from ≥250×10 9 /L to 50×10 9 /L) due to HIT development caused by heparin administration during coronary artery bypass graft surgery. In addition we report that fondaparinux, given intra-operatively in association with antithrombin, may be a suitable alternative anticoagulant for successfully preventing the devastating consequences of intra-operative HIT development. To our knowledge, this is the first report describing the development of acute intra-operative HIT, secondary to high-dose UFH administered for coronary revascularization, in which the unexpected presence of platelet-activating anti-PF4/heparin antibodies at surgery was explained by preoperative administration of a one-week course of LMWH but without any preoperative evidence for HIT. Copyright © 2016 Elsevier Ltd. All rights reserved.

A network collaboration implementing technology to improve medication dispensing and administration in critical access hospitals.

PubMed

Wakefield, Douglas S; Ward, Marcia M; Loes, Jean L; O'Brien, John

2010-01-01

We report how seven independent critical access hospitals collaborated with a rural referral hospital to standardize workflow policies and procedures while jointly implementing the same health information technologies (HITs) to enhance medication care processes. The study hospitals implemented the same electronic health record, computerized provider order entry, pharmacy information systems, automated dispensing cabinets (ADC), and barcode medication administration systems. We conducted interviews and examined project documents to explore factors underlying the successful implementation of ADC and barcode medication administration across the network hospitals. These included a shared culture of collaboration; strategic sequencing of HIT component implementation; interface among HIT components; strategic placement of ADCs; disciplined use and sharing of workflow analyses linked with HIT applications; planning for workflow efficiencies; acquisition of adequate supply of HIT-related devices; and establishing metrics to monitor HIT use and outcomes.

Inhibitory control differentiates rare target search performance in children.

PubMed

Li, Hongting; Chan, John S Y; Cheung, Sui-Yin; Yan, Jin H

2012-02-01

Age-related differences in rare-target search are primarily explained by the speed-accuracy trade-off, primed responses, or decision making. The goal was to examine how motor inhibition influences visual search. Children pressed a key when a rare target was detected. On no-target trials, children withheld reactions. Response time (RT), hits, misses, correct rejection, and false alarms were measured. Tapping tests assessed motor control. Older children tapped faster, were more sensitive to rare targets (higher d'), and reacted more slowly than younger ones. Girls outperformed boys in search sensitivity but not in RT. Motor speed was closely associated with hit rate and RT. Results suggest that development of inhibitory control plays a key role in visual detection. The potential implications for cognitive-motor development and individual differences are discussed.

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.

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...

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

The effects of health information technology adoption and hospital-physician integration on hospital efficiency.

PubMed

Cho, Na-Eun; Chang, Jongwha; Atems, Bebonchu

2014-11-01

To determine the impact of health information technology (HIT) adoption and hospital-physician integration on hospital efficiency. Using 2010 data from the American Hospital Association's (AHA) annual survey, the AHA IT survey, supplemented by the CMS Case Mix Index, and the US Census Bureau's small area income and poverty estimates, we examined how the adoption of HIT and employment of physicians affected hospital efficiency and whether they were substitutes or complements. The sample included 2173 hospitals. We employed a 2-stage approach. In the first stage, data envelopment analysis was used to estimate technical efficiency of hospitals. In the second stage, we used instrumental variable approaches, notably 2-stage least squares and the generalized method of moments, to examine the effects of IT adoption and integration on hospital efficiency. We found that HIT adoption and hospital-physician integration, when considered separately, each have statistically significant positive impacts on hospital efficiency. Also, we found that hospitals that adopted HIT with employed physicians will achieve less efficiency compared with hospitals that adopted HIT without employed physicians. Although HIT adoption and hospital-physician integration both seem to be key parts of improving hospital efficiency when one or the other is utilized individually, they can hurt hospital efficiency when utilized together.

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.

Ethical Issues in Corpus Linguistics And Annotation

PubMed Central

Cohen, K. Bretonnel; Fort, Karën; Adda, Gilles; Zhou, Sophia; Farri, Dimeji

2017-01-01

Ethical issues reported with paid crowdsourcing include unfairly low wages. It is assumed that such issues are under the control of the task requester. Can one control the amount that a worker earns by controlling the amount that one pays? 412 linguistic data development tasks were submitted to Amazon Mechanical Turk. The pay per HIT was manipulated through a range of values. We examined the relationship between the pay that is offered per HIT and the effective pay rate. There is no such relationship. Paying more per HIT does not cause workers to earn more: the higher the pay per HIT, the more time workers spend on them (R = 0.92). So, the effective hourly rate stays roughly the same. The finding has clear implications for language resource builders who want to behave ethically: other means must be found in order to compensate workers fairly. The findings of this paper should not be taken as an endorsement of unfairly low pay rates for crowdsourcing workers. Rather, the intention is to point out that additional measures, such as pre-calculating and communicating to the workers an average hourly, rather than per-task, rate must be found in order to ensure an ethical rate of pay. PMID:29568822

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.

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.

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...

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...

Visual strategies underpinning the development of visual-motor expertise when hitting a ball.

PubMed

Sarpeshkar, Vishnu; Abernethy, Bruce; Mann, David L

2017-10-01

It is well known that skilled batters in fast-ball sports do not align their gaze with the ball throughout ball-flight, but instead adopt a unique sequence of eye and head movements that contribute toward their skill. However, much of what we know about visual-motor behavior in hitting is based on studies that have employed case study designs, and/or used simplified tasks that fall short of replicating the spatiotemporal demands experienced in the natural environment. The aim of this study was to provide a comprehensive examination of the eye and head movement strategies that underpin the development of visual-motor expertise when intercepting a fast-moving target. Eye and head movements were examined in situ for 4 groups of cricket batters, who were crossed for playing level (elite or club) and age (U19 or adult), when hitting balls that followed either straight or curving ('swinging') trajectories. The results provide support for some widely cited markers of expertise in batting, while questioning the legitimacy of others. Swinging trajectories alter the visual-motor behavior of all batters, though in large part because of the uncertainty generated by the possibility of a variation in trajectory rather than any actual change in trajectory per se. Moreover, curving trajectories influence visual-motor behavior in a nonlinear fashion, with targets that curve away from the observer influencing behavior more than those that curve inward. The findings provide a more comprehensive understanding of the development of visual-motor expertise in interception. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

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.

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.

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.

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...

HITCal: a software tool for analysis of video head impulse test responses.

PubMed

Rey-Martinez, Jorge; Batuecas-Caletrio, Angel; Matiño, Eusebi; Perez Fernandez, Nicolás

2015-09-01

The developed software (HITCal) may be a useful tool in the analysis and measurement of the saccadic video head impulse test (vHIT) responses and with the experience obtained during its use the authors suggest that HITCal is an excellent method for enhanced exploration of vHIT outputs. To develop a (software) method to analyze and explore the vHIT responses, mainly saccades. HITCal was written using a computational development program; the function to access a vHIT file was programmed; extended head impulse exploration and measurement tools were created and an automated saccade analysis was developed using an experimental algorithm. For pre-release HITCal laboratory tests, a database of head impulse tests (HITs) was created with the data collected retrospectively in three reference centers. This HITs database was evaluated by humans and was also computed with HITCal. The authors have successfully built HITCal and it has been released as open source software; the developed software was fully operative and all the proposed characteristics were incorporated in the released version. The automated saccades algorithm implemented in HITCal has good concordance with the assessment by human observers (Cohen's kappa coefficient = 0.7).

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.

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.

High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors.

PubMed

Myers, Stephanie M; Bawn, Ruth H; Bisset, Louise C; Blackburn, Timothy J; Cottyn, Betty; Molyneux, Lauren; Wong, Ai-Ching; Cano, Celine; Clegg, William; Harrington, Ross W; Leung, Hing; Rigoreau, Laurent; Vidot, Sandrine; Golding, Bernard T; Griffin, Roger J; Hammonds, Tim; Newell, David R; Hardcastle, Ian R

2016-08-08

The extracellular-related kinase 5 (ERK5) is a promising target for cancer therapy. A high-throughput screen was developed for ERK5, based on the IMAP FP progressive binding system, and used to identify hits from a library of 57 617 compounds. Four distinct chemical series were evident within the screening hits. Resynthesis and reassay of the hits demonstrated that one series did not return active compounds, whereas three series returned active hits. Structure-activity studies demonstrated that the 4-benzoylpyrrole-2-carboxamide pharmacophore had excellent potential for further development. The minimum kinase binding pharmacophore was identified, and key examples demonstrated good selectivity for ERK5 over p38α kinase.

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.

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.

A participatory approach to designing and enhancing integrated health information technology systems for veterans: protocol.

PubMed

Haun, Jolie N; Nazi, Kim M; Chavez, Margeaux; Lind, Jason D; Antinori, Nicole; Gosline, Robert M; Martin, Tracey L

2015-02-27

The Department of Veterans Affairs (VA) has developed health information technologies (HIT) and resources to improve veteran access to health care programs and services, and to support a patient-centered approach to health care delivery. To improve VA HIT access and meaningful use by veterans, it is necessary to understand their preferences for interacting with various HIT resources to accomplish health management related tasks and to exchange information. The objective of this paper was to describe a novel protocol for: (1) developing a HIT Digital Health Matrix Model; (2) conducting an Analytic Hierarchy Process called pairwise comparison to understand how and why veterans want to use electronic health resources to complete tasks related to health management; and (3) developing visual modeling simulations that depict veterans' preferences for using VA HIT to manage their health conditions and exchange health information. The study uses participatory research methods to understand how veterans prefer to use VA HIT to accomplish health management tasks within a given context, and how they would like to interact with HIT interfaces (eg, look, feel, and function) in the future. This study includes two rounds of veteran focus groups with self-administered surveys and visual modeling simulation techniques. This study will also convene an expert panel to assist in the development of a VA HIT Digital Health Matrix Model, so that both expert panel members and veteran participants can complete an Analytic Hierarchy Process, pairwise comparisons to evaluate and rank the applicability of electronic health resources for a series of health management tasks. This protocol describes the iterative, participatory, and patient-centered process for: (1) developing a VA HIT Digital Health Matrix Model that outlines current VA patient-facing platforms available to veterans, describing their features and relevant contexts for use; and (2) developing visual model simulations based on direct veteran feedback that depict patient preferences for enhancing the synchronization, integration, and standardization of VA patient-facing platforms. Focus group topics include current uses, preferences, facilitators, and barriers to using electronic health resources; recommendations for synchronizing, integrating, and standardizing VA HIT; and preferences on data sharing and delegation within the VA system. This work highlights the practical, technological, and personal factors that facilitate and inhibit use of current VA HIT, and informs an integrated system redesign. The Digital Health Matrix Model and visual modeling simulations use knowledge of veteran preferences and experiences to directly inform enhancements to VA HIT and provide a more holistic and integrated user experience. These efforts are designed to support the adoption and sustained use of VA HIT to support patient self-management and clinical care coordination in ways that are directly aligned with veteran preferences.

A Participatory Approach to Designing and Enhancing Integrated Health Information Technology Systems for Veterans: Protocol

PubMed Central

Nazi, Kim M; Chavez, Margeaux; Lind, Jason D; Antinori, Nicole; Gosline, Robert M; Martin, Tracey L

2015-01-01

Background The Department of Veterans Affairs (VA) has developed health information technologies (HIT) and resources to improve veteran access to health care programs and services, and to support a patient-centered approach to health care delivery. To improve VA HIT access and meaningful use by veterans, it is necessary to understand their preferences for interacting with various HIT resources to accomplish health management related tasks and to exchange information. Objective The objective of this paper was to describe a novel protocol for: (1) developing a HIT Digital Health Matrix Model; (2) conducting an Analytic Hierarchy Process called pairwise comparison to understand how and why veterans want to use electronic health resources to complete tasks related to health management; and (3) developing visual modeling simulations that depict veterans’ preferences for using VA HIT to manage their health conditions and exchange health information. Methods The study uses participatory research methods to understand how veterans prefer to use VA HIT to accomplish health management tasks within a given context, and how they would like to interact with HIT interfaces (eg, look, feel, and function) in the future. This study includes two rounds of veteran focus groups with self-administered surveys and visual modeling simulation techniques. This study will also convene an expert panel to assist in the development of a VA HIT Digital Health Matrix Model, so that both expert panel members and veteran participants can complete an Analytic Hierarchy Process, pairwise comparisons to evaluate and rank the applicability of electronic health resources for a series of health management tasks. Results This protocol describes the iterative, participatory, and patient-centered process for: (1) developing a VA HIT Digital Health Matrix Model that outlines current VA patient-facing platforms available to veterans, describing their features and relevant contexts for use; and (2) developing visual model simulations based on direct veteran feedback that depict patient preferences for enhancing the synchronization, integration, and standardization of VA patient-facing platforms. Focus group topics include current uses, preferences, facilitators, and barriers to using electronic health resources; recommendations for synchronizing, integrating, and standardizing VA HIT; and preferences on data sharing and delegation within the VA system. Conclusions This work highlights the practical, technological, and personal factors that facilitate and inhibit use of current VA HIT, and informs an integrated system redesign. The Digital Health Matrix Model and visual modeling simulations use knowledge of veteran preferences and experiences to directly inform enhancements to VA HIT and provide a more holistic and integrated user experience. These efforts are designed to support the adoption and sustained use of VA HIT to support patient self-management and clinical care coordination in ways that are directly aligned with veteran preferences. PMID:25803324

Low incidence of heparin-induced skin lesions in orthopedic surgery patients with low-molecular-weight heparins.

PubMed

Schindewolf, M; Paulik, M; Kroll, H; Kaufmann, R; Wolter, M; Boehncke, W-H; Lindhoff-Last, E; Recke, A; Ludwig, R J

2018-04-23

Heparins are widely prescribed for prevention and therapy of arterial and venous thromboembolic diseases. Heparin-induced skin lesions are the most frequent adverse effects of subcutaneous heparin treatment in non-surgical patients (7.5-39.8%); no data exist on surgical patients. Commonly, they are due to a delayed-type hypersensitivity reaction (DTH), but may also be a manifestation of life-threatening heparin-induced thrombocytopenia (HIT). Lesions of both entities resemble initially. The risk of HIT is highest among heparin-anticoagulated orthopedic surgery patients. To determine incidence and causes of heparin-induced skin lesions in major orthopedic surgery patients. In a prospective cohort study consecutive patients with subcutaneous low-molecular-weight heparin (LMWH) treatment were examined for cutaneous adverse effects. Further diagnostics (skin biopsy, clinical/laboratory assessment for thrombosis, bleeding, HIT, cross-allergies) were performed. Six of 316 enrolled patients (1.9%; 95% CI 0.4%-3.4%) developed heparin-induced skin lesions. All were caused by a DTH reaction, none was due to HIT or other rare heparin-associated skin diseases. Therapeutic use (dosage) of LMWH was identified as only risk factor (odds ratio: 3.1, 95%CI: 1.4-4.9; p=0.00141). In addition to DTH, 5 thromboembolic, 4 major bleeding complications but no cases of HIT or cross-allergies were observed. Orthopedic surgery patients have - unlike non-surgical patients - a low risk for heparin-induced skin lesions during LMWH treatment; all lesions were due to a DTH reaction. The risk for DTH differs considerably between individual patient cohorts. No association with HIT was observed. These data help to tailor anticoagulatory treatment individually and to increase patient safety. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nedley Depression Hit Hypothesis: Identifying Depression and Its Causes.

PubMed

Nedley, Neil; Ramirez, Francisco E

2016-11-01

Depression is often diagnosed using the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle choices and non-modifiable factors can predict the development of depression. We identified 10 cause categories (hits or "blows" to the brain) and theorize that four or more active hits could trigger a depression episode. Methods. A sample of 4271 participants from our community-based program (70% female; ages 17-94 years) was assessed at baseline and at the eighth week of the program using a custom test. Ten cause categories were examined as predictors of depression are (1) Genetic, (2)Developmental, (3)Lifestyle, (4)Circadian Rhythm, (5)Addiction, (6)Nutrition, (7)Toxic, (8)Social/Complicated Grief, (9)Medical Condition, and (10)Frontal Lobe. Results. The relationship between the DSM-5 score and a person having four hits categories in the first program week showed a sensitivity of 89.98 % (95% CI: 89.20 % - 90.73%), specificity 48.84% (CI 45.94-51.75) and Matthew Correlation Coefficient (MCC) .41 . For the eight-week test, the results showed a sensitivity 83.6% (CI 81.9-85.5), specificity 53.7% (CI 51.7-55.6) and MCC .38. Overall, the hits that improved the most from baseline after the eighth week were: Nutrition (47%), Frontal lobe (36%), Addiction (24%), Circadian rhythm (24%), Lifestyle (20%), Social (12%) and Medical (10%). Conclusions. The Nedley four-hit hypothesis seems to predict a depressive episode and correlates well with the DSM-5 criteria with good sensitivity and MCC but less specificity. Identifying these factors and applying lifestyle therapies could play an important role in the treatment of depressed individuals.

An Overview of Research and Design Activities at CTFusion

NASA Astrophysics Data System (ADS)

Sutherland, D. A.; Jarboe, T. R.; Hossack, A. C.

2016-10-01

CTFusion, a newly formed company dedicated to the development of compact, toroidal fusion energy, is a spin-off from the University of Washington that will build upon the successes of the HIT-SI research program. The mission of the company to develop net-gain fusion power cores that will serve as the heart of economical fusion power plants or radioactive-waste destroying burner reactors. The overarching vision and development plan of the company will be presented, along with a detailed justification and design for our next device, the HIT-TD (Technology Demonstration) prototype. By externally driving the edge current and imposing non-axisymmetric magnetic perturbations, HIT-TD should demonstrate the sustainment of stable spheromak configurations with Imposed-Dynamo Current Drive (IDCD), as was accomplished in the HIT-SI device, with higher current gains and temperatures than previously possible. HIT-TD, if successful, will be an instrumental step along this path to economical fusion energy, and will serve as the stepping stone to our Proof-Of-Principle device (HIT-PoP). Beyond the implications of higher performance, sustained spheromaks for fusion applications, the HIT-TD platform will provide a unique system to observe plasma self-organizational phenomena of interest for other fusion devices, and astrophysical systems as well. Lastly, preliminary nuclear engineering design simulations with the MCNP6 code of the HIT-FNSF (Fusion Nuclear Science Facility) device will be presented.

Mapping from disease-specific measures to health-state utility values in individuals with migraine.

PubMed

Gillard, Patrick J; Devine, Beth; Varon, Sepideh F; Liu, Lei; Sullivan, Sean D

2012-05-01

The objective of this study was to develop empirical algorithms that estimate health-state utility values from disease-specific quality-of-life scores in individuals with migraine. Data from a cross-sectional, multicountry study were used. Individuals with episodic and chronic migraine were randomly assigned to training or validation samples. Spearman's correlation coefficients between paired EuroQol five-dimensional (EQ-5D) questionnaire utility values and both Headache Impact Test (HIT-6) scores and Migraine-Specific Quality-of-Life Questionnaire version 2.1 (MSQ) domain scores (role restrictive, role preventive, and emotional function) were examined. Regression models were constructed to estimate EQ-5D questionnaire utility values from the HIT-6 score or the MSQ domain scores. Preferred algorithms were confirmed in the validation samples. In episodic migraine, the preferred HIT-6 and MSQ algorithms explained 22% and 25% of the variance (R(2)) in the training samples, respectively, and had similar prediction errors (root mean square errors of 0.30). In chronic migraine, the preferred HIT-6 and MSQ algorithms explained 36% and 45% of the variance in the training samples, respectively, and had similar prediction errors (root mean square errors 0.31 and 0.29). In episodic and chronic migraine, no statistically significant differences were observed between the mean observed and the mean estimated EQ-5D questionnaire utility values for the preferred HIT-6 and MSQ algorithms in the validation samples. The relationship between the EQ-5D questionnaire and the HIT-6 or the MSQ is adequate to use regression equations to estimate EQ-5D questionnaire utility values. The preferred HIT-6 and MSQ algorithms will be useful in estimating health-state utilities in migraine trials in which no preference-based measure is present. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Acute high-intensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycaemia in patients with type 2 diabetes.

PubMed

Gillen, J B; Little, J P; Punthakee, Z; Tarnopolsky, M A; Riddell, M C; Gibala, M J

2012-06-01

High-volume endurance exercise (END) improves glycaemic control in type 2 diabetes (T2D) but many individuals cite 'lack of time' as a barrier to regular participation. High-intensity interval training (HIT) is a time-efficient method to induce physiological adaptations similar to END, but little is known regarding the effect of HIT in T2D. Using continuous glucose monitoring (CGM), we examined the 24-h blood glucose response to one session of HIT consisting of 10 × 60 s cycling efforts at ~90% maximal heart rate, interspersed with 60 s rest. Seven adults with T2D underwent CGM for 24-h on two occasions under standard dietary conditions: following acute HIT and on a non-exercise control day (CTL). HIT reduced hyperglycaemia measured as proportion of time spent above 10 mmol/l (HIT: 4.5 ± 4.4 vs. CTL: 15.2 ± 12.3%, p = 0.04). Postprandial hyperglycaemia, measured as the sum of post-meal areas under the glucose curve, was also lower after HIT vs. CTL (728 ± 331 vs. 1142 ± 556 mmol/l·9 h, p = 0.01). These findings highlight the potential for HIT to improve glycaemic control in T2D. © 2012 Blackwell Publishing Ltd.

Using statistical text classification to identify health information technology incidents

PubMed Central

Chai, Kevin E K; Anthony, Stephen; Coiera, Enrico; Magrabi, Farah

2013-01-01

Objective To examine the feasibility of using statistical text classification to automatically identify health information technology (HIT) incidents in the USA Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database. Design We used a subset of 570 272 incidents including 1534 HIT incidents reported to MAUDE between 1 January 2008 and 1 July 2010. Text classifiers using regularized logistic regression were evaluated with both ‘balanced’ (50% HIT) and ‘stratified’ (0.297% HIT) datasets for training, validation, and testing. Dataset preparation, feature extraction, feature selection, cross-validation, classification, performance evaluation, and error analysis were performed iteratively to further improve the classifiers. Feature-selection techniques such as removing short words and stop words, stemming, lemmatization, and principal component analysis were examined. Measurements κ statistic, F1 score, precision and recall. Results Classification performance was similar on both the stratified (0.954 F1 score) and balanced (0.995 F1 score) datasets. Stemming was the most effective technique, reducing the feature set size to 79% while maintaining comparable performance. Training with balanced datasets improved recall (0.989) but reduced precision (0.165). Conclusions Statistical text classification appears to be a feasible method for identifying HIT reports within large databases of incidents. Automated identification should enable more HIT problems to be detected, analyzed, and addressed in a timely manner. Semi-supervised learning may be necessary when applying machine learning to big data analysis of patient safety incidents and requires further investigation. PMID:23666777

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.

Knudson's hypothesis revisited in Indian retinoblastoma patients.

PubMed

Gaikwad, Namrata; Vanniarajan, Ayyasamy; Husain, Akram; Jeyaram, Illaiyaraja; Thirumalairaj, Kannan; Santhi, Radhakrishnan; Muthukkaruppan, Veerappan; Kim, Usha

2015-12-01

Retinoblastoma (RB) is the most common primary intraocular malignancy affecting children under 5 years of age. This study aims to correlate the clinical parameters with RB1 mutation in the light of Knudson's two-hit hypothesis in Indian RB patients. We analyzed the clinical details of 73 RB patients visiting Aravind Eye Hospital, Madurai, India, between January and October 2012. Data on gender, presenting age and sign, laterality, number of tumors in each eye and family history were collected. A semi log plot was derived based on Knudson's two-hit hypothesis. Genetic analysis of RB1 was carried out to identify the two hits. The mean age at diagnosis for unilateral and bilateral cases was 24.0 ± 15.1 and 9.8 ± 11.5 months, respectively. Familial RB was seen in 13 (17.8%) patients of whom 11 were bilateral. Multiple tumors were observed more frequently in bilateral than in unilateral cases. All unilateral and bilateral patients followed the two-hit and one-hit curves, respectively, confirming Knudson's hypothesis in Indian patients. Genetic analysis identified two somatic mutations in tumor samples of sporadic unilateral cases. Among the two bilateral patients, one received the first hit from her father and the other patient developed a de novo germline mutation during early development. The two-hit hypothesis has been reestablished in Indian patients. Genetic analysis of tumor samples has also complemented the statistical analysis to reaffirm the two hits in tumor development. © 2015 Wiley Publishing Asia Pty Ltd.

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.

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.

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.

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.

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.

A complex adaptive systems perspective of health information technology implementation.

PubMed

Keshavjee, Karim; Kuziemsky, Craig; Vassanji, Karim; Ghany, Ahmad

2013-01-01

Implementing health information technology (HIT) is a challenge because of the complexity and multiple interactions that define HIT implementation. Much of the research on HIT implementation is descriptive in nature and has focused on distinct processes such as order entry or decision support. These studies fail to take into account the underlying complexity of the processes, people and settings that are typical of HIT implementations. Complex adaptive systems (CAS) is a promising field that could elucidate the complexity and non-linear interacting issues that are typical in HIT implementation. Initially we sought new models that would enable us to better understand the complex nature of HIT implementation, to proactively identify problem issues that could be a precursor to unintended consequences and to develop new models and new approaches to successful HIT implementations. Our investigation demonstrates that CAS does not provide prediction, but forces us to rethink our HIT implementation paradigms and question what we think we know. CAS provides new ways to conceptualize HIT implementation and suggests new approaches to increasing HIT implementation successes.

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.

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.

Relationships between Parents' Use of Corporal Punishment and Their Children's Endorsement of Spanking and Hitting Other Children

ERIC Educational Resources Information Center

Simons, Dominique A.; Wurtele, Sandy K.

2010-01-01

Objectives: 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. Method: Participants consisted of…

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…

Factors influencing nurses' attitudes towards healthcare information technology.

PubMed

Huryk, Laurie A

2010-07-01

This literature review examines the current trend in nurses' attitudes toward healthcare information technology (HIT). HIT implementation and expansion are at the core of global efforts to improve healthcare quality and patient safety. As a large portion of the healthcare workforce, nurses' attitudes towards HIT are likely to have a major impact on the electronic health record (EHR) implementation process. A search of PubMed, CINAHL and Medline databases produced 1930 combined hits. Returned articles were scanned for relevancy and applicability. Thirteen articles met all criteria and were subsequently reviewed in their entirety. In accordance with two change theories, if HIT implementation projects are to be successful, nurses must recognize that incorporating EHRs into their daily practice is beneficial to patient outcomes. Overall, the attitudes of nurses toward HIT are positive. Increased computer experience is the main demographic indicator for positive attitudes. The most common detractors are poor system design, system slowdown and system downtime. Nurses are also fearful that the use of technology will dehumanize patient care. Involving nurses in system design is likely to improve post-implementation satisfaction. Creating a positive, supportive atmosphere appears to be instrumental to sustainability.

Developments in Participatory Design of Health Information Technology - A Review of PDC Publications from 1990-2016.

PubMed

Kanstrup, Anne Marie; Madsen, Jacob; Nøhr, Christian; Bygholm, Ann; Bertelsen, Pernille

2017-01-01

The landscape of Participatory Design (PD) of Health Information Technology (HIT) is diverse and constantly evolving. This paper reviews the publications in the proceedings from the Participatory Design Conferences (PDCs) that have been held every two years since 1990. We used the Matrix Method to identify, describe and synthesise HIT publications from the proceedings. A total of 47 papers were included in the review and analysed in relation to six themes. The analysis reveals a significant volume of HIT research at PDCs, with a large amount of attention to digitalisation of health information, work procedures, records, secondary healthcare and health professionals. However, the analysis also shows a development from a primary focus on health workers and hospitals to a recent attention on HIT in everyday life and PD with patients, relatives, neighbourhoods and citizens in general. Additionally, the review shows a growing number of PD methods being applied. This paper concludes that research on PD and HIT appears to be maturing and developing with ongoing technological and societal development.

The effect of health information technology implementation in Veterans Health Administration hospitals on patient outcomes.

PubMed

Spetz, Joanne; Burgess, James F; Phibbs, Ciaran S

2014-03-01

The impact of health information technology (HIT) in hospitals is dependent in large part on how it is used by nurses. This study examines the impact of HIT on the quality of care in hospitals in the Veterans Health Administration (VA), focusing on nurse-sensitive outcomes from 1995 to 2005. Data were obtained from VA databases and original data collection. Fixed-effects Poisson regression was used, with the dependent variables measured using the Agency for Healthcare Research and Quality Inpatient Quality Indicators and Patient Safety Indicators software. Dummy variables indicated when each facility began and completed implementation of each type of HIT. Other explanatory variables included hospital volume, patient characteristics, nurse characteristics, and a quadratic time trend. The start of computerized patient record implementation was associated with significantly lower mortality for two diagnoses but significantly higher pressure ulcer rates, and full implementation was associated with significantly more hospital-acquired infections. The start of bar-code medication administration implementation was linked to significantly lower mortality for one diagnosis, but full implementation was not linked to any change in patient outcomes. The commencement of HIT implementation had mixed effects on patient outcomes, and the completion of implementation had little or no effect on outcomes. This longitudinal study provides little support for the perception of VA staff and leaders that HIT has improved mortality rates or nurse-sensitive patient outcomes. Future research should examine patient outcomes associated with specific care processes affected by HIT. Copyright © 2014 Elsevier Inc. All rights reserved.

Film in the College Classroom: Using "Twilight" to Examine Adolescent Development

ERIC Educational Resources Information Center

Tagsold, Jennifer T.; Decuir-Gunby, Jessica

2012-01-01

The hit movie saga "Twilight" has made an impact on viewers of all ages. This article seeks to explore the uses of film in psychology classes with a focus on ways in which instructors may find scenes from the "Twilight" series helpful and engaging for students. The authors describe scenes and themes from the first three movies…

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.

A biomechanical comparison in the lower limb and lumbar spine between a hit and drag flick in field hockey.

PubMed

Ng, Leo; Rosalie, Simon M; Sherry, Dorianne; Loh, Wei Bing; Sjurseth, Andreas M; Iyengar, Shrikant; Wild, Catherine Y

2018-03-01

Research has revealed that field hockey drag flickers have greater odds of hip and lumbar injuries compared to non-drag flickers (DF). This study aimed to compare the biomechanics of a field hockey hit and a specialised field hockey drag flick. Eighteen male and seven female specialised hockey DF performed a hit and a drag flick in a motion analysis laboratory with an 18-camera three-dimensional motion analysis system and a calibrated multichannel force platform to examine differences in lower limb and lumbar kinematics and kinetics. Results revealed that drag flicks were performed with more of a forward lunge on the left lower limb resulting in significantly greater left ankle dorsiflexion, knee, hip and lumbar flexion (Ps<0.001) compared to a hit. Drag flicks were also performed with significantly greater lateral flexion (P < 0.002) and rotation of the lumbar spine (P < 0.006) compared to a hit. Differences in kinematics lead to greater shear, compression and tensile forces in multiple left lower limb and lumbar joints in the drag flick compared to the hit (P < 0.05). The biomechanical differences in drag flicks compared to a hit may have ramifications with respect to injury in field hockey drag flickers.

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.

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

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

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.

An Archer's Perceived Form Scales the "Hitableness" of Archery Targets

ERIC Educational Resources Information Center

Lee, Yang; Lee, Sih; Carello, Claudia; Turvey, M. T.

2012-01-01

For skills that involve hitting a target, subsequent judgments of target size correlate with prior success in hitting that target. We used an archery context to examine the judgment-success relationship with varied target sizes in the absence of explicit knowledge of results. Competitive archers shot at targets 50 m away that varied in size among…

Comparing among the Experiences of Self-Cutting, Hitting, and Scratching in Chinese Adolescents Attending Secondary Schools: An Interview Study

ERIC Educational Resources Information Center

You, Jianing; Ma, Congfen; Lin, Min-Pei; Leung, Freedom

2015-01-01

This study examined adolescents' experiences associated with nonsuicidal self-injury (NSSI) and compared among the experiences of self-cutting, hitting, and scratching. Participants included 42 Chinese adolescents attending secondary schools. They had at least three NSSI episodes in the preceding year. Information about their experiences of NSSI…

Integration of the enterprise electronic health record and anesthesia information management systems.

PubMed

Springman, Scott R

2011-09-01

Fewer than 5% of anesthesia departments use an electronic medical record (EMR) that is anesthesia specific. Many anesthesia information management systems (AIMS) have been developed with a focus only on the unique needs of anesthesia providers, without being fully integrated into other electronic health record components of the entire enterprise medical system. To understand why anesthesia providers should embrace health information technology (HIT) on a health system-wide basis, this article reviews recent HIT history and reviews HIT concepts. The author explores current developments in efforts to expand enterprise HIT, and the pros and cons of full enterprise integration with an AIMS. Copyright © 2011 Elsevier Inc. All rights reserved.

The potential for high-intensity interval training to reduce cardiometabolic disease risk.

PubMed

Kessler, Holly S; Sisson, Susan B; Short, Kevin R

2012-06-01

In the US, 34% of adults currently meet the criteria for the metabolic syndrome defined by elevated waist circumference, plasma triglycerides (TG), fasting glucose and/or blood pressure, and decreased high-density lipoprotein cholesterol (HDL-C). While these cardiometabolic risk factors can be treated with medication, lifestyle modification is strongly recommended as a first-line approach. The purpose of this review is to focus on the effect of physical activity interventions and, specifically, on the potential benefits of incorporating higher intensity exercise. Several recent studies have suggested that compared with continuous moderate exercise (CME), high-intensity interval training (HIT) may result in a superior or equal improvement in fitness and cardiovascular health. HIT is comprised of brief periods of high-intensity exercise interposed with recovery periods at a lower intensity. The premise of using HIT in both healthy and clinical populations is that the vigorous activity segments promote greater adaptations via increased cellular stress, yet their short length, and the ensuing recovery intervals, allow even untrained individuals to work harder than would otherwise be possible at steady-state intensity. In this review, we examine the impact of HIT on cardiometabolic risk factors, anthropometric measures of obesity and cardiovascular fitness in both healthy and clinical populations with cardiovascular and metabolic disease. The effects of HIT versus CME on health outcomes were compared in 14 of the 24 studies featuring HIT. Exercise programmes ranged from 2 weeks to 6 months. All 17 studies that measured aerobic fitness and all seven studies that measured insulin sensitivity showed significant improvement in response to HIT, although these changes did not always exceed responses to CME comparison groups. A minimum duration of 12 weeks was necessary to demonstrate improvement in fasting glucose in four of seven studies (57%). A minimum duration of 8 weeks of HIT was necessary to demonstrate improvement in HDL-C in three of ten studies (30%). No studies reported that HIT resulted in improvement of total cholesterol, low-density lipoprotein cholesterol (LDL-C), or TG. At least 12 weeks of HIT was required for reduction in blood pressure to emerge in five studies of participants not already being treated for hypertension. A minimum duration of 12 weeks was necessary to see consistent improvement in the six studies that examined anthropometric measures of obesity in overweight/obese individuals. In the 13 studies with a matched-exercise-volume CME group, improvement in aerobic fitness in response to HIT was equal to (5 studies), or greater than (8 studies) in response to CME. Additionally, HIT has been shown to be safe and effective in patients with a range of cardiac and metabolic dysfunction. In conclusion, HIT appears to promote superior improvements in aerobic fitness and similar improvements in some cardiometabolic risk factors in comparison to CME, when performed by healthy subjects or clinical patients for at least 8-12 weeks. Future studies need to address compliance and efficacy of HIT in the real world with a variety of populations.

Source monitoring and false memories in children: relation to certainty and executive functioning.

PubMed

Ruffman, T; Rustin, C; Garnham, W; Parkin, A J

2001-10-01

We presented children aged 6, 8, and 10 years with a video and then an audio tape about a dog named Mick. Some information was repeated in the two sources and some was unique to one source. We examined: (a) children's hit rate for remembering whether events occurred and their tendency to make false alarms, (b) their memory for the context in which events occurred (source monitoring), (c) their certainty about hits, false alarms, and source, and (d) whether working memory and inhibition were related to hits, false alarms, and source monitoring. The certainty ratings revealed deficits in children's understanding of when they had erred on source questions and of when they had made false alarms. In addition, inhibitory ability accounted for unique variance in the ability to avoid false alarms and in some kinds of source monitoring but not hits. In contrast, working memory tended to correlate with all forms of memory including hits. Copyright 2001 Academic Press.

77 FR 23250 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

... quality, clinical operations, implementation, and privacy and security. Other groups are convened to address specific issues as needed, such as the Nationwide Health Information Network Power Team, the... appropriate workgroup or other special group to develop a report for the HIT Standards Committee, to the...

Heparin-induced thrombocytopenia in solid organ transplant recipients: The current scientific knowledge

PubMed Central

Assfalg, Volker; Hüser, Norbert

2016-01-01

Exposure to heparin is associated with a high incidence of immunization against platelet factor 4 (PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia (HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on anti-heparin/PF4 antibodies and HIT in transplant recipients a systematic PubMed literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far. PMID:27011914

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.

Veterans’ Preferences for Exchanging Information Using Veterans Affairs Health Information Technologies: Focus Group Results and Modeling Simulations

PubMed Central

Chavez, Margeaux; Nazi, Kim; Antinori, Nicole; Melillo, Christine; Cotner, Bridget A; Hathaway, Wendy; Cook, Ashley; Wilck, Nancy; Noonan, Abigail

2017-01-01

Background The Department of Veterans Affairs (VA) has multiple health information technology (HIT) resources for veterans to support their health care management. These include a patient portal, VetLink Kiosks, mobile apps, and telehealth services. The veteran patient population has a variety of needs and preferences that can inform current VA HIT redesign efforts to meet consumer needs. Objective This study aimed to describe veterans’ experiences using the current VA HIT and identify their vision for the future of an integrated VA HIT system. Methods Two rounds of focus group interviews were conducted with a single cohort of 47 veterans and one female caregiver recruited from Bedford, Massachusetts, and Tampa, Florida. Focus group interviews included simulation modeling activities and a self-administered survey. This study also used an expert panel group to provide data and input throughout the study process. High-fidelity, interactive simulations were created and used to facilitate collection of qualitative data. The simulations were developed based on system requirements, data collected through operational efforts, and participants' reported preferences for using VA HIT. Pairwise comparison activities of HIT resources were conducted with both focus groups and the expert panel. Rapid iterative content analysis was used to analyze qualitative data. Descriptive statistics summarized quantitative data. Results Data themes included (1) current use of VA HIT, (2) non-VA HIT use, and (3) preferences for future use of VA HIT. Data indicated that, although the Secure Messaging feature was often preferred, a full range of HIT options are needed. These data were then used to develop veteran-driven simulations that illustrate user needs and expectations when using a HIT system and services to access VA health care services. Conclusions Patient participant redesign processes present critical opportunities for creating a human-centered design. Veterans value virtual health care options and prefer standardized, integrated, and synchronized user-friendly interface designs. PMID:29061553

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

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

PubMed

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

2016-01-01

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. 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. General critical care units in England, Wales, and Northern Ireland participating in the ICNARC programme between 1 January, 2007 and 30 June, 2012. 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. 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. 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.

Effective implementation of health information technologies in U.S. hospitals.

PubMed

Khatri, Naresh; Gupta, Vishal

2016-01-01

Two issues pertaining to the effective implementation of health information technologies (HITs) in U.S. hospitals are examined. First, which information technology (IT) system is better--a homegrown or an outsourced one? In the second issue, the critical role of in-house IT expertise/capabilities in the effective implementation of HITs is investigated. The data on type of HIT system and IT expertise/capabilities were collected from a national sample of senior executives of U.S. hospitals. The data on quality of patient care were gathered from the Hospital Compare Web site. The quality of patient care was significantly higher in hospitals deploying a homegrown HIT system than hospitals deploying an outsourced HIT system. Furthermore, the professional competence and compelling vision of the chief information officer was found to be a major driver of another key IT capability of hospitals-professionalism of IT staff. The positive relationship of professionalism of IT staff with quality of patient care was mediated by proactive employee behavior. A homegrown HIT system achieves better quality of patient care than an outsourced one. The chief information officer's IT vision and the professional expertise and professionalism of IT staff are important IT capabilities in U.S. hospitals.

Effects of autonomous motivational priming on motivation and affective responses towards high-intensity interval training.

PubMed

Brown, Denver M Y; Teseo, Amanda J; Bray, Steven R

2016-08-01

This study examined the effect of autonomous motivational priming on motivation, attitudes and intentions towards high-intensity interval training (HIT). Participants (N = 42) performed a graded exercise test to determine their peak aerobic power (WPEAK). At a subsequent testing session, participants were randomised to complete either an autonomous or neutral motivational priming task followed by a 10 × 1 HIT exercise protocol, alternating 1-min bouts of hard (70% WPEAK) and light (12.5% WPEAK) exercises for 20 min. Participants primed with autonomous motivation reported greater enjoyment, P = .009, ηp(2) = .16, and perceived competence, P = .005, ηp(2) = .18, post-exercise compared to those in the neutral priming condition. Participants in the autonomous motivational priming condition also reported more positive attitudes, P = .014, ηp(2) = .14, towards HIT; however, there was no difference between the conditions for task motivation during HIT or intentions, P = .53, ηp(2) = .01, to engage in HIT. These findings highlight autonomous motivational priming as a method of enhancing affective and motivational experiences regarding HIT.

[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.

Using health information technology to manage a patient population in accountable care organizations.

PubMed

Wu, Frances M; Rundall, Thomas G; Shortell, Stephen M; Bloom, Joan R

2016-06-20

Purpose - The purpose of this paper is to describe the current landscape of health information technology (HIT) in early accountable care organizations (ACOs), the different strategies ACOs are using to develop HIT-based capabilities, and how ACOs are using these capabilities within their care management processes to advance health outcomes for their patient population. Design/methodology/approach - Mixed methods study pairing data from a cross-sectional National Survey of ACOs with in-depth, semi-structured interviews with leaders from 11 ACOs (both completed in 2013). Findings - Early ACOs vary widely in their electronic health record, data integration, and analytic capabilities. The most common HIT capability was drug-drug and drug-allergy interaction checks, with 53.2 percent of respondents reporting that the ACO possessed the capability to a high degree. Outpatient and inpatient data integration was the least common HIT capability (8.1 percent). In the interviews, ACO leaders commented on different HIT development strategies to gain a more comprehensive picture of patient needs and service utilization. ACOs realize the necessity for robust data analytics, and are exploring a variety of approaches to achieve it. Research limitations/implications - Data are self-reported. The qualitative portion was based on interviews with 11 ACOs, limiting generalizability to the universe of ACOs but allowing for a range of responses. Practical implications - ACOs are challenged with the development of sophisticated HIT infrastructure. They may benefit from targeted assistance and incentives to implement health information exchanges with other providers to promote more coordinated care management for their patient population. Originality/value - Using new empirical data, this study increases understanding of the extent of ACOs' current and developing HIT capabilities to support ongoing care management.

"Hits" (Not "Discussion Posts") Predict Student Success in Online Courses: A Double Cross-Validation Study

ERIC Educational Resources Information Center

Ramos, Cheryl; Yudko, Errol

2008-01-01

The efficacy of individual components of an online course on positive course outcome was examined via stepwise multiple regression analysis. Outcome was measured as the student's total score on all exams given during the course. The predictors were page hits, discussion posts, and discussion reads. The vast majority of the variance of outcome was…

Relationship between Use of Online Support Materials and Student Performance in an Introductory Finance Course

ERIC Educational Resources Information Center

Biktimirov, Ernest N.; Klassen, Kenneth J.

2008-01-01

The authors examined the relationship between student online activity, including access to specific course materials, and performance in a traditional face-to-face introductory finance course that a class Web site supported. The authors used 6 measures: (a) total hits, (b) hit consistency, (c) number of unique files that the students accessed, (d)…

Student Hits in an Internet-Supported Course: How Can Instructors Use Them and What Do They Mean?

ERIC Educational Resources Information Center

Baugher, Dan; Varanelli, Andrew; Weisbord, Ellen

2003-01-01

The world of education is changing as Web-based technology and courseware are increasingly used for delivery of course material. In this environment, instructors may need new measures for determining student involvement, and ultimately student performance. This study examines whether hits to a Web site have any value for predicting student…

Computing Principal Eigenvectors of Large Web Graphs: Algorithms and Accelerations Related to PageRank and HITS

ERIC Educational Resources Information Center

Nagasinghe, Iranga

2010-01-01

This thesis investigates and develops a few acceleration techniques for the search engine algorithms used in PageRank and HITS computations. PageRank and HITS methods are two highly successful applications of modern Linear Algebra in computer science and engineering. They constitute the essential technologies accounted for the immense growth and…

HIT collaborative base project at APS of Argonne

NASA Astrophysics Data System (ADS)

Liu, H.; Wang, L.

2012-12-01

Harbin Institute of Technology (HIT) launched collaborative base project at Argonne National Laboratory in 2010, and progress will be presented in this paper. The staff and students from HIT involved in advanced technological developments, which included tomography. high energy PDF, diffraction and scattering, and inelastic scattering techniques in APS to study structures changes under high pressure conditions.

Rapid lead discovery through iterative screening of one bead one compound libraries.

PubMed

Gao, Yu; Amar, Sabrina; Pahwa, Sonia; Fields, Gregg; Kodadek, Thomas

2015-01-12

Primary hits that arise from screening one bead one compound (OBOC) libraries against a target of interest rarely have high potency. However, there has been little work focused on the development of an efficient workflow for primary hit improvement. In this study, we show that by characterizing the binding constants for all of the hits that arise from a screen, structure-activity relationship (SAR) data can be obtained to inform the design of "derivative libraries" of a primary hit that can then be screened under more demanding conditions to obtain improved compounds. Here, we demonstrate the rapid improvement of a primary hit against matrix metalloproteinase-14 using this approach.

Rapid development of two factor IXa inhibitors from hit to lead.

PubMed

Parker, Dann L; Walsh, Shawn; Li, Bing; Kim, Esther; Sharipour, Aurash; Smith, Cameron; Chen, Yi-Heng; Berger, Richard; Harper, Bart; Zhang, Ting; Park, Min; Shu, Min; Wu, Jane; Xu, Jiayi; Dewnani, Sunita; Sherer, Edward C; Hruza, Alan; Reichert, Paul; Geissler, Wayne; Sonatore, Lisa; Ellsworth, Kenneth; Balkovec, James; Greenlee, William; Wood, Harold B

2015-06-01

Two high-throughput screening hits were investigated for SAR against human factor IXa. Both hits feature a benzamide linked to a [6-5]-heteroaryl via an alkyl amine. In the case where this system is a benzimidazolyl-ethyl amine the binding potency for the hit was improved >500-fold, from 9 μM to 0.016 μM. For the other hit, which contains a tetrahydropyrido-indazole amine, potency was improved 20-fold, from 2 μM to 0.09 μM. X-ray crystal structures were obtained for an example of each class which improved understanding of the binding, and will enable further drug discovery efforts. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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

Cell Cycle Deregulation in the Neurons of Alzheimer’s Disease

PubMed Central

Moh, Calvin; Kubiak, Jacek Z.; Bajic, Vladan P.; Zhu, Xiongwei; Smith, Mark A.

2018-01-01

The cell cycle consists of four main phases: G1, S, G2, and M. Most cells undergo these cycles up to 40–60 times in their life. However, neurons remain in a nondividing, nonreplicating phase, G0. Neurons initiate but do not complete cell division, eventually entering apoptosis. Research has suggested that like cancer, Alzheimer’s disease (AD) involves dysfunction in neuronal cell cycle reentry, leading to the development of the two-hit hypothesis of AD. The first hit is abnormal cell cycle reentry, which typically results in neuronal apoptosis and prevention of AD. However, with the second hit of chronic oxidative damage preventing apoptosis, neurons gain “immortality” analogous to tumor cells. Once both of these hits are activated, AD can develop and produce senile plaques and neurofibrillary tangles throughout brain tissue. In this review, we propose a mechanism for neuronal cell cycle reentry and the development of AD. PMID:21630160

Two-hit exposure to polychlorinated biphenyls at gestational and juvenile life stages: 2. Sex-specific neuromolecular effects in the brain

PubMed Central

Bell, Margaret R.; Hart, Bethany G.; Gore, Andrea C.

2015-01-01

Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments. PMID:26620572

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

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.

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.

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

Being selective at the plate: processing dependence between perceptual variables relates to hitting goals and performance.

PubMed

Gray, Rob

2013-08-01

Performance of a skill that involves acting on a goal object (e.g., a ball to be hit) can influence one's judgment of the size and speed of that object. The present study examined how these action-specific effects are affected when the goal of the actor is varied and they are free to choose between alternative actions. In Experiment 1, expert baseball players were asked to perform three different directional hitting tasks in a batting simulation and make interleaved perceptual judgments about three ball parameters (speed, plate crossing location, and size). Perceived ball size was largest (and perceived speed was slowest) when the ball crossing location was optimal for the particular hitting task the batter was performing (e.g., an "outside" pitch for opposite-field hitting). The magnitude of processing dependency between variables (speed vs. location and size vs. location) was positively correlated with batting performance. In Experiment 2, the action-specific effects observed in Experiment 1 were mimicked by systematically changing the ball diameter in the simulation as a function of plate crossing location. The number of swing initiations was greater when ball size was larger, and batters were more successful in the hitting task for which the larger pitches were optimal (e.g., greater number of pull hits than opposite-field hits when "inside" pitches were larger). These findings suggest attentional accentuation of goal-relevant targets underlies action-related changes in perception and are consistent with an action selection role for these effects. 2013 APA, all rights reserved

C6 GPMG and 40 mm AGL Weapon Integrated on RWS Mounted on TAPV Platform: Probability of Hit Methodology

DTIC Science & Technology

2010-09-01

nationale, 2010 DRDC Valcartier CR 2010-237 i Abstract …….. A probability of hit ( PHit ) methodology has been developed to characterize the...CFB (Canadian Forces Base). Résumé …..... Une méthodologie de probabilité d’impact ( PHit ) a été développée pour caractériser la performance globale...the crew commander and gunner from their respective crew stations inside the vehicle. A probability of hit ( PHit ) methodology has been developed to

Where does HIT fit? An examination of the affective response to high-intensity intervals in comparison to continuous moderate- and continuous vigorous-intensity exercise in the exercise intensity-affect continuum.

PubMed

Jung, Mary E; Bourne, Jessica E; Little, Jonathan P

2014-01-01

Affect experienced during an exercise session is purported to predict future exercise behaviour. Compared to continuous moderate-intensity exercise (CMI), the affective response to continuous vigorous-intensity exercise (CVI) has consistently been shown to be more aversive. The affective response, and overall tolerability to high-intensity interval training (HIT), is less studied. To date, there has yet to be a comparison between HIT, CVI, and CMI. The purpose of this study was to compare the tolerability and affective responses during HIT to CVI and CMI. This study utilized a repeated measures, randomized, counter-balanced design. Forty-four participants visited the laboratory on four occasions. Baseline fitness testing was conducted to establish peak power output in Watts (W peak). Three subsequent visits involved a single bout of a) HIT, corresponding to 1-minute at ∼ 100% W peak and 1-minute at ∼ 20% W peak for 20 minutes, b) CMI, corresponding to ∼ 40% W peak for 40 minutes, and c) CVI, corresponding to ∼ 80% W peak for 20 minutes. The order of the sessions was randomized. Affective responses were measured before, during and after each session. Task self-efficacy, intentions, enjoyment and preference were measured after sessions. Participants reported greater enjoyment of HIT as compared to CMI and CVI, with over 50% of participants reporting a preference to engage in HIT as opposed to either CMI or CVI. HIT was considered more pleasurable than CVI after exercise, but less pleasurable than CMI at these times. Despite this participants reported being just as confident to engage in HIT as they were CMI, but less confident to engage in CVI. This study highlights the utility of HIT in inactive individuals, and suggests that it may be a viable alternative to traditionally prescribed continuous modalities of exercise for promoting self-efficacy and enjoyment of exercise.

Where Does HIT Fit? An Examination of the Affective Response to High-Intensity Intervals in Comparison to Continuous Moderate- and Continuous Vigorous-Intensity Exercise in the Exercise Intensity-Affect Continuum

PubMed Central

Jung, Mary E.; Bourne, Jessica E.; Little, Jonathan P.

2014-01-01

Affect experienced during an exercise session is purported to predict future exercise behaviour. Compared to continuous moderate-intensity exercise (CMI), the affective response to continuous vigorous-intensity exercise (CVI) has consistently been shown to be more aversive. The affective response, and overall tolerability to high-intensity interval training (HIT), is less studied. To date, there has yet to be a comparison between HIT, CVI, and CMI. The purpose of this study was to compare the tolerability and affective responses during HIT to CVI and CMI. This study utilized a repeated measures, randomized, counter-balanced design. Forty-four participants visited the laboratory on four occasions. Baseline fitness testing was conducted to establish peak power output in Watts (Wpeak). Three subsequent visits involved a single bout of a) HIT, corresponding to 1-minute at ∼100% Wpeak and 1-minute at ∼20% Wpeak for 20 minutes, b) CMI, corresponding to ∼40% Wpeak for 40 minutes, and c) CVI, corresponding to ∼80% Wpeak for 20 minutes. The order of the sessions was randomized. Affective responses were measured before, during and after each session. Task self-efficacy, intentions, enjoyment and preference were measured after sessions. Participants reported greater enjoyment of HIT as compared to CMI and CVI, with over 50% of participants reporting a preference to engage in HIT as opposed to either CMI or CVI. HIT was considered more pleasurable than CVI after exercise, but less pleasurable than CMI at these times. Despite this participants reported being just as confident to engage in HIT as they were CMI, but less confident to engage in CVI. This study highlights the utility of HIT in inactive individuals, and suggests that it may be a viable alternative to traditionally prescribed continuous modalities of exercise for promoting self-efficacy and enjoyment of exercise. PMID:25486273

Predictive properties of the video head impulse test: measures of caloric symmetry and self-report dizziness handicap.

PubMed

McCaslin, Devin L; Jacobson, Gary P; Bennett, Marc L; Gruenwald, Jill M; Green, Andrea P

2014-01-01

The purpose of this investigation was to determine whether a predictable relationship existed between self-reported dizziness handicap and video Head Impulse Test (vHIT) results in a large sample of patients reporting to a dizziness clinic. Secondary objectives included describing the characteristics of the vHIT ipsilesional and contralesional vestibulo-ocular reflex slow-phase velocity in patients with varying levels of canal paresis. Finally, the authors calculated the sensitivity and specificity of the vHIT for detecting horizontal semicircular canal impairment using the caloric test as the "gold standard." Participants were 115 adults presenting to a tertiary medical care center with symptoms of dizziness. Participants were administered a measure of self-report dizziness handicap (i.e., Dizziness Handicap Inventory) and underwent caloric testing and vHIT at the same appointment. Results showed that (1) there were no significant group differences (i.e., vHIT normal versus vHIT abnormal) in the Dizziness Handicap Inventory total score, (2) both ipsilesional and contralateral velocity gain decreased with increases in caloric paresis, and (3) a caloric asymmetry of 39.5% was determined to be the cutoff that maximized discrimination of vHIT outcome. The level of self-reported dizziness handicap is not predicted by the outcome of the vHIT, which is consistent with the majority of published reports describing the poor relationship between quantitative tests of vestibular function and dizziness handicap. Further, the study findings have demonstrated that vHIT and caloric data are not redundant, and each test provides unique information regarding the functional integrity of the horizontal semicircular canal at different points on the frequency spectrum. The vHIT does offer some advantages over caloric testing, but at the expense of sensitivity. The vHIT can be completed in less time, is not noxious to the patient, and requires very little laboratory space. However, the study data show that a caloric asymmetry of 39.5% is required to optimize discrimination between an abnormal and normal vHIT. It is the authors' contention that the vHIT is a complementary test to the balance function examination and should viewed as such rather than as a replacement for caloric testing.

Methods to identify, study and understand end-user participation in HIT development.

PubMed

Høstgaard, Anna Marie; Bertelsen, Pernille; Nøhr, Christian

2011-09-28

Experience has shown that for new health-information-technology (HIT) to be suc-cessful clinicians must obtain positive clinical benefits as a result of its implementation and joint-ownership of the decisions made during the development process. A prerequisite for achieving both success criteria is real end-user-participation. Experience has also shown that further research into developing improved methods to collect more detailed information on social groups participating in HIT development is needed in order to support, facilitate and improve real end-user participation. A case study of an EHR planning-process in a Danish county from October 2003 until April 2006 was conducted using process-analysis. Three social groups (physicians, IT-professionals and administrators) were identified and studied in the local, present perspective. In order to understand the interactions between the three groups, the national, historic perspective was included through a literature-study. Data were collected through observations, interviews, insight gathered from documents and relevant literature. In the local, present perspective, the administrator's strategy for the EHR planning process meant that there was no clinical workload-reduction. This was seen as one of the main barriers to the physicians to achieving real influence. In the national, historic perspective, physicians and administrators have had/have different perceptions of the purpose of the patient record and they have both struggled to influence this definition. To date, the administrators have won the battle. This explains the conditions made available for the physicians' participation in this case, which led to their role being reduced to that of clinical consultants--rather than real participants. In HIT-development the interests of and the balance of power between the different social groups involved are decisive in determining whether or not the end-users become real participants in the development process. Real end-user-participation is essential for the successful outcome of the process. By combining and developing existing theories and methods, this paper presents an improved method to collect more detailed information on social groups participating in HIT-development and their interaction during the development. This allows HIT management to explore new avenues during the HIT development process in order to support, facilitate and improve real end-user participation.

Suppression of guinea pig ileum induced contractility by plasma albumin of hibernators

USGS Publications Warehouse

Bruce, David S.; Ambler, Douglas L.; Henschel, Timothy M.; Oeltgen, Peter R.; Nilekani, Sita P.; Amstrup, Steven C.

1992-01-01

Previous studies suggest that hibernation may be regulated by internal opioids and that the putative “hibernation induction trigger” (HIT) may itself be an opioid. This study examined the effect of plasma albumin (known to bind HIT) on induced contractility of the guinea pig ileum muscle strip. Morphine (400 nM) depressed contractility and 100 nM naloxone restored it. Ten milligrams of lyophilized plasma albumin fractions from hibernating ground squirrels, woodchucks, black bears, and polar bears produced similar inhibition, with partial reversal by naloxone. Five hundredths mg of d-Ala2-d-Leu5-enkephalin (DADLE) also inhibited contractility and naloxone reversed it. Conclusions are that hibernating individuals of these species contain an HIT substance that is opioid in nature and summer animals do not; an endogenous opioid similar to leu-enkephalin may be the HIT compound or give rise to it.

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.

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.

Health services research evaluation principles. Broadening a general framework for evaluating health information technology.

PubMed

Sockolow, P S; Crawford, P R; Lehmann, H P

2012-01-01

Our forthcoming national experiment in increased health information technology (HIT) adoption funded by the American Recovery and Reinvestment Act of 2009 will require a comprehensive approach to evaluating HIT. The quality of evaluation studies of HIT to date reveals a need for broader evaluation frameworks that limits the generalizability of findings and the depth of lessons learned. Develop an informatics evaluation framework for health information technology (HIT) integrating components of health services research (HSR) evaluation and informatics evaluation to address identified shortcomings in available HIT evaluation frameworks. A systematic literature review updated and expanded the exhaustive review by Ammenwerth and deKeizer (AdK). From retained studies, criteria were elicited and organized into classes within a framework. The resulting Health Information Technology Research-based Evaluation Framework (HITREF) was used to guide clinician satisfaction survey construction, multi-dimensional analysis of data, and interpretation of findings in an evaluation of a vanguard community health care EHR. The updated review identified 128 electronic health record (EHR) evaluation studies and seven evaluation criteria not in AdK: EHR Selection/Development/Training; Patient Privacy Concerns; Unintended Consequences/ Benefits; Functionality; Patient Satisfaction with EHR; Barriers/Facilitators to Adoption; and Patient Satisfaction with Care. HITREF was used productively and was a complete evaluation framework which included all themes that emerged. We can recommend to future EHR evaluators that they consider adding a complete, research-based HIT evaluation framework, such as HITREF, to their evaluation tools suite to monitor HIT challenges as the federal government strives to increase HIT adoption.

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual-hit hypothesis of neurodegeneration.

PubMed

Heinemann, Scott D; Posimo, Jessica M; Mason, Daniel M; Hutchison, Daniel F; Leak, Rehana K

2016-08-01

The dual-hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, a relatively high-throughput dual-hit model of stress synergy was developed in primary hippocampal neurons. In order to increase the rigor of the study and strengthen the interpretations, three independent, unbiased viability assays were employed at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48 h. MG132 and paraquat only elicited additive effects 24 h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48 h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. These findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, a new model of hippocampal vulnerability was developed for the testing of therapies, because neuroprotective treatments that are effective against severe, synergistic stress are more likely to succeed in the clinic. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Veterans' Preferences for Exchanging Information Using Veterans Affairs Health Information Technologies: Focus Group Results and Modeling Simulations.

PubMed

Haun, Jolie N; Chavez, Margeaux; Nazi, Kim; Antinori, Nicole; Melillo, Christine; Cotner, Bridget A; Hathaway, Wendy; Cook, Ashley; Wilck, Nancy; Noonan, Abigail

2017-10-23

The Department of Veterans Affairs (VA) has multiple health information technology (HIT) resources for veterans to support their health care management. These include a patient portal, VetLink Kiosks, mobile apps, and telehealth services. The veteran patient population has a variety of needs and preferences that can inform current VA HIT redesign efforts to meet consumer needs. This study aimed to describe veterans' experiences using the current VA HIT and identify their vision for the future of an integrated VA HIT system. Two rounds of focus group interviews were conducted with a single cohort of 47 veterans and one female caregiver recruited from Bedford, Massachusetts, and Tampa, Florida. Focus group interviews included simulation modeling activities and a self-administered survey. This study also used an expert panel group to provide data and input throughout the study process. High-fidelity, interactive simulations were created and used to facilitate collection of qualitative data. The simulations were developed based on system requirements, data collected through operational efforts, and participants' reported preferences for using VA HIT. Pairwise comparison activities of HIT resources were conducted with both focus groups and the expert panel. Rapid iterative content analysis was used to analyze qualitative data. Descriptive statistics summarized quantitative data. Data themes included (1) current use of VA HIT, (2) non-VA HIT use, and (3) preferences for future use of VA HIT. Data indicated that, although the Secure Messaging feature was often preferred, a full range of HIT options are needed. These data were then used to develop veteran-driven simulations that illustrate user needs and expectations when using a HIT system and services to access VA health care services. Patient participant redesign processes present critical opportunities for creating a human-centered design. Veterans value virtual health care options and prefer standardized, integrated, and synchronized user-friendly interface designs. ©Jolie N. Haun, Margeaux Chavez, Kim Nazi, Nicole Antinori, Christine Melillo, Bridget A Cotner, Wendy Hathaway, Ashley Cook, Nancy Wilck, Abigail Noonan. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.10.2017.

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.

Efficiency Improvement of HIT Solar Cells on p-Type Si Wafers.

PubMed

Wei, Chun-You; Lin, Chu-Hsuan; Hsiao, Hao-Tse; Yang, Po-Chuan; Wang, Chih-Ming; Pan, Yen-Chih

2013-11-22

Single crystal silicon solar cells are still predominant in the market due to the abundance of silicon on earth and their acceptable efficiency. Different solar-cell structures of single crystalline Si have been investigated to boost efficiency; the heterojunction with intrinsic thin layer (HIT) structure is currently the leading technology. The record efficiency values of state-of-the art HIT solar cells have always been based on n-type single-crystalline Si wafers. Improving the efficiency of cells based on p-type single-crystalline Si wafers could provide broader options for the development of HIT solar cells. In this study, we varied the thickness of intrinsic hydrogenated amorphous Si layer to improve the efficiency of HIT solar cells on p-type Si wafers.

Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit.

PubMed

Akizawa, Yoshika; Miyashita, Toshiyuki; Sasaki, Ryo; Nagata, Reiko; Aoki, Ryoko; Ishitani, Ken; Nagashima, Yoji; Matsui, Hideo; Saito, Kayoko

2016-04-01

We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS. © 2016 Wiley Periodicals, Inc.

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.

Aging reduces veridical remembering but increases false remembering: Neuropsychological test correlates of remember–know judgments

PubMed Central

McCabe, David P.; Roediger, Henry L.; McDaniel, Mark A.; Balota, David A.

2011-01-01

In 1985 Tulving introduced the remember–know procedure, whereby subjects are asked to distinguish between memories that involve retrieval of contextual details (remembering) and memories that do not (knowing). Several studies have been reported showing age-related declines in remember hits, which has typically been interpreted as supporting dual-process theories of cognitive aging that align remembering with a recollection process and knowing with a familiarity process. Less attention has been paid to remember false alarms, or their relation to age. We reviewed the literature examining aging and remember/know judgments and show that age-related increases in remember false alarms, i.e., false remembering, are as reliable as age-related decreases in remember hits, i.e., veridical remembering. Moreover, a meta-analysis showed that the age effect size for remember hits and false alarms are similar, and larger than age effects on know hits and false alarms. We also show that the neuropsychological correlates of remember hits and false alarms differ. Neuropsychological tests of medial-temporal lobe functioning were related to remember hits, but tests of frontal-lobe functioning and age were not. By contrast, age and frontal-lobe functioning predicted unique variance in remember false alarms, but MTL functioning did not. We discuss various explanations for these findings and conclude that any comprehensive explanation of recollective experience will need to account for the processes underlying both remember hits and false alarms. PMID:19100756

Where are we on the diffusion curve? Trends and drivers of primary care physicians' use of health information technology.

PubMed

Audet, Anne-Marie; Squires, David; Doty, Michelle M

2014-02-01

To describe trends in primary care physicians' use of health information technology (HIT) between 2009 and 2012, examine practice characteristics associated with greater HIT capacity in 2012, and explore factors such as delivery system and payment reforms that may affect adoption and functionality. We used data from the 2012 and 2009 Commonwealth Fund International Health Policy Surveys of Primary Care Physicians. The data were collected in both years by postal mail between March and July among a nationally representative sample of primary care physicians in the United States. We compared primary care physicians' HIT capacity in 2009 and 2012. We employed multivariable logistic regression to analyze whether participating in an integrated delivery system, sharing resources and support with other practices, and being eligible for financial incentives were associated with greater HIT capacity in 2012. Primary care physicians' HIT capacity has significantly expanded since 2009, although solo practices continue to lag. Practices that are part of an integrated delivery system or share resources with other practices have higher rates of electronic medical record (EMR) adoption, multifunctional HIT, electronic information exchange, and electronic access for patients. Receiving or being eligible for financial incentives is associated with greater adoption of EMRs and information exchange. Federal efforts to increase adoption have coincided with a rapid increase in HIT capacity. Delivery system and payment reforms and federally funded extension programs could offer promising pathways for further diffusion. © Health Research and Educational Trust.

High-intensity interval training programme for obese youth (HIP4YOUTH): A pilot feasibility study.

PubMed

Lee, SoJung; Spector, Jenna; Reilly, Stephanie

2017-09-01

Recently, there has been growing interest in high-intensity interval training (HIT) as a strategy to improve health. In this pilot study, we examined the feasibility of a 4-week low-volume HIT and its effects on cardiorespiratory fitness (CRF), blood pressure (BP) and enjoyment in overweight and obese youth. Twelve adolescents (body mass index (BMI): 34.8 ± 3.9 kg · m ‒ 2 , 14.9 ± 1.5 years) participated in 12 sessions of HIT (10 × 60 s cycling bouts eliciting ~90% maximal heart rate, interspersed with 90 s recovery, 30 min/session, 3 sessions/week) over ~4 weeks. All the participants completed the study and exercise attendance averaged 92%. Despite no changes in body weight and total fat, HIT resulted in significant (P < 0.01) increases in CRF (pre: 20.1 versus post: 22.2 ml · kg ‒1 · min ‒1 ) and exercise time (pre: 425 versus post: 509 s) during peak oxygen uptake test, and a reduction in resting systolic BP (pre: 115.8 versus post: 107.6 mmHg). The majority of study participants (83%) enjoyed HIT and more than half of the participants (58%) reported that HIT is a more enjoyable form of exercise compared to other types of exercises. Low-volume HIT is a useful strategy to promote exercise participation and improve cardiovascular health in overweight and obese youth.

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.

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.

Perceptions on use of home telemonitoring in patients with long term conditions - concordance with the Health Information Technology Acceptance Model: a qualitative collective case study.

PubMed

Middlemass, Jo B; Vos, Jolien; Siriwardena, A Niroshan

2017-06-26

Health information technology (HIT) may be used to improve care for increasing numbers of older people with long term conditions (LTCs) who make high demands on health and social care services. Despite its potential benefits for reducing disease exacerbations and hospitalisations, HIT home monitoring is not always accepted by patients. Using the Health Information Technology Acceptance Model (HITAM) this qualitative study examined the usefulness of the model for understanding acceptance of HIT in older people (≥60 years) participating in a RCT for older people with Chronic Obstructive Pulmonary Disease (COPD) and associated heart diseases (CHROMED). An instrumental, collective case study design was used with qualitative interviews of patients in the intervention arm of CHROMED. These were conducted at two time points, one shortly after installation of equipment and again at the end of (or withdrawal from) the study. We used Framework Analysis to examine how well the HITAM accounted for the data. Participants included 21 patients aged between 60-99 years and their partners or relatives where applicable. Additional concepts for the HITAM for older people included: concerns regarding health professional access and attachment; heightened illness anxiety and desire to avoid continuation of the 'sick-role'. In the technology zone, HIT self-efficacy was associated with good organisational processes and informal support; while ease of use was connected to equipment design being suitable for older people. HIT perceived usefulness was related to establishing trends in health status, detecting early signs of infection and potential to self-manage. Due to limited feedback to users opportunities to self-manage were reduced. HITAM helped understand the likelihood that older people with LTCs would use HIT, but did not explain how this might result in improved self-management. In order to increase HIT acceptance among older people, equipment design and organisational factors need to be considered. ClinicalTrials.gov Identifier: NCT01960907 October 9 2013 (retrospectively registered) Clinical tRials fOr elderly patients with MultiplE Disease (CHROMED). Start date October 2012, end date March 2016. Date of enrolment of the first participant was February 2013.

Fragment-based hit identification: thinking in 3D.

PubMed

Morley, Andrew D; Pugliese, Angelo; Birchall, Kristian; Bower, Justin; Brennan, Paul; Brown, Nathan; Chapman, Tim; Drysdale, Martin; Gilbert, Ian H; Hoelder, Swen; Jordan, Allan; Ley, Steven V; Merritt, Andy; Miller, David; Swarbrick, Martin E; Wyatt, Paul G

2013-12-01

The identification of high-quality hits during the early phases of drug discovery is essential if projects are to have a realistic chance of progressing into clinical development and delivering marketed drugs. As the pharmaceutical industry goes through unprecedented change, there are increasing opportunities to collaborate via pre-competitive networks to marshal multifunctional resources and knowledge to drive impactful, innovative science. The 3D Fragment Consortium is developing fragment-screening libraries with enhanced 3D characteristics and evaluating their effect on the quality of fragment-based hit identification (FBHI) projects. Copyright © 2013 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.

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.

Anticipating mismatches of HIT investments: Developing a viability-fit model for e-health services.

PubMed

Mettler, Tobias

2016-01-01

Albeit massive investments in the recent years, the impact of health information technology (HIT) has been controversial and strongly disputed by both research and practice. While many studies are concerned with the development of new or the refinement of existing measurement models for assessing the impact of HIT adoption (ex post), this study presents an initial attempt to better understand the factors affecting viability and fit of HIT and thereby underscores the importance of also having instruments for managing expectations (ex ante). We extend prior research by undertaking a more granular investigation into the theoretical assumptions of viability and fit constructs. In doing so, we use a mixed-methods approach, conducting qualitative focus group discussions and a quantitative field study to improve and validate a viability-fit measurement instrument. Our findings suggest two issues for research and practice. First, the results indicate that different stakeholders perceive HIT viability and fit of the same e-health services very unequally. Second, the analysis also demonstrates that there can be a great discrepancy between the organizational viability and individual fit of a particular e-health service. The findings of this study have a number of important implications such as for health policy making, HIT portfolios, and stakeholder communication. Copyright © 2015. Published by Elsevier Ireland Ltd.

The validation of Huffaz Intelligence Test (HIT)

NASA Astrophysics Data System (ADS)

Rahim, Mohd Azrin Mohammad; Ahmad, Tahir; Awang, Siti Rahmah; Safar, Ajmain

2017-08-01

In general, a hafiz who can memorize the Quran has many specialties especially in respect to their academic performances. In this study, the theory of multiple intelligences introduced by Howard Gardner is embedded in a developed psychometric instrument, namely Huffaz Intelligence Test (HIT). This paper presents the validation and the reliability of HIT of some tahfiz students in Malaysia Islamic schools. A pilot study was conducted involving 87 huffaz who were randomly selected to answer the items in HIT. The analysis method used includes Partial Least Square (PLS) on reliability, convergence and discriminant validation. The study has validated nine intelligences. The findings also indicated that the composite reliabilities for the nine types of intelligences are greater than 0.8. Thus, the HIT is a valid and reliable instrument to measure the multiple intelligences among huffaz.

An Ethnographic Study of Health Information Technology Use in Three Intensive Care Units.

PubMed

Leslie, Myles; Paradis, Elise; Gropper, Michael A; Kitto, Simon; Reeves, Scott; Pronovost, Peter

2017-08-01

To identify the impact of a full suite of health information technology (HIT) on the relationships that support safety and quality among intensive care unit (ICU) clinicians. A year-long comparative ethnographic study of three academic ICUs was carried out. A total of 446 hours of observational data was collected in the form of field notes. A subset of these observations-134 hours-was devoted to job-shadowing individual clinicians and conducting a time study of their HIT usage. Significant variation in HIT implementation rates and usage was noted. Average HIT use on the two "high-use" ICUs was 49 percent. On the "low-use" ICU, it was 10 percent. Clinicians on the high-use ICUs experienced "silo" effects with potential safety and quality implications. HIT work was associated with spatial, data, and social silos that separated ICU clinicians from one another and their patients. Situational awareness, communication, and patient satisfaction were negatively affected by this siloing. HIT has the potential to accentuate social and professional divisions as clinical communications shift from being in-person to electronically mediated. Socio-technically informed usability testing is recommended for those hospitals that have yet to implement HIT. For those hospitals already implementing HIT, we suggest rapid, locally driven qualitative assessments focused on developing solutions to identified gaps between HIT usage patterns and organizational quality goals. © Health Research and Educational Trust.

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.

Development of a health information technology-based data system in community-based hospice and palliative care.

PubMed

Abernethy, Amy P; Wheeler, Jane L; Bull, Janet

2011-05-01

Few hospice and palliative care organizations use health information technology (HIT) for data collection and management; the feasibility and utility of a HIT-based approach in this multi-faceted, interdisciplinary context is unclear. To develop a HIT-based data infrastructure that serves multiple hospice and palliative care sites, meeting clinical and administrative needs with data, technical, and analytic support. Through a multi-site academic/community partnership, a data infrastructure was collaboratively developed, pilot-tested at a community-based site, refined, and demonstrated for data collection and preliminary analysis. Additional sites, which participated in system development, became prepared to contribute data to the growing aggregate database. Electronic data collection proved feasible in community-based hospice and palliative care. The project highlighted "success factors" for implementing HIT in this field: engagement of site-based project "champions" to promote the system from within; involvement of stakeholders at all levels of the organization, to promote culture change and buy-in; attention to local needs (e.g., data for quality reporting) and requirements (e.g., affordable cost, efficiency); consideration of practical factors (e.g., potential to interfere with clinical flow); provision of adequate software, technical, analytic, and statistical support; availability of flexible HIT options (e.g., different data-collection platforms); and adoption of a consortium approach in which sites can support one another, learn from each others' experiences, pool data, and benefit from economies of scale. In hospice and palliative care, HIT-based data collection/management has potential to generate better understanding of populations and outcomes, support quality assessment/quality improvement, and prepare sites to participate in research. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Implementation of Health Insurance Support Tools in Community Health Centers.

PubMed

Huguet, Nathalie; Hatch, Brigit; Sumic, Aleksandra; Tillotson, Carrie; Hicks, Elizabeth; Nelson, Joan; DeVoe, Jennifer E

2018-01-01

Health information technology (HIT) provides new opportunities for primary care clinics to support patients with health insurance enrollment and maintenance. We present strategies, early findings, and clinic reflections on the development and implementation of HIT tools designed to streamline and improve health insurance tracking at community health centers. We are conducting a hybrid implementation-effectiveness trial to assess novel health insurance enrollment and support tools in primary care clinics. Twenty-three clinics in 7 health centers from the OCHIN practice-based research network are participating in the implementation component of the trial. Participating health centers were randomized to 1 of 2 levels of implementation support, including arm 1 (n = 4 health centers, 11 clinic sites) that received HIT tools and educational materials and arm 2 (n = 3 health centers, 12 clinic sites) that received HIT tools, educational materials, and individualized implementation support with a practice coach. We used mixed-methods (qualitative and quantitative) to assess tool use rates and facilitators and barriers to implementation in the first 6 months. Clinics reported favorable attitudes toward the HIT tools, which replace less efficient and more cumbersome processes, and reflect on the importance of clinic engagement in tool development and refinement. Five of 7 health centers are now regularly using the tools and are actively working to increase tool use. Six months after formal implementation, arm 2 clinics demonstrated higher rates of tool use, compared with arm 1. These results highlight the value of early clinic input in tool development, the potential benefit of practice coaching during HIT tool development and implementation, and a novel method for coupling a hybrid implementation-effectiveness design with principles of improvement science in primary care research. © Copyright 2018 by the American Board of Family Medicine.

Transforming rural health care through information technology: an interventional study in China.

PubMed

Liu, Gordon Guoen; Chen, Yiqun; Qin, Xuezheng

2014-12-01

This article estimates the impacts of health information technology (HIT) on health-care delivery in the Wenchuan County of China, where the devastation of the 2008 Great Wenchuan Earthquake and the subsequent large-scale HIT implementation (the Healthy Wenchuan Program) offers a 'natural experiment' opportunity, enabling us to conduct a difference-in-difference evaluation of the potential benefits of HIT on accessibility, affordability and appropriateness of health-care services in the underdeveloped rural area. Based on data collected from two field surveys in township hospitals, we find that for both the inpatient and outpatient samples, the HIT system promotes access to medical care by increasing doctor referrals and encouraging within-county medical utilization, reduces patient financial burden in certain expenditure categories, and contributes to higher patient satisfaction on medical care quality. On the other hand, we also find that HIT leads to increased patient waiting time for hospital registration, reflecting the unique challenges in implementing HIT in the underdeveloped areas. Our study contributes to the growing body of literature on evaluating the impacts of HIT application in the developing regions, and provides implications on the potential role of HIT in China's national health system reforms. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

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.

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

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.

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.

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.

Development of the PRE-HIT instrument: patient readiness to engage in health information technology.

PubMed

Koopman, Richelle J; Petroski, Gregory F; Canfield, Shannon M; Stuppy, Julie A; Mehr, David R

2014-01-28

Technology-based aids for lifestyle change are becoming more prevalent for chronic conditions. Important "digital divides" remain, as well as concerns about privacy, data security, and lack of motivation. Researchers need a way to characterize participants' readiness to use health technologies. To address this need, we created an instrument to measure patient readiness to engage with health technologies among adult patients with chronic conditions. Initial focus groups to determine domains, followed by item development and refinement, and exploratory factor analysis to determine final items and factor structure. The development sample included 200 patients with chronic conditions from 6 family medicine clinics. From 98 potential items, 53 best candidate items were examined using exploratory factor analysis. Pearson's Correlation for Test/Retest reliability at 3 months. The final instrument had 28 items that sorted into 8 factors with associated Cronbach's alpha: 1) Health Information Need (0.84), 2) Computer/Internet Experience (0.87), 3) Computer Anxiety (0.82), 4) Preferred Mode of Interaction (0.73), 5) Relationship with Doctor (0.65), 6) Cell Phone Expertise (0.75), 7) Internet Privacy (0.71), and 8) No News is Good News (0.57). Test-retest reliability for the 8 subscales ranged from (0.60 to 0.85). The Patient Readiness to Engage in Health Internet Technology (PRE-HIT) instrument has good psychometric properties and will be an aid to researchers investigating technology-based health interventions. Future work will examine predictive validity.

Development of the PRE-HIT instrument: patient readiness to engage in health information technology

PubMed Central

2014-01-01

Background Technology-based aids for lifestyle change are becoming more prevalent for chronic conditions. Important “digital divides” remain, as well as concerns about privacy, data security, and lack of motivation. Researchers need a way to characterize participants’ readiness to use health technologies. To address this need, we created an instrument to measure patient readiness to engage with health technologies among adult patients with chronic conditions. Methods Initial focus groups to determine domains, followed by item development and refinement, and exploratory factor analysis to determine final items and factor structure. The development sample included 200 patients with chronic conditions from 6 family medicine clinics. From 98 potential items, 53 best candidate items were examined using exploratory factor analysis. Pearson’s Correlation for Test/Retest reliability at 3 months. Results The final instrument had 28 items that sorted into 8 factors with associated Cronbach’s alpha: 1) Health Information Need (0.84), 2) Computer/Internet Experience (0.87), 3) Computer Anxiety (0.82), 4) Preferred Mode of Interaction (0.73), 5) Relationship with Doctor (0.65), 6) Cell Phone Expertise (0.75), 7) Internet Privacy (0.71), and 8) No News is Good News (0.57). Test-retest reliability for the 8 subscales ranged from (0.60 to 0.85). Conclusion The Patient Readiness to Engage in Health Internet Technology (PRE-HIT) instrument has good psychometric properties and will be an aid to researchers investigating technology-based health interventions. Future work will examine predictive validity. PMID:24472182

Judgement on "hit or non-hit" of CHO cells exposed to accelerated heavy-ions (Fe- or Ar-ions) using division delay and CR-39 plastics as an indicator.

PubMed

Mehnati, P; Yatagai, F; Tsuzuki, T; Hanaoka, F; Sasaki, H

2001-03-01

The cell killing effect of ionizing radiation depends on the degree of linear energy transfer (LET). The relative biological effectiveness (RBE) reaches a maximum at LET of around 100-200 keV/micron and decreases at higher levels. The ion clusters produced by high-LET radiation are not uniformly distributed. The incidence of non-hit cell events is higher in high LET irradiation than in the cases of low-LET irradiation. This fact could explain the decrease in the cell killing effect at higher levels of LET irradiation. Since the cell killing effect may be related to the nuclear traversal of heavy-ions, it is necessary to establish methods to distinguish the hit cells from the non-hit cells, especially in case with high LET irradiation. Using time-lapse photography, we first examined the hit events by observing the division delay in the cells caused by high-LET irradiation. In addition, we explored the use of CR-39 plastics to detect the exact position of heavy-ion traversal on the surface of a flask where cells were growing. When Chinese hamster ovary (CHO-K1) cells were exposed to 4 Gy of accelerated Fe-ions (2000 keV/micron) or Ar (1640 keV/micron)-ions, the surviving fraction decreased to about 30% in both cases of irradiation. Eighty percent of the irradiated cells, suffered a division delay in contrast to the remaining 20% of the cells which showed a normal division time (12-13 hrs). The later 20% of the cells is considered to be a population of cells which were not actually traversed by heavy-ions. The difference between the higher values of the surviving fraction (approximately 30%) and the non-hit cell population (20%) indicates that some hit cells can grow even after being hit by heavy-ions. The fraction of recovered cells determined by the time-lapse photography method was 10%, and this value closely correlated with the difference between the surviving fraction and the non-hit cells. We used the Poisson distribution of the hit-events by heavy-ions among the cell population in order to calculate the fraction of cells receiving at least a single-hit in the cell nucleus (130 micron 2 in average size). From this calculation we determined that 80% of the cells had a single hit to their nuclei by a heavy-ion which induced such early cellular responses as division delay. Our finding in the experiments using CR-39 plastics as a detector for hit-sites further supported the idea that the hit lethality of a cell is related to heavy-ion traversal through its nucleus. This study indicates the possible usefulness of both the division delay and CR-39 plastic methods for evaluating the biological effects of heavy-ions, especially when these two methods are combined.

Workarounds to Intended Use of Health Information Technology: A Narrative Review of the Human Factors Engineering Literature.

PubMed

Patterson, Emily S

2018-05-01

Objective To integrate and synthesize insights from recent studies of workarounds to the intended use of health information technology (HIT) by health care professionals. Background Systems are safest when the documentation of how work is done in policies and procedures closely matches what people actually do when they are working. Proactively identifying and managing workarounds to the intended use of technology, including deviations from expected workflows, can improve system safety. Method A narrative review of studies of workarounds with HIT was conducted to identify themes in the literature. Results Three themes were identified: (1) Users circumvented new additional steps in the workflow when using HIT, (2) interdisciplinary team members communicated via HIT in text fields that were intended for other purposes, and (3) locally developed paper-based and manual whiteboard systems were used instead of HIT to support situation awareness of individuals and groups; an example of a locally developed system was handwritten notes about a patient on a piece of paper folded up and carried in a nurse's pocket. Conclusion Workarounds were employed to avoid changes to workflow, enable interdisciplinary communication, coordinate activities, and have real-time portable access to summarized and synthesized information. Application Implications for practice include providing summary overview displays, explicitly supporting role-based communication and coordination through HIT, and reducing the risk to reputation due to electronic monitoring of individual performance.

Low-Resolution Screening of Early Stage Acquisition Simulation Scenario Development Decisions

DTIC Science & Technology

2012-12-01

6 seconds) incorporating reload times and assumptions. Phit for min range is assumed to be 100% (excepting FGM- 148, which was estimated for a...User Interface HTN Hierarchical Task Network MCCDC Marine Corps Combat Development Command Phit Probability to hit the intended target Pkill...well beyond the scope of this study. 5. Weapon Capabilities Translation COMBATXXI develops situation probabilities to hit ( Phit ) and probabilities to

[Survivability and morphologic anomalies in higher plants wolffia arrhiza following exposure to heavy ions of the galactic space radiation].

PubMed

Nevzgodina, L V; Kaminskaia, E V; Maksimova, E N; Fatsius, R; Sherrer, K; Shtraukh, V

2000-01-01

Experimental data on the effects of spaceflight factors, space radiation in particular, on higher plant Wolffia arrhiza firstly exposed in the "Bioblock" assembly and measurements made by physical track detectors of heavy ions (HI) are presented. Death of individual Wolffia plants and morphologic anomalies were the basic evaluation criteria. The peculiar feature of this biological object consists in the possibility to reveal delayed effects after 1-2 months since space flight as Wolffia has a high rate of vegetative reproduction. German investigators through microscopic examination of track detectors performed identification of individual plants affected by HI. With specially developed software and a coordinate system of supposition of biolayers and track detectors with the accuracy of 1 micron, tracks and even separate sections of individual HI tracks were determined in biological objects. Thereafter each Wolffia plant hit by HI was examined and data were compared with other variants. As a result, correlation between Wolffia death rate and morphologic anomalies were determined at different times post flight and topography of HI tracks was found. It is hypothesized that morphological anomalies in Walffia were caused by direct hits of plant germs by heavy ions or close passage of particles.

Helicopter In-Flight Tracking System (HITS) for the Gulf of Mexico

NASA Technical Reports Server (NTRS)

Martone, Patrick; Tucker, George; Aiken, Edwin W. (Technical Monitor)

2001-01-01

The National Aeronautics and Space Administration (NASA) Ames Research Center (ARC) is sponsoring deployment and testing of the Helicopter In-flight Tracking System (HITS) in a portion of the Gulf of Mexico offshore area. Using multilateration principles, HITS determines the location and altitude of all transponder-equipped aircraft without requiring changes to current Mode A, C or S avionics. HITS tracks both rotary and fixed-wing aircraft operating in the 8,500 sq. mi. coverage region. The minimum coverage altitude of 100 ft. is beneficial for petroleum industry, allowing helicopters to be tracked onto the pad of most derricks. In addition to multilateration, HITS provides surveillance reports for aircraft equipped for Automatic Dependent Surveillance - Broadcast (ADS-B), a new surveillance system under development by the Federal Aviation Administration (FAA). The U.S. Department of Transportation (DOT) Volpe National Transportation Systems Center (Volpe Center) is supporting NASA in managing HITS installation and operation, and in evaluating the system's effectiveness. Senses Corporation is supplying, installing and maintaining the HITS ground system. Project activities are being coordinated with the FAA and local helicopter operators. Flight-testing in the Gulf will begin in early 2002. This paper describes the HITS project - specifically, the system equipment (architecture, remote sensors, central processing system at Intracoastal City, LA, and communications) and its performance (accuracy, coverage, and reliability). The paper also presents preliminary results of flight tests.

Identification of New Molecular Entities (NMEs) as Potential Leads against Tuberculosis from Open Source Compound Repository.

PubMed

Kotapalli, Sudha Sravanti; Nallam, Sri Satya Anila; Nadella, Lavanya; Banerjee, Tanmay; Rode, Haridas B; Mainkar, Prathama S; Ummanni, Ramesh

2015-01-01

The purpose of this study was to provide a number of diverse and promising early-lead compounds that will feed into the drug discovery pipeline for developing new antitubercular agents. The results from the phenotypic screening of the open-source compound library against Mycobacterium smegmatis and Mycobacterium bovis (BCG) with hit validation against M. tuberculosis (H37Rv) have identified novel potent hit compounds. To determine their druglikeness, a systematic analysis of physicochemical properties of the hit compounds has been performed using cheminformatics tools. The hit molecules were analysed by clustering based on their chemical finger prints and structural similarity determining their chemical diversity. The hit compound library is also filtered for druglikeness based on the physicochemical descriptors following Lipinski filters. The robust filtration of hits followed by secondary screening against BCG, H37Rv and cytotoxicity evaluation has identified 12 compounds with potential against H37Rv (MIC range 0.4 to 12.5 μM). Furthermore in cytotoxicity assays, 12 compounds displayed low cytotoxicity against liver and lung cells providing high therapeutic index > 50. To avoid any variations in activity due to the route of chemical synthesis, the hit compounds were re synthesized independently and confirmed for their potential against H37Rv. Taken together, the hits reported here provides copious potential starting points for generation of new leads eventually adds to drug discovery pipeline against tuberculosis.

Computers in the clinical encounter: a scoping review and thematic analysis.

PubMed

Crampton, Noah H; Reis, Shmuel; Shachak, Aviv

2016-05-01

Patient-clinician communication has been associated with increased patient satisfaction, trust in the clinician, adherence to prescribed therapy, and various health outcomes. The impact of health information technology (HIT) on the clinical encounter in general and patient-clinician communication in particular is a growing concern. The purpose of this study was to review the current literature on HIT use during the clinical encounter to update best practices and inform the continuous development of HIT policies and educational interventions. We conducted a literature search of four databases. After removing duplicates, reviewing titles and abstracts, performing a full-text review, and snowballing from references and citations, 51 articles were included in the analysis. We employed a qualitative thematic analysis to compare and contrast the findings across studies. Our analysis revealed that the use of HIT affects consultations in complex ways, impacting eye contact and gaze, information sharing, building relationships, and pauses in the conversation. Whether these impacts are positive or negative largely depends on the combination of consultation room layout, patient and clinician styles of interaction with HIT as well as each other, and the strategies and techniques employed by clinicians to integrate HIT into consultations. The in-depth insights into the impact of HIT on the clinical encounter, especially the strategies and techniques employed by clinicians to adapt to using HIT in consultations, can inform policies, educational interventions, and research. In contrast to the common negative views of HIT, it affects the clinical encounter in multiple ways. By applying identified strategies and best practices, HIT can support patient-clinician interactions rather than interfering with them. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hit-and-run, hit-and-stay, and commensal bacteria present different peptide content when viewed from the perspective of the T cell.

PubMed

He, Lu; De Groot, Anne S; Bailey-Kellogg, Chris

2015-11-27

Different types of bacteria face different pressures from the immune system, with those that persist ("hit-and-stay") potentially having to adapt more in order to escape than those prone to short-lived infection ("hit-and-run"), and with commensal bacteria potentially different from both due to additional physical mechanisms for avoiding immune detection. The Janus Immunogenicity Score (JIS) was recently developed to assess the likelihood of T cell recognition of an antigen, using an analysis that considers both binding of a peptide within the antigen by major histocompatability complex (MHC) and recognition of the peptide:MHC complex by cognate T cell receptor (TCR). This score was shown to be predictive of T effector vs. T regulatory or null responses in experimental data, as well as to distinguish viruses representative of the hit-and-stay vs. hit-and-run phenotypes. Here, JIS-based analyses were conducted in order to characterize the extent to which the pressure to avoid T cell recognition is manifested in genomic differences among representative hit-and-run, hit-and-stay, and commensal bacteria. Overall, extracellular proteins were found to have different JIS profiles from cytoplasmic ones. Contrasting the bacterial groups, extracellular proteins were shown to be quite different across the groups, much more so than intracellular proteins. The differences were evident even at the level of corresponding peptides in homologous protein pairs from hit-and-run and hit-and-stay bacteria. The multi-level analysis of patterns of immunogenicity across different groups of bacteria provides a new way to approach questions of bacterial immune camouflage or escape, as well as to approach the selection and optimization of candidates for vaccine design. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

PubMed

Palatianos, George; Michalis, Alkiviadis; Alivizatos, Petros; Lacoumenda, Stavroula; Geroulanos, Stefanos; Karabinis, Andreas; Iliopoulou, Eugenia; Soufla, Giannoula; Kanthou, Chryso; Khoury, Mazen; Sfyrakis, Petros; Stavridis, George; Astras, George; Vassili, Maria; Antzaka, Christina; Marathias, Katerina; Kriaras, Ioannis; Tasouli, Androniki; Papadopoulos, Kyrillos; Katafygioti, Marina; Matoula, Nikoletta; Angelidis, Antonios; Melissari, Euthemia

2015-07-01

Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT. © 2015 Wiley Periodicals, Inc.

Development of a risk prediction model among professional hockey players with visible signs of concussion.

PubMed

Bruce, Jared M; Echemendia, Ruben J; Meeuwisse, Willem; Hutchison, Michael G; Aubry, Mark; Comper, Paul

2017-04-04

Little research examines how to best identify concussed athletes. The purpose of the present study was to develop a preliminary risk decision model that uses visible signs (VS) and mechanisms of injury (MOI) to predict the likelihood of subsequent concussion diagnosis. Coders viewed and documented VS and associated MOI for all NHL games over the course of the 2013-2014 and 2014-2015 regular seasons. After coding was completed, player concussions were identified from the NHL injury surveillance system and it was determined whether players exhibiting VS were subsequently diagnosed with concussions by club medical staff as a result of the coded event. Among athletes exhibiting VS, suspected loss of consciousness, motor incoordination or balance problems, being in a fight, having an initial hit from another player's shoulder and having a secondary hit on the ice were all associated with increased risk of subsequent concussion diagnosis. In contrast, having an initial hit with a stick was associated with decreased risk of subsequent concussion diagnosis. A risk prediction model using a combination of the above VS and MOI was superior to approaches that relied on individual VS and associated MOI (sensitivity=81%, specificity=72%, positive predictive value=26%). Combined use of VS and MOI significantly improves a clinician's ability to identify players who need to be evaluated for possible concussion. A preliminary concussion prediction log has been developed from these data. Pending prospective validation, the use of these methods may improve early concussion detection and evaluation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Unintended consequences of information technologies in health care--an interactive sociotechnical analysis.

PubMed

Harrison, Michael I; Koppel, Ross; Bar-Lev, Shirly

2007-01-01

Many unintended and undesired consequences of Healthcare Information Technologies (HIT) flow from interactions between the HIT and the healthcare organization's sociotechnical system-its workflows, culture, social interactions, and technologies. This paper develops and illustrates a conceptual model of these processes that we call Interactive Sociotechnical Analysis (ISTA). ISTA captures common types of interaction with special emphasis on recursive processes, i.e., feedback loops that alter the newly introduced HIT and promote second-level changes in the social system. ISTA draws on prior studies of unintended consequences, along with research in sociotechnical systems, ergonomics, social informatics, technology-in-practice, and social construction of technology. We present five types of sociotechnical interaction and illustrate each with cases from published research. The ISTA model should further research on emergent and recursive processes in HIT implementation and their unintended consequences. Familiarity with the model can also foster practitioners' awareness of unanticipated consequences that only become evident during HIT implementation.

HITS-CLIP yields genome-wide insights into brain alternative RNA processing

NASA Astrophysics Data System (ADS)

Licatalosi, Donny D.; Mele, Aldo; Fak, John J.; Ule, Jernej; Kayikci, Melis; Chi, Sung Wook; Clark, Tyson A.; Schweitzer, Anthony C.; Blume, John E.; Wang, Xuning; Darnell, Jennifer C.; Darnell, Robert B.

2008-11-01

Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.

Just-in-time Database-Driven Web Applications

PubMed Central

2003-01-01

"Just-in-time" database-driven Web applications are inexpensive, quickly-developed software that can be put to many uses within a health care organization. Database-driven Web applications garnered 73873 hits on our system-wide intranet in 2002. They enabled collaboration and communication via user-friendly Web browser-based interfaces for both mission-critical and patient-care-critical functions. Nineteen database-driven Web applications were developed. The application categories that comprised 80% of the hits were results reporting (27%), graduate medical education (26%), research (20%), and bed availability (8%). The mean number of hits per application was 3888 (SD = 5598; range, 14-19879). A model is described for just-in-time database-driven Web application development and an example given with a popular HTML editor and database program. PMID:14517109

Video Head Impulse Testing (vHIT) and the Assessment of Horizontal Semicircular Canal Function.

PubMed

Riska, Kristal M; Murnane, Owen; Akin, Faith W; Hall, Courtney

2015-05-01

Vestibular function (specifically, horizontal semicircular canal function) can be assessed across a broad frequency range using several different techniques. The head impulse test is a qualitative test of horizontal semicircular canal function that can be completed at bedside. Recently, a new instrument (video head impulse test [vHIT]) has been developed to provide an objective assessment to the clinical test. Questions persist regarding how this test may be used in the overall vestibular test battery. The purpose of this case report is to describe vestibular test results (vHIT, rotational testing, vestibular evoked myogenic potentials, and balance and gait performance) in an individual with a 100% unilateral caloric weakness who was asymptomatic for dizziness, vertigo or imbalance. Comprehensive assessment was completed to evaluate vestibular function. Caloric irrigations, rotary chair testing, vHIT, and vestibular evoked myogenic potentials were completed. A 100% left-sided unilateral caloric weakness was observed in an asymptomatic individual. vHIT produced normal gain with covert saccades. This case demonstrates the clinical usefulness of vHIT as a diagnostic tool and indicator of vestibular compensation and functional status. American Academy of Audiology.

Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

PubMed

Favaloro, Emmanuel J

2018-02-01

Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ("anti-PF4-heparin"). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ("screening"), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow, and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief article overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. © 2017 Wiley Periodicals, Inc.

lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1.

PubMed

Yu, L; Fang, F; Lu, S; Li, X; Yang, Y; Wang, Z

2017-05-01

Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part via regulating the occupancy of E2F1 in the promoter regions of its target genes. The lncRNA-HIT-E2F1 complex may be a potential target for NSCLC treatment.

Two Methods for Efficient Solution of the Hitting-Set Problem

NASA Technical Reports Server (NTRS)

Vatan, Farrokh; Fijany, Amir

2005-01-01

A paper addresses much of the same subject matter as that of Fast Algorithms for Model-Based Diagnosis (NPO-30582), which appears elsewhere in this issue of NASA Tech Briefs. However, in the paper, the emphasis is more on the hitting-set problem (also known as the transversal problem), which is well known among experts in combinatorics. The authors primary interest in the hitting-set problem lies in its connection to the diagnosis problem: it is a theorem of model-based diagnosis that in the set-theory representation of the components of a system, the minimal diagnoses of a system are the minimal hitting sets of the system. In the paper, the hitting-set problem (and, hence, the diagnosis problem) is translated from a combinatorial to a computational problem by mapping it onto the Boolean satisfiability and integer- programming problems. The paper goes on to describe developments nearly identical to those summarized in the cited companion NASA Tech Briefs article, including the utilization of Boolean-satisfiability and integer- programming techniques to reduce the computation time and/or memory needed to solve the hitting-set problem.

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.

Using FDA reports to inform a classification for health information technology safety problems

PubMed Central

Ong, Mei-Sing; Runciman, William; Coiera, Enrico

2011-01-01

Objective To expand an emerging classification for problems with health information technology (HIT) using reports submitted to the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database. Design HIT events submitted to MAUDE were retrieved using a standardized search strategy. Using an emerging classification with 32 categories of HIT problems, a subset of relevant events were iteratively analyzed to identify new categories. Two coders then independently classified the remaining events into one or more categories. Free-text descriptions were analyzed to identify the consequences of events. Measurements Descriptive statistics by number of reported problems per category and by consequence; inter-rater reliability analysis using the κ statistic for the major categories and consequences. Results A search of 899 768 reports from January 2008 to July 2010 yielded 1100 reports about HIT. After removing duplicate and unrelated reports, 678 reports describing 436 events remained. The authors identified four new categories to describe problems with software functionality, system configuration, interface with devices, and network configuration; the authors' classification with 32 categories of HIT problems was expanded by the addition of these four categories. Examination of the 436 events revealed 712 problems, 96% were machine-related, and 4% were problems at the human–computer interface. Almost half (46%) of the events related to hazardous circumstances. Of the 46 events (11%) associated with patient harm, four deaths were linked to HIT problems (0.9% of 436 events). Conclusions Only 0.1% of the MAUDE reports searched were related to HIT. Nevertheless, Food and Drug Administration reports did prove to be a useful new source of information about the nature of software problems and their safety implications with potential to inform strategies for safe design and implementation. PMID:21903979

Challenges in ethics, safety, best practices, and oversight regarding HIT vendors, their customers, and patients: a report of an AMIA special task force.

PubMed

Goodman, Kenneth W; Berner, Eta S; Dente, Mark A; Kaplan, Bonnie; Koppel, Ross; Rucker, Donald; Sands, Daniel Z; Winkelstein, Peter

2011-01-01

The current commercial health information technology (HIT) arena encompasses a number of competing firms that provide electronic health applications to hospitals, clinical practices, and other healthcare-related entities. Such applications collect, store, and analyze patient information. Some vendors incorporate contract language whereby purchasers of HIT systems, such as hospitals and clinics, must indemnify vendors for malpractice or personal injury claims, even if those events are not caused or fostered by the purchasers. Some vendors require contract clauses that force HIT system purchasers to adopt vendor-defined policies that prevent the disclosure of errors, bugs, design flaws, and other HIT-software-related hazards. To address this issue, the AMIA Board of Directors appointed a Task Force to provide an analysis and insights. Task Force findings and recommendations include: patient safety should trump all other values; corporate concerns about liability and intellectual property ownership may be valid but should not over-ride all other considerations; transparency and a commitment to patient safety should govern vendor contracts; institutions are duty-bound to provide ethics education to purchasers and users, and should commit publicly to standards of corporate conduct; and vendors, system purchasers, and users should encourage and assist in each others' efforts to adopt best practices. Finally, the HIT community should re-examine whether and how regulation of electronic health applications could foster improved care, public health, and patient safety.

Challenges in ethics, safety, best practices, and oversight regarding HIT vendors, their customers, and patients: a report of an AMIA special task force

PubMed Central

Berner, Eta S; Dente, Mark A; Kaplan, Bonnie; Koppel, Ross; Rucker, Donald; Sands, Daniel Z; Winkelstein, Peter

2010-01-01

The current commercial health information technology (HIT) arena encompasses a number of competing firms that provide electronic health applications to hospitals, clinical practices, and other healthcare-related entities. Such applications collect, store, and analyze patient information. Some vendors incorporate contract language whereby purchasers of HIT systems, such as hospitals and clinics, must indemnify vendors for malpractice or personal injury claims, even if those events are not caused or fostered by the purchasers. Some vendors require contract clauses that force HIT system purchasers to adopt vendor-defined policies that prevent the disclosure of errors, bugs, design flaws, and other HIT-software-related hazards. To address this issue, the AMIA Board of Directors appointed a Task Force to provide an analysis and insights. Task Force findings and recommendations include: patient safety should trump all other values; corporate concerns about liability and intellectual property ownership may be valid but should not over-ride all other considerations; transparency and a commitment to patient safety should govern vendor contracts; institutions are duty-bound to provide ethics education to purchasers and users, and should commit publicly to standards of corporate conduct; and vendors, system purchasers, and users should encourage and assist in each others' efforts to adopt best practices. Finally, the HIT community should re-examine whether and how regulation of electronic health applications could foster improved care, public health, and patient safety. PMID:21075789

The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans

PubMed Central

Zheng, Ming; Zhang, Haili; Dill, David L.; Clark, J. David; Tu, Susan; Yablonovitch, Arielle L.; Tan, Meng How; Zhang, Rui; Rujescu, Dan; Wu, Manhong; Tessarollo, Lino; Vieira, Wilfred; Gottesman, Michael M.; Deng, Suhua; Eberlin, Livia S.; Zare, Richard N.; Billard, Jean-Martin; Gillet, Jean-Pierre; Li, Jin Billy; Peltz, Gary

2015-01-01

Background We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study. Methods and Findings A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered. Conclusions ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity. PMID:25647612

Incidence and diagnosis of heparin-induced thrombocytopenia (HIT) in patients with traumatic injuries treated with unfractioned or low-molecular-weight heparin: a literature review.

PubMed

Bloemen, A; Testroote, M J G; Janssen-Heijnen, M L G; Janzing, H M J

2012-05-01

The incidence of thromboembolic complications after major traumatic injuries is high (>50%). Thromboprophylaxis, often by low-molecular-weight heparin (LMWH) or unfractioned heparin (UH) is therefore routinely administered. Thromboprophylaxis is also advised after immobilisation for isolated lower leg injuries. Heparin induced thrombocytopenia (HIT) is a rare but very serious immune mediated complication of treatment with LMWH, which can cause potentially fatal thromboembolism. In the general medical and surgical population the incidence of HIT is 0.2%. Little is known about the incidence of HIT and value of screening in trauma patients and in isolated lower extremity injuries. Therefore, we performed a systematic literature review. The online databases Medline and EMBASE were searched independently by two authors. Manuscripts were selected for analysis by quantitative and qualitative selection. After eliminating duplicate articles and irrelevant studies, seven relevant papers reporting on the incidence of HIT in trauma patients were identified and two studies reported the incidence of HIT in patients with lower leg injuries. The selected papers varied in study design: three randomised controlled trials, three cohort studies and one case report were identified. The methodological quality of the studies varied. In a total population of 1920 patients, HIT was identified in seven patients (0.36%). Pooling of data was impossible due to heterogeneity in study design and populations. No HIT was reported in 826 patients with lower extremity injuries, requiring immobilisation. Only a few studies have reported on the incidence of HIT in trauma patients who receive prophylactic LMWH. In the heterogenous populations of the available studies, the incidence of HIT appears to be very low and comparable to other patient populations. There is hardly any literature on the incidence of HIT in patients with isolated lower leg injuries receiving LMWH, but incidence seems to be very low. The incidence of HIT in trauma patients who receive LMWH thromboprophylaxis appears to be low (0.36%). Incidence of HIT in patients with isolated lower leg injuries receiving LMWH seems very low. Monitoring of platelet count could be considered in hospitalised patients with a high risk for development of HIT. A pre-test scoring system may identify these patients. Copyright © 2011. Published by Elsevier Ltd.

Synergistic stress exacerbation in hippocampal neurons: Evidence favoring the dual hit hypothesis of neurodegeneration

PubMed Central

Heinemann, Scott D.; Posimo, Jessica M.; Mason, Daniel M.; Hutchison, Daniel F.; Leak, Rehana K.

2016-01-01

The dual hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, we developed a relatively high-throughput dual hit model of stress synergy in primary hippocampal neurons. In order to increase the rigor of our study and strengthen our interpretations, we employed three independent, unbiased viability assays at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48h. MG132 and paraquat only elicited additive effects 24h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. Our findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, we present a new model of hippocampal vulnerability in which to test therapies, because neuroprotective treatments that are effective against severe, synergistic stress are more likely to succeed in the clinic. PMID:26934478

Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations.

PubMed

Monte, Aline Santos; Mello, Bruna Stefânia Ferreira; Borella, Vládia Célia Moreira; da Silva Araujo, Tatiane; da Silva, Francisco Eliclécio Rodrigues; Sousa, Francisca Cléa F de; de Oliveira, Antônio Carlos Pinheiro; Gama, Clarissa Severino; Seeman, Mary V; Vasconcelos, Silvânia Maria Mendes; Lucena, David Freitas De; Macêdo, Danielle

2017-07-28

Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence

PubMed Central

Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M

2015-01-01

Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases. PMID:25833341

High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence.

PubMed

Lucas, Samuel J E; Cotter, James D; Brassard, Patrice; Bailey, Damian M

2015-06-01

Exercise is a uniquely effective and pluripotent medicine against several noncommunicable diseases of westernised lifestyles, including protection against neurodegenerative disorders. High-intensity interval exercise training (HIT) is emerging as an effective alternative to current health-related exercise guidelines. Compared with traditional moderate-intensity continuous exercise training, HIT confers equivalent if not indeed superior metabolic, cardiac, and systemic vascular adaptation. Consequently, HIT is being promoted as a more time-efficient and practical approach to optimize health thereby reducing the burden of disease associated with physical inactivity. However, no studies to date have examined the impact of HIT on the cerebrovasculature and corresponding implications for cognitive function. This review critiques the implications of HIT for cerebrovascular function, with a focus on the mechanisms and translational impact for patient health and well-being. It also introduces similarly novel interventions currently under investigation as alternative means of accelerating exercise-induced cerebrovascular adaptation. We highlight a need for studies of the mechanisms and thereby also the optimal dose-response strategies to guide exercise prescription, and for studies to explore alternative approaches to optimize exercise outcomes in brain-related health and disease prevention. From a clinical perspective, interventions that selectively target the aging brain have the potential to prevent stroke and associated neurovascular diseases.

The role of the bi-compartmental stem cell niche in delaying cancer

NASA Astrophysics Data System (ADS)

Shahriyari, Leili; Komarova, Natalia L.

2015-10-01

In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

Anticipating and addressing the unintended consequences of health IT and policy: a report from the AMIA 2009 Health Policy Meeting.

PubMed

Bloomrosen, Meryl; Starren, Justin; Lorenzi, Nancy M; Ash, Joan S; Patel, Vimla L; Shortliffe, Edward H

2011-01-01

Federal legislation (Health Information Technology for Economic and Clinical Health (HITECH) Act) has provided funds to support an unprecedented increase in health information technology (HIT) adoption for healthcare provider organizations and professionals throughout the U.S. While recognizing the promise that widespread HIT adoption and meaningful use can bring to efforts to improve the quality, safety, and efficiency of healthcare, the American Medical Informatics Association devoted its 2009 Annual Health Policy Meeting to consideration of unanticipated consequences that could result with the increased implementation of HIT. Conference participants focused on possible unintended and unanticipated, as well as undesirable, consequences of HIT implementation. They employed an input-output model to guide discussion on occurrence of these consequences in four domains: technical, human/cognitive, organizational, and fiscal/policy and regulation. The authors outline the conference's recommendations: (1) an enhanced research agenda to guide study into the causes, manifestations, and mitigation of unintended consequences resulting from HIT implementations; (2) creation of a framework to promote sharing of HIT implementation experiences and the development of best practices that minimize unintended consequences; and (3) recognition of the key role of the Federal Government in providing leadership and oversight in analyzing the effects of HIT-related implementations and policies.

Hit discovery of 4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel EGFR inhibitor from a designed small library.

PubMed

Elkamhawy, Ahmed; Paik, Sora; Hassan, Ahmed H E; Lee, Yong Sup; Roh, Eun Joo

2017-12-01

Searching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC 50 1.05-5.37 μM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticipating and addressing the unintended consequences of health IT and policy: a report from the AMIA 2009 Health Policy Meeting

PubMed Central

Starren, Justin; Lorenzi, Nancy M; Ash, Joan S; Patel, Vimla L; Shortliffe, Edward H

2010-01-01

Federal legislation (Health Information Technology for Economic and Clinical Health (HITECH) Act) has provided funds to support an unprecedented increase in health information technology (HIT) adoption for healthcare provider organizations and professionals throughout the U.S. While recognizing the promise that widespread HIT adoption and meaningful use can bring to efforts to improve the quality, safety, and efficiency of healthcare, the American Medical Informatics Association devoted its 2009 Annual Health Policy Meeting to consideration of unanticipated consequences that could result with the increased implementation of HIT. Conference participants focused on possible unintended and unanticipated, as well as undesirable, consequences of HIT implementation. They employed an input–output model to guide discussion on occurrence of these consequences in four domains: technical, human/cognitive, organizational, and fiscal/policy and regulation. The authors outline the conference's recommendations: (1) an enhanced research agenda to guide study into the causes, manifestations, and mitigation of unintended consequences resulting from HIT implementations; (2) creation of a framework to promote sharing of HIT implementation experiences and the development of best practices that minimize unintended consequences; and (3) recognition of the key role of the Federal Government in providing leadership and oversight in analyzing the effects of HIT-related implementations and policies. PMID:21169620

Developing a Framework of Scientific Enquiry in Early Childhood: An Action Research Project to Support Staff Development and Improve Science Teaching

ERIC Educational Resources Information Center

McNerney, Karen; Hall, Nichola

2017-01-01

Research in science in early childhood is an area that has not received much attention (Fleer, M., & Robbins, J. (2003). "Hit and run research" with "hit and miss" results in early childhood science education. "Research in Science Education," 33, 405-431.) and it has been reported that early children teachers lack…

Impact of Thailand universal coverage scheme on the country's health information systems and health information technology.

PubMed

Kijsanayotin, Boonchai

2013-01-01

Thailand achieved universal healthcare coverage with the implementation of the Universal Coverage Scheme (UCS) in 2001. This study employed qualitative method to explore the impact of the UCS on the country's health information systems (HIS) and health information technology (HIT) development. The results show that health insurance beneficiary registration system helps improve providers' service workflow and country vital statistics. Implementation of casemix financing tool, Thai Diagnosis-Related Groups, has stimulated health providers' HIS and HIT capacity building, data and medical record quality and the adoption of national administrative data standards. The system called "Disease Management Information Systems" aiming at reimbursement for select diseases increased the fragmentation of HIS and increase burden on data management to providers. The financial incentive of outpatient data quality improvement project enhance providers' HIS and HIT investment and also induce data fraudulence tendency. Implementation of UCS has largely brought favorable impact on the country HIS and HIT development. However, the unfavorable effects are also evident.

The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

PubMed

Buzzetti, Elena; Pinzani, Massimo; Tsochatzis, Emmanuel A

2016-08-01

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis. Copyright © 2016 Elsevier Inc. All rights reserved.

An Approach for All in Pharmacy Informatics Education.

PubMed

Fox, Brent I; Flynn, Allen; Clauson, Kevin A; Seaton, Terry L; Breeden, Elizabeth

2017-03-25

Computerization is transforming health care. All clinicians are users of health information technology (HIT). Understanding fundamental principles of informatics, the field focused on information needs and uses, is essential if HIT is going to support improved patient outcomes. Informatics education for clinicians is a national priority. Additionally, some informatics experts are needed to bring about innovations in HIT. A common approach to pharmacy informatics education has been slow to develop. Meanwhile, accreditation standards for informatics in pharmacy education continue to evolve. A gap remains in the implementation of informatics education for all pharmacy students and it is unclear what expert informatics training should cover. In this article, we propose the first of two complementary approaches to informatics education in pharmacy: to incorporate fundamental informatics education into pharmacy curricula for all students. The second approach, to train those students interested in becoming informatics experts to design, develop, implement, and evaluate HIT, will be presented in a subsequent issue of the Journal .

Identification and prioritization of novel anti-Wolbachia chemotypes from screening a 10,000-compound diversity library

PubMed Central

Johnston, Kelly L.; Cook, Darren A. N.; Berry, Neil G.; David Hong, W.; Clare, Rachel H.; Goddard, Megan; Ford, Louise; Nixon, Gemma L.; O’Neill, Paul M.; Ward, Stephen A.; Taylor, Mark J.

2017-01-01

Lymphatic filariasis and onchocerciasis are two important neglected tropical diseases (NTDs) that cause severe disability. Control efforts are hindered by the lack of a safe macrofilaricidal drug. Targeting the Wolbachia bacterial endosymbionts in these parasites with doxycycline leads to a macrofilaricidal outcome, but protracted treatment regimens and contraindications restrict its widespread implementation. The Anti-Wolbachia consortium aims to develop improved anti-Wolbachia drugs to overcome these barriers. We describe the first screening of a large, diverse compound library against Wolbachia. This whole-organism screen, streamlined to reduce bottlenecks, produced a hit rate of 0.5%. Chemoinformatic analysis of the top 50 hits led to the identification of six structurally diverse chemotypes, the disclosure of which could offer interesting avenues of investigation to other researchers active in this field. An example of hit-to-lead optimization is described to further demonstrate the potential of developing these high-quality hit series as safe, efficacious, and selective anti-Wolbachia macrofilaricides. PMID:28959730

An Approach for All in Pharmacy Informatics Education

PubMed Central

Flynn, Allen; Clauson, Kevin A.; Seaton, Terry L.; Breeden, Elizabeth

2017-01-01

Computerization is transforming health care. All clinicians are users of health information technology (HIT). Understanding fundamental principles of informatics, the field focused on information needs and uses, is essential if HIT is going to support improved patient outcomes. Informatics education for clinicians is a national priority. Additionally, some informatics experts are needed to bring about innovations in HIT. A common approach to pharmacy informatics education has been slow to develop. Meanwhile, accreditation standards for informatics in pharmacy education continue to evolve. A gap remains in the implementation of informatics education for all pharmacy students and it is unclear what expert informatics training should cover. In this article, we propose the first of two complementary approaches to informatics education in pharmacy: to incorporate fundamental informatics education into pharmacy curricula for all students. The second approach, to train those students interested in becoming informatics experts to design, develop, implement, and evaluate HIT, will be presented in a subsequent issue of the Journal. PMID:28381898

Isolation and characterization of gallium resistant Pseudomonas aeruginosa mutants.

PubMed

García-Contreras, Rodolfo; Lira-Silva, Elizabeth; Jasso-Chávez, Ricardo; Hernández-González, Ismael L; Maeda, Toshinari; Hashimoto, Takahiro; Boogerd, Fred C; Sheng, Lili; Wood, Thomas K; Moreno-Sánchez, Rafael

2013-12-01

Pseudomonas aeruginosa PA14 cells resistant to the novel antimicrobial gallium nitrate (Ga) were developed using transposon mutagenesis and by selecting spontaneous mutants. The mutants showing the highest growth in the presence of Ga were selected for further characterization. These mutants showed 4- to 12-fold higher Ga minimal inhibitory growth concentrations and a greater than 8-fold increase in the minimum biofilm eliminating Ga concentration. Both types of mutants produced Ga resistant biofilms whereas the formation of wild-type biofilms was strongly inhibited by Ga. The gene interrupted in the transposon mutant was hitA, which encodes a periplasmic iron binding protein that delivers Fe³⁺ to the HitB iron permease; complementation of the mutant with the hitA gene restored the Ga sensitivity. This hitA mutant showed a 14-fold decrease in Ga internalization versus the wild-type strain, indicating that the HitAB system is also involved in the Ga uptake. Ga uptake in the spontaneous mutant was also lower, although no mutations were found in the hitAB genes. Instead, this mutant harbored 64 non-silent mutations in several genes including those of the phenazine pyocyanin biosynthesis. The spontaneous mutant produced 2-fold higher pyocyanin basal levels than the wild-type; the addition of this phenazine to wild-type cultures protected them from the Ga bacteriostatic effect. The present data indicate that mutations affecting Ga transport and probably pyocyanin biosynthesis enable cells to develop resistance to Ga. Copyright © 2013 Elsevier GmbH. All rights reserved.

Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example.

PubMed

Xie, Yiyue; Dahlin, Jayme L; Oakley, Aaron J; Casarotto, Marco G; Board, Philip G; Baell, Jonathan B

2018-05-10

Early stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme glutathione transferase omega-1 (GSTO1-1) as an example of a relatively difficult target and review the associated literature involving small-molecule inhibitors. As part of this process we deliberately pay closer-than-usual attention to assay interference and hit quality aspects. We believe this Perspective will be a useful guide for future development of GSTO1-1 inhibitors, as well serving as a template for future review formats of new or difficult targets.

Heparin-induced thrombocytopenia

PubMed Central

Shaikh, Nissar

2011-01-01

In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT). HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI) are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock. PMID:21633576

Prospective evaluation of a rapid nanoparticle-based lateral flow immunoassay (STic Expert(®) HIT) for the diagnosis of heparin-induced thrombocytopenia.

PubMed

Leroux, Dorothée; Hezard, Nathalie; Lebreton, Aurélien; Bauters, Anne; Suchon, Pierre; de Maistre, Emmanuel; Biron, Christine; Huisse, Marie-Genevieve; Ternisien, Catherine; Voisin, Sophie; Gruel, Yves; Pouplard, Claire

2014-09-01

A rapid lateral flow immunoassay (LFIA) (STic Expert(®) HIT), recently developed for the diagnosis of heparin-induced thrombocytopenia (HIT), was evaluated in a prospective multicentre cohort of 334 consecutive patients. The risk of HIT was estimated by the 4Ts score as low, intermediate and high in 28·7%, 61·7% and 9·6% of patients, respectively. Definite HIT was diagnosed in 40 patients (12·0%) with positive results on both enzyme-linked immunosorbent assay (Asserachrom(®) HPIA IgG) and serotonin release assay. The inter-reader reproducibility of results obtained was excellent (kappa ratio > 0·9). The negative predictive value of LFIA with plasma samples was 99·6% with a negative likelihood ratio (LR) of 0·03, and was comparable to those of the particle gel immunoassay (H/PF4-PaGIA(®) ) performed in 124 cases. Positive predictive value and positive LR were 44·4% and 5·87, respectively, and the results were similar for serum samples. The probability of HIT in intermediate risk patients decreased from 11·2% to 0·4% when the LFIA result was negative and increased to 42·5% when it was positive. In conclusion, the STic Expert(®) HIT combined with the 4Ts score is a reliable tool to rule out the diagnosis of HIT. © 2014 John Wiley & Sons Ltd.

Numerical assessment of wind turbine blade damage due to contact/impact with tower during installation

NASA Astrophysics Data System (ADS)

Shankar Verma, Amrit; Petter Vedvik, Nils; Gao, Zhen

2017-12-01

The use of floating crane vessel for installation of offshore wind turbine blades presents a great challenge in terms of its random motions and is likely to increase the probability of the blade hitting the preassembled tower during lifting operation. To evaluate the consequences of such scenarios and to determine the allowable motions or sea states for such operations, it is very important to understand the damage development in the blade due to impact. The present paper employs the application of high fidelity finite element method to investigate the damage behavior in the blade when the leading edge of the blade hits the tower. A nonlinear time domain structural analysis using ABAQUS was conducted on the DTU 10 MW reference blade model which is based on shell elements. Damage assessment along with the nature of evolution of various energies is examined and presented for two different impact velocities with modified layup stacking sequence at the contact region.

CMOS image sensor for detection of interferon gamma protein interaction as a point-of-care approach.

PubMed

Marimuthu, Mohana; Kandasamy, Karthikeyan; Ahn, Chang Geun; Sung, Gun Yong; Kim, Min-Gon; Kim, Sanghyo

2011-09-01

Complementary metal oxide semiconductor (CMOS)-based image sensors have received increased attention owing to the possibility of incorporating them into portable diagnostic devices. The present research examined the efficiency and sensitivity of a CMOS image sensor for the detection of antigen-antibody interactions involving interferon gamma protein without the aid of expensive instruments. The highest detection sensitivity of about 1 fg/ml primary antibody was achieved simply by a transmission mechanism. When photons are prevented from hitting the sensor surface, a reduction in digital output occurs in which the number of photons hitting the sensor surface is approximately proportional to the digital number. Nanoscale variation in substrate thickness after protein binding can be detected with high sensitivity by the CMOS image sensor. Therefore, this technique can be easily applied to smartphones or any clinical diagnostic devices for the detection of several biological entities, with high impact on the development of point-of-care applications.

"Hit the ground running": perspectives of new nurses and nurse managers on role transition and integration of new graduates.

PubMed

Chernomas, Wanda M; Care, W Dean; McKenzie, Jo-Ann Lapointe; Guse, Lorna; Currie, Jan

2010-01-01

The workplace for new graduates must be a constructive learning environment to facilitate their development. Nurse managers need new graduates who can "hit the ground running." Conflict between the needs of new nurses and the realities of the workplace often creates role confusion and tension in new graduates and threatens employers' ability to retain them. As part of a larger study that examined the effectiveness of a new strategy on new nurse retention and workplace integration, we conducted focus groups with new nurses and nurse managers. This paper discusses the perspectives of new nurses on their role transition from graduates to practising professionals and the perspectives of nurse managers on the workplace integration of new nurses. The thematic findings integrate new nurses' perspectives on their needs during role transition with the perspectives of nurse managers in meeting those needs. The discussion includes strategies to facilitate successful transition and integration of new nurses into the workplace within the context of recruitment and retention.

Transforming healthcare with information technology in Japan: a review of policy, people, and progress.

PubMed

Abraham, Chon; Nishihara, Eitaro; Akiyama, Miki

2011-03-01

Healthcare reform as part of the economic recovery plan in Japan is placing emphasis on the use of healthcare information technology (HIT). This research mainly focuses on the HIT efforts in Japan with reference to the US for context. The purpose is to: (a) provide detail on governmental policy impacting promotion of HIT adoption to provide services to the people of Japan, (b) describe the outcomes of past and present policy impacting progress based on a case study of HIT use in the Kyoto Yamashina area, and (c) discuss issues for refinement of current policy. The method is case study, and data collection techniques include: (a) interviews of people involved in policy making for HIT in Japan (Japanese healthcare professionals, government officials, and academics involved in HIT research in Japan) and use in the medical community of HIT in the Kyoto Yamashina area, (b) archived document analysis of reports regarding government policy for HIT policy and user assessment for HIT mainly in the case study site, and (c) the literature review about HIT progression and effectiveness assessments to explore and describe issues concerning the transformation with HIT in Japan. This study reveals the aspects of governmental policy that have been effective in promoting successful HIT initiatives as well as some that have been detriments in Japan to help solve pressing social issues regarding healthcare delivery. For example, Japan has stipulated some standardized protocols and formats for HIT but does not mandate exactly how to engage in inter-organizational or intra-organizational health information exchange. This provides some desired autonomy for healthcare organizations and or governments in medical communities and allows for more advanced organizations to leverage current resources while providing a basis for lesser equipped organizations to use in planning the initiative. The insights gained from the Kyoto Yamashina area initiative reflect the success of past governmental policy efforts and the current intent to promote HIT adoption. Insights from the case study as well as other social issues facing Japan warrant some refinement of policy. The refinement concerns: (a) the necessity for leadership and IT knowledge in the medical communities, (b) provider incentives, (c) legislation regarding accountability, security, privacy and confidentiality, (d) inclusion of stakeholders in solution development, and (e) creating sustainable business models. The research highlights the efforts of Japan for using HIT in healthcare reform. We present outcomes from a case study of the Kyoto Yamashina area medical community as proof of concept for past and present policy in Japan that are insightful for proliferation of successful projects in Japan and adoption of HIT in general. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Discovering new PI3Kα inhibitors with a strategy of combining ligand-based and structure-based virtual screening

NASA Astrophysics Data System (ADS)

Yu, Miao; Gu, Qiong; Xu, Jun

2018-02-01

PI3Kα is a promising drug target for cancer chemotherapy. In this paper, we report a strategy of combing ligand-based and structure-based virtual screening to identify new PI3Kα inhibitors. First, naïve Bayesian (NB) learning models and a 3D-QSAR pharmacophore model were built based upon known PI3Kα inhibitors. Then, the SPECS library was screened by the best NB model. This resulted in virtual hits, which were validated by matching the structures against the pharmacophore models. The pharmacophore matched hits were then docked into PI3Kα crystal structures to form ligand-receptor complexes, which are further validated by the Glide-XP program to result in structural validated hits. The structural validated hits were examined by PI3Kα inhibitory assay. With this screening protocol, ten PI3Kα inhibitors with new scaffolds were discovered with IC50 values ranging 0.44-31.25 μM. The binding affinities for the most active compounds 33 and 74 were estimated through molecular dynamics simulations and MM-PBSA analyses.

Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database

NASA Astrophysics Data System (ADS)

Sommer, Thomas; Hübner, Harald; El Kerdawy, Ahmed; Gmeiner, Peter; Pischetsrieder, Monika; Clark, Timothy

2017-03-01

The dopamine D2 receptor (D2R) is involved in food reward and compulsive food intake. The present study developed a virtual screening (VS) method to identify food components, which may modulate D2R signalling. In contrast to their common applications in drug discovery, VS methods are rarely applied for the discovery of bioactive food compounds. Here, databases were created that exclusively contain substances occurring in food and natural sources (about 13,000 different compounds in total) as the basis for combined pharmacophore searching, hit-list clustering and molecular docking into D2R homology models. From 17 compounds finally tested in radioligand assays to determine their binding affinities, seven were classified as hits (hit rate = 41%). Functional properties of the five most active compounds were further examined in β-arrestin recruitment and cAMP inhibition experiments. D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity. Application of our databases provides new perspectives for the discovery of bioactive food constituents using VS methods. Based on its presence in beer, we suggest that hordenine significantly contributes to mood-elevating effects of beer.

Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex

PubMed Central

Tyburczy, Magdalena E.; Wang, Ji-an; Li, Shaowei; Thangapazham, Rajesh; Chekaluk, Yvonne; Moss, Joel; Kwiatkowski, David J.; Darling, Thomas N.

2014-01-01

Tuberous sclerosis complex (TSC) is characterized by the formation of tumors in multiple organs and is caused by germline mutation in one of two tumor suppressor genes, TSC1 and TSC2. As for other tumor suppressor gene syndromes, the mechanism of somatic second-hit events in TSC tumors is unknown. We grew fibroblast-like cells from 29 TSC skin tumors from 22 TSC subjects and identified germline and second-hit mutations in TSC1/TSC2 using next-generation sequencing. Eighteen of 22 (82%) subjects had a mutation identified, and 8 of the 18 (44%) subjects were mosaic with mutant allele frequencies of 0 to 19% in normal tissue DNA. Multiple tumors were available from four patients, and in each case, second-hit mutations in TSC2 were distinct indicating they arose independently. Most remarkably, 7 (50%) of the 14 somatic point mutations were CC>TT ultraviolet ‘signature’ mutations, never seen as a TSC germline mutation. These occurred exclusively in facial angiofibroma tumors from sun-exposed sites. These results implicate UV-induced DNA damage as a cause of second-hit mutations and development of TSC facial angiofibromas and suggest that measures to limit UV exposure in TSC children and adults should reduce the frequency and severity of these lesions. PMID:24271014

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.

Chemical Space of DNA-Encoded Libraries.

PubMed

Franzini, Raphael M; Randolph, Cassie

2016-07-28

In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

Compound Libraries: Recent Advances and Their Applications in Drug Discovery.

PubMed

Gong, Zhen; Hu, Guoping; Li, Qiang; Liu, Zhiguo; Wang, Fei; Zhang, Xuejin; Xiong, Jian; Li, Peng; Xu, Yan; Ma, Rujian; Chen, Shuhui; Li, Jian

2017-01-01

Hit identification is the starting point of small-molecule drug discovery and is therefore very important to the pharmaceutical industry. One of the most important approaches to identify a new hit is to screen a compound library using an in vitro assay. High-throughput screening has made great contributions to drug discovery since the 1990s but requires expensive equipment and facilities, and its success depends on the size of the compound library. Recent progress in the development of compound libraries has provided more efficient ways to identify new hits for novel drug targets, thereby helping to promote the development of the pharmaceutical industry, especially for firstin- class drugs. A multistage and systematic research of articles published between 1986 and 2017 has been performed, which was organized into 5 sections and discussed in detail. In this review, the sources and classification of compound libraries are summarized. The progress made in combinatorial libraries and DNA-encoded libraries is reviewed. Library design methods, especially for focused libraries, are introduced in detail. In the final part, the status of the compound libraries at WuXi is reported. The progress related to compound libraries, especially drug template libraries, DELs, and focused libraries, will help to identify better hits for novel drug targets and promote the development of the pharmaceutical industry. Moreover, these libraries can facilitate hit identification, which benefits most research organizations, including academics and small companies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Second hit in cervical carcinogenesis process: involvement of wnt/beta catenin pathway

PubMed Central

Perez-Plasencia, Carlos; Duenas-Gonzalez, Alfonso; Alatorre-Tavera, Brenda

2008-01-01

The Human papillomavirus plays an important role in the initiation and progression of cervical cancer. However, it is a necessary but not sufficient cause to develop invasive carcinoma; hence, other factors are required in the pathogenesis of this malignancy. In this review we explore the hypothesis of the deregulation of wnt/β-catenin signaling pathway as a "second hit" required to develop cervical cancer. PMID:18606007

75 FR 51819 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health [[Page 51820

Atomic description of the immune complex involved in heparin-induced thrombocytopenia

DOE PAGES

Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; ...

2015-09-22

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

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

Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

Increased fatalities and cost of traumatic injuries in elderly pedestrians in Hawaii: a challenge for prevention and outreach.

PubMed

Takanishi, Danny M; Yu, Mihae; Morita, Shane Y

2008-01-01

This study was carried out to evaluate and quantify risk factors, mechanisms, and cost of traumatic injuries in Hawaii's elderly and to identify potential preventive strategies. A retrospective review of a prospective database of patients admitted to the only Trauma Center in the Pacific Basin, between January 2000 and December 2001, was conducted. Of 2634 trauma admissions, 11% were >or=65 years of age. Mechanisms of injury included falls, motor vehicle crashes (MVCs), pedestrians hit by automobiles, and miscellaneous causes. The incidence of elderly pedestrians hit by automobiles in Hawaii is higher than previously reported. Hospital mortality rate was highest for the pedestrian hit group, followed by falls, and then MVCs. The pedestrian hit group consumed the largest quantity of resources and MVCs the least. Given the high mortality rate and associated resource consumption in the pedestrian hit group, it would be appropriate to give priority to this group while developing preventive measures for this age group.

Using ProHits to store, annotate and analyze affinity purification - mass spectrometry (AP-MS) data

PubMed Central

Liu, Guomin; Zhang, Jianping; Choi, Hyungwon; Lambert, Jean-Philippe; Srikumar, Tharan; Larsen, Brett; Nesvizhskii, Alexey I.; Raught, Brian; Tyers, Mike; Gingras, Anne-Claude

2012-01-01

Affinity purification coupled with mass spectrometry (AP-MS) is a robust technique used to identify protein-protein interactions. With recent improvements in sample preparation, and dramatic advances in MS instrumentation speed and sensitivity, this technique is becoming more widely used throughout the scientific community. To meet the needs of research groups both large and small, we have developed software solutions for tracking, scoring and analyzing AP-MS data. Here, we provide details for the installation and utilization of ProHits, a Laboratory Information Management System designed specifically for AP-MS interaction proteomics. This protocol explains: (i) how to install the complete ProHits system, including modules for the management of mass spectrometry files and the analysis of interaction data, and (ii) alternative options for the use of pre-existing search results in simpler versions of ProHits, including a virtual machine implementation of our ProHits Lite software. We also describe how to use the main features of the software to analyze AP-MS data. PMID:22948730

Optical Diagnostics on HIT-SI3

NASA Astrophysics Data System (ADS)

Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

2016-10-01

Interferometry and Thomson Scattering are implemented on the HIT-SI3 (Helicity Injected Torus - Steady Inductive 3) device to provide time resolved measurements of electron density and spatially resolved measurements of electron temperature, respectively. HIT-SI3 is a modification of the original HIT-SI apparatus that uses three injectors instead of two. The scientific aim of HIT-SI3 is to develop a deeper understanding of how injector behavior and interactions influence current drive and spheromak stability. The interferometer system makes use of an intermediate frequency between two parallel 184.3 μm Far-Infrared (FIR) laser cavities which are optically pumped by a CO2 laser. The phase shift in this beat frequency due to the plasma index of refraction is used to calculate the line-integrated electron density. To measure the electron temperature, Thomson Scattered light from a 20 J (1 GW pulse) Ruby laser off of free electrons in the HIT-SI3 plasma is measured simultaneously at four locations across the spheromak (nominally 23 cm minor radius). Polychromators bin the collected light into 3 spectral bands to detect the relative level of scattering. Work supported by the D.O.E.

CXCL4-platelet factor 4, heparin-induced thrombocytopenia and cancer.

PubMed

Sandset, Per Morten

2012-04-01

Platelet factor 4 (CXCL4-PF4) is a chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development. In some patients exposed to heparin, antibodies are generated against the CXCL-PF4/heparin complex that may activate platelets and coagulation and lead to thrombocytopenia and arterial or venous thrombosis, a condition commonly named heparin induced thrombocytopenia (HIT). HIT has been investigated in numerous clinical settings, but there is limited data on the epidemiology and phenotype of HIT in cancer patients. The present review describes the role of CXCL4-PF4 in cancer, the immunobiology, clinical presentation and diagnosis of HIT, and the specific problems faced in cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology

PubMed Central

Hodzic, Ermin; Sauerwald, Thomas; Dao, Phuong; Wang, Kendric; Yeung, Jake; Anderson, Shawn; Vandin, Fabio; Haffari, Gholamreza; Collins, Colin C.; Sahinalp, S. Cenk

2017-01-01

Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the “random walk facility location” (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: “multihitting time,” the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients’ survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology. PMID:28768687

A Health- and Resource-Oriented Perspective on NSLBP

PubMed Central

Rolli Salathé, Cornelia; Elfering, Achim

2013-01-01

Nonspecific low back pain (NSLBP) is an important health issue of our time. Personal as well as economic factors, like suffering pain and experiencing disability on the one hand and enormous and still increasing costs to the economy and society on the other hand, display the importance of the matter. Tremendous research has been conducted in the last few decades on NSLBP. A PubMed search (June 17, 2013) on “low back pain” provided 22,980 hits, and when specifying for “low back pain, systematic review,” 3,134 hits were still generated. Most research has been done examining the development, risk factors, or therapeutic measures of NSLBP, but hardly any literature exists on resources related to NSLBP. The aims of this review are twofold. In order to shade light on the salutogenetic approach of NSLBP, and thus to focus on health instead of illness, the first aim is to facilitate the understanding of which therapeutic measures enhance the ability to cope with chronic NSLBP and enable (more) normal functioning in life. The second aim is to stimulate the understanding of resources protecting against the onset of NSLBP or against the development of chronic NSLBP and its resulting work absence. PMID:27335880

Biomarkers for IgA nephropathy on the basis of multi-hit pathogenesis.

PubMed

Suzuki, Hitoshi

2018-05-08

IgA nephropathy (IgAN) is the most prevalent glomerular disease worldwide and is associated with a poor prognosis. Development of curative treatment strategies and approaches for early diagnosis is necessary. Renal biopsy is the gold standard for the diagnosis and assessment of disease activity. However, reliable biomarkers are needed for the noninvasive diagnosis of this disease and to more fully delineate the risk of progression. With regard to the pathogenesis of IgAN, the multi-hit hypothesis, including production of galactose-deficient IgA1 (Gd-IgA1; Hit 1), IgG or IgA autoantibodies that recognize Gd-IgA1 (Hit 2), and their subsequent immune complexes formation (Hit 3) and glomerular deposition (Hit 4), has been widely supported by many studies. Although the prognostic values of several biomarkers have been discussed, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of Gd-IgA1 and Gd-IgA1-containing immune complexes. In addition, urinary Gd-IgA1 may represent a disease-specific biomarker for IgAN. We also confirmed that there is a significant correlation between serum levels of these effector molecules and disease activity, suggesting that each can be considered a practical surrogate marker of therapeutic response. Thus, these disease-oriented specific serum and urine biomarkers may be useful for screening of potential IgAN with isolated hematuria, earlier diagnosis, disease activity, and eventually, response to treatment. In this review, we discuss these concepts, with a focus on potential clinical applications of these biomarkers.

Treatment and Prevention of Heparin-Induced Thrombocytopenia

PubMed Central

Dans, Antonio L.; Moores, Lisa K.; Bona, Robert; Davidson, Bruce L.; Schulman, Sam; Crowther, Mark

2012-01-01

Background: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Conclusions: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID:22315270

Biosensor-based small molecule fragment screening with biolayer interferometry

NASA Astrophysics Data System (ADS)

Wartchow, Charles A.; Podlaski, Frank; Li, Shirley; Rowan, Karen; Zhang, Xiaolei; Mark, David; Huang, Kuo-Sen

2011-07-01

Biosensor-based fragment screening is a valuable tool in the drug discovery process. This method is advantageous over many biochemical methods because primary hits can be distinguished from non-specific or non-ideal interactions by examining binding profiles and responses, resulting in reduced false-positive rates. Biolayer interferometry (BLI), a technique that measures changes in an interference pattern generated from visible light reflected from an optical layer and a biolayer containing proteins of interest, is a relatively new method for monitoring small molecule interactions. The BLI format is based on a disposable sensor that is immersed in 96-well or 384-well plates. BLI has been validated for small molecule detection and fragment screening with model systems and well-characterized targets where affinity constants and binding profiles are generally similar to those obtained with surface plasmon resonsance (SPR). Screens with challenging targets involved in protein-protein interactions including BCL-2, JNK1, and eIF4E were performed with a fragment library of 6,500 compounds, and hit rates were compared for these targets. For eIF4E, a protein containing a PPI site and a nucleotide binding site, results from a BLI fragment screen were compared to results obtained in biochemical HTS screens. Overlapping hits were observed for the PPI site, and hits unique to the BLI screen were identified. Hit assessments with SPR and BLI are described.

Development of New a-Si/c-Si Heterojunction Solar Cells: ACJ-HIT (Artificially Constructed Junction-Heterojunction with Intrinsic Thin-Layer)

NASA Astrophysics Data System (ADS)

Tanaka, Makoto; Taguchi, Mikio; Matsuyama, Takao; Sawada, Toru; Tsuda, Shinya; Nakano, Shoichi; Hanafusa, Hiroshi; Kuwano, Yukinori

1992-11-01

A new type of a-Si/c-Si heterojunction solar cell, called the HIT (Heterojunction with Intrinsic Thin-layer) solar cell, has been developed based on ACJ (Artificially Constructed Junction) technology. A conversion efficiency of more than 18% has been achieved, which is the highest ever value for solar cells in which the junction was fabricated at a low temperature (<200°C).

Influence analysis of Github repositories.

PubMed

Hu, Yan; Zhang, Jun; Bai, Xiaomei; Yu, Shuo; Yang, Zhuo

2016-01-01

With the support of cloud computing techniques, social coding platforms have changed the style of software development. Github is now the most popular social coding platform and project hosting service. Software developers of various levels keep entering Github, and use Github to save their public and private software projects. The large amounts of software developers and software repositories on Github are posing new challenges to the world of software engineering. This paper tries to tackle one of the important problems: analyzing the importance and influence of Github repositories. We proposed a HITS based influence analysis on graphs that represent the star relationship between Github users and repositories. A weighted version of HITS is applied to the overall star graph, and generates a different set of top influential repositories other than the results from standard version of HITS algorithm. We also conduct the influential analysis on per-month star graph, and study the monthly influence ranking of top repositories.

A follow-up study of the association between mobile phone use and symptoms of ill health.

PubMed

Cho, Yong Min; Lim, Hee Jin; Jang, Hoon; Kim, Kyunghee; Choi, Jae Wook; Shin, Chol; Lee, Seung Ku; Kwon, Jong Hwa; Kim, Nam

2016-01-01

The duration and frequency of mobile phone calls, and their relationship with various health effects, have been investigated in our previous cross-sectional study. This 2-year period follow-up study aimed to assess the changes in these variables of same subjects. The study population comprised 532 non-patient adult subjects sampled from the Korean Genome Epidemiology Study. The subjects underwent a medical examination at a hospital in 2012/2013 and revisited the same hospital in 2014/2015 to have the same examination for the characteristics of mobile phone use performed. In addition, to evaluate the effects on health, the Headache Impact Test-6 (HIT-6), Psychosocial Well-being Index-Short Form, Beck Depression Inventory, Korean-Instrumental Activities of Daily Living, Perceived Stress Scale, Pittsburgh Sleep Quality Index, and 12-item Short Form Health Survey were analyzed. For all these tests, the higher the score, the greater the effect on health. Variances between scores in all the indices in the baseline and follow-up surveys were calculated, and correlations of each index were analyzed. The average duration per call and HIT-6 score of the subjects decreased significantly compared with those recorded two years ago. The results showed a slight but significant correlation between call duration changes and HIT-6 score changes for female subjects, but not for males. HIT-6 scores in the follow-up survey significantly decreased compared to those in the baseline survey, but long-time call users (subjects whose call duration was ≥5 minutes in both the baseline and follow-up surveys) had no statistically significant reduction in HIT-6 scores. This study suggests that increased call duration is a greater risk factor for increases in headache than any other type of adverse health effect, and that this effect can be chronic.

75 FR 16126 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

76 FR 4352 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2011-01-25

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 5595 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2010-02-03

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 8953 - Office of the National Coordinator for Health Information Technology HIT Policy Committee...

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2010-02-26

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... a policy framework for the development and adoption of a nationwide health information technology...

75 FR 42091 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2010-07-20

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 151 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2010-01-04

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 29762 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2010-05-27

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 65486 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2010-10-25

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

76 FR 9784 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 57026 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

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2010-09-17

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

75 FR 51820 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... Coordinator for Health Information Technology, HHS. ACTION: Notice of meeting. This notice announces a... Information Technology (ONC). The meeting will be open to the public. Name of Committee: HIT Policy Committee... framework for the development and adoption of a nationwide health information technology infrastructure that...

Fragment-based drug discovery and molecular docking in drug design.

PubMed

Wang, Tao; Wu, Mian-Bin; Chen, Zheng-Jie; Chen, Hua; Lin, Jian-Ping; Yang, Li-Rong

2015-01-01

Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed.

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia.

PubMed

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-04-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple 'hits' are required for disease progression; an initial genetic abnormality followed by additional secondary 'hits'. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development.

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.

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.

Comprehension of wh-questions precedes their production in typical development and autism spectrum disorders

PubMed Central

Goodwin, Anthony; Fein, Deborah; Naigles, Letitia R.

2011-01-01

Lay Abstract Children with autism produce few wh-questions, compared to their typically developing peers. It is unclear if this is because of social-pragmatic difficulties, or if they have not yet learned the grammar for asking wh-questions. If children do not know how to use grammatical rules to produce questions, they might simply repeat sentences that they have heard without completely understanding them first. We visited the homes of 15 children with autism and 18 typically developing children with similar language abilities, across a three-year period. At each visit, children watched a video that depicted an apple hitting a flower and keys hitting a book. The children were then shown the items side-by-side on the screen and the audio asked “what hit the flower?” and “what did the keys hit?” We filmed the children’s eye movements and analyzed how long they looked at the named item, compared to when they heard “where is the flower/keys?” At each visit, we also filmed a 30-minute mother-child play session and analyzed the types of questions that the children asked. Children with autism showed comprehension of wh-questions at a later age than typically developing children, but at a similar level of overall language development. Neither group produced wh-questions before they had demonstrated that they understood the underlying grammatical rules. Therefore, children with autism seem to process wh-questions in the same way as their typically developing peers, just at a later age. This paper discusses the implications of our findings for the language development of children with autism. Scientific Abstract Children with autism (ASD) rarely produce wh-questions (e.g., “What hit the book?”) in naturalistic speech. It is unclear if this is due to social-pragmatic difficulties, or if grammatical deficits are also involved. If grammar is impaired, production of wh-questions by rote memorization might precede comprehension of similar forms. In a longitudinal study, 15 children with ASD and 18 initially-language-matched typically developing toddlers were visited in their homes at four-month intervals across a three-year period. The wh-question task was presented via intermodal preferential looking. Silent ‘hitting’ events (e.g., an apple hitting a flower) were followed by test trials in which the apple and flower were juxtaposed on the screen. During test trials, subject-wh and object-wh-question audios were sequentially presented (e.g., “What hit the flower?”/”What did the apple hit?”). Control audios were also presented (e.g., “Where’s the apple/flower?”). Children’s eye movements were coded off-line, frame-by-frame. To show reliable comprehension, children should look longer to the named item (i.e., apple or flower) during the “where” questions, but less at the named item during the subject-wh and object-wh-questions. To compare comprehension to production, we coded 30-minute spontaneous speech samples drawn from mother-child interactions at each visit. Results indicated that comprehension of subject and object-wh-questions was delayed in children with ASD compared to age-matched TD children, but not when matched on overall language levels. Additionally, both groups comprehended wh-questions before producing similar forms, indicating that development occurred in a similar manner. This paper discusses the implications of our findings for language acquisition in ASD. PMID:22359403

Autonomic cardiovascular modulation in masters and young cyclists following high-intensity interval training.

PubMed

Borges, Nattai R; Reaburn, Peter R; Doering, Thomas M; Argus, Christos K; Driller, Matthew W

2017-04-01

This study aimed at examining the autonomic cardiovascular modulation in well-trained masters and young cyclists following high-intensity interval training (HIT). Nine masters (age 55.6 ± 5.0 years) and eight young cyclists (age 25.9 ± 3.0 years) completed a HIT protocol of 6 x 30 sec at 175% of peak power output, with 4.5-min' rest between efforts. Immediately following HIT, heart rate and R-R intervals were monitored for 30-min during passive supine recovery. Autonomic modulation was examined by i) heart rate recovery in the first 60-sec of recovery (HRR 60 ); ii) the time constant of the 30-min heart rate recovery curve (HRRτ); iii) the time course of the root mean square for successive 30-sec R-R interval (RMSSD 30 ); and iv) time and frequency domain analyses of subsequent 5-min R-R interval segments. No significant between-group differences were observed for HRR 60 (P = 0.096) or HRR τ (P = 0.617). However, a significant interaction effect was found for RMSSD 30 (P = 0.021), with the master cyclists showing higher RMSSD 30 values following HIT. Similar results were observed in the time and frequency domain analyses with significant interaction effects found for the natural logarithm of the RMSSD (P = 0.008), normalised low-frequency power (P = 0.016) and natural logarithm of high-frequency power (P = 0.012). Following high-intensity interval training, master cyclists demonstrated greater post-exercise parasympathetic reactivation compared to young cyclists, indicating that physical training at older ages has significant effects on autonomic function.

Effects of competition on video-task performance in monkeys (Macaca mulatta)

NASA Technical Reports Server (NTRS)

Washburn, David A.; Hopkins, William D.; Rumbaugh, Duane M.

1990-01-01

The effects of competition on performance of a video-formatted task were examined in a series of experiments. Two rhesus monkeys (Macaca mulatta) were trained to manipulate a joystick to shoot at moving targets on a computer screen. The task was made competitive by requiring both animals to shoot at the same target and by rewarding only the animal that hit the target first each trial. The competitive task produced a significant and robust speed-accuracy trade-off in performance. The monkeys hit the target in significantly less time on contested than on uncontested trials. However, they required significantly more shots to hit the target on contested trials in relation to uncontested trials. This effect was unchanged when various schedules of reinforcement were introduced in the uncontested trials. This supports the influence of competition qua competition on performance, a point further bolstered by other findings of behavioral contrast presented here.

Don't get the message: the effect of a warning text before visiting a proanorexia website.

PubMed

Martijn, Carolien; Smeets, Elke; Jansen, Anita; Hoeymans, Nancy; Schoemaker, Casper

2009-03-01

This study examined the effect of the placement of a warning text before visiting proanorexia websites on actual access of these websites. A separate webpage with a warning text aiming at first-time visitors was placed before each proanorexia website hosted by a Dutch Internet provider. During the research period of 1 year, the numbers of hits at the warning webpage were registered together with the numbers of hits at the underlying proanorexia website. Of the total number of hits registered at the warning webpage, about two-third of the visitors were registered at the underlying proanorexia website. This indicates that about one-third of the visitors did not continue their visit to a proanorexia website after being exposed to the warning text. Placement of a warning text before proanorexia websites appears a promising strategy in holding back potential visitors.

Effects of High-Intensity Interval Training versus Continuous Training on Physical Fitness, Cardiovascular Function and Quality of Life in Heart Failure Patients.

PubMed

Benda, Nathalie M M; Seeger, Joost P H; Stevens, Guus G C F; Hijmans-Kersten, Bregina T P; van Dijk, Arie P J; Bellersen, Louise; Lamfers, Evert J P; Hopman, Maria T E; Thijssen, Dick H J

2015-01-01

Physical fitness is an important prognostic factor in heart failure (HF). To improve fitness, different types of exercise have been explored, with recent focus on high-intensity interval training (HIT). We comprehensively compared effects of HIT versus continuous training (CT) in HF patients NYHA II-III on physical fitness, cardiovascular function and structure, and quality of life, and hypothesize that HIT leads to superior improvements compared to CT. Twenty HF patients (male:female 19:1, 64±8 yrs, ejection fraction 38±6%) were allocated to 12-weeks of HIT (10*1-minute at 90% maximal workload-alternated by 2.5 minutes at 30% maximal workload) or CT (30 minutes at 60-75% of maximal workload). Before and after intervention, we examined physical fitness (incremental cycling test), cardiac function and structure (echocardiography), vascular function and structure (ultrasound) and quality of life (SF-36, Minnesota living with HF questionnaire (MLHFQ)). Training improved maximal workload, peak oxygen uptake (VO2peak) related to the predicted VO2peak, oxygen uptake at the anaerobic threshold, and maximal oxygen pulse (all P<0.05), whilst no differences were present between HIT and CT (N.S.). We found no major changes in resting cardiovascular function and structure. SF-36 physical function score improved after training (P<0.05), whilst SF-36 total score and MLHFQ did not change after training (N.S.). Training induced significant improvements in parameters of physical fitness, although no evidence for superiority of HIT over CT was demonstrated. No major effect of training was found on cardiovascular structure and function or quality of life in HF patients NYHA II-III. Nederlands Trial Register NTR3671.

Environmental factors and health information technology management strategy.

PubMed

Menachemi, Nir; Shin, Dong Yeong; Ford, Eric W; Yu, Feliciano

2011-01-01

: Previous studies have provided theoretical and empirical evidence that environmental forces influence hospital strategy. : Rooted in resource dependence theory and the information uncertainty perspective, this study examined the relationship between environmental market characteristics and hospitals' selection of a health information technology (HIT) management strategy. : A cross-sectional design is used to analyze secondary data from the American Hospital Association Annual Survey, the Healthcare Information and Management Systems Society Analytics Database, and the Area Resource File. Univariate and multinomial logistic regression analyses are used. : Overall, 3,221 hospitals were studied, of which 60.9% pursed a single-vendor HIT management strategy, 28.9% pursued a best-of-suite strategy, and 10.2% used a best-of-breed strategy. Multivariate analyses controlling for hospital characteristics found that measures of environmental factors representing munificence, dynamism, and/or complexity were systematically associated with various hospital HIT management strategy use. Specifically, the number of generalist physicians per capita was positively associated with the single-vendor strategy (B = -5.64, p = .10). Hospitals in urban markets were more likely to pursue the best-of-suite strategy (B = 0.622, p < .001). Dynamism, measured as the number of managed care contracts for a given hospital, was negatively associated with the single-vendor strategy (B = 0.004, p = .049). Lastly, complexity, measured as market competition, was positively associated with the best-of-breed strategy (B = 0.623, p = .042). : By and large, environmental factors are associated with hospital HIT management strategies in mostly theoretically supported ways. Hospital leaders and policy makers interested in influencing the adoption of hospital HIT should consider how market conditions influence HIT management decisions as part of programs to promote meaningful use.

The impact of health information technology on cancer care across the continuum: a systematic review and meta-analysis.

PubMed

Tarver, Will L; Menachemi, Nir

2016-03-01

Health information technology (HIT) has the potential to play a significant role in the management of cancer. The purpose of this review is to identify and examine empirical studies that investigate the impact of HIT in cancer care on different levels of the care continuum. Electronic searches were performed in four academic databases. The authors used a three-step search process to identify 122 studies that met specific inclusion criteria. Next, a coding sheet was used to extract information from each included article to use in an analysis. Logistic regression was used to determine study-specific characteristics that were associated with positive findings. Overall, 72.4% of published analyses reported a beneficial effect of HIT. Multivariate analysis found that the impact of HIT differs across the cancer continuum with studies targeting diagnosis and treatment being, respectively, 77 (P = .001) and 39 (P = .039) percentage points less likely to report a beneficial effect when compared to those targeting prevention. In addition, studies targeting HIT to patients were 31 percentage points less likely to find a beneficial effect than those targeting providers (P = .030). Lastly, studies assessing behavior change as an outcome were 41 percentage points less likely to find a beneficial effect (P = .006), while studies targeting decision making were 27 percentage points more likely to find a beneficial effect (P = .034). Based on current evidence, HIT interventions seem to be more successful when targeting physicians, care in the prevention phase of the cancer continuum, and/or decision making. An agenda for future research is discussed. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of backward cell migration in two-hit mutants' production in the stem cell niche.

PubMed

Bollas, Audrey; Shahriyari, Leili

2017-01-01

It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell's divisions are asymmetric.

The role of backward cell migration in two-hit mutants’ production in the stem cell niche

PubMed Central

Bollas, Audrey

2017-01-01

It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell’s divisions are asymmetric. PMID:28931019

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.

[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.

Use and clinical efficacy of standard and health information technology fall risk assessment tools.

PubMed

Teh, Ruth C; Wilson, Anne; Ranasinghe, Damith; Visvanathan, Renuka

2017-12-01

To evaluate the health information technology (HIT) compared to Fall Risk for Older Persons (FROP) tool in fall risk screening. A HIT tool trial was conducted on the geriatric evaluation and management (GEM, n = 111) and acute medical units (AMU, n = 424). Health information technology and FROP scores were higher on GEM versus AMU, with no differences between people who fell and people who did not fall. Both score completion rates were similar, and their values correlated marginally (Spearman's correlation coefficient 0.33, P < 0.01). HIT and FROP scores demonstrated similar sensitivity (80 vs 82%) and specificity (32 vs 36%) for detecting hospital falls. Hospital fall rates trended towards reduction on AMU (4.20 vs 6.96, P = 0.15) and increase on GEM (10.98 vs 6.52, P = 0.54) with HIT tool implementation. Health information technology tool acceptability and scoring were comparable to FROP screening, with mixed effects on fall rate with HIT tool implementation. Clinician partnership remains key to effective tool development. © 2017 AJA Inc.

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.

Health Care Information Technology in Rural America: Electronic Medical Record Adoption Status in Meeting the National Agenda

ERIC Educational Resources Information Center

Bahensky, James A.; Jaana, Mirou; Ward, Marcia M.

2008-01-01

Continuing is a national political drive for investments in health care information technology (HIT) that will allow the transformation of health care for quality improvement and cost reduction. Despite several initiatives by the federal government to spur this development, HIT implementation has been limited, particularly in the rural market. The…

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.

Development of confocal laser microscope system for examination of microscopic characteristics of radiophotoluminescence glass dosemeters.

PubMed

Maki, Daisuke; Ishii, Tetsuya; Sato, Fuminobu; Kato, Yushi; Yamamoto, Takayoshi; Iida, Toshiyuki

2011-03-01

A confocal laser microscope system was developed for the measurement of radiophotoluminescence (RPL) photons emitted from a minute alpha-ray-irradiated area in an RPL glass dosemeter. The system was composed mainly of an inverted-type microscope, an ultraviolet laser, an XY movable stage and photon-counting circuits. The photon-counting circuits were effective in the reduction of the background noise level in the measurement of RPL photons. The performance of this microscope system was examined by the observation of standard RPL glass samples irradiated using (241)Am alpha rays. The spatial resolution of this system was ∼ 3 μm, and with regard to the sensitivity of this system, a hit of more than four to five alpha rays in unit area produced enough amount of RPL photons to construct the image.

The Developmental Trajectory of Self-Injurious Behaviours in Individuals with Prader Willi Syndrome, Autism Spectrum Disorder and Intellectual Disability.

PubMed

Rice, Lauren J; Gray, Kylie M; Howlin, Patricia; Taffe, John; Tonge, Bruce J; Einfeld, Stewart L

2016-02-06

In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS) and autism spectrum disorder (ASD). The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description of the behaviour phenotype, that is, which types and natural history of self-injurious behaviour are more common in PWS and ASD and which are shared with other forms of developmental disability. Self-injury displayed by individuals with PWS and individuals with ASD was compared with that reported in a group of individuals with intellectual disability due to mixed aetiology (ID group). Three self-injurious behaviours (head banging, skin-picking and hitting and/or biting self) were measured on five occasions over 18 years using the Developmental Behaviour Checklist (DBC) a well-validated caregiver report measure. Rates of skin picking were higher in individuals with PWS and hitting and/or biting self was higher in individuals with ASD compared to the ID group. Rates of head banging were similar across the three groups. Over time, skin-picking and head banging increased with age for individuals with ASD and hitting and/or biting self increased for the PWS group. In the PWS and mixed ID groups head banging decreased with age. These findings suggest that the typology and developmental trajectories of self-injurious behaviours differ between those with PWS and ASD.

The Developmental Trajectory of Self-Injurious Behaviours in Individuals with Prader Willi Syndrome, Autism Spectrum Disorder and Intellectual Disability

PubMed Central

Rice, Lauren J.; Gray, Kylie M.; Howlin, Patricia; Taffe, John; Tonge, Bruce J.; Einfeld, Stewart L.

2016-01-01

In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS) and autism spectrum disorder (ASD). The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description of the behaviour phenotype, that is, which types and natural history of self-injurious behaviour are more common in PWS and ASD and which are shared with other forms of developmental disability. Self-injury displayed by individuals with PWS and individuals with ASD was compared with that reported in a group of individuals with intellectual disability due to mixed aetiology (ID group). Three self-injurious behaviours (head banging, skin-picking and hitting and/or biting self) were measured on five occasions over 18 years using the Developmental Behaviour Checklist (DBC) a well-validated caregiver report measure. Rates of skin picking were higher in individuals with PWS and hitting and/or biting self was higher in individuals with ASD compared to the ID group. Rates of head banging were similar across the three groups. Over time, skin-picking and head banging increased with age for individuals with ASD and hitting and/or biting self increased for the PWS group. In the PWS and mixed ID groups head banging decreased with age. These findings suggest that the typology and developmental trajectories of self-injurious behaviours differ between those with PWS and ASD. PMID:28933389

HitWalker2: visual analytics for precision medicine and beyond.

PubMed

Bottomly, Daniel; McWeeney, Shannon K; Wilmot, Beth

2016-04-15

The lack of visualization frameworks to guide interpretation and facilitate discovery is a potential bottleneck for precision medicine, systems genetics and other studies. To address this we have developed an interactive, reproducible, web-based prioritization approach that builds on our earlier work. HitWalker2 is highly flexible and can utilize many data types and prioritization methods based upon available data and desired questions, allowing it to be utilized in a diverse range of studies such as cancer, infectious disease and psychiatric disorders. Source code is freely available at https://github.com/biodev/HitWalker2 and implemented using Python/Django, Neo4j and Javascript (D3.js and jQuery). We support major open source browsers (e.g. Firefox and Chromium/Chrome). wilmotb@ohsu.edu Supplementary data are available at Bioinformatics online. Additional information/instructions are available at https://github.com/biodev/HitWalker2/wiki. © The Author 2015. Published by Oxford University Press.

In-silico guided discovery of novel CCR9 antagonists

NASA Astrophysics Data System (ADS)

Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

2018-03-01

Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

Measuring Workload Demand of Informatics Systems with the Clinical Case Demand Index

PubMed Central

Iyengar, M. Sriram; Rogith, Deevakar; Florez-Arango, Jose F

2017-01-01

Introduction: The increasing use of Health Information Technology (HIT) can add substantially to workload on clinical providers. Current methods for assessing workload do not take into account the nature of clinical cases and the use of HIT tools while solving them. Methods: The Clinical Case Demand Index (CCDI), consisting of a summary score and visual representation, was developed to meet this need. Consistency with current perceived workload measures was evaluated in a Randomized Control Trial of a mobile health system. Results: CCDI is significantly correlated with existing workload measures and inversely related to provider performance. Discussion: CCDI combines subjective and objective characteristics of clinical cases along with cognitive and clinical dimensions. Applications include evaluation of HIT tools, clinician scheduling, medical education. Conclusion: CCDI supports comparative effectiveness research of HIT tools. In addition, CCDI could have numerous applications including training, clinical trials, design of clinical workflows, and others. PMID:29854166

Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy.

PubMed

Song, Hyeseung; Lee, Yun Suk; Roh, Eun Joo; Seo, Jae Hong; Oh, Kwang-Seok; Lee, Byung Ho; Han, Hogyu; Shin, Kye Jung

2012-09-01

Regulation of NF-κB activation through the inhibition of IKKβ has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKKβ inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKKβ inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-κB activation and TNFα production in cell as well as inhibition activity against IKKβ. Among them, compound 3q showed the potent inhibitory activity against IKKβ, and excellent selectivity over other kinases such as p38α, p38β, JNK1, JNK2, and JNK3 as well as IKKα. Copyright © 2012 Elsevier Ltd. All rights reserved.

Elevated false recognition in patients with frontal lobe damage is neither a general nor a unitary phenomenon.

PubMed

Verfaellie, Mieke; Rapcsak, Steven Z; Keane, Margaret M; Alexander, Michael P

2004-01-01

This study examined verbal recognition memory in amnesic patients with frontal lesions (AF), nonamnesic patients with frontal lesions (NAF), and amnesic patients with medial temporal lesions (MT). To examine susceptibility to false alarms, the number of studied words drawn from various categories was varied. The AF and MT groups demonstrated reduced hits and increased false alarms. False alarms were especially elevated when item-specific recollection was strongest in control participants. The NAF group performed indistinguishably from control participants, but several patients showed excessive false alarms in the context of normal hit rates. These patients exhibited impaired monitoring and verification processes. The findings demonstrate that elevated false recognition is not characteristic of all frontal patients and may result from more than 1 underlying mechanism. ((c) 2004 APA, all rights reserved)

Recognizing nurse stakeholder dissonance as a critical determinant of patient safety in new healthcare information technologies.

PubMed

Samaras, Elizabeth A; Real, Sara D; Curtis, Amber M; Meunier, Tessa S

2012-01-01

Proper identification of all stakeholders and the comprehensive assessment of their evolving and often conflicting Needs, Wants, and Desires (NWDs) is a fundamental principle of human factors science and human-centered systems engineering; it is not yet a consistent element in development and deployment of new health information technologies (HIT). As the single largest group of healthcare professionals, nurses are critical stakeholders for these new technologies. Careful analysis can reveal nurse stakeholder dissonance (NSD) when integrating new technologies into the healthcare environment. Stakeholder dissonance is a term that describes the conflict between the NWDs of different stakeholders which, if left unresolved, can result in dissatisfaction, workarounds, errors, and threats to patient safety. Three case studies drawn from the authors' experience in a variety of acute-care settings where new HITs have been recently deployed are examined to illustrate the concept of NSD. Conflicting NWDs, other stakeholders, and possible root causes of the NSD are analyzed and mapped to threats to patient safety. Lessons learned, practical guidance for anticipating, identifying, and mitigating NSD, future research and implications for HFE and nursing practice are discussed.

[Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

PubMed

Mitomo, Hideki; Miyamoto, Akira; Tabata, Toshiharu; Sugawara, Takafumi; Yabuki, Hiroshi; Fujimura, Shigefumi

2014-12-01

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

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

A Diastereoselective Multicomponent Reaction for Construction of Alkynylamide-Substituted α,β-Diamino Acid Derivatives To Hunt Hits.

PubMed

Lei, Ruirui; Wu, Yong; Dong, Suzhen; Jia, Kaili; Liu, Shunying; Hu, Wenhao

2017-03-17

A highly diasetereoselective Mannich-type multicomponent reaction was developed to rapidly construct alkynylamide-substituted α,β-diamino acid derivatives from simple starting materials under mild conditions in moderate to good yields for hit hunting. Most of the resulting products 4 exhibited good anticancer activity in HCT116, BEL7402, and SMMC7721 cells.

Identifying Novel Type ZBGs and Nonhydroxamate HDAC Inhibitors Through a SVM Based Virtual Screening Approach.

PubMed

Liu, X H; Song, H Y; Zhang, J X; Han, B C; Wei, X N; Ma, X H; Cui, W K; Chen, Y Z

2010-05-17

Histone deacetylase inhibitors (HDACi) have been successfully used for the treatment of cancers and other diseases. Search for novel type ZBGs and development of non-hydroxamate HDACi has become a focus in current research. To complement this, it is desirable to explore a virtual screening (VS) tool capable of identifying different types of potential inhibitors from large compound libraries with high yields and low false-hit rates similar to HTS. This work explored the use of support vector machines (SVM) combined with our newly developed putative non-inhibitor generation method as such a tool. SVM trained by 702 pre-2008 hydroxamate HDACi and 64334 putative non-HDACi showed good yields and low false-hit rates in cross-validation test and independent test using 220 diverse types of HDACi reported since 2008. The SVM hit rates in scanning 13.56 M PubChem and 168K MDDR compounds are comparable to HTS rates. Further structural analysis of SVM virtual hits suggests its potential for identification of non-hydroxamate HDACi. From this analysis, a series of novel ZBG and cap groups were proposed for HDACi design. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data

PubMed Central

Van Loo, Peter; Kay, Jonathan D.; Matthews, Lucy; Haase, Kerstin; Clark, Jeremy; Thomas, Sarah; Butler, Adam P.; Gundem, Gunes; Merson, Sue; Luxton, Hayley; Hawkins, Steve; Ghori, Mohammed; Marsden, Luke; Lambert, Adam; Pelvender, Gill; Massie, Charlie E.; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Nicol, David; Yu, Yongwei; Zhang, Hongwei; Isaacs, William; Visakorpi, Tapio; Verrill, Clare; Lynch, Andrew G.; Lu, Yong Jie; Whitaker, Hayley C.; Neal, David E.; Cooper, Colin S.

2017-01-01

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses. PMID:28945760

Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data.

PubMed

Camacho, Niedzica; Van Loo, Peter; Edwards, Sandra; Kay, Jonathan D; Matthews, Lucy; Haase, Kerstin; Clark, Jeremy; Dennis, Nening; Thomas, Sarah; Kremeyer, Barbara; Zamora, Jorge; Butler, Adam P; Gundem, Gunes; Merson, Sue; Luxton, Hayley; Hawkins, Steve; Ghori, Mohammed; Marsden, Luke; Lambert, Adam; Karaszi, Katalin; Pelvender, Gill; Massie, Charlie E; Kote-Jarai, Zsofia; Raine, Keiran; Jones, David; Howat, William J; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Nicol, David; Mayer, Erik; Dudderidge, Tim; Yu, Yongwei; Zhang, Hongwei; Shah, Nimish C; Gnanapragasam, Vincent J; Isaacs, William; Visakorpi, Tapio; Hamdy, Freddie; Berney, Dan; Verrill, Clare; Warren, Anne Y; Wedge, David C; Lynch, Andrew G; Foster, Christopher S; Lu, Yong Jie; Bova, G Steven; Whitaker, Hayley C; McDermott, Ultan; Neal, David E; Eeles, Rosalind; Cooper, Colin S; Brewer, Daniel S

2017-09-01

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.

Patient-Centred Coordinated Care in Times of Emerging Diseases and Epidemics. Contribution of the IMIA Working Group on Patient Safety.

PubMed

Borycki, E; Cummings, E; Dexheimer, J W; Gong, Y; Kennebeck, S; Kushniruk, A; Kuziemsky, C; Saranto, K; Weber, J; Takeda, H

2015-08-13

In this paper the researchers describe how existing health information technologies (HIT) can be repurposed and new technologies can be innovated to provide patient-centered care to individuals affected by new and emerging diseases. The researchers conducted a focused review of the published literature describing how HIT can be used to support safe, patient-centred, coordinated care to patients who are affected by Ebola (an emerging disease). New and emerging diseases present opportunities for repurposing existing technologies and for stimulating the development of new HIT innovation. Innovative technologies may be developed such as new software used for tracking patients during new or emerging disease outbreaks or by repurposing and extending existing technologies so they can be used to support patients, families and health professionals who may have been exposed to a disease. The paper describes the development of new technologies and the repurposing and extension of existing ones (such as electronic health records) using the most recent outbreak of Ebola as an example.

Health Informatics in Developing Countries: A Review of Unintended Consequences of IT Implementations, as They Affect Patient Safety and Recommendations on How to Address Them.

PubMed

Park, Hyeoun-Ae

2016-11-10

Patient safety concerns every healthcare organization. Adoption of Health information technology (HIT) appears to have the potential to address this issue, however unanticipated and undesirable consequences from implementing HIT could lead to new and more complex hazards. This could be particularly problematic in developing countries, where regulations, policies and implementations are few, less standandarized and in some cases almost non-existing. Based on the available information and our own experience, we conducted a review of unintended consequences of HIT implementations, as they affect patient safety in developing countries. We found that user dependency on the system, alert fatigue, less communications among healthcare actors and workarounds topics should be prioritize. Institution should consider existing knowledge, learn from other experiences and model their implementations to avoid known consequences. We also recommend that they monitor and communicate their own efforts to expand knowledge in the region.

Health information technology and implementation science: partners in progress in the VHA.

PubMed

Hynes, Denise M; Whittier, Erika R; Owens, Arika

2013-03-01

The Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has demonstrated how implementation science can enhance the quality of health care. During this time an increasing number of implementation research projects have developed or utilized health information technology (HIT) innovations to leverage the VA's electronic health record and information systems. To describe the HIT approaches used and to characterize the facilitators and barriers to progress within implementation research projects in the VA QUERI program. Nine case studies were selected from among 88 projects and represented 8 of 14 HIT categories identified. Each case study included key informants whose roles on the project were principal investigator, implementation science and informatics development. We conducted documentation analysis and semistructured in-person interviews with key informants for each of the 9 case studies. We used qualitative analysis software to identify and thematically code information and interview responses. : Thematic analyses revealed 3 domains or pathways critical to progression through the QUERI steps. These pathways addressed: (1) compliance and collaboration with information technology policies and procedures; (2) operating within organizational policies and building collaborations with end users, clinicians, and administrators; and (3) obtaining and maintaining research resources and approvals. Sustained efforts in HIT innovation and in implementation science in the Veterans Health Administration demonstrates the interdependencies of these initiatives and the critical pathways that can contribute to progress. Other health care quality improvement efforts that rely on HIT can learn from the Veterans Health Administration experience.

Chronic porcine two-hit model with hemorrhagic shock and Pseudomonas aeruginosa sepsis.

PubMed

Eissner, B; Matz, K; Smorodchenko, A; Röschmann, A; v Specht, B U

2002-01-01

Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as 'first hit' followed by a Pseudomonas aeruginosa infusion as 'second hit'. Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic shock with a 50% reduction of the mean arterial pressure and/or cardiac index for 45 min, followed by resuscitation, while the control group (n = 6) received no pretreatment. All chronically catheterized conscious pigs were challenged with a P. aeruginosa infusion (1.6 x 10(7) CFU/kg/h for the first 24 h followed by 1.6 x 10(6) CFU/kg/h for the next 24 h) and observed for another 48 h. The two-hit group showed the following significant differences to the control group: higher APACHE II scores prior to sepsis induction, increased persisting mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) during bacterial challenge. In contrast, systemic vascular resistance (SVRI) was reduced at the end of the study. Throughout the observation period, the mean arterial pressure (MAP) was significantly reduced. The present study shows that the clinical course and hemodynamic effects of a P. aeruginosa sepsis will be aggravated by a preceding hemorrhagic shock during an observation period of 96 h. This two-hit model represents a valid, clinically relevant experimental protocol in sepsis research. Copyright 2002 S. Karger AG, Basel

The three-hit concept of vulnerability and resilience: towards understanding adaptation to early-life adversity outcome

PubMed Central

Daskalakis, Nikolaos P.; Bagot, Rosemary C.; Parker, Karen J.; Vinkers, Christiaan H.; de Kloet, E. R.

2013-01-01

Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual’s predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. PMID:23838101

Video Head Impulse Test to Preoperatively Identify the Nerve of Origin of Vestibular Schwannomas.

PubMed

Constanzo, Felipe; Sens, Patricia; Teixeira, Bernardo Corrêa de Almeida; Ramina, Ricardo

2018-05-10

Identification of the nerve of origin in vestibular schwannoma (VS) is an important prognostic factor for hearing preservation surgery. Thus far, vestibular functional tests and magnetic resonance imaging have not yielded reliable results to preoperatively evaluate this information. The development of the video head impulse test (vHIT) has allowed a precise evaluation of each semicircular canal, and its localizing value has been tested for some peripheral vestibular diseases, but not for VS. To correlate patterns of semicircular canal alteration on vHIT to intraoperative identification of the nerve of origin of VSs. A total 31 patients with sporadic VSs were preoperatively evaluated with vHIT (gain of vestibule-ocular reflex, overt and covert saccades on each semicircular canal) and then the nerve of origin was surgically identified during surgical resection via retrosigmoid approach. vHIT results were classified as normal, isolated superior vestibular nerve (SVN) pattern, isolated inferior vestibular nerve (IVN) pattern, predominant SVN pattern, and predominant IVN pattern. Hannover classification, cystic component, and distance between the tumor and the end of the internal auditory canal were also considered for analysis. Three patients had a normal vHIT, 12 had an isolated SVN pattern, 5 had an isolated IVN pattern, 7 had a predominant SVN pattern, and 4 had a predominant IVN pattern. vHIT was able to correctly identify the nerve of origin in 89.7% of cases (100% of altered exams). The pattern of semicircular canal dysfunction on vHIT has a localizing value to identify the nerve of origin in VSs.

The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.

PubMed

Daskalakis, Nikolaos P; Bagot, Rosemary C; Parker, Karen J; Vinkers, Christiaan H; de Kloet, E R

2013-09-01

Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

PubMed

Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

2016-07-01

Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebral Venous Sinus Thrombosis Due to Low-molecular-weight Heparin-induced Thrombocytopenia.

PubMed

Gleichgerrcht, Ezequiel; Lim, Ming Y; Turan, Tanya N

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis (CVST) as the presenting thrombotic event induced by HIT, only one of which occurred with exposure to low-molecular-weight heparin (LMWH), with death as outcome. Here, we present a unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome. A 52-year-old woman received subcutaneous LMWH for deep vein thrombosis prophylaxis while in rehabilitation following kyphoplasty for spinal fracture related to recent trauma. On postoperative day 15, she developed acute onset altered mental status with significant agitation and nonsensical speech and was found to have brain imaging findings suggestive of CVST. Work-up revealed a drop in platelets associated with HIT, which did not improve off heparin products and with steroids, requiring intravenous immunoglobulin therapy, likely due to an overlapping immune thrombocytopenic purpura. Patient was managed on an argatroban drip until platelet count normalized and was able to transition to warfarin. Her clinical outcome was very favorable with near-normal neurological exam except for subtle cognitive changes. This unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome highlights the importance of linking CVST with HIT and of establishing the need for early alternative antithrombotic therapeutic strategies.

Intra- and Interexaminer Variability of Two Separate Video Head Impulse Test Systems Assessing All Six Semicircular Canals.

PubMed

Abrahamsen, Emil Riis; Christensen, Ann-Eva; Hougaard, Dan Dupont

2018-02-01

To evaluate intra- and interexaminer variability of the video Head Impulse Test (v-HIT) when assessing all six semicircular canals (SCCs) of two separate v-HIT systems. Prospective study. Department of Otolaryngology, Head and Neck Surgery, Aalborg University Hospital, Denmark. One hundred twenty healthy subjects. Four separate tests of all six SCCs with either system A or system B. Two examiners tested all subjects twice. Pretest randomization included type of v-HIT system, order of paired SCC testing, as well as initial examiner. Gain values and the presence of pathological saccades were registered. Ninety-five percent limits of agreement (LOAs) were calculated for both intra- and interexaminer variability. Adding or subtracting the value from the mean difference achieves the upper and lower bound LOA. Ninety-five percent of the differences lie within these limits. Interexaminer reliability: System A: LOAs between 0.13 and 0.24 for the horizontal SCCs and between 0.42 and 0.74 for the vertical SCCs. System B: LOAs between 0.09 and 0.13 for the horizontal SCCs and between 0.13 and 0.20 for the vertical SCCs. Intraexaminer reliability: System A: LOAs were 0.19 and 0.14 for the horizontal SCCs and varied from 0.43 to 0.53 for the vertical SCCs. System B: LOAs were 0.14 for the horizontal SCCs and varied from 0.13 to 0.22 for the vertical SCCs. Horizontal SCC testing: both v-HIT systems displayed good intra- and interexaminer variability. Vertical SCC testing: System B displayed good intra- and interexaminer variability whereas the opposite was true with system A.

Describing and Modeling Workflow and Information Flow in Chronic Disease Care

PubMed Central

Unertl, Kim M.; Weinger, Matthew B.; Johnson, Kevin B.; Lorenzi, Nancy M.

2009-01-01

Objectives The goal of the study was to develop an in-depth understanding of work practices, workflow, and information flow in chronic disease care, to facilitate development of context-appropriate informatics tools. Design The study was conducted over a 10-month period in three ambulatory clinics providing chronic disease care. The authors iteratively collected data using direct observation and semi-structured interviews. Measurements The authors observed all aspects of care in three different chronic disease clinics for over 150 hours, including 157 patient-provider interactions. Observation focused on interactions among people, processes, and technology. Observation data were analyzed through an open coding approach. The authors then developed models of workflow and information flow using Hierarchical Task Analysis and Soft Systems Methodology. The authors also conducted nine semi-structured interviews to confirm and refine the models. Results The study had three primary outcomes: models of workflow for each clinic, models of information flow for each clinic, and an in-depth description of work practices and the role of health information technology (HIT) in the clinics. The authors identified gaps between the existing HIT functionality and the needs of chronic disease providers. Conclusions In response to the analysis of workflow and information flow, the authors developed ten guidelines for design of HIT to support chronic disease care, including recommendations to pursue modular approaches to design that would support disease-specific needs. The study demonstrates the importance of evaluating workflow and information flow in HIT design and implementation. PMID:19717802

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.

Visible and Ultraviolet Detectors for High Earth Orbit and Lunar Observatories

NASA Technical Reports Server (NTRS)

Woodgate, Bruce E.

1989-01-01

The current status of detectors for the visible and UV for future large observatories in earth orbit and the moon is briefly reviewed. For the visible, CCDs have the highest quantum efficiency, but are subject to contamination of the data by cosmic ray hits. For the moon, the level of hits can be brought down to that at the earth's surface by shielding below about 20 meters of rock. For high earth orbits above the geomagnetic shield, CCDs might be able to be used by combining many short exposures and vetoing the cosmic ray hits, otherwise photoemissive detectors will be necessary. For the UV, photoemissive detectors will be necessary to reject the visible; to use CCDs would require the development of UV-efficient filters which reject the visible by many orders of magnitude. Development of higher count rate capability would be desirable for photoemissive detectors.

Fibre-Specific Responses to Endurance and Low Volume High Intensity Interval Training: Striking Similarities in Acute and Chronic Adaptation

PubMed Central

Scribbans, Trisha D.; Edgett, Brittany A.; Vorobej, Kira; Mitchell, Andrew S.; Joanisse, Sophie D.; Matusiak, Jennifer B. L.; Parise, Gianni; Quadrilatero, Joe; Gurd, Brendon J.

2014-01-01

The current study involved the completion of two distinct experiments. Experiment 1 compared fibre specific and whole muscle responses to acute bouts of either low-volume high-intensity interval training (LV-HIT) or moderate-intensity continuous endurance exercise (END) in a randomized crossover design. Experiment 2 examined the impact of a six-week training intervention (END or LV-HIT; 4 days/week), on whole body and skeletal muscle fibre specific markers of aerobic and anaerobic capacity. Six recreationally active men (Age: 20.7±3.8 yrs; VO2peak: 51.9±5.1 mL/kg/min) reported to the lab on two separate occasions for experiment 1. Following a muscle biopsy taken in a fasted state, participants completed an acute bout of each exercise protocol (LV-HIT: 8, 20-second intervals at ∼170% of VO2peak separated by 10 seconds of rest; END: 30 minutes at ∼65% of VO2peak), immediately followed by a muscle biopsy. Glycogen content of type I and IIA fibres was significantly (p<0.05) reduced, while p-ACC was significantly increased (p<0.05) following both protocols. Nineteen recreationally active males (n = 16) and females (n = 3) were VO2peak-matched and assigned to either the LV-HIT (n = 10; 21±2 yrs) or END (n = 9; 20.7±3.8 yrs) group for experiment 2. After 6 weeks, both training protocols induced comparable increases in aerobic capacity (END: Pre: 48.3±6.0, Mid: 51.8±6.0, Post: 55.0±6.3 mL/kg/min LV-HIT: Pre: 47.9±8.1, Mid: 50.4±7.4, Post: 54.7±7.6 mL/kg/min), fibre-type specific oxidative and glycolytic capacity, glycogen and IMTG stores, and whole-muscle capillary density. Interestingly, only LV-HIT induced greater improvements in anaerobic performance and estimated whole-muscle glycolytic capacity. These results suggest that 30 minutes of END exercise at ∼65% VO2peak or 4 minutes of LV-HIT at ∼170% VO2peak induce comparable changes in the intra-myocellular environment (glycogen content and signaling activation); correspondingly, training-induced adaptations resulting for these protocols, and other HIT and END protocols are strikingly similar. PMID:24901767

Watching the Evolution of the American Family? Amazon's Transparent, Ecological Systems Theory, and the Changing Dynamics of Public Opinion.

PubMed

Becker, Amy B; Todd, Maureen E

2018-01-01

Using Bronfenbrenner's (1979) ecological systems theory as an organizing framework, the research closely examines the text of the Amazon Studios hit show Transparent and, by extension, the evolution of public opinion toward transgender individuals. By examining the Pfefferman family in detail and their related microsystem and macrosystem, we are able to closely unpack the transition of Jeffrey Tambor's character from Mort to Maura and the show's connections with broader developments in the Los Angeles LGBT community and the Jewish diaspora in postwar and contemporary Los Angeles. In addition, by focusing on the influence of the chronosystem, we are able to examine how both opinions toward Maura and public opinion toward transgender issues more generally have evolved within the family system and the larger American community over time.

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.

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.

Harbin Institute of Technology collaborative base project at APS of Argonne

NASA Astrophysics Data System (ADS)

Liu, H.; Liu, L. L.

2013-05-01

In this paper, the progress of Harbin Institute of Technology (HIT) collaborative base project, which was launched at Argonne National Laboratory in 2010, will be presented. The staff and students from HIT involved in advanced technological developments, which included tomography, high energy PDF, diffraction and scattering, and inelastic scattering techniques in APS to study structures changes of minerals and materials under high pressure conditions.

Development and Validation of a High Throughput Screen for Compounds with Antiviral Activity Against Encephalitic Alphaviruses

DTIC Science & Technology

2010-09-15

viruses , including West Nile virus (WNV) 7 (PubChem AID: 1635), respiratory syncytial virus (PubChem AID: 2440...such as West Nile virus assay with a threshold value of 3.42%. D. Single Dose experiment with Arbo virus ...compounds. RESULT 1. Hit compounds nomination A. Arbo virus hits (1) SMR000372439 and SMR000058373 : Informatics analysis discovered

Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.

PubMed

Backes, Bradley J; Longenecker, Kenton; Hamilton, Gregory L; Stewart, Kent; Lai, Chunqiu; Kopecka, Hana; von Geldern, Thomas W; Madar, David J; Pei, Zhonghua; Lubben, Thomas H; Zinker, Bradley A; Tian, Zhenping; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Black-Schaefer, Candace; Sham, Hing L; Trevillyan, James M

2007-04-01

A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a >400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal.

Development of a potent and selective FLT3 kinase inhibitor by systematic expansion of a non-selective fragment-screening hit.

PubMed

Nakano, Hirofumi; Hasegawa, Tsukasa; Imamura, Riyo; Saito, Nae; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo

2016-05-01

A non-selective inhibitor (1) of FMS-like tyrosine kinase-3 (FLT3) was identified by fragment screening and systematically modified to afford a potent and selective inhibitor 26. We confirmed that 26 inhibited the growth of FLT-3-activated human acute myeloid leukemia cell line MV4-11. Our design strategy enabled rapid development of a novel type of FLT3 inhibitor from the hit fragment in the absence of target-structural information. Copyright © 2016 Elsevier Ltd. All rights reserved.

Memory for radio advertisements: the effect of program and typicality.

PubMed

Martín-Luengo, Beatriz; Luna, Karlos; Migueles, Malen

2013-01-01

We examined the influence of the type of radio program on the memory for radio advertisements. We also investigated the role in memory of the typicality (high or low) of the elements of the products advertised. Participants listened to three types of programs (interesting, boring, enjoyable) with two advertisements embedded in each. After completing a filler task, the participants performed a true/false recognition test. Hits and false alarm rates were higher for the interesting and enjoyable programs than for the boring one. There were also more hits and false alarms for the high-typicality elements. The response criterion for the advertisements embedded in the boring program was stricter than for the advertisements in other types of programs. We conclude that the type of program in which an advertisement is inserted and the nature of the elements of the advertisement affect both the number of hits and false alarms and the response criterion, but not the accuracy of the memory.

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

Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

PubMed

Raschke, R A; Gallo, T; Curry, S C; Whiting, T; Padilla-Jones, A; Warkentin, T E; Puri, A

2017-08-01

Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An algorithm incorporating 4Ts scoring and a stratified interpretation of the anti-PF4/H ELISA has good operating characteristics and the potential to improve management of suspected HIT patients. © 2017 International Society on Thrombosis and Haemostasis.

Fragment-Based Whole Cell Screen Delivers Hits against M. tuberculosis and Non-tuberculous Mycobacteria.

PubMed

Moreira, Wilfried; Lim, Jia Jie; Yeo, Si Ying; Ramanujulu, Pondy M; Dymock, Brian W; Dick, Thomas

2016-01-01

Reactive multi-target 'fragment drugs' represent critical components of current tuberculosis regimens. These compounds, such as pyrazinamide, are old synthetic antimycobacterials that are activated inside Mycobacterium tuberculosis bacilli and are smaller than the usual drug-like, single-target molecules. Based on the success of small 'dirty' drugs in the chemotherapy of tuberculosis, we suggested previously that fragment-based whole cell screens should be introduced in our current antimycobacterial drug discovery efforts. Here, we carried out such a screen and characterized bactericidal activity, selectivity and spectrum of hits we obtained. A library of 1725 fragments was tested at a single concentration for growth inhibitory activity against M. bovis BCG as screening strain and 38 of 116 primary hits were confirmed in dose response analyses to be active against virulent M. tuberculosis. Bacterial kill experiments showed that most hits displayed bactericidal activity at their minimal inhibitory concentration. Cytotoxicity assays established that a large proportion of hits displayed a favorable selectivity index for mammalian cells. Importantly, one third of M. tuberculosis active fragments were also active against M. abscessus and M. avium, two emerging non-tuberculous mycobacterial (NTM) pathogens, opening the opportunity to develop broad spectrum antimycobacterials. Activity determination against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa) bacteria, as well as fungi (Candida albicans, Cryptococcus neoformans) showed only a small overlap indicating a generally narrow spectrum of these novel antimicrobial hits for mycobacteria. In conclusion, we carried out the first fragment-based whole cell screen against bacteria and identified a substantial number of hits with excellent physicochemical properties and dual activity against M. tuberculosis and NTM pathogens. These hits will now be evaluated in animal models of mycobacterial infection to determine whether any of them can be moved forward as a new antimycobacterial fragment drug candidate.

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.

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.

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

PubMed Central

Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

2011-01-01

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

Hit Record Trends, 1940-1977.

ERIC Educational Resources Information Center

Anderson, Bruce; And Others

1980-01-01

Examines trends in popular music by analyzing the number one recordings from 1940 to 1977 in terms of the relationships among four variables: manufacturer (market concentration), song type (musical genre), artist type (performance mode), and lyric content (vocal message). (JMF)

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.

Hit, Robbed, and Put Down (but not Bullied): Underreporting of Bullying by Minority and Male Students.

PubMed

Lai, Tianjian; Kao, Grace

2018-03-01

To tackle adolescent bullying and identify students most vulnerable to being bullied, it is essential to examine both occurrences of bullying behaviors and students' own likelihoods of reporting bullying. This study examines ethnic and gender differences in students' odds of reporting bullying using the Education Longitudinal Study of 2002, a nationally representative study of United States high school sophomores (N = 15,362; ages 15-19; 50.2% female). Compared to White and female students, minority (particularly Black and Hispanic) and male students report comparable or greater experiences of bullying behaviors (such as being threatened, hit, put down by peers, or having belongings forced from them, stolen or damaged), but are less likely to report that they have been "bullied." These findings point to racialized and gendered differences in reporting bullying experiences such that indicators of "weakness" in peer relations may carry a greater stigma for minority and male students.

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.

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.

Informatics technology mimics ecology: dense, mutualistic collaboration networks are associated with higher publication rates.

PubMed

Sorani, Marco D

2012-01-01

Information technology (IT) adoption enables biomedical research. Publications are an accepted measure of research output, and network models can describe the collaborative nature of publication. In particular, ecological networks can serve as analogies for publication and technology adoption. We constructed network models of adoption of bioinformatics programming languages and health IT (HIT) from the literature.We selected seven programming languages and four types of HIT. We performed PubMed searches to identify publications since 2001. We calculated summary statistics and analyzed spatiotemporal relationships. Then, we assessed ecological models of specialization, cooperativity, competition, evolution, biodiversity, and stability associated with publications.Adoption of HIT has been variable, while scripting languages have experienced rapid adoption. Hospital systems had the largest HIT research corpus, while Perl had the largest language corpus. Scripting languages represented the largest connected network components. The relationship between edges and nodes was linear, though Bioconductor had more edges than expected and Perl had fewer. Spatiotemporal relationships were weak. Most languages shared a bioinformatics specialization and appeared mutualistic or competitive. HIT specializations varied. Specialization was highest for Bioconductor and radiology systems. Specialization and cooperativity were positively correlated among languages but negatively correlated among HIT. Rates of language evolution were similar. Biodiversity among languages grew in the first half of the decade and stabilized, while diversity among HIT was variable but flat. Compared with publications in 2001, correlation with publications one year later was positive while correlation after ten years was weak and negative.Adoption of new technologies can be unpredictable. Spatiotemporal relationships facilitate adoption but are not sufficient. As with ecosystems, dense, mutualistic, specialized co-habitation is associated with faster growth. There are rapidly changing trends in external technological and macroeconomic influences. We propose that a better understanding of how technologies are adopted can facilitate their development.

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.

Healthcare professionals' organisational barriers to health information technologies-a literature review.

PubMed

Lluch, Maria

2011-12-01

This literature review identifies and categorises, from an organisational management perspective, barriers to the use of HIT or ICT for health. Based on the review, it offers policy interventions. This systematic literature review was carried out during December 2009 and January 2010. Additional on-going reviews of updates through automated system alerts took place up until this paper was submitted. A total of thirty-one sources were searched including nine software platforms/databases, fifteen specialised websites/targeted databases, Google Scholar, ISI Science Citation Index and five journals hand-searched. The study covers seventy-nine articles on organisational barriers to ICT adoption by healthcare professionals. These are categorised under five main headings - (I) Structure of healthcare organisations; (II) Tasks; (III) People policies; (IV) Incentives; and (V) Information and decision processes. A total of ten subcategories are also identified. By adopting an organisational management approach, some recommendations to remove organisational management barriers are made. Despite their apparent promise, health information technologies (HIT) have proved difficult to implement. This systematic review reveals the implementation barriers associated to organisational management and their interrelations. Several important future directions in the field are also suggested: (1) there is a need for further research providing evidence of HIT cost-effectiveness as well as the development of optimal HIT applications; (2) more information is needed regarding organisational change, incentives, liability issues, end-users HIT competences and skills, structure and work process issues involved in realising the benefits from HIT. Future policy interventions should consider the five dimensions identified when addressing the impact of HIT in healthcare organisational systems, and how the impact of an intervention aimed at a particular dimension would interrelate with others. 2011 Elsevier Ireland Ltd. All rights reserved.

The utility of pre-test clinical scoring for clinical diagnosis of heparin-induced thrombocytopenia in cardiac surgery patients of a tertiary care centre in north India.

PubMed

Sachan, D; Gupta, N; Agarwal, P; Chaudhary, R

2011-08-01

Heparin-induced thrombocytopenia (HIT) should be diagnosed clinically as well as by laboratory assays for timely recognition, prevention and management of complications. To evaluate the clinical utility of pre-test clinical scoring system in combination with two immunoassays for the diagnosis of HIT in cardiac surgery patients. A total of 100 consecutive patients undergoing cardiac surgery were studied. Pre-test clinical scoring was carried out in patients with thrombocytopenia and further tested by two immunoassays, i.e., Heparin platelet factor 4 (H-PF4) enzyme-linked immunosorbent assay (ELISA) and particle gel immunoassay (PaGIA). Of the 100 patients studied, 42 patients developed thrombocytopenia post-operatively. On pre-test clinical scoring, low T-score was observed in 6 patients, intermediate in 28 and high score in 8 patients, whereas 19 patients (45.2%) were positive by H-PF4 ELISA and 10 (23.8%) by PaGIA for H-PF4 antibody. The difference in the incidence of clinically significant HIT antibodies in the three categories was statistically significant. A good correlation was also observed with ELISA optical density, T-scoring and PaGIA. Pre-test clinical scoring correlates well with the development of H-PF4 antibodies which are incriminated in the causation of thrombotic complications in patients with HIT. We also propose a protocol for diagnosing patients with clinical suspicion of HIT using pre-test clinical scoring and immunoassay. © 2011 The Authors. Transfusion Medicine © 2011 British Blood Transfusion Society.

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.

Evidential significance of automotive paint trace evidence using a pattern recognition based infrared library search engine for the Paint Data Query Forensic Database.

PubMed

Lavine, Barry K; White, Collin G; Allen, Matthew D; Fasasi, Ayuba; Weakley, Andrew

2016-10-01

A prototype library search engine has been further developed to search the infrared spectral libraries of the paint data query database to identify the line and model of a vehicle from the clear coat, surfacer-primer, and e-coat layers of an intact paint chip. For this study, search prefilters were developed from 1181 automotive paint systems spanning 3 manufacturers: General Motors, Chrysler, and Ford. The best match between each unknown and the spectra in the hit list generated by the search prefilters was identified using a cross-correlation library search algorithm that performed both a forward and backward search. In the forward search, spectra were divided into intervals and further subdivided into windows (which corresponds to the time lag for the comparison) within those intervals. The top five hits identified in each search window were compiled; a histogram was computed that summarized the frequency of occurrence for each library sample, with the IR spectra most similar to the unknown flagged. The backward search computed the frequency and occurrence of each line and model without regard to the identity of the individual spectra. Only those lines and models with a frequency of occurrence greater than or equal to 20% were included in the final hit list. If there was agreement between the forward and backward search results, the specific line and model common to both hit lists was always the correct assignment. Samples assigned to the same line and model by both searches are always well represented in the library and correlate well on an individual basis to specific library samples. For these samples, one can have confidence in the accuracy of the match. This was not the case for the results obtained using commercial library search algorithms, as the hit quality index scores for the top twenty hits were always greater than 99%. Copyright © 2016 Elsevier B.V. All rights reserved.

Whole Organism High-Content Screening by Label-Free, Image-Based Bayesian Classification for Parasitic Diseases

PubMed Central

Paveley, Ross A.; Mansour, Nuha R.; Hallyburton, Irene; Bleicher, Leo S.; Benn, Alex E.; Mikic, Ivana; Guidi, Alessandra; Gilbert, Ian H.; Hopkins, Andrew L.; Bickle, Quentin D.

2012-01-01

Sole reliance on one drug, Praziquantel, for treatment and control of schistosomiasis raises concerns about development of widespread resistance, prompting renewed interest in the discovery of new anthelmintics. To discover new leads we designed an automated label-free, high content-based, high throughput screen (HTS) to assess drug-induced effects on in vitro cultured larvae (schistosomula) using bright-field imaging. Automatic image analysis and Bayesian prediction models define morphological damage, hit/non-hit prediction and larval phenotype characterization. Motility was also assessed from time-lapse images. In screening a 10,041 compound library the HTS correctly detected 99.8% of the hits scored visually. A proportion of these larval hits were also active in an adult worm ex-vivo screen and are the subject of ongoing studies. The method allows, for the first time, screening of large compound collections against schistosomes and the methods are adaptable to other whole organism and cell-based screening by morphology and motility phenotyping. PMID:22860151

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.

Are We There Yet? Applying Thermodynamic and Kinetic Profiling on Embryonic Ectoderm Development (EED) Hit-to-Lead Program.

PubMed

Wang, Ying; Edalji, Rohinton P; Panchal, Sanjay C; Sun, Chaohong; Djuric, Stevan W; Vasudevan, Anil

2017-10-26

It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k off ) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K i and k off . Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.

Five Weeks of Sprint and High-Intensity Interval Training Improves Paddling Performance in Adolescent Surfers.

PubMed

Farley, Oliver R L; Secomb, Josh L; Parsonage, Joanna R; Lundgren, Lina E; Abbiss, Chris R; Sheppard, Jeremy M

2016-09-01

Farley, ORL, Secomb, JL, Parsonage, JR, Lundgren, LE, Abbiss, CR, and Sheppard, JM. Five weeks of sprint and high-intensity interval training improves paddling performance in adolescent surfers. J Strength Cond Res 30(9): 2446-2452, 2016-The purpose of our study was to examine the effects of sprint interval training (SIT; 10 seconds) and high-intensity interval training (HIT; 30 seconds) on surfing athletes paddling performance (400-m time trial and repeat-sprint paddle performance). Twenty-four competitive adolescent surfers (19 male, 5 female; age = 14.4 ± 1.3 years, mass: 50.1 ± 10.7 kg, and stature: 159.9 ± 10.3 cm) were assigned to perform either 5 weeks of SIT and HIT. Participants completed a repeated-sprint paddle ability test (RSPT, 15-m surfboard sprint paddle initiated every 40 seconds × 10 bouts) and 400-m endurance surfboard paddle time trial before and after training. High-intensity interval training decreased the total time to complete the 400 m by 15.8 ± 16.1 seconds (p = 0.03), and SIT decreased the total time to complete the RSPT by 6.5 ± 4.3 seconds (p = 0.02). Fatigue index during the RSPT (first-slowest effort) was lower after HIT and SIT (p ≤ 0.001 and p = 0.02, respectively). There were no significant differences in performance changes in the 400 m (total time) and RSPT (total time, fastest 15 m time, and peak velocity) between HIT and SIT. Our study indicates that HIT and SIT may be implemented to the training program of surfers to improve aerobic and repeat-sprint paddle ability, both of which are identified as key aspects of the sport. In addition, these findings indicate that 400-m paddle and RSPT can discriminate between aerobic and anaerobic training adaptations, with aerobic gains likely from HIT and anaerobic gains from SIT.

The relationship between the external environment and physician e-mail communication: The mediating role of health information technology availability.

PubMed

Mazurenko, Olena; Hearld, Larry R; Menachemi, Nir

Physician e-mail communication, with patients and other providers, is one of the cornerstones of effective care coordination but varies significantly across physicians. A physician's external environment may contribute to such variations by enabling or constraining a physician's ability to adopt innovations such as health information technology (HIT) that can be used to support e-mail communication. The aim of the study was to examine whether the relationship of the external environment and physician e-mail communication with patients and other providers is mediated by the practice's HIT availability. The data were obtained from the Health Tracking Physician Survey (2008) and the Area Resource File (2008). Cross-sectional multivariable subgroup path analysis was used to investigate the mediating role of HIT availability across 2,850 U.S. physicians. Solo physicians' perceptions about malpractice were associated with 0.97 lower odds (p < .05) of e-mail communication with patients and other providers, as compared to group and hospital practices, even when mediated by HIT availability. Subgroup analyses indicated that different types of practices are responsive to the different dimensions of the external environment. Specifically, solo practitioners were more responsive to the availability of resources in their environment, with per capita income associated with lower likelihood of physician e-mail communication (OR = 0.99, p < .01). In contrast, physicians working in the group practices were more responsive to the complexity of their environment, with a physician's perception of practicing in environments with higher malpractice risks associated with greater information technology availability, which in turn was associated with a greater likelihood of communicating via e-mail with patients (OR = 1.02, p < .05) and other physicians (OR = 1.03, p < .001). The association between physician e-mail communication and the external environment is mediated by the practice's HIT availability. Efforts to improve physician e-mail communication and HIT adoption may need to reflect the varied perceptions of different types of practices.

High- and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity.

PubMed

Hafstad, Anne D; Lund, Jim; Hadler-Olsen, Elin; Höper, Anje C; Larsen, Terje S; Aasum, Ellen

2013-07-01

Although exercise reduces several cardiovascular risk factors associated with obesity/diabetes, the metabolic effects of exercise on the heart are not well-known. This study was designed to investigate whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in counteracting obesity-induced impairment of left ventricular (LV) mechanoenergetics and function. C57BL/6J mice with diet-induced obesity (DIO mice) displaying a cardiac phenotype with altered substrate utilization and impaired mechanoenergetics were subjected to a sedentary lifestyle or 8-10 weeks of isocaloric HIT or MIT. Although both modes of exercise equally improved aerobic capacity and reduced obesity, only HIT improved glucose tolerance. Hearts from sedentary DIO mice developed concentric LV remodeling with diastolic and systolic dysfunction, which was prevented by both HIT and MIT. Both modes of exercise also normalized LV mechanical efficiency and mechanoenergetics. These changes were associated with altered myocardial substrate utilization and improved mitochondrial capacity and efficiency, as well as reduced oxidative stress, fibrosis, and intracellular matrix metalloproteinase 2 content. As both modes of exercise equally ameliorated the development of diabetic cardiomyopathy by preventing LV remodeling and mechanoenergetic impairment, this study advocates the therapeutic potential of physical activity in obesity-related cardiac disorders.

High- and Moderate-Intensity Training Normalizes Ventricular Function and Mechanoenergetics in Mice With Diet-Induced Obesity

PubMed Central

Hafstad, Anne D.; Lund, Jim; Hadler-Olsen, Elin; Höper, Anje C.; Larsen, Terje S.; Aasum, Ellen

2013-01-01

Although exercise reduces several cardiovascular risk factors associated with obesity/diabetes, the metabolic effects of exercise on the heart are not well-known. This study was designed to investigate whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in counteracting obesity-induced impairment of left ventricular (LV) mechanoenergetics and function. C57BL/6J mice with diet-induced obesity (DIO mice) displaying a cardiac phenotype with altered substrate utilization and impaired mechanoenergetics were subjected to a sedentary lifestyle or 8–10 weeks of isocaloric HIT or MIT. Although both modes of exercise equally improved aerobic capacity and reduced obesity, only HIT improved glucose tolerance. Hearts from sedentary DIO mice developed concentric LV remodeling with diastolic and systolic dysfunction, which was prevented by both HIT and MIT. Both modes of exercise also normalized LV mechanical efficiency and mechanoenergetics. These changes were associated with altered myocardial substrate utilization and improved mitochondrial capacity and efficiency, as well as reduced oxidative stress, fibrosis, and intracellular matrix metalloproteinase 2 content. As both modes of exercise equally ameliorated the development of diabetic cardiomyopathy by preventing LV remodeling and mechanoenergetic impairment, this study advocates the therapeutic potential of physical activity in obesity-related cardiac disorders. PMID:23493573

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.

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

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.

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.

The Head Tracks and Gaze Predicts: How the World’s Best Batters Hit a Ball

PubMed Central

Mann, David L.; Spratford, Wayne; Abernethy, Bruce

2013-01-01

Hitters in fast ball-sports do not align their gaze with the ball throughout ball-flight; rather, they use predictive eye movement strategies that contribute towards their level of interceptive skill. Existing studies claim that (i) baseball and cricket batters cannot track the ball because it moves too quickly to be tracked by the eyes, and that consequently (ii) batters do not – and possibly cannot – watch the ball at the moment they hit it. However, to date no studies have examined the gaze of truly elite batters. We examined the eye and head movements of two of the world’s best cricket batters and found both claims do not apply to these batters. Remarkably, the batters coupled the rotation of their head to the movement of the ball, ensuring the ball remained in a consistent direction relative to their head. To this end, the ball could be followed if the batters simply moved their head and kept their eyes still. Instead of doing so, we show the elite batters used distinctive eye movement strategies, usually relying on two predictive saccades to anticipate (i) the location of ball-bounce, and (ii) the location of bat-ball contact, ensuring they could direct their gaze towards the ball as they hit it. These specific head and eye movement strategies play important functional roles in contributing towards interceptive expertise. PMID:23516460

Reduction of plasma density in the Helicity Injected Torus with Steady Inductance experiment by using a helicon pre-ionization source.

PubMed

Hossack, Aaron C; Firman, Taylor; Jarboe, Thomas R; Prager, James R; Victor, Brian S; Wrobel, Jonathan S; Ziemba, Timothy

2013-10-01

A helicon based pre-ionization source has been developed and installed on the Helicity Injected Torus with Steady Inductance (HIT-SI) spheromak. The source initiates plasma breakdown by injecting impurity-free, unmagnetized plasma into the HIT-SI confinement volume. Typical helium spheromaks have electron density reduced from (2-3) × 10(19) m(-3) to 1 × 10(19) m(-3). Deuterium spheromak formation is possible with density as low as 2 × 10(18) m(-3). The source also enables HIT-SI to be operated with only one helicity injector at injector frequencies above 14.5 kHz. A theory explaining the physical mechanism driving the reduction of breakdown density is presented.

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

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.

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

Examining Health Information Technology Implementations: Case of the Patient-Centered Medical Home

ERIC Educational Resources Information Center

Behkami, Nima A.

2012-01-01

It has been shown that the use of Health Information Technology (HIT) is associated with reduced cost and increased quality of care. This dissertation examined the use of registries in Patient Centered Medical Home (PCMH) practices. A survey questionnaire was sent to a nationwide group of clinics certified for being a PCMH. They were asked to…

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.

Liquid Argon TPC Signal Formation, Signal Processing and Hit Reconstruction

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

Baller, Bruce

2017-03-11

This document describes the early stage of the reconstruction chain that was developed for the ArgoNeuT and MicroBooNE experiments at Fermilab. These experiments study accelerator neutrino interactions that occur in a Liquid Argon Time Projection Chamber. Reconstructing the properties of particles produced in these interactions requires knowledge of the micro-physics processes that affect the creation and transport of ionization electrons to the readout system. A wire signal deconvolution technique was developed to convert wire signals to a standard form for hit reconstruction, to remove artifacts in the electronics chain and to remove coherent noise.

Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account.

PubMed

Wu, Frank; Büttner, Frank H; Chen, Rhonda; Hickey, Eugene; Jakes, Scott; Kaplita, Paul; Kashem, Mohammed A; Kerr, Steven; Kugler, Stanley; Paw, Zofia; Prokopowicz, Anthony; Shih, Cheng-Kon; Snow, Roger; Young, Erick; Cywin, Charles L

2010-06-01

Two closely related scaffolds were identified through an uHTS campaign as desirable starting points for the development of Rho-Kinase (ROCK) inhibitors. Here, we describe our hit-to-lead evaluation process which culminated in the rapid discovery of potent leads such as 22 which successfully demonstrated an early in vivo proof of concept for anti-hypertensive activity. Copyright 2010 Elsevier Ltd. All rights reserved.

Emerging Trends in China’s Development of Unmanned Systems

DTIC Science & Technology

2015-01-01

missions is another area of emphasis, as highlighted by reports about such systems’ use during the 2008 Sichuan earth - quake , and unmanned systems could...China Strategic Perspectives No. 5, National Defense University, September 2012. 27 “Drones Dispatched to Capture Images of Quake -Hit Regions,” Xinhua...china-deliver-packages-even-a- birthday-cake/ “Drones Dispatched to Capture Images of Quake -Hit Regions,” Xinhua, April 20, 2013. Easton, Ian M

Building and strengthening infrastructure for data exchange: lessons from the beacon communities.

PubMed

Torres, Gretchen W; Swietek, Karen; Ubri, Petry S; Singer, Rachel F; Lowell, Kristina H; Miller, Wilhelmine

2014-01-01

The Beacon Community Cooperative Agreement Program supports interventions, including care-delivery innovations, provider performance measurement and feedback initiatives, and tools for providers and consumers to enhance care. Using a learning health system framework, we examine the Beacon Communities' processes in building and strengthening health IT (HIT) infrastructures, specifically successes and challenges in sharing patient information to improve clinical care. In 2010, the Office of the National Coordinator for Health Information Technology (ONC) launched the three-year program, which provided $250 million to 17 Beacon Communities to invest in HIT and health information exchange (HIE) infrastructure. Beacon Communities used this funding to develop and disseminate HIT-enabled quality improvement practices found effective in particular community and practice environments. NORC conducted 7 site visits, November 2012-March 2013, selecting Communities to represent diverse program features. From August-October 2013, NORC held discussions with the remaining 10 Communities. Following each visit or discussion, NORC summarized the information gathered, including transcripts, team observations, and other documents the Community provided, to facilitate a within-Community analysis of context and stakeholders, intervention strategies, enabling factors, and challenges. Although each Community designed and implemented data-sharing strategies in a unique environment, similar challenges and enabling factors emerged across the Beacons. From a learning health system perspective, their strategies to build and strengthen data-sharing infrastructures address the following crosscutting priorities: promoting technical advances and innovations by helping providers adapt EHRs for data exchange and performance measurement with customizable IT and offering technical support to smaller, independent providers; engaging key stakeholders; and fostering transparent governance and stewardship of the infrastructure with neutral conveners. While all the Communities developed or strengthened data-exchange infrastructure, each did this in a unique environment of existing health care market and legal factors. The Communities, however, encountered similar challenges and enabling factors. Organizations undertaking collaborative data sharing, performance measurement and clinical transformation can learn from the Beacon Communities' experience.

Building and Strengthening Infrastructure for Data Exchange: Lessons from the Beacon Communities

PubMed Central

Torres, Gretchen W.; Swietek, Karen; Ubri, Petry S.; Singer, Rachel F.; Lowell, Kristina H.; Miller, Wilhelmine

2014-01-01

Introduction: The Beacon Community Cooperative Agreement Program supports interventions, including care-delivery innovations, provider performance measurement and feedback initiatives, and tools for providers and consumers to enhance care. Using a learning health system framework, we examine the Beacon Communities’ processes in building and strengthening health IT (HIT) infrastructures, specifically successes and challenges in sharing patient information to improve clinical care. Background: In 2010, the Office of the National Coordinator for Health Information Technology (ONC) launched the three-year program, which provided $250 million to 17 Beacon Communities to invest in HIT and health information exchange (HIE) infrastructure. Beacon Communities used this funding to develop and disseminate HIT-enabled quality improvement practices found effective in particular community and practice environments. Methods: NORC conducted 7 site visits, November 2012–March 2013, selecting Communities to represent diverse program features. From August–October 2013, NORC held discussions with the remaining 10 Communities. Following each visit or discussion, NORC summarized the information gathered, including transcripts, team observations, and other documents the Community provided, to facilitate a within-Community analysis of context and stakeholders, intervention strategies, enabling factors, and challenges. Results: Although each Community designed and implemented data-sharing strategies in a unique environment, similar challenges and enabling factors emerged across the Beacons. From a learning health system perspective, their strategies to build and strengthen data-sharing infrastructures address the following crosscutting priorities: promoting technical advances and innovations by helping providers adapt EHRs for data exchange and performance measurement with customizable IT and offering technical support to smaller, independent providers; engaging key stakeholders; and fostering transparent governance and stewardship of the infrastructure with neutral conveners. Conclusion: While all the Communities developed or strengthened data-exchange infrastructure, each did this in a unique environment of existing health care market and legal factors. The Communities, however, encountered similar challenges and enabling factors. Organizations undertaking collaborative data sharing, performance measurement and clinical transformation can learn from the Beacon Communities’ experience. PMID:25848619

A shower of second hit events as the cause of multifocal renal cell carcinoma in tuberous sclerosis complex

PubMed Central

Tyburczy, Magdalena E.; Jozwiak, Sergiusz; Malinowska, Izabela A.; Chekaluk, Yvonne; Pugh, Trevor J.; Wu, Chin-Lee; Nussbaum, Robert L.; Seepo, Sara; Dzik, Tomasz; Kotulska, Katarzyna; Kwiatkowski, David J.

2015-01-01

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by seizures and tumor formation in multiple organs, mainly in the brain, skin, kidney, lung and heart. Renal cell carcinoma (RCC) occurs in ∼3% of TSC patients, and typically develops at age <50. Here we describe genetic findings in two TSC patients with multiple renal tumors, each of whom had the germline mutation TSC2 p.R905Q. The first (female) TSC patient had a left followed by a right nephrectomy at ages 24 and 27. Both kidneys showed multifocal TSC-associated papillary RCC (PRCC). Targeted, next-generation sequencing (NGS) analysis of TSC2 in five tumors (four from the left kidney, one from the right) showed loss of heterozygosity in one tumor, and four different TSC2 point mutations (p.E1351*, p.R1032*, p.R1713H, c.4178_4179delCT) in the other four samples. Only one of the 11 other tumors available from this patient had one of the TSC2 second hit mutations identified. Whole-exome analysis of the five tumors identified a very small number of additional mutated genes, with an average of 3.4 nonsilent coding, somatic mutations per tumor, none of which were seen in >1 tumor. The second (male) TSC patient had bilateral partial nephrectomies (both at age 36), with similar findings of multifocal PRCC. NGS analysis of TSC2 in two of these tumors identified a second hit mutation c.2355+1G>T in one sample that was not seen in other tumors. In conclusion, we report the first detailed genetic analysis of RCCs in TSC patients. Molecular studies indicate that tumors developed independently due to various second hit events, suggesting that these patients experienced a ‘shower’ of second hit mutations in TSC2 during kidney development leading to this severe phenotype. PMID:25432535

Reconfiguring the AR-TIF2 Protein–Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen

PubMed Central

Fancher, Ashley T.; Hua, Yun; Camarco, Daniel P.; Close, David A.; Strock, Christopher J.

2016-01-01

Abstract The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein–protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins. We reconfigured the AR-TIF2 PPI biosensor (PPIB) assay in the PC-3 CaP cell line to determine whether AR modulators and hits from an AR-TIF2 PPIB screen conducted in U-2 OS cells would behave differently in the CaP cell background. Although we did not observe any significant differences in the compound responses between the assay performed in osteosarcoma and CaP cells, the U-2 OS AR-TIF2 PPIB assay would be more amenable to screening, because both the virus and cell culture demands are lower. We implemented a testing paradigm of counter-screens and secondary hit characterization assays that allowed us to identify and deprioritize hits that inhibited/disrupted AR-TIF2 PPIs and AR transcriptional activation (AR-TA) through antagonism of AR ligand binding or by non-specifically blocking nuclear receptor trafficking. Since AR-TIF2 PPI inhibitor/disruptor molecules act distally to AR ligand binding, they have the potential to modulate AR-TA in a cell-specific manner that is distinct from existing anti-androgen drugs, and to overcome the development of resistance to AR antagonism. We anticipate that the application of this testing paradigm to characterize the hits from an AR-TIF2 PPI high-content screening campaign will enable us to prioritize the AR-TIF2 PPI inhibitor/disruptor leads that have potential to be developed into novel therapeutics for CaP and CRPC. PMID:27606620

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.

Abbott Physicochemical Tiering (APT)--a unified approach to HTS triage.

PubMed

Cox, Philip B; Gregg, Robert J; Vasudevan, Anil

2012-07-15

The selection of the highest quality chemical matter from high throughput screening (HTS) is the ultimate aim of any triage process. Typically there are many hundreds or thousands of hits capable of modulating a given biological target in HTS with a wide range of physicochemical properties that should be taken into consideration during triage. Given the multitude of physicochemical properties that define drug-like space, a system needs to be in place that allows for a rapid selection of chemical matter based on a prioritized range of these properties. With this goal in mind, we have developed a tool, coined Abbott Physicochemical Tiering (APT) that enables hit prioritization based on ranges of these important physicochemical properties. This tool is now used routinely at Abbott to help prioritize hits out of HTS during the triage process. Herein we describe how this tool was developed and validated using Abbott internal high throughput ADME data (HT-ADME). Copyright © 2012 Elsevier Ltd. All rights reserved.

An investigation of the 'von Restorff' phenomenon in post-test workload ratings

NASA Technical Reports Server (NTRS)

Thornton, D. C.

1985-01-01

The von Restorff effect in post-task ratings of task difficulty is examined. Nine subjects performed a hovercraft simulation task which combined elements of skill-based tracking and rule- and knowledge-based process control for five days of one hour sessions. The effects of isolated increases in workload on rating of task performance, and on the number of command errors and river band hits are analyzed. It is observed that the position of the workload increase affects the number of bank hits and command errors. The data reveal that factors not directly related to the task performance influence subjective rating, and post-task ratings of workload are biased.

Workarounds in the Workplace: A Second Look.

PubMed

Seaman, Jennifer B; Erlen, Judith A

2015-01-01

Nursing workarounds have garnered increased attention over the past 15 years, corresponding with an increased focus on patient safety and evidence-based practice and a rise in the use of health information technologies (HITs). Workarounds have typically been viewed as deviations from best practice that put patients at risk for poor outcomes. However, this narrow view fails to take into consideration the multifactorial origins of workarounds. The authors explore the ways in which evidence-based protocols and HIT, designed to improve patient safety and quality, can have an unintended consequence of increasing the likelihood of nurses engaging in workarounds. The article also examines workarounds considering the ethical obligations of both nurses and administrative leaders to optimize patient safety and quality.

Automatic creation of object hierarchies for ray tracing

NASA Technical Reports Server (NTRS)

Goldsmith, Jeffrey; Salmon, John

1987-01-01

Various methods for evaluating generated trees are proposed. The use of the hierarchical extent method of Rubin and Whitted (1980) to find the objects that will be hit by a ray is examined. This method employs tree searching; the construction of a tree of bounding volumes in order to determine the number of objects that will be hit by a ray is discussed. A tree generation algorithm, which uses a heuristic tree search strategy, is described. The effects of shuffling and sorting on the input data are investigated. The cost of inserting an object into the hierarchy during the construction of a tree algorithm is estimated. The steps involved in estimating the number of intersection calculations are presented.

Ultrasonographic evaluation of the shoulder in elite Italian beach volleyball players.

PubMed

Monteleone, G; Tramontana, A; Mc Donald, K; Sorge, R; Tiloca, A; Foti, C

2015-10-01

Beach volleyball is an overhead sport that subjects the hitting shoulder to intense functional loads. The purpose of this study is to identify ultrasonographically the prevalence of myotendinous alterations in professional Italian beach volleyball players at the Italian championship and to look for associations between ultrasound findings and the other data collected. Fifty-three beach volleyball players (31 women, 22 men) were recruited during the second stage of the Italian championship held in July 2012 in Rome, Italy. Clinical history was obtained from all subjects, followed by physical exam. Each athlete completed a questionnaire regarding sports activities. Bilateral ultrasonographic evaluation of the shoulders was then performed. Calcific tendinopathy of the rotator cuff of the hitting shoulder was identified ultrasonographically in 30% of the athletes. The mean age of the athletes with calcific tendinopathy was older than subjects with other abnormalities on ultrasonographic examination (33.1 years vs. 25.8 years, t-test; P<0.0001). Impingement was recognized ultrasonographically in the hitting shoulder in 10 of the athletes (18.8%). The Neer's test was positive in the cases of anterior impingement (χ2; P<0.002). Calcific tendinopathy of the rotator cuff of the hitting shoulder in professional beach volleyball players has a prevalence of 30% ultrasonographically, greater than that reported in the general population. In these athletes, the presence of calcific tendinopathy correlates positively with age.

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 Combinatorial H4 Tail Library to Explore the Histone Code

PubMed Central

Garske, Adam L.; Craciun, Gheorghe; Denu, John M.

2008-01-01

Histone modifications modulate chromatin structure and function. A posttranslational modification-randomized, combinatorial library based on the first twenty-one residues of histone H4 was designed for systematic examination of proteins that interpret a histone code. The 800-member library represented all permutations of most known modifications within the N-terminal tail of histone H4. To determine its utility in a protein-binding assay, the on-bead library was screened with an antibody directed against phosphoserine 1 of H4. Among the hits, 59/60 sequences were phosphorylated at S1, while 30/30 of those selected from the non-hits were unphosphorylated. A 512-member version of the library was then used to determine the binding specificity of the double tudor domain of hJMJD2A, a histone demethylase involved in transcriptional repression. Global linear least squares fitting of modifications from the identified peptides (40 hits and 34 non-hits) indicated that methylation of K20 was the primary determinant for binding, but that phosphorylation/acetylation on neighboring sites attenuated the interaction. To validate the on-bead screen, isothermal titration calorimetry was performed with thirteen H4 peptides. Dissociation constants ranged from 1 mM - 1μM and corroborated the screening results. The general approach should be useful for probing the specificity of any histone-binding protein. PMID:18616348

Is the polar bear (Ursus maritimus) a hibernator? Continued studies on opioids and hibernation

USGS Publications Warehouse

Bruce, David S.; Darling, Nancy K.; Seeland, Katheleen J.; Oeltgen, Peter R.; Nilekani, Sita P.; Amstrup, Steven C.

1990-01-01

Polar bear behavior and biochemistry suggest they may have the ability to hibernate year-round, even though this species is not considered to be a true hibernator. This observation, plus the discovery of a hibernation-induced trigger (HIT) in the blood of black bears, prompted the examination of polar bear blood collected thoughout the year for evidence ofr HIT, and to determine if it displayed opioid activity, as black bear blood does. A bioassay was conducted by injected summer 13-lined ground squirrels with serum collected from polar bears at different seasons. One group of squirrels was previously implanted with osmotic pumps containing naloxone. The rest had pumps containing saline. Squirrels with saline pumps all hibernated significantly more than those with naloxone, except the group receiving blood from a November polar bear, observed to be highly active and hyperphagic. An in vitro study, using guinea pig ileum, showed that 400 nM morphine inhibited induced contractions and 100 nM naloxone reversed the inhibition. Ten mg of winter polar bear serum albumin fraction (to which HIT binds in ground squirrels and woodchucks) had a similar inhibiting effect, but naloxone, even at 4,000 nM, didn't reverse it. It is concluded that polar bear contains HIT, that it has an opioid effct, but may not itself be an opioid.

Intrinsic motivation in two exercise interventions: Associations with fitness and body composition.

PubMed

Thøgersen-Ntoumani, Cecilie; Shepherd, Sam O; Ntoumanis, Nikos; Wagenmakers, Anton J M; Shaw, Christopher S

2016-02-01

To examine the motivational process through which increases in aerobic capacity and decreases in total body fat are achieved during high-intensity intermittent training (HIT) and moderate-intensity continuous training (MICT) interventions. Eighty-seven physically inactive adults (65% women, age = 42 ± 12, BMI = 27.67 ± 4.99 kg/m²) took part in a 10-week randomized intervention testing group-based HIT, operationalized as repeated sprints of 15-60 s interspersed with periods of recovery cycling ≤ 25 min/session, 3 sessions/wk⁻¹, or MICT, operationalized as cycling at constant workload of ∼65% maximum aerobic capacity (VO2max, 30-45 min/session⁻¹, 5 sessions/wk⁻¹. Assessments of VO2max and total body fat were made pre- and postintervention. Motivation variables were assessed midintervention and class attendance was monitored throughout. Path analysis was employed, controlling for treatment arm and baseline values of VO2max and total body fat. The 2 groups differed in adherence only, favoring HIT. Baseline VO2max predicted intrinsic motivation midintervention. Intrinsic motivation predicted program adherence, which in turn predicted increases in VO2max and decreases in total body fat by the end of the study. Intrinsic motivation in HIT and MICT is positively linked to adherence to these programs, which can facilitate improvements in fitness and body composition. (c) 2016 APA, all rights reserved).

Spontaneous HIT syndrome post-knee replacement surgery with delayed recovery of thrombocytopenia: a case report and literature review.

PubMed

Poudel, Dilli Ram; Ghimire, Sushil; Dhital, Rashmi; Forman, Daniel A; Warkentin, Theodore E

2017-09-01

Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 10 9 /L. Prior to diagnostic consideration of spontaneous HIT syndrome, the patient briefly received unfractionated heparin (UFH) and one dose of enoxaparin. The patient's serum tested strongly positive for anti-PF4/heparin antibodies by two different PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin release assay (SRA). Failure of fondaparinux anticoagulation (persisting HIT-associated disseminated intravascular coagulation) prompted switching to argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 × 10 9 /L, on POD21), and 9 days after starting argatroban symptomatic right leg deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, her course was uneventful, although platelet count recovery was prolonged, reaching 99 × 10 9 /L by POD45 and 199 × 10 9 /L by POD79. The patient's serum elicited strong serotonin release in the absence of heparin (seen even with 1/32 serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 and 0.3 IU/mL) and fondaparinux (0.1-1.2 μg/mL, i.e., in vitro fondaparinux "cross-reactivity"). Ultimately, platelet count recovery was associated with seroreversion to a negative SRA (documented at POD151). Our literature review identified joint replacement surgery, specifically knee replacement, to be a relatively common trigger of spontaneous HIT syndrome. Further, including our patient case, 5 of 7 patients with spontaneous HIT syndrome post-orthopedic surgery who received treatment with argatroban developed new and/or progressive lower-limb DVT or recurrent PE despite anticoagulation with this parenteral direct thrombin inhibitor, suggesting that this patient population is at high risk of breakthrough thrombotic events despite treatment with this HIT treatment-approved anticoagulant. Our case also illustrates successful outcome with rivaroxaban for treatment of spontaneous HIT syndrome, consistent with emerging literature supporting safety and efficacy of direct oral anticoagulant therapy for treatment of acute HIT.

Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

PubMed Central

Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

2015-01-01

BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

Development of a laboratory model to assess fear and anxiety in cats.

PubMed

de Rivera, Christina; Ley, Jacqui; Milgram, Bill; Landsberg, Gary

2017-06-01

Objectives The objectives of this study were: (1) to develop a laboratory-based model to assess fear and anxiety in cats using the feline open-field test (OFT) and the feline human interaction test (HIT); and (2) to validate the model using diazepam, a known anxiolytic. Methods Laboratory-housed cats (n = 41) were first classified as fearful, mildly fearful or non-fearful by a technician familiar with the cats and also by veterinary behaviorists (GL, JL), by assessing the cats' behavior in their home rooms. In experiment 1, each cat's behavior was assessed in an OFT and an HIT. In experiment 2, after administration of the anxiolytic diazepam, a subset of the cats was re-tested. Results In experiment 1, the OFT revealed significant group effects on two measures: duration of inactivity, and vocalization. Fearful animals had significantly longer periods of inactivity than non-fearful animals. Non-fearful and mildly fearful cats vocalized more frequently than fearful cats. In the HIT, fearful cats travelled less than non-fearful and mildly fearful cats. Fearful and mildly fearful animals had significantly longer durations of inactivity, and non-fearful and mildly fearful cats had a significantly higher frequency of vocalization compared with fearful cats. In experiment 2, in the OFT, treatment with diazepam caused an increase in distance travelled, shorter durations of inactivity, and more frequent inactivity and vocalization. In the HIT, diazepam increased distance travelled and decreased duration of inactivity. Fearful cats spent significantly less time near the human compared with non-fearful cats, and this persisted under diazepam. Conclusions and relevance The feline OFT and feline HIT can be used jointly to assess the effects of medications or other therapies on fear and anxiety in the domestic cat.

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.

Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet-Based System to Improve Prevention of Mother-to-Child Transmission of HIV.

PubMed

Bull, Sheana; Thomas, Deborah Sk; Nyanza, Elias C; Ngallaba, Sospatro E

2018-01-15

The prevention of mother-to-child transmission (PMTCT) of HIV requires innovative solutions. Although routine monitoring is effective in some areas, standardized and easy-to-scale solutions to identify and monitor pregnant women, test them for HIV, and treat them and their children is still lacking. Mobile health (mHealth) offers opportunities for surveillance and reporting in rural areas of low- and middle-income countries. The aim of this study was to document the preliminary impacts of the Tanzania Health Information Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT care delivery and capacity building in a rural area of Tanzania. We developed T-HIT as a tablet-based system for an electronic data collection system designed to capture and report PMTCT data during antenatal, delivery, and postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a pilot randomized trial comparing seven sites using T-HIT assigned at random to seven control sites; all sites maintained standard paper record-keeping during the pilot intervention period. We compared numbers of antenatal visits, number of HIV tests administered, and women testing positive across all sites. Health workers recorded data from antenatal visits for 1530 women; of these, 695 (45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of lack of reagent, which is not captured on paper logs. There was no difference in the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We observed a significant postintervention increase in the numbers of women testing positive for HIV compared with the preintervention period (P=.04), but this was likely not attributable to the T-HIT system. T-HIT had a high degree of acceptability and feasibility and is perceived as useful by health workers, who documented more antenatal visits during the pilot intervention compared with a traditional system of paper logs, suggesting potential for improvements in antenatal care for women at risk for HIV. ©Sheana Bull, Deborah SK Thomas, Elias C Nyanza, Sospatro E Ngallaba. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 15.01.2018.

Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet-Based System to Improve Prevention of Mother-to-Child Transmission of HIV

PubMed Central

Bull, Sheana; Nyanza, Elias C; Ngallaba, Sospatro E

2018-01-01

Background The prevention of mother-to-child transmission (PMTCT) of HIV requires innovative solutions. Although routine monitoring is effective in some areas, standardized and easy-to-scale solutions to identify and monitor pregnant women, test them for HIV, and treat them and their children is still lacking. Mobile health (mHealth) offers opportunities for surveillance and reporting in rural areas of low- and middle-income countries. Objective The aim of this study was to document the preliminary impacts of the Tanzania Health Information Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT care delivery and capacity building in a rural area of Tanzania. Methods We developed T-HIT as a tablet-based system for an electronic data collection system designed to capture and report PMTCT data during antenatal, delivery, and postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a pilot randomized trial comparing seven sites using T-HIT assigned at random to seven control sites; all sites maintained standard paper record-keeping during the pilot intervention period. We compared numbers of antenatal visits, number of HIV tests administered, and women testing positive across all sites. Results Health workers recorded data from antenatal visits for 1530 women; of these, 695 (45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of lack of reagent, which is not captured on paper logs. There was no difference in the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We observed a significant postintervention increase in the numbers of women testing positive for HIV compared with the preintervention period (P=.04), but this was likely not attributable to the T-HIT system. Conclusions T-HIT had a high degree of acceptability and feasibility and is perceived as useful by health workers, who documented more antenatal visits during the pilot intervention compared with a traditional system of paper logs, suggesting potential for improvements in antenatal care for women at risk for HIV. PMID:29335236

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.

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.

A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

PubMed

Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

2016-01-01

The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

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

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.

Application of activity sensors for estimating behavioral patterns

USGS Publications Warehouse

Roberts, Caleb P.; Cain, James W.; Cox, Robert D.

2016-01-01

The increasing use of Global Positioning System (GPS) collars in habitat selection studies provides large numbers of precise location data points with reduced field effort. However, inclusion of activity sensors in many GPS collars also grants the potential to remotely estimate behavioral state. Thus, only using GPS collars to collect location data belies their full capabilities. Coupling behavioral state with location data would allow researchers and managers to refine habitat selection models by using diel behavioral state changes to partition fine-scale temporal shifts in habitat selection. We tested the capability of relatively unsophisticated GPS-collar activity sensors to estimate behavior throughout diel periods using free-ranging female elk (Cervus canadensis) in the Jemez Mountains of north-central New Mexico, USA, 2013–2014. Collars recorded cumulative number of movements (hits) per 15-min recording period immediately preceding GPS fixes at 0000, 0600, 1200, and 1800 hr. We measured diel behavioral patterns of focal elk, categorizing active (i.e., foraging, traveling, vigilant, grooming) and inactive (i.e., resting) states. Active behaviors (foraging, traveling) produced more average hits (0.87 ± 0.69 hits/min, 4.0 ± 2.2 hits/min, respectively; 95% CI) and inactive (resting) behavior fewer hits (−1.1 ± 0.61 95% CI). We differentiated active and inactive behavioral states with a bootstrapped threshold of 5.9 ± 3.9 hits/15-min recording period. Mean cumulative activity-sensor hits corresponded with observed diel behavioral patterns: hits increased during crepuscular (0600, 1800 hr) observations when elk were most active (0000–0600 hr: d = 0.19; 1200–1800 hr: d = 0.64) and decreased during midday and night (0000 hr, 1200 hr) when elk were least active (1800–0000 hr: d = −0.39; 0600–1200 hr: d = −0.43). Even using relatively unsophisticated GPS-collar activity sensors, managers can remotely estimate behavioral states, approximate diel behavioral patterns, and potentially complement location data in developing habitat selection models.

Laser Hit on Martian Sand Target, Before and After

NASA Image and Video Library

2012-10-22

The Chemistry and Camera ChemCam instrument on NASA Mars rover Curiosity used its laser and spectrometers to examine what chemical elements are in a drift of Martian sand during the mission 74th Martian day, or sol Oct. 20, 2012.

Fragment-based drug design.

PubMed

Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

2011-01-01

Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

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.

Effects of childhood adversity on bullying and cruelty to animals in the United States: findings from a national sample.

PubMed

Vaughn, Michael G; Fu, Qiang; Beaver, Kevin M; Delisi, Matt; Perron, Brian E; Howard, Matthew O

2011-11-01

This study examined effects of type of and cumulative burden of childhood adversities on bullying and cruelty to animals in the United States. Data were derived from Waves I and II of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of U.S. adults. Structured psychiatric interviews were completed by trained lay interviewers between 2001-2002 and 2003-2004. Although the effects of childhood adversity diminished with the inclusion of confounding variables, several adversities remained significant. For bullying, these included being made to do chores that were too difficult or dangerous, threatening to hit or throw something, pushing, shoving, slapping, or hitting, and hitting that left bruises, marks, or injuries. With respect to cruelty to animals, swearing and saying hurtful things, having a parent or other adult living within the home that went to jail or prison, and adult/other person fondling/touching in a sexual way were significant. The final models indicated that the cumulative burden of childhood adversities had strong effects on the increased likelihood of bullying behavior but not cruelty to animals.

3D flow effects on measuring turbulence statistics using 2D PIV

NASA Astrophysics Data System (ADS)

Lee, Hoonsang; Hwang, Wontae

2017-11-01

Homogeneous & isotropic turbulence (HIT) with no mean flow is the simplest type of turbulent flow which can be used to study various phenomena. Although HIT is inherently three dimensional in nature, various turbulence statistics can be measured with 2D PIV utilizing various assumptions. In this study, the loss of tracer particle pairs due to out-of-plane motion, and the effect it has on statistics such as turbulence kinetic energy, dissipation rate, and velocity correlations is investigated. Synthetic PIV images created from HIT direct numerical simulation (DNS) data are utilized to quantify this effect. We estimate the out-of-plane error by adjusting parameters such as PIV time interval, interrogation window size, and particle size. This information can be utilized to optimize experimental parameters when examining 3D turbulence via 2D PIV. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2017R1A2B4007372), and also by SNU new faculty Research Resettlement Fund.

A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

PubMed Central

Davis, Justin; Eyre, Harris; Jacka, Felice N; Dodd, Seetal; Dean, Olivia; McEwen, Sarah; Debnath, Monojit; McGrath, John; Maes, Michael; Amminger, Paul; McGorry, Patrick D; Pantelis, Christos; Berk, Michael

2016-01-01

Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype—the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders. PMID:27073049

Methods for Addressing Technology-induced Errors: The Current State.

PubMed

Borycki, E; Dexheimer, J W; Hullin Lucay Cossio, C; Gong, Y; Jensen, S; Kaipio, J; Kennebeck, S; Kirkendall, E; Kushniruk, A W; Kuziemsky, C; Marcilly, R; Röhrig, R; Saranto, K; Senathirajah, Y; Weber, J; Takeda, H

2016-11-10

The objectives of this paper are to review and discuss the methods that are being used internationally to report on, mitigate, and eliminate technology-induced errors. The IMIA Working Group for Health Informatics for Patient Safety worked together to review and synthesize some of the main methods and approaches associated with technology- induced error reporting, reduction, and mitigation. The work involved a review of the evidence-based literature as well as guideline publications specific to health informatics. The paper presents a rich overview of current approaches, issues, and methods associated with: (1) safe HIT design, (2) safe HIT implementation, (3) reporting on technology-induced errors, (4) technology-induced error analysis, and (5) health information technology (HIT) risk management. The work is based on research from around the world. Internationally, researchers have been developing methods that can be used to identify, report on, mitigate, and eliminate technology-induced errors. Although there remain issues and challenges associated with the methodologies, they have been shown to improve the quality and safety of HIT. Since the first publications documenting technology-induced errors in healthcare in 2005, we have seen in a short 10 years researchers develop ways of identifying and addressing these types of errors. We have also seen organizations begin to use these approaches. Knowledge has been translated into practice in a short ten years whereas the norm for other research areas is of 20 years.

A Novel Fluorescence Resonance Energy Transfer-Based Screen in High-Throughput Format To Identify Inhibitors of Malarial and Human Glucose Transporters.

PubMed

Kraft, Thomas E; Heitmeier, Monique R; Putanko, Marina; Edwards, Rachel L; Ilagan, Ma Xenia G; Payne, Maria A; Autry, Joseph M; Thomas, David D; Odom, Audrey R; Hruz, Paul W

2016-12-01

The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose sensor. This allows assessment of the ability of small molecules to inhibit glucose uptake with high accuracy (Z' factor of >0.8), thereby eliminating the need for radiolabeled substrates. Furthermore, we have adapted this assay to counterscreen PfHT hits against the human orthologues GLUT1, -2, -3, and -4. We report the identification of several hits after screening the Medicines for Malaria Venture (MMV) Malaria Box, a library of 400 compounds known to inhibit erythrocytic development of P. falciparum Hit compounds were characterized by determining the half-maximal inhibitory concentration (IC 50 ) for the uptake of radiolabeled glucose into isolated P. falciparum parasites. One of our hits, compound MMV009085, shows high potency and orthologue selectivity, thereby successfully validating our assay for antimalarial screening. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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.

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.

A business case for HIT adoption: effects of "meaningful use" EHR financial incentives on clinic revenue.

PubMed

Behkami, Nima A; Dorr, David A; Morrice, Stuart

2010-01-01

The goal of this study is to describe a framework that allows decision makers to efficiently evaluate factors that affect Electronic Health Record (EHR) adoption and test suitable interventions; specifically financial incentives. The United States healthcare delivery system is experiencing a transformation to improve population health. There is strong agreement that "meaningful use" of Health Information Technology (HIT) is a major enabler in this effort. However it's also understood that the high cost of implementing an EHR is an obstacle for adoption. To help understand these complexities we developed a simulation model designed to capture the dynamic nature of policy interventions that affect the adoption of EHR. We found that "Effective" use of HIT approaches break-even-point and larger clinic revenue many times faster that "average" or "poor" use of HIT. This study uses a systems perspective to the evaluate EHR adoption process through the "meaningful use" redesign as proposed in the American Reinvestment and Recovery Act 2009 in the United States healthcare industry by utilizing the System Dynamics methodology and Scenario Analysis.

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists.

PubMed

Schiebel, Johannes; Radeva, Nedyalka; Köster, Helene; Metz, Alexander; Krotzky, Timo; Kuhnert, Maren; Diederich, Wibke E; Heine, Andreas; Neumann, Lars; Atmanene, Cedric; Roecklin, Dominique; Vivat-Hannah, Valérie; Renaud, Jean-Paul; Meinecke, Robert; Schlinck, Nina; Sitte, Astrid; Popp, Franziska; Zeeb, Markus; Klebe, Gerhard

2015-09-01

Fragment-based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit-to-lead-to-drug optimization, the screening process should distinguish reliably between binders and non-binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease-relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361-entry library by using a reporter-displacement assay, saturation-transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Individual Responses to Completion of Short-Term and Chronic Interval Training: A Retrospective Study

PubMed Central

Astorino, Todd A.; Schubert, Matthew M.

2014-01-01

Alterations in maximal oxygen uptake (VO2max), heart rate (HR), and fat oxidation occur in response to chronic endurance training. However, many studies report frequent incidence of “non-responders” who do not adapt to continuous moderate exercise. Whether this is the case in response to high intensity interval training (HIT), which elicits similar adaptations as endurance training, is unknown. The aim of this retrospective study was to examine individual responses to two paradigms of interval training. In the first study (study 1), twenty active men and women (age and baseline VO2max = 24.0±4.6 yr and 42.8±4.8 mL/kg/min) performed 6 d of sprint interval training (SIT) consisting of 4–6 Wingate tests per day, while in a separate study (study 2), 20 sedentary women (age and baseline VO2max = 23.7±6.2 yr and 30.0±4.9 mL/kg/min) performed 12 wk of high-volume HIT at workloads ranging from 60–90% maximal workload. Individual changes in VO2max, HR, and fat oxidation were examined in each study, and multiple regression analysis was used to identify predictors of training adaptations to SIT and HIT. Data showed high frequency of increased VO2max (95%) and attenuated exercise HR (85%) in response to HIT, and low frequency of response for VO2max (65%) and exercise HR (55%) via SIT. Frequency of improved fat oxidation was similar (60–65%) across regimens. Only one participant across both interventions showed non-response for all variables. Baseline values of VO2max, exercise HR, respiratory exchange ratio, and body fat were significant predictors of adaptations to interval training. Frequency of positive responses to interval training seems to be greater in response to prolonged, higher volume interval training compared to similar durations of endurance training. PMID:24847797

Informatics Technology Mimics Ecology: Dense, Mutualistic Collaboration Networks Are Associated with Higher Publication Rates

PubMed Central

Sorani, Marco D.

2012-01-01

Information technology (IT) adoption enables biomedical research. Publications are an accepted measure of research output, and network models can describe the collaborative nature of publication. In particular, ecological networks can serve as analogies for publication and technology adoption. We constructed network models of adoption of bioinformatics programming languages and health IT (HIT) from the literature. We selected seven programming languages and four types of HIT. We performed PubMed searches to identify publications since 2001. We calculated summary statistics and analyzed spatiotemporal relationships. Then, we assessed ecological models of specialization, cooperativity, competition, evolution, biodiversity, and stability associated with publications. Adoption of HIT has been variable, while scripting languages have experienced rapid adoption. Hospital systems had the largest HIT research corpus, while Perl had the largest language corpus. Scripting languages represented the largest connected network components. The relationship between edges and nodes was linear, though Bioconductor had more edges than expected and Perl had fewer. Spatiotemporal relationships were weak. Most languages shared a bioinformatics specialization and appeared mutualistic or competitive. HIT specializations varied. Specialization was highest for Bioconductor and radiology systems. Specialization and cooperativity were positively correlated among languages but negatively correlated among HIT. Rates of language evolution were similar. Biodiversity among languages grew in the first half of the decade and stabilized, while diversity among HIT was variable but flat. Compared with publications in 2001, correlation with publications one year later was positive while correlation after ten years was weak and negative. Adoption of new technologies can be unpredictable. Spatiotemporal relationships facilitate adoption but are not sufficient. As with ecosystems, dense, mutualistic, specialized co-habitation is associated with faster growth. There are rapidly changing trends in external technological and macroeconomic influences. We propose that a better understanding of how technologies are adopted can facilitate their development. PMID:22279593

Sex-specific disruptions in spatial memory and anhedonia in a "two hit" rat model correspond with alterations in hippocampal brain-derived neurotrophic factor expression and signaling.

PubMed

Hill, Rachel A; Klug, Maren; Kiss Von Soly, Szerenke; Binder, Michele D; Hannan, Anthony J; van den Buuse, Maarten

2014-10-01

Post-mortem studies have demonstrated reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of schizophrenia and major depression patients. The "two hit" hypothesis proposes that two or more major disruptions at specific time points during development are involved in the pathophysiology of these mental illnesses. However, the role of BDNF in these "two hit" effects is unclear. Our aim was to behaviorally characterize a "two hit" rat model of developmental stress accompanied by an in-depth assessment of BDNF expression and signalling. Wistar rats were exposed to neonatal maternal separation (MS) stress and/or adolescent/young-adult corticosterone (CORT) treatment. In adulthood, models of cognitive and negative symptoms of mental illness were analyzed. The hippocampus was then dissected into dorsal (DHP) and ventral (VHP) regions and analyzed by qPCR for exon-specific BDNF gene expression or by Western blot for BDNF protein expression and downstream signaling. Male "two hit" rats showed marked disruptions in short-term spatial memory (Y-maze) which were absent in females. However, female "two hit" rats showed signs of anhedonia (sucrose preference test), which were absent in males. Novel object recognition and anxiety (elevated plus maze) were unchanged by either of the two "hits". In the DHP, MS caused a male-specific increase in BDNF Exons I, II, IV, VII, and IX mRNA but a decrease in mature BDNF and phosphorylated TrkB (pTrkB) protein expression in adulthood. In the VHP, BDNF transcript expression was unchanged; however, in female rats only, MS significantly decreased mature BDNF and pTrkB protein expression in adulthood. These data demonstrate that MS causes region-specific and sex-specific long-term effects on BDNF expression and signaling and, importantly, mRNA expression does not always infer protein expression. Alterations to BDNF signaling may mediate the sex-specific effects of developmental stress on anhedonic behaviors. © 2014 Wiley Periodicals, Inc.

PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

PubMed

Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be construed to represent any Agency determination or policy. Published by Elsevier Ltd.

3D-QSAR pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation toward identifying lead compounds for NS2B-NS3 protease inhibitors.

PubMed

Luo, Pei H; Zhang, Xuan R; Huang, Lan; Yuan, Lun; Zhou, Xang Z; Gao, X; Li, Ling S

2017-10-01

NS2B-NS3 protease has been identified to serve as lead drug design target due to its significant role in West Nile viral (WNV) and dengue virus (DENV) reproduction and replication. There are currently no approved chemotherapeutic drugs and effective vaccines to inhibit DENV and WNV infections. In this work, 3D-QSAR pharmacophore model has been developed to discover potential inhibitory candidates. Validation through Fischer's model and decoy test indicate that the developed 3D pharmacophore model is highly predictive for DENV inhibitors, which was then employed to screen ZINC chemical library to obtain reasonable hits. Following ADMET filtering, 15 hits were subjected to further filter through molecular docking and CoMFA modeling. Finally, top three hits were identified as lead compounds or potential inhibitory candidates with IC 50 values of ∼0.4637 µM and fitness of ∼57.73. It is implied from CoMFA modeling that substituents at the side site of benzotriazole such as a p-nitro group (e.g. biphenyl head) and a carbonyl (e.g. carboxylate function) at the side site of furan or amino group may improve bioactivity of ZINC85645245, respectively. Molecular dynamics simulations (MDS) were performed to discover new interactions and reinforce the binding modes from docking for the hits also. The QSAR and MDS results obtained from this work should be useful in determining structural requirements for inhibitor development as well as in designing more potential inhibitors for NS2B-NS3 protease.

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.

Comparative analysis of RNAi screening technologies at genome-scale reveals an inherent processing inefficiency of the plasmid-based shRNA hairpin.

PubMed

Bhinder, Bhavneet; Shum, David; Djaballah, Hakim

2014-02-01

RNAi screening in combination with the genome-sequencing projects would constitute the Holy Grail of modern genetics; enabling discovery and validation towards a better understanding of fundamental biology leading to novel targets to combat disease. Hit discordance at inter-screen level together with the lack of reproducibility is emerging as the technology's main pitfalls. To examine some of the underlining factors leading to such discrepancies, we reasoned that perhaps there is an inherent difference in knockdown efficiency of the various RNAi technologies. For this purpose, we utilized the two most popular ones, chemically synthesized siRNA duplex and plasmid-based shRNA hairpin, in order to perform a head to head comparison. Using a previously developed gain-of-function assay probing modulators of the miRNA biogenesis pathway, we first executed on a siRNA screen against the Silencer Select V4.0 library (AMB) nominating 1,273, followed by an shRNA screen against the TRC1 library (TRC1) nominating 497 gene candidates. We observed a poor overlap of only 29 hits given that there are 15,068 overlapping genes between the two libraries; with DROSHA as the only common hit out of the seven known core miRNA biogenesis genes. Distinct genes interacting with the same biogenesis regulators were observed in both screens, with a dismal cross-network overlap of only 3 genes (DROSHA, TGFBR1, and DIS3). Taken together, our study demonstrates differential knockdown activities between the two technologies, possibly due to the inefficient intracellular processing and potential cell-type specificity determinants in generating intended targeting sequences for the plasmid-based shRNA hairpins; and suggests this observed inefficiency as potential culprit in addressing the lack of reproducibility.

Health information technology interventions enhance care completion, engagement in HIV care and treatment, and viral suppression among HIV-infected patients in publicly funded settings.

PubMed

Shade, Starley B; Steward, Wayne T; Koester, Kimberly A; Chakravarty, Deepalika; Myers, Janet J

2015-04-01

The National HIV/AIDS Strategy (NHAS) emphasizes the use of technology to facilitate coordination of comprehensive care for people with HIV. We examined the effect of six health information technology (HIT) interventions in a Ryan White-funded Special Projects of National Significance (SPNS) on care completion services, engagement in HIV care, and viral suppression. Interventions included use of surveillance data to identify out-of-care individuals, extending access to electronic health records to support service providers, use of electronic laboratory ordering and prescribing, and development of a patient portal. Data from a sample of electronic patient records from each site were analyzed to assess changes in utilization of comprehensive care (prevention screening, support service utilization), engagement in primary HIV medical care (receipt of services and use of antiretroviral therapy), and viral suppression. We used weighted generalized estimating equations to estimate outcomes while accounting for the unequal contribution of data and differences in the distribution of patient characteristics across sites and over time. We observed statistically significant changes in the desired direction in comprehensive care utilization and engagement in primary care outcomes targeted by each site. Five of six sites experienced statistically significant increases in viral suppression. These results provide additional support for the use of HIT as a valuable tool for achieving the NHAS goal of providing comprehensive care for all people living with HIV. HIT has the potential to increase utilization of services, improve health outcomes for people with HIV, and reduce community viral load and subsequent transmission of HIV. © 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 For affiliation see end of article.

Reporter enzyme inhibitor study to aid assembly of orthogonal reporter gene assays.

PubMed

Ho, Pei-i; Yue, Kimberley; Pandey, Pramod; Breault, Lyne; Harbinski, Fred; McBride, Aaron J; Webb, Brian; Narahari, Janaki; Karassina, Natasha; Wood, Keith V; Hill, Adam; Auld, Douglas S

2013-05-17

Reporter gene assays (RGAs) are commonly used to measure biological pathway modulation by small molecules. Understanding how such compounds interact with the reporter enzyme is critical to accurately interpret RGA results. To improve our understanding of reporter enzymes and to develop optimal RGA systems, we investigated eight reporter enzymes differing in brightness, emission spectrum, stability, and substrate requirements. These included common reporter enzymes such as firefly luciferase (Photinus pyralis), Renilla reniformis luciferase, and β-lactamase, as well as mutated forms of R. reniformis luciferase emitting either blue- or green-shifted luminescence, a red-light emitting form of Luciola cruciata firefly luciferase, a mutated form of Gaussia princeps luciferase, and a proprietary luciferase termed "NanoLuc" derived from the luminescent sea shrimp Oplophorus gracilirostris. To determine hit rates and structure-activity relationships, we screened a collection of 42,460 PubChem compounds at 10 μM using purified enzyme preparations. We then compared hit rates and chemotypes of actives for each enzyme. The hit rates ranged from <0.1% for β-lactamase to as high as 10% for mutated forms of Renilla luciferase. Related luciferases such as Renilla luciferase mutants showed high degrees of inhibitor overlap (40-70%), while unrelated luciferases such as firefly luciferases, Gaussia luciferase, and NanoLuc showed <10% overlap. Examination of representative inhibitors in cell-based assays revealed that inhibitor-based enzyme stabilization can lead to increases in bioluminescent signal for firefly luciferase, Renilla luciferase, and NanoLuc, with shorter half-life reporters showing increased activation responses. From this study we suggest strategies to improve the construction and interpretation of assays employing these reporter enzymes.

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.

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

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.

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.

Identification of B. anthracis N(5)-carboxyaminoimidazole ribonucleotide mutase (PurE) active site binding compounds via fragment library screening.

PubMed

Lei, Hao; Jones, Christopher; Zhu, Tian; Patel, Kavankumar; Wolf, Nina M; Fung, Leslie W-M; Lee, Hyun; Johnson, Michael E

2016-02-15

The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial for Bacillus anthracis survival in serum. In this study we adopted a fragment-based hit discovery approach, using three screening methods-saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR), against B. anthracis PurE (BaPurE) to identify active site binding fragments by initially testing 352 compounds in a Zenobia fragment library. Competition STD NMR with the BaPurE product effectively eliminated non-active site binding hits from the primary hits, selecting active site binders only. Binding affinities (dissociation constant, KD) of these compounds varied between 234 and 301μM. Based on test results from the Zenobia compounds, we subsequently developed and applied a streamlined fragment screening strategy to screen a much larger library consisting of 3000 computationally pre-selected fragments. Thirteen final fragment hits were confirmed to exhibit binding affinities varying from 14μM to 700μM, which were categorized into five different basic scaffolds. All thirteen fragment hits have ligand efficiencies higher than 0.30. We demonstrated that at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme. Published by Elsevier Ltd.

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

PubMed Central

Ballester, Pedro J.; Mangold, Martina; Howard, Nigel I.; Robinson, Richard L. Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B. O.

2012-01-01

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated Ki ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification. PMID:22933186

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.

PubMed

Ballester, Pedro J; Mangold, Martina; Howard, Nigel I; Robinson, Richard L Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B O

2012-12-07

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K(i) ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

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

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.

The Martian: Examining Human Physical Judgments across Virtual Gravity Fields.

PubMed

Ye, Tian; Qi, Siyuan; Kubricht, James; Zhu, Yixin; Lu, Hongjing; Zhu, Song-Chun

2017-04-01

This paper examines how humans adapt to novel physical situations with unknown gravitational acceleration in immersive virtual environments. We designed four virtual reality experiments with different tasks for participants to complete: strike a ball to hit a target, trigger a ball to hit a target, predict the landing location of a projectile, and estimate the flight duration of a projectile. The first two experiments compared human behavior in the virtual environment with real-world performance reported in the literature. The last two experiments aimed to test the human ability to adapt to novel gravity fields by measuring their performance in trajectory prediction and time estimation tasks. The experiment results show that: 1) based on brief observation of a projectile's initial trajectory, humans are accurate at predicting the landing location even under novel gravity fields, and 2) humans' time estimation in a familiar earth environment fluctuates around the ground truth flight duration, although the time estimation in unknown gravity fields indicates a bias toward earth's gravity.

Using technology to engage hospitalised patients in their care: a realist review.

PubMed

Roberts, Shelley; Chaboyer, Wendy; Gonzalez, Ruben; Marshall, Andrea

2017-06-06

Patient participation in health care is associated with improved outcomes for patients and hospitals. New technologies are creating vast potential for patients to participate in care at the bedside. Several studies have explored patient use, satisfaction and perceptions of health information technology (HIT) interventions in hospital. Understanding what works for whom, under what conditions, is important when considering interventions successfully engaging patients in care. This realist review aimed to determine key features of interventions using bedside technology to engage hospital patients in their care and analyse these in terms of context, mechanisms and outcomes. A realist review was chosen to explain how and why complex HIT interventions work or fail within certain contexts. The review was guided by Pawson's realist review methodology, involving: clarifying review scope; searching for evidence; data extraction and evidence appraisal; synthesising evidence and drawing conclusions. Author experience and an initial literature scope provided insight and review questions and theories (propositions) around why interventions worked were developed and iteratively refined. A purposive search was conducted to find evidence to support, refute or identify further propositions, which formed an explanatory model. Each study was 'mined' for evidence to further develop the propositions and model. Interactive learning was the overarching theme of studies using technology to engage patients in their care. Several propositions underpinned this, which were labelled: information sharing; self-assessment and feedback; tailored education; user-centred design; and support in use of HIT. As studies were mostly feasibility or usability studies, they reported patient-centred outcomes including patient acceptability, satisfaction and actual use of HIT interventions. For each proposition, outcomes were proposed to come about by mechanisms including improved communication, shared decision-making, empowerment and self-efficacy; which acted as facilitators to patient participation in care. Overall, there was a stronger representation of health than IT disciplines in studies reviewed, with a lack of IT input in terms of theoretical underpinning, methodological design and reporting of outcomes. HIT interventions have great potential for engaging hospitalised patients in their care. However, stronger interdisciplinary collaboration between health and IT researchers is needed for effective design and evaluation of HIT interventions.

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.

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.

Advances in fragment-based drug discovery platforms.

PubMed

Orita, Masaya; Warizaya, Masaichi; Amano, Yasushi; Ohno, Kazuki; Niimi, Tatsuya

2009-11-01

Fragment-based drug discovery (FBDD) has been established as a powerful alternative and complement to traditional high-throughput screening techniques for identifying drug leads. At present, this technique is widely used among academic groups as well as small biotech and large pharmaceutical companies. In recent years, > 10 new compounds developed with FBDD have entered clinical development, and more and more attention in the drug discovery field is being focused on this technique. Under the FBDD approach, a fragment library of relatively small compounds (molecular mass = 100 - 300 Da) is screened by various methods and the identified fragment hits which normally weakly bind to the target are used as starting points to generate more potent drug leads. Because FBDD is still a relatively new drug discovery technology, further developments and optimizations in screening platforms and fragment exploitation can be expected. This review summarizes recent advances in FBDD platforms and discusses the factors important for the successful application of this technique. Under the FBDD approach, both identifying the starting fragment hit to be developed and generating the drug lead from that starting fragment hit are important. Integration of various techniques, such as computational technology, X-ray crystallography, NMR, surface plasmon resonance, isothermal titration calorimetry, mass spectrometry and high-concentration screening, must be applied in a situation-appropriate manner.

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.

Hit Generation in TB Drug Discovery: From Genome to Granuloma

PubMed Central

2018-01-01

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two decades have not delivered new TB drugs. Mycobacterium tuberculosis (Mtb), the causative agent of TB, encounters diverse microenvironments and can be found in a variety of metabolic states in the human host. Due to the complexity and heterogeneity of Mtb infection, no single model can fully recapitulate the in vivo conditions in which Mtb is found in TB patients, and there is no single “standard” screening condition to generate hit compounds for TB drug development. However, current screening assays have become more sophisticated as researchers attempt to mirror the complexity of TB disease in the laboratory. In this review, we describe efforts using surrogates and engineered strains of Mtb to focus screens on specific targets. We explain model culture systems ranging from carbon starvation to hypoxia, and combinations thereof, designed to represent the microenvironment which Mtb encounters in the human body. We outline ongoing efforts to model Mtb infection in the lung granuloma. We assess these different models, their ability to generate hit compounds, and needs for further TB drug development, to provide direction for future TB drug discovery. PMID:29384369

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.

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.

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.

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.

Development of a Single-Longitudinal-Mode Ho:YAG Laser Based on Corner Cube

NASA Astrophysics Data System (ADS)

Jing, Wu; You-Lun, Ju; Tong-Yu, Dai; Zhen-Guo, Zhang; Bao-Quan, Yao; Yue-Zhu, Wang

2016-04-01

Not Available Supported by the National Natural Science Foundation of China under Grant Nos 61308009 and 61405047, the China Postdoctoral Science Foundation Funded Project under Grant No 2013M540288, the Fundamental Research Funds for the Central Universities under Grant Nos HIT.NSRIF.2014044 and HIT.NSRIF.2015042, the Science Fund for Outstanding Youths of Heilongjiang Province under Grant No JQ201310, and the Heilongjiang Postdoctoral Science Foundation Funded Project under Grant No LBH-Z14085.

Journal of Rehabilitation Research and Development. Volume 27 Number 3, Summer 1990

DTIC Science & Technology

1990-01-01

First 119. Reflex Sympathetic Dystrophy in an Amputee: Case St., Springfield, IL 62794-9265 Study. Odderson IR. Czerniecki JM, Arch Ph\\vs Med Rehabil 71...60206 Compiegne cedex. France Persons with Disabilities. Becker HA. et al.. hit J Rehabil Res 12(3):235-250. 1989. 201. Psychological Aspects of...Hearing Aid Treatment. Contact: Heather A. Becker . University of Texas at Austin. Borre S. Courtois J. hit J Rehabil Res 12(3):347-348. 1989. School of

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.

The Challenges and Issues Regarding E-Health and Health Information Technology Trends in the Healthcare Sector

NASA Astrophysics Data System (ADS)

Esmaeilzadeh, Pouyan; Sambasivan, Murali; Kumar, Naresh

Like other industries, the utilization of the internet and Information Technology (IT) has increased in the health sector. Different applications attributed to the internet and IT in healthcare practice. It includes a range of services that intersect the edge of medicine, computer and information science. The presence of the internet helps healthcare practice with the use of electronic processes and communication. Also, health IT (HIT) deals with the devices, clinical guidelines and methods required to improve the management of information in healthcare. Although the internet and HIT has been considered as an influential means to enhance health care delivery, it is completely naive to imagine all new tools and mechanisms supported by the internet and HIT systems are simply adopted and used by all organizational members. As healthcare professionals play an important role in the healthcare sector, there is no doubt that mechanism of newly introduced HIT and new application of the internet in medical practice should be coupled with healthcare professionals' acceptance. Therefore, with great resistance by healthcare professionals new mechanism and tools supported by IT and the internet cannot be used properly and subsequently may not improve the quality of medical care services. However, factors affecting the healthcare professionals' adoption behavior concerning new e-health and HIT mechanism are still not conclusively identified. This research (as a theoretical study) tries to propose the source of resistance in order to handle the challenges over new e-technology in the health industry. This study uses the involved concepts and develops a conceptual framework to improve overall acceptance of e-health and HIT by healthcare professionals.

High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility

PubMed Central

Herington, Jennifer L.; Swale, Daniel R.; Brown, Naoko; Shelton, Elaine L.; Choi, Hyehun; Williams, Charles H.; Hong, Charles C.; Paria, Bibhash C.; Denton, Jerod S.; Reese, Jeff

2015-01-01

The uterine myometrium (UT-myo) is a therapeutic target for preterm labor, labor induction, and postpartum hemorrhage. Stimulation of intracellular Ca2+-release in UT-myo cells by oxytocin is a final pathway controlling myometrial contractions. The goal of this study was to develop a dual-addition assay for high-throughput screening of small molecular compounds, which could regulate Ca2+-mobilization in UT-myo cells, and hence, myometrial contractions. Primary murine UT-myo cells in 384-well plates were loaded with a Ca2+-sensitive fluorescent probe, and then screened for inducers of Ca2+-mobilization and inhibitors of oxytocin-induced Ca2+-mobilization. The assay exhibited robust screening statistics (Z´ = 0.73), DMSO-tolerance, and was validated for high-throughput screening against 2,727 small molecules from the Spectrum, NIH Clinical I and II collections of well-annotated compounds. The screen revealed a hit-rate of 1.80% for agonist and 1.39% for antagonist compounds. Concentration-dependent responses of hit-compounds demonstrated an EC50 less than 10μM for 21 hit-antagonist compounds, compared to only 7 hit-agonist compounds. Subsequent studies focused on hit-antagonist compounds. Based on the percent inhibition and functional annotation analyses, we selected 4 confirmed hit-antagonist compounds (benzbromarone, dipyridamole, fenoterol hydrobromide and nisoldipine) for further analysis. Using an ex vivo isometric contractility assay, each compound significantly inhibited uterine contractility, at different potencies (IC50). Overall, these results demonstrate for the first time that high-throughput small-molecules screening of myometrial Ca2+-mobilization is an ideal primary approach for discovering modulators of uterine contractility. PMID:26600013

α-lipoic acid inhibits high glucose-induced apoptosis in HIT-T15 cells.

PubMed

Yang, Yi; Wang, Weiping; Liu, Yinan; Guo, Ting; Chen, Ping; Ma, Kangtao; Zhou, Chunyan

2012-06-01

High blood glucose plays an important role in the pathogenesis of diabetes. α-lipoic acid (LA) has been used to prevent and treat diabetes, and is thought to act by increasing insulin sensitivity in many tissues. However, whether LA also has a cytoprotective effect on pancreatic islet beta cells remains unclear. In this study, we assessed whether LA could inhibit apoptosis in beta cells exposed to high glucose concentrations. HIT-T15 pancreatic beta cells were treated with 30 mmol/L glucose in the presence or absence of 0.5 mmol/L LA for 8 days. LA significantly reduced the numbers of apoptotic HIT-T15 cells and inhibited the cell overgrowth normally induced by high glucose treatment. Additionally, LA inhibited insulin expression and secretion in HIT-T15 cells induced by high glucose. Further study demonstrated that LA upregulated Pdx1 and Bcl2 gene expression, reduced Bax gene expression, and promoted phosphorylation of Akt in HIT-T15 cells treated with high glucose. Intriguingly, knockdown of Pdx1 expression partially offset the anti-apoptotic effect of LA. However, inhibition of Akt by PI3K/AKT antagonist LY294002 only slightly reversed the anti-apoptosis effect of LA and mildly decreased the gene expression level of Pdx1 (P > 0.05). Moreover, LA only slightly attenuated reactive oxygen species (ROS) production and augmented mitochondrial membrane potential. Therefore, our data suggest that α-lipoic acid can effectively attenuate high glucose-induced HIT-T15 cell apoptosis probably by increasing Pdx1 expression. These findings provide a new interpretation on the role of LA in the treatment of diabetes. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

The role of chemicals and radiation in the etiology of cancer

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

Huberman, E.; Barr, S.H.

In this volume, investigators consider the mechanisms of oncogenesis, cell transformation, and carcinogen metabolism and present new findings on chemical and radiation carcinogenesis and chemically induced mutagenesis and chromosomal changes. As background to the studies of chemical and radiation carcinogenesis, the book surveys knowledge of cell transformation and carcinogen metabolism. Among the topics reviewed are the transforming genes involved in human malignancy, the genetics and epigenetics of neoplasia, and the single-hit and multi-hit concepts of hepatocarcinogenesis. Also examined are organ, species, and interindividual differences in carcinogen metabolism; chemical and biochemical dosimetry of genotoxic chemical exposure; and the role of pharmacokineticsmore » and DNA dosimetry in relating in vitro to in vivo actions of N-nitroso compounds.« less

Antidiabetic and Beta Cell-Protection Activities of Purple Corn Anthocyanins

PubMed Central

Hong, Su Hee; Heo, Jee-In; Kim, Jeong-Hyeon; Kwon, Sang-Oh; Yeo, Kyung-Mok; Bakowska-Barczak, Anna M.; Kolodziejczyk, Paul; Ryu, Ok-Hyun; Choi, Moon-Ki; Kang, Young-Hee; Lim, Soon Sung; Suh, Hong-Won; Huh, Sung-Oh; Lee, Jae-Yong

2013-01-01

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice. PMID:24244813

Counting of oligomers in sequences generated by markov chains for DNA motif discovery.

PubMed

Shan, Gao; Zheng, Wei-Mou

2009-02-01

By means of the technique of the imbedded Markov chain, an efficient algorithm is proposed to exactly calculate first, second moments of word counts and the probability for a word to occur at least once in random texts generated by a Markov chain. A generating function is introduced directly from the imbedded Markov chain to derive asymptotic approximations for the problem. Two Z-scores, one based on the number of sequences with hits and the other on the total number of word hits in a set of sequences, are examined for discovery of motifs on a set of promoter sequences extracted from A. thaliana genome. Source code is available at http://www.itp.ac.cn/zheng/oligo.c.

Bilingual recognition memory: stronger performance but weaker levels-of-processing effects in the less fluent language.

PubMed

Francis, Wendy S; Gutiérrez, Marisela

2012-04-01

The effects of bilingual proficiency on recognition memory were examined in an experiment with Spanish-English bilinguals. Participants learned lists of words in English and Spanish under shallow- and deep-encoding conditions. Overall, hit rates were higher, discrimination greater, and response times shorter in the nondominant language, consistent with effects previously observed for lower frequency words. Levels-of-processing effects in hit rates, discrimination, and response time were stronger in the dominant language. Specifically, with shallow encoding, the advantage for the nondominant language was larger than with deep encoding. The results support the idea that memory performance in the nondominant language is impacted by both the greater demand for cognitive resources and the lower familiarity of the words.

Challenges for developing RHIOs in rural America: a study in Appalachian Ohio.

PubMed

Phillips, Brian O; Welch, Elissa E

2007-01-01

A healthy population is essential for the socioeconomic success of the Appalachian region and other rural, underserved areas in the United States. However, rural communities are only beginning to deploy the advanced health information technologies being used by larger urban institutions. Regional health information organizations have the potential to be the building blocks that will harmonize HIT exchange on a national scale. But there are many challenges to developing RHIOs in rural communities. In 2004, the Ohio University College of Osteopathic Medicine convened the Appalachian Regional Informatics Consortium, a community-based cross-section of healthcare providers in southeastern Ohio. The consortium was awarded an Integrated Advanced Information Management Systems planning grant from the National Institutes of Health to investigate rural RHIO development, the first such rural project. This article examines the consortium and the challenges facing rural RHIO development in Appalachian Ohio.

The Own-Age Bias in Face Recognition: A Meta-Analytic and Theoretical Review

ERIC Educational Resources Information Center

Rhodes, Matthew G.; Anastasi, Jeffrey S.

2012-01-01

A large number of studies have examined the finding that recognition memory for faces of one's own age group is often superior to memory for faces of another age group. We examined this "own-age bias" (OAB) in the meta-analyses reported. These data showed that hits were reliably greater for same-age relative to other-age faces (g = 0.23) and that…

Alternative Databases for Anthropology Searching.

ERIC Educational Resources Information Center

Brody, Fern; Lambert, Maureen

1984-01-01

Examines online search results of sample questions in several databases covering linguistics, cultural anthropology, and physical anthropology in order to determine if and where any overlap in results might occur, and which files have greatest number of relevant hits. Search results by database are given for each subject area. (EJS)

Reduction of plasma density in the Helicity Injected Torus with Steady Inductance experiment by using a helicon pre-ionization source

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

Hossack, Aaron C.; Jarboe, Thomas R.; Victor, Brian S.

2013-10-15

A helicon based pre-ionization source has been developed and installed on the Helicity Injected Torus with Steady Inductance (HIT-SI) spheromak. The source initiates plasma breakdown by injecting impurity-free, unmagnetized plasma into the HIT-SI confinement volume. Typical helium spheromaks have electron density reduced from (2–3) × 10{sup 19} m{sup −3} to 1 × 10{sup 19} m{sup −3}. Deuterium spheromak formation is possible with density as low as 2 × 10{sup 18} m{sup −3}. The source also enables HIT-SI to be operated with only one helicity injector at injector frequencies above 14.5 kHz. A theory explaining the physical mechanism driving the reductionmore » of breakdown density is presented.« less

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.

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.

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.

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.

Evaluation of marginal failures of dental composite restorations by acoustic emission analysis.

PubMed

Gu, Ja-Uk; Choi, Nak-Sam

2013-01-01

In this study, a nondestructive method based on acoustic emission (AE) analysis was developed to evaluate the marginal failure states of dental composite restorations. Three types of ring-shaped substrates, which were modeled after a Class I cavity, were prepared from polymethyl methacrylate, stainless steel, and human molar teeth. A bonding agent and a composite resin were applied to the ring-shaped substrates and cured by light exposure. At each time-interval measurement, the tooth substrate presented a higher number of AE hits than polymethyl methacrylate and steel substrates. Marginal disintegration estimations derived from cumulative AE hits and cumulative AE energy parameters showed that a signification portion of marginal gap formation was already realized within 1 min at the initial light-curing stage. Estimation based on cumulative AE energy gave a higher level of marginal failure than that based on AE hits. It was concluded that the AE analysis method developed in this study was a viable approach in predicting the clinical survival of dental composite restorations efficiently within a short test period.

Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization

PubMed Central

Kong, Xiangqian; Qin, Jie; Li, Zeng; Vultur, Adina; Tong, Linjiang; Feng, Enguang; Rajan, Geena; Liu, Shien; Lu, Junyan; Liang, Zhongjie; Zheng, Mingyue; Zhu, Weiliang; Jiang, Hualiang; Herlyn, Meenhard; Liu, Hong; Marmorstein, Ronen; Luo, Cheng

2012-01-01

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-RafV600E mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we described the development of novel B-RafV600E selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC50 values were identified as B-RafV600E inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC50 values with selectivity for B-RafV600E in vitro and exclusive cytotoxicity against B-RafV600E harboring cancer cells. PMID:22875039

Development of a novel class of B-Raf(V600E)-selective inhibitors through virtual screening and hierarchical hit optimization.

PubMed

Kong, Xiangqian; Qin, Jie; Li, Zeng; Vultur, Adina; Tong, Linjiang; Feng, Enguang; Rajan, Geena; Liu, Shien; Lu, Junyan; Liang, Zhongjie; Zheng, Mingyue; Zhu, Weiliang; Jiang, Hualiang; Herlyn, Meenhard; Liu, Hong; Marmorstein, Ronen; Luo, Cheng

2012-09-28

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-Raf(V600E) mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-Raf(V600E) selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC(50) values were identified as B-Raf(V600E) inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC(50) values with selectivity for B-Raf(V600E)in vitro and exclusive cytotoxicity against B-Raf(V600E) harboring cancer cells.

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.

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.

Development and Validation of 2D Difference Intensity Analysis for Chemical Library Screening by Protein-Detected NMR Spectroscopy.

PubMed

Egner, John M; Jensen, Davin R; Olp, Michael D; Kennedy, Nolan W; Volkman, Brian F; Peterson, Francis C; Smith, Brian C; Hill, R Blake

2018-03-02

An academic chemical screening approach was developed by using 2D protein-detected NMR, and a 352-chemical fragment library was screened against three different protein targets. The approach was optimized against two protein targets with known ligands: CXCL12 and BRD4. Principal component analysis reliably identified compounds that induced nonspecific NMR crosspeak broadening but did not unambiguously identify ligands with specific affinity (hits). For improved hit detection, a novel scoring metric-difference intensity analysis (DIA)-was devised that sums all positive and negative intensities from 2D difference spectra. Applying DIA quickly discriminated potential ligands from compounds inducing nonspecific NMR crosspeak broadening and other nonspecific effects. Subsequent NMR titrations validated chemotypes important for binding to CXCL12 and BRD4. A novel target, mitochondrial fission protein Fis1, was screened, and six hits were identified by using DIA. Screening these diverse protein targets identified quinones and catechols that induced nonspecific NMR crosspeak broadening, hampering NMR analyses, but are currently not computationally identified as pan-assay interference compounds. The results established a streamlined screening workflow that can easily be scaled and adapted as part of a larger screening pipeline to identify fragment hits and assess relative binding affinities in the range of 0.3-1.6 mm. DIA could prove useful in library screening and other applications in which NMR chemical shift perturbations are measured. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimated Radiation on Mars, Hits per Cell Nucleus

NASA Technical Reports Server (NTRS)

2002-01-01

This global map of Mars shows estimates for amounts of high-energy-particle cosmic radiation reaching the surface, a serious health concern for any future human exploration of the planet.

The estimates are based on cosmic-radiation measurements made on the way to Mars by the Mars radiation environment experiment, an instrument on NASA's 2001 Mars Odyssey spacecraft, plus information about Mars' surface elevations from the laser altimeter instrument on NASA's Mars Global Surveyor. The areas of Mars expected to have least radiation are where elevation is lowest, because those areas have more atmosphere above them to block out some of the radiation. Earth's thick atmosphere shields us from most cosmic radiation, but Mars has a much thinner atmosphere than Earth does.

Colors in the map refer to the estimated average number of times per year each cell nucleus in a human there would be hit by a high-energy cosmic ray particle. The range is generally from two hits (color-coded green), a moderate risk level, to eight hits (coded red), a high risk level.

NASA's Jet Propulsion Laboratory, Pasadena, Calif. manages the 2001 Mars Odyssey and Mars Global Surveyor missions for NASA's Office of Space Science, Washington D.C. The Mars radiation environment experiment was developed by NASA's Johnson Space Center. Lockheed Martin Astronautics, Denver, is the prime contractor for Odyssey, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

Methods for Addressing Technology-Induced Errors: The Current State

PubMed Central

Dexheimer, J. W.; Hullin Lucay Cossio, C.; Gong, Y.; Jensen, S.; Kaipio, J.; Kennebeck, S.; Kirkendall, E.; Kushniruk, A. W.; Kuziemsky, C.; Marcilly, R.; Röhrig, R.; Saranto, K.; Senathirajah, Y.; Weber, J.; Takeda, H.

2016-01-01

Summary Objectives The objectives of this paper are to review and discuss the methods that are being used internationally to report on, mitigate, and eliminate technology-induced errors. Methods The IMIA Working Group for Health Informatics for Patient Safety worked together to review and synthesize some of the main methods and approaches associated with technology-induced error reporting, reduction, and mitigation. The work involved a review of the evidence-based literature as well as guideline publications specific to health informatics. Results The paper presents a rich overview of current approaches, issues, and methods associated with: (1) safe HIT design, (2) safe HIT implementation, (3) reporting on technology-induced errors, (4) technology-induced error analysis, and (5) health information technology (HIT) risk management. The work is based on research from around the world. Conclusions Internationally, researchers have been developing methods that can be used to identify, report on, mitigate, and eliminate technology-induced errors. Although there remain issues and challenges associated with the methodologies, they have been shown to improve the quality and safety of HIT. Since the first publications documenting technology-induced errors in healthcare in 2005, we have seen in a short 10 years researchers develop ways of identifying and addressing these types of errors. We have also seen organizations begin to use these approaches. Knowledge has been translated into practice in a short ten years whereas the norm for other research areas is of 20 years. PMID:27830228

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

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.

Behavioral Treatment of Aggression in the Mentally Retarded: A Review.

ERIC Educational Resources Information Center

Feldstein, Jerome H.

The paper reviews 34 behavioral treatment studies (1967-1983) examining reduction of aggressive behavior in mentally retarded people. Research reviewed was limited to treatment of physically aggressive responses such as hits, kicks, bites, chokes, scratches, and throwing objects by persons designated as mentally retarded. Among results reported…

Just Talk? Discourses and Deinstitutionalization in School District Policy Making

ERIC Educational Resources Information Center

Spain, Angeline K.

2017-01-01

Extracurricular programs, which tend to be both highly institutionalized and popular with parents, were hard hit by cutbacks during the Great Recession. This study uses conceptual research on organizational routines and institutional processes to examine this case of controversial policy making. Observing school district policy making in two…

The Earliest Electrophysiological Correlate of Visual Awareness?

ERIC Educational Resources Information Center

Koivisto, Mika; Lahteenmaki, Mikko; Sorensen, Thomas Alrik; Vangkilde, Signe; Overgaard, Morten; Revonsuo, Antti

2008-01-01

To examine the neural correlates and timing of human visual awareness, we recorded event-related potentials (ERPs) in two experiments while the observers were detecting a grey dot that was presented near subjective threshold. ERPs were averaged for conscious detections of the stimulus (hits) and nondetections (misses) separately. Our results…

Radiocytogenetic effects on bone marrow cells of opossum in vivo

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

Prasad, N.; Bushong, S.C.; MacIntyre, R.S.

1973-03-01

Bone marrow cells of the opossum, Didelphis virginiana, were examined 24 hr following a whole-body /sup 60/Co radiation dosc of 100, and the chromosomal aberrations resulted in a radiation sensitivity of 0.000605 aberrations/cell/rad/ sup 2/ for single-hit and multihit type damage respectively. (auth)

Retrospective Conversion: A Question of Time, Standards, and Purpose.

ERIC Educational Resources Information Center

Valentine, Phyllis A.; McDonald, David R.

1986-01-01

Examines the factors that determine the cost of retrospective conversion (definition of conversion, standards of acceptance, method of conversion, hit rate, standards for creation of machine-readable records for nonhits); reports results of cost study at University of Michigan library; and introduces an alternative strategy for discussion. Seven…

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.

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.

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.

Protein Supplementation to Augment the Effects of High Intensity Resistance Training in Untrained Middle-Aged Males: The Randomized Controlled PUSH Trial.

PubMed

Wittke, Andreas; von Stengel, Simon; Hettchen, Michael; Fröhlich, Michael; Giessing, Jürgen; Lell, Michael; Scharf, Michael; Bebenek, Michael; Kohl, Matthias; Kemmler, Wolfgang

2017-01-01

High intensity (resistance exercise) training (HIT) defined as a "single set resistance exercise to muscular failure" is an efficient exercise method that allows people with low time budgets to realize an adequate training stimulus. Although there is an ongoing discussion, recent meta-analysis suggests the significant superiority of multiple set (MST) methods for body composition and strength parameters. The aim of this study is to determine whether additional protein supplementation may increase the effect of a HIT-protocol on body composition and strength to an equal MST-level. One hundred and twenty untrained males 30-50 years old were randomly allocated to three groups: (a) HIT, (b) HIT and protein supplementation (HIT&P), and (c) waiting-control (CG) and (after cross-over) high volume/high-intensity-training (HVHIT). HIT was defined as "single set to failure protocol" while HVHIT consistently applied two equal sets. Protein supplementation provided an overall intake of 1.5-1.7 g/kg/d/body mass. Primary study endpoint was lean body mass (LBM). LBM significantly improved in all exercise groups ( p ≤ 0.043); however only HIT&P and HVHIT differ significantly from control ( p ≤ 0.002). HIT diverges significantly from HIT&P ( p = 0.017) and nonsignificantly from HVHIT ( p = 0.059), while no differences were observed for HIT&P versus HVHIT ( p = 0.691). In conclusion, moderate to high protein supplementation significantly increases the effects of a HIT-protocol on LBM in middle-aged untrained males.

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.

Interpretation of mutation induction by accelerated heavy ions in bacteria

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

Kozubek, S.; Ryznar, L.; Horneck, G.

In this report, a quantitative interpretation of mutation induction cross sections by heavy charged particles in bacterial cells is presented. The approach is based on the calculation of the fraction of energy deposited by indirect hits in the sensitive structure. In these events the particle does not pass through the sensitive volume, but this region is hit by {delta} rays. Four track structure models, developed by Katz, Chatterjee et al, Kiefer and Straaten and Kudryashov et al., respectively, were used for the calculations. With the latter two models, very good agreement of the calculations with experimental results on mutagenesis inmore » bacteria was obtained. Depending on the linear energy transfer (LET{infinity}) of the particles, two different modes of mutagenic action of heavy ions are distinguished: {open_quotes}{delta}-ray mutagenesis,{close_quotes} which is related to those radiation qualities that preferentially kill the cells in direct hits (LET{infinity} {ge} 100 keV/{mu}m), and {open_quotes}track core mutagenesis,{close_quotes} which arises from direct hits and is observed for lighter ions or ions with high energy (LET{infinity} {le} 100 keV/{mu}m). 37 refs., 6 figs., 1 tab.« less

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.

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

Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation-Structure-Based Hit Evaluation and Chemistry Exploration.

PubMed

Xue, Yafeng; Olsson, Thomas; Johansson, Carina A; Öster, Linda; Beisel, Hans-Georg; Rohman, Mattias; Karis, David; Bäckström, Stefan

2016-03-04

Soluble epoxide hydrolase (sEH) is involved in the regulation of many biological processes by metabolizing the key bioactive lipid mediator, epoxyeicosatrienoic acids. For the development of sEH inhibitors with improved physicochemical properties, we performed both a fragment screening and a high-throughput screening aiming at an integrated hit evaluation and lead generation. Followed by a joint dose-response analysis to confirm the hits, the identified actives were then effectively triaged by a structure-based hit-classification approach to three prioritized series. Two distinct scaffolds were identified as tractable starting points for potential lead chemistry work. The oxoindoline series bind at the right-hand side of the active-site pocket with hydrogen bonds to the protein. The 2-phenylbenzimidazole-4-sulfonamide series bind at the central channel with significant induced fit, which has not been previously reported. On the basis of the encouraging initial results, we envision that a new lead series with improved properties could be generated if a vector is found that could merge the cyclohexyl functionality of the oxoindoline series with the trifluoromethyl moiety of the 2-phenylbenzimidazole-4-sulfonamide series. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Binding-Site Assessment by Virtual Fragment Screening

PubMed Central

Huang, Niu; Jacobson, Matthew P.

2010-01-01

The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules) would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock ∼11000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors. PMID:20404926

Prospective performance evaluation of selected common virtual screening tools. Case study: Cyclooxygenase (COX) 1 and 2.

PubMed

Kaserer, Teresa; Temml, Veronika; Kutil, Zsofia; Vanek, Tomas; Landa, Premysl; Schuster, Daniela

2015-01-01

Computational methods can be applied in drug development for the identification of novel lead candidates, but also for the prediction of pharmacokinetic properties and potential adverse effects, thereby aiding to prioritize and identify the most promising compounds. In principle, several techniques are available for this purpose, however, which one is the most suitable for a specific research objective still requires further investigation. Within this study, the performance of several programs, representing common virtual screening methods, was compared in a prospective manner. First, we selected top-ranked virtual screening hits from the three methods pharmacophore modeling, shape-based modeling, and docking. For comparison, these hits were then additionally predicted by external pharmacophore- and 2D similarity-based bioactivity profiling tools. Subsequently, the biological activities of the selected hits were assessed in vitro, which allowed for evaluating and comparing the prospective performance of the applied tools. Although all methods performed well, considerable differences were observed concerning hit rates, true positive and true negative hits, and hitlist composition. Our results suggest that a rational selection of the applied method represents a powerful strategy to maximize the success of a research project, tightly linked to its aims. We employed cyclooxygenase as application example, however, the focus of this study lied on highlighting the differences in the virtual screening tool performances and not in the identification of novel COX-inhibitors. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Experimental Study on Mechanical and Acoustic Emission Characteristics of Rock-Like Material Under Non-uniformly Distributed Loads

NASA Astrophysics Data System (ADS)

Wang, Xiao; Wen, Zhijie; Jiang, Yujing; Huang, Hao

2018-03-01

The mechanical and acoustic emission characteristics of rock-like materials under non-uniform loads were investigated by means of a self-developed mining-induced stress testing system and acoustic emission monitoring system. In the experiments, the specimens were divided into three regions and different initial vertical stresses and stress loading rates were used to simulate different mining conditions. The mechanical and acoustic emission characteristics between regions were compared, and the effects of different initial vertical stresses and different stress loading rates were analysed. The results showed that the mechanical properties and acoustic emission characteristics of rock-like materials can be notably localized. When the initial vertical stress and stress loading rate are fixed, the peak strength of region B is approximately two times that of region A, and the maximum acoustic emission hit value of region A is approximately 1-2 times that of region B. The effects of the initial vertical stress and stress loading rate on the peck strain, maximum hit value, and occurrence time of the maximum hit are similar in that when either of the former increase, the latter all decrease. However, peck strength will increase with the increase in loading rate and decrease with the increase in initial vertical stress. The acoustic emission hits can be used to analyse the damage in rock material, but the number of acoustic emission hits cannot be used alone to determine the degree of rock damage directly.

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...

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...

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.

Adolescent social isolation stress unmasks the combined effects of adolescent exercise and adult inflammation on hippocampal neurogenesis and behavior.

PubMed

Hueston, Cara M; Cryan, John F; Nolan, Yvonne M

2017-12-04

Hippocampal neurogenesis and associated cognitive behaviors are regulated by a number of factors including stress, inflammation, and exercise. However, the interplay between these factors remains relatively unexplored, especially across the lifespan. In the current study, the effect of social isolation stress during the adolescent period on neurogenesis and hippocampal-dependent cognitive behaviors was examined. This period of the lifespan has been demonstrated to be an important time for hippocampal growth and plasticity, during which changes to hippocampal neurogenesis may have long lasting effects. Additionally, we aimed to determine whether a 'dual-hit' of adolescent stress and adult chronic neuroinflammation would potentiate any negative effects of either insult alone. Lastly, the potential positive effects of exercise during adolescence was examined to determine whether exercise could attenuate any negative impacts of these insults on hippocampal neurogenesis and behavior. The results from the current study demonstrate that social isolation stress during adolescence followed by intra-hippocampal exposure to the pro-inflammatory cytokine IL-1β in early adulthood produces deficits in both spontaneous alternations and novel object recognition. Exercise attenuated deficits in neurogenesis and novel object recognition in mice that had been exposed to the 'dual-hit' of stress and neuroinflammation. These findings indicate that adolescence represents a key period of the lifespan during which external factors such as stress and exercise can impact on hippocampal development, and may alter the response to challenges such as neuroinflammation in later life. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Motives for adherence to a gluten-free diet: a qualitative investigation involving adults with coeliac disease.

PubMed

Dowd, A J; Tamminen, K A; Jung, M E; Case, S; McEwan, D; Beauchamp, M R

2014-12-01

Currently , the only treatment for coeliac disease is life long adherence to a strict gluten-free diet. Strict adherence to a gluten-free diet is challenging, with recent reports suggesting that adherence rates range from 42% to 91%. The present study aimed to: (i) identify motives for adhering to a gluten-free diet and (ii) explore factors implicated in adherence and non-adherence behaviour in terms of accidental and purposeful gluten consumption among adults with coeliac disease. Two hundred and three adults with coeliac disease completed an online questionnaire. Using a qualitative design, relationships were examined between reported adherence and motivation to follow a gluten-free diet, as well as the onset, duration and severity of symptoms. Feelings of desperation (‘hitting rock bottom’) and needing to gain or lose weight were associated with the strictest adherence to a gluten-free diet. Participants who accidentally consumed gluten over the past week developed symptoms the most quickly and reported the most pain over the past 6 months. Participants who consumed gluten on purpose over the past week reported a shorter duration of symptoms and less pain over the past 6 months. Hitting rock bottom and needing to gain or lose weight were factors associated with the strictest adherence, when considered in the context of both accidental and purposeful gluten consumption. Future research is warranted to develop resources to help people with coeliac disease follow a strict gluten-free diet.

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.

Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Ponomarev, Artem

2009-01-01

A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

Hospital-Based Comparative Effectiveness Centers: Translating Research into Practice to Improve the Quality, Safety and Value of Patient Care

PubMed Central

Williams, Kendal; Brennan, Patrick J.

2010-01-01

Hospital-based comparative effectiveness (CE) centers provide a model that clinical leaders can use to improve evidence-based practice locally. The model is used by integrated health systems outside the US, but is less recognized in the US. Such centers can identify and adapt national evidence-based policies for the local setting, create local evidence-based policies in the absence of national policies, and implement evidence into practice through health information technology (HIT) and quality initiatives. Given the increasing availability of CE evidence and incentives to meaningfully use HIT, the relevance of this model to US practitioners is increasing. This is especially true in the context of healthcare reform, which will likely reduce reimbursements for care deemed unnecessary by published evidence or guidelines. There are challenges to operating hospital-based CE centers, but many of these challenges can be overcome using solutions developed by those currently leading such centers. In conclusion, these centers have the potential to improve the quality, safety and value of care locally, ultimately translating into higher quality and more cost-effective care nationally. To better understand this potential, the current activity and impact of hospital-based CE centers in the US should be rigorously examined. PMID:20697961

African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

PubMed Central

Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi

2015-01-01

Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. PMID:25949944

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

Effects of Childhood Adversity on Bullying and Cruelty to Animals in the United States: Findings From a National Sample

PubMed Central

Vaughn, Michael G.; Fu, Qiang; Beaver, Kevin M.; DeLisi, Matt; Perron, Brian E.; Howard, Matthew O.

2012-01-01

This study examined effects of type of and cumulative burden of childhood adversities on bullying and cruelty to animals in the United States. Data were derived from Waves I and II of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of U.S. adults. Structured psychiatric interviews were completed by trained lay interviewers between 2001–2002 and 2003–2004. Although the effects of childhood adversity diminished with the inclusion of confounding variables, several adversities remained significant. For bullying, these included being made to do chores that were too difficult or dangerous, threatening to hit or throw something, pushing, shoving, slapping, or hitting, and hitting that left bruises, marks, or injuries. With respect to cruelty to animals, swearing and saying hurtful things, having a parent or other adult living within the home that went to jail or prison, and adult/other person fondling/touching in a sexual way were significant. The final models indicated that the cumulative burden of childhood adversities had strong effects on the increased likelihood of bullying behavior but not cruelty to animals. PMID:21602208

Pelvic rotation torque during fast-pitch softball hitting under three ball height conditions.

PubMed

Iino, Yoichi; Fukushima, Atsushi; Kojima, Takeji

2014-08-01

The purpose of this study was to investigate the relevance of hip joint angles to the production of the pelvic rotation torque in fast-pitch softball hitting and to examine the effect of ball height on this production. Thirteen advanced female softball players hit stationary balls at three different heights: high, middle, and low. The pelvic rotation torque, defined as the torque acting on the pelvis through the hip joints about the pelvic superior-inferior axis, was determined from the kinematic and force plate data using inverse dynamics. Irrespective of the ball heights, the rear hip extension, rear hip external rotation, front hip adduction, and front hip flexion torques contributed to the production of pelvic rotation torque. Although the contributions of the adduction and external rotation torques at each hip joint were significantly different among the ball heights, the contributions of the front and rear hip joint torques were similar among the three ball heights owing to cancelation of the two torque components. The timings of the peaks of the hip joint torque components were significantly different, suggesting that softball hitters may need to adjust the timings of the torque exertions fairly precisely to rotate the upper body effectively.

A note on the velocity derivative flatness factor in decaying HIT

NASA Astrophysics Data System (ADS)

Djenidi, L.; Danaila, L.; Antonia, R. A.; Tang, S.

2017-05-01

We develop an analytical expression for the velocity derivative flatness factor, F, in decaying homogenous and isotropic turbulence (HIT) starting with the transport equation of the third-order moment of the velocity increment and assuming self-preservation. This expression, fully consistent with the Navier-Stokes equations, relates F to the product between the second-order pressure derivative (∂2p /∂x2) and second-order moment of the longitudinal velocity derivative ((∂u/∂x ) 2), highlighting the role the pressure plays in the scaling of the fourth-order moment of the longitudinal velocity derivative. It is also shown that F has an upper bound which follows the integral of k*4Ep*(k* ) where Ep and k are the pressure spectrum and the wavenumber, respectively (the symbol * represents the Kolmogorov normalization). Direct numerical simulations of forced HIT suggest that this integral converges toward a constant as the Reynolds number increases.

Health information technology and the medical school curriculum.

PubMed

Triola, Marc M; Friedman, Erica; Cimino, Christopher; Geyer, Enid M; Wiederhorn, Jo; Mainiero, Crystal

2010-12-01

Medical schools must teach core biomedical informatics competencies that address health information technology (HIT), including explaining electronic medical record systems and computerized provider order entry systems and their role in patient safety; describing the research uses and limitations of a clinical data warehouse; understanding the concepts and importance of information system interoperability; explaining the difference between biomedical informatics and HIT; and explaining the ways clinical information systems can fail. Barriers to including these topics in the curricula include lack of teachers; the perception that informatics competencies are not applicable during preclinical courses and there is no place in the clerkships to teach them; and the legal and policy issues that conflict with students' need to develop skills. However, curricular reform efforts are creating opportunities to teach these topics with new emphasis on patient safety, team-based medical practice, and evidence-based care. Overarching HIT competencies empower our students to be lifelong technology learners.

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.

Using event-related fMRI to examine sustained attention processes and effects of APOE ε4 in young adults.

PubMed

Evans, Simon; Clarke, Devin; Dowell, Nicholas G; Tabet, Naji; King, Sarah L; Hutton, Samuel B; Rusted, Jennifer M

2018-01-01

In this study we investigated effects of the APOE ε4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimer's Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE ε4 allele, and 26 non carriers (aged 18-28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that ε4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only ε4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in ε4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult ε4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories.

Do health information technology self-management interventions improve glycemic control in medically underserved adults with diabetes? A systematic review and meta-analysis.

PubMed

Heitkemper, Elizabeth M; Mamykina, Lena; Travers, Jasmine; Smaldone, Arlene

2017-09-01

The purpose of this systematic review and meta-analysis was to examine the effect of health information technology (HIT) diabetes self-management education (DSME) interventions on glycemic control in medically underserved patients. Following an a priori protocol, 5 databases were searched. Studies were appraised for quality using the Cochrane Risk of Bias assessment. Studies reporting either hemoglobin A1c pre- and post-intervention or its change at 6 or 12 months were eligible for inclusion in the meta-analysis using random effects models. Thirteen studies met the criteria for the systematic review and 10 for the meta-analysis and represent data from 3257 adults with diabetes (mean age 55 years; 66% female; 74% racial/ethnic minorities). Most studies ( n  = 10) reflected an unclear risk of bias. Interventions varied by HIT type: computer software without Internet ( n  = 2), cellular/automated telephone ( n  = 4), Internet-based ( n  = 4), and telemedicine/telehealth ( n  = 3). Pooled A1c decreases were found at 6 months (-0.36 (95% CI, -0.53 and -0.19]; I 2  = 35.1%, Q  = 5.0), with diminishing effect at 12 months (-0.27 [95% CI, -0.49 and -0.04]; I 2  = 42.4%, Q  = 10.4). Findings suggest that medically underserved patients with diabetes achieve glycemic benefit following HIT DSME interventions, with dissipating but significant effects at 12 months. Telemedicine/telehealth interventions were the most successful HIT type because they incorporated interaction with educators similar to in-person DSME. These results are similar to in-person DSME in medically underserved patients, showing that well-designed HIT DSME has the potential to increase access and improve outcomes for this vulnerable group. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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

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.

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.