Eyewitness Identification Reforms: Are Suggestiveness-Induced Hits and Guesses True Hits?

PubMed

Wells, Gary L; Steblay, Nancy K; Dysart, Jennifer E

2012-05-01

Research-based reforms for collecting eyewitness identification evidence (e.g., unbiased pre-lineup instructions, double-blind administration) have been proposed by psychologists and adopted in increasing numbers of jurisdictions across the United States. It is well known that reducing rates of mistaken identifications can also reduce accurate identification rates (hits). But the reforms are largely designed to reduce the suggestiveness of the procedures they are meant to replace. Accordingly, we argue that it is misleading to label any hits obtained because of suggestive procedures as "hits" and then saddle reforms with the charge that they reduce the rate of these illegitimate hits. Eyewitness identification evidence should be based solely on the independent memory of the witness, not aided by biased instructions, cues from lineup administrators, or the use of lineup fillers who make the suspect stand out. Failure to call out these hits as being illegitimate can give solace to those who are motivated to preserve the status quo. © The Author(s) 2012.

"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…

Is routine voiding cystourethrogram necessary following double hit for primary vesicoureteral reflux?

PubMed

Arlen, Angela M; Scherz, Hal C; Filimon, Eleonora; Leong, Traci; Kirsch, Andrew J

2015-02-01

Current AUA guidelines recommend voiding cystourethrogram (VCUG) following endoscopic treatment of vesicoureteral reflux (VUR). We evaluated the clinical and radiographic outcomes of children undergoing Double HIT (hydrodistention implantation technique) for primary VUR to determine success rates and the necessity of postoperative VCUG. Children with a history of febrile urinary tract infection (fUTI) undergoing Double HIT for primary VUR between 2009 and 2012 were identified. Patients were prospectively classified as high or low clinical and radiographic risk. Children were categorized as high clinical risk if they had ≥ 3 fUTIs or documented bladder bowel dysfunction (BBD). High radiographic risk included those <2 years of age or with grade 4-5 VUR. Initially, all children underwent postoperative VCUG ("routine" group), while only those with an indication (high radiographic risk or clinical failure) did so during the latter portion of the study ("indicated" group). Clinical success was defined as no postoperative fUTI and radiographic success as negative postoperative VCUG. Average clinical follow-up was 34.7 ± 17.2 months. Two hundred and twenty-two children (198 girls, 24 boys) underwent Double HIT at a mean age of 4.1 ± 2.7 years. Mean maximum VUR grade was 3 ± 0.8. Sixty-eight children (30.6%) had documented BBD. Fourteen children (6.3%) experienced postoperative fUTI, for a clinical success rate of 93.7%. One hundred and fourteen patients (51.4%) underwent postoperative VCUG; 76 were "routine" and 38 were "indicated" [Figure]. Of children classified as low clinical/radiographic risk, 96.6% did not have a postoperative fUTI, compared to 91.1% for high risk patients (P = 0.771). Odds of clinical success for routine VCUG group were 9.9 times higher than for the indicated VCUG group (95% CI, 2-50). Odds of radiographic success for the routine cohort were 13 times higher than for the indicated group (95% CI, 4.2-40). Nine children (4.1%) underwent additional procedures. We found no difference in clinical success among the different risk groups; the number of children with postoperative fUTI was relatively few so there was not statistical power to discern any differences between patients who experienced clinical success versus clinical failure. However, children with an "indicated" VCUG (i.e. those less than 2 years of age, grade 4-5 VUR or those with a fUTI) were 13 times more likely to experience a radiographic failure. This cohort of 38 patients had a 50% radiographic cure rate and a 78.9% clinical cure rate, compared to the overall long-term clinical success rate of 93.7%. Our data demonstrates that we can predict failures with relatively high sensitivity, and it may therefore be prudent to selectively obtain postoperative VCUG rather than recommend it for all children undergoing dextranomer hyaluronic acid co-polymer (Dx/HA) injection. Our study has several limitations that warrant consideration. Not all children underwent a postoperative VCUG, so the true radiographic success rate is unknown. Incidence of fUTI may also be artificially low, as some radiographic failures proceeded directly to another injection or reimplantation. While we were able to demonstrate that children undergoing an "indicated" VCUG were more likely to experience radiographic failure, a larger patient cohort is necessary to determine whether age or VUR grade is more predictive of failure. Finally all patients underwent endoscopic Dx/HA injection, therefore the incidence "spontaneous resolution" is unknown. Long-term clinical success following Double HIT for the endoscopic correction of primary VUR is high, and the majority of children avoid additional procedures. Unless indicated by high-grade, young age, clinical failure, or family/surgeon preference, consideration should be given to making postoperative VCUG an option rather than a recommendation in children undergoing endoscopic treatment of primary VUR using the Double HIT method. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

A novel method for the line-of-response and time-of-flight reconstruction in TOF-PET detectors based on a library of synchronized model signals

NASA Astrophysics Data System (ADS)

Moskal, P.; Zoń, N.; Bednarski, T.; Białas, P.; Czerwiński, E.; Gajos, A.; Kamińska, D.; Kapłon, Ł.; Kochanowski, A.; Korcyl, G.; Kowal, J.; Kowalski, P.; Kozik, T.; Krzemień, W.; Kubicz, E.; Niedźwiecki, Sz.; Pałka, M.; Raczyński, L.; Rudy, Z.; Rundel, O.; Salabura, P.; Sharma, N. G.; Silarski, M.; Słomski, A.; Smyrski, J.; Strzelecki, A.; Wieczorek, A.; Wiślicki, W.; Zieliński, M.

2015-03-01

A novel method of hit time and hit position reconstruction in scintillator detectors is described. The method is based on comparison of detector signals with results stored in a library of synchronized model signals registered for a set of well-defined positions of scintillation points. The hit position is reconstructed as the one corresponding to the signal from the library which is most similar to the measurement signal. The time of the interaction is determined as a relative time between the measured signal and the most similar one in the library. A degree of similarity of measured and model signals is defined as the distance between points representing the measurement- and model-signal in the multi-dimensional measurement space. Novelty of the method lies also in the proposed way of synchronization of model signals enabling direct determination of the difference between time-of-flights (TOF) of annihilation quanta from the annihilation point to the detectors. The introduced method was validated using experimental data obtained by means of the double strip prototype of the J-PET detector and 22Na sodium isotope as a source of annihilation gamma quanta. The detector was built out from plastic scintillator strips with dimensions of 5 mm×19 mm×300 mm, optically connected at both sides to photomultipliers, from which signals were sampled by means of the Serial Data Analyzer. Using the introduced method, the spatial and TOF resolution of about 1.3 cm (σ) and 125 ps (σ) were established, respectively.

Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

PubMed

Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

2014-04-01

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for double hit and triple hit B-cell lymphomas.

PubMed

Cinar, Munevver; Rosenfelt, Fred; Rokhsar, Sepehr; Lopategui, Jean; Pillai, Raju; Cervania, Melissa; Pao, Andy; Cinar, Bekir; Alkan, Serhan

2015-07-01

Double hit lymphoma or triple hit lymphoma (DHL/THL) is a rare form of aggressive B-Cell Lymphoma. Overexpression of MYC, BCL2 or/and BCL6 due to genomic rearrangements are the key molecular features of DHL/THL. Patients with DHL/THL show very aggressive disease course and poor survival due to the lack of effective treatment modalities. Here, we established new THL cell model and assessed its in vitro growth characteristics along with the DHL cell line in response to potent MYC inhibitors, 10058-F4 and JQ-1, and a BCL2 inhibitor, ABT-199, with or without chemotherapeutic agent vincristine or doxorubicin. We found that 10058-F4, JQ-1 or ABT-199 exposure as a single agent inhibited the growth of DHL/THL cells in a dose-dependent manner. Combined exposure of 10058-F4 or JQ-1 and ABT-199 as well as vincristine or doxorubicin markedly suppressed the growth of DHL/THL cells compared with the single treatment. As assessed by multiple approaches, apoptosis induced by ABT-199, 10058-F4 or JQ-1 was underlying cause of the observed growth suppression. These findings suggest that co-inhibition of MYC and BCL2 signaling is a promising therapeutic strategy for patients with DHL/THL lymphomas. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Comparison of Video Head Impulse Test (vHIT) Gains Between Two Commercially Available Devices and by Different Gain Analytical Methods.

PubMed

Lee, Sang Hun; Yoo, Myung Hoon; Park, Jun Woo; Kang, Byung Chul; Yang, Chan Joo; Kang, Woo Suk; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

2018-06-01

To evaluate whether video head impulse test (vHIT) gains are dependent on the measuring device and method of analysis. Prospective study. vHIT was performed in 25 healthy subjects using two devices simultaneously. vHIT gains were compared between these instruments and using five different methods of comparing position and velocity gains during head movement intervals. The two devices produced different vHIT gain results with the same method of analysis. There were also significant differences in the vHIT gains measured using different analytical methods. The gain analytic method that compares the areas under the velocity curve (AUC) of the head and eye movements during head movements showed lower vHIT gains than a method that compared the peak velocities of the head and eye movements. The former method produced the vHIT gain with the smallest standard deviation among the five procedures tested in this study. vHIT gains differ in normal subjects depending on the device and method of analysis used, suggesting that it is advisable for each device to have its own normal values. Gain calculations that compare the AUC of the head and eye movements during the head movements show the smallest variance.

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.

Effects of Sweet Flavorings and Nicotine on the Appeal and Sensory Properties of e-Cigarettes Among Young Adult Vapers: Application of a Novel Methodology*

PubMed Central

Goldenson, Nicholas I.; Kirkpatrick, Matthew G.; Barrington-Trimis, Jessica L.; Pang, Raina D.; McBeth, Julia F.; Pentz, Mary Ann; Samet, Jonathan M.; Leventhal, Adam M.

2016-01-01

Introduction Product characteristics that impact e-cigarette appeal by altering the sensory experience of vaping need to be identified to formulate evidence-based regulatory policies. While products that contain sweet flavorings and produce a “throat hit” (i.e., desirable airway irritation putatively caused by nicotine) are anecdotally cited as desirable reasons for vaping among young adults, experimental evidence of their impact on user appeal is lacking. This experiment applied a novel laboratory protocol to assess whether: (1) sweet flavorings and nicotine affect e-cigarette appeal; (2) sweet flavorings increase perceived sweetness; (3) nicotine increases throat hit; and (4) perceived sweetness and throat hit are associated with appeal. Methods Young adult vapers (N=20; age 19–34) self-administered 20 standardized doses of aerosolized e-cigarette solutions varied according to a 3 flavor (sweet [e.g., cotton candy] vs. non-sweet [e.g., tobacco-flavored] vs. flavorless) × 2 nicotine (6 mg/mL nicotine vs. 0 mg/mL [placebo]) double-blind, cross-over design. Participants rated appeal (liking, willingness to use again and perceived monetary value), perceived sweetness and throat hit strength after each administration. Results Sweet-flavored (vs. non-sweet and flavorless) solutions produced greater appeal and perceived sweetness ratings. Nicotine produced greater throat hit ratings than placebo, but did not significantly increase appeal nor interact with flavor effects on appeal. Controlling for flavor and nicotine, perceived sweetness was positively associated with appeal ratings; throat hit was not positively associated with appeal. Conclusions Further identification of compounds in e-cigarette solutions that enhance sensory perceptions of sweetness, appeal, and utilization of e-cigarettes are warranted to inform evidence-based regulatory policies. PMID:27676583

Emerging Strategies in Treating Double Hit Lymphomas.

PubMed

Nabhan, Chadi; Mato, Anthony R

2017-09-01

Double hit lymphomas (DHLs) are a new category in the World Health Organization newest classification for lymphoid malignancies. DHL encompasses various histologies of lymphomas where the MYC oncogene and either BCL2 or BCL6 oncogenes are present concomitantly. Several observational studies and retrospective series have demonstrated that patients with DHL carry a poor prognosis and respond less and for a shorter duration to standard R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone). These studies have also proposed that dose intensification (with Burkitt-like regimens such as DA-EPOCH-R [dose-adjusted rituximab, etoposide, vincristine, Adriamycin, cyclophosphamide, and prednisone]) might offer patients with DHL better outcomes and improved prognosis. In this timely review, we discuss incidence of DHL, testing implications of MYC translocation, current treatment strategies, and future directions. Understanding this entity and its therapeutic consequences is essential to improve patients' outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

A double hit model for the distribution of time to AIDS onset

NASA Astrophysics Data System (ADS)

Chillale, Nagaraja Rao

2013-09-01

Incubation time is a key epidemiologic descriptor of an infectious disease. In the case of HIV infection this is a random variable and is probably the longest one. The probability distribution of incubation time is the major determinant of the relation between the incidences of HIV infection and its manifestation to Aids. This is also one of the key factors used for accurate estimation of AIDS incidence in a region. The present article i) briefly reviews the work done, points out uncertainties in estimation of AIDS onset time and stresses the need for its precise estimation, ii) highlights some of the modelling features of onset distribution including immune failure mechanism, and iii) proposes a 'Double Hit' model for the distribution of time to AIDS onset in the cases of (a) independent and (b) dependent time variables of the two markers and examined the applicability of a few standard probability models.

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

PubMed

Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation

PubMed Central

Herrera, Alex F.; Mei, Matthew; Low, Lawrence; Kim, Haesook T.; Griffin, Gabriel K.; Song, Joo Y.; Merryman, Reid W.; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R.; Budde, Lihua E.; Chan, Wing C.; Chen, Robert; Davids, Matthew S.; Freedman, Arnold S.; Fisher, David C.; Jacobsen, Eric D.; Jacobson, Caron A.; LaCasce, Ann S.; Murata-Collins, Joyce; Nademanee, Auayporn P.; Palmer, Joycelynne M.; Pihan, German A.; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R.; Zain, Jasmine; Rosen, Steven T.; Kwak, Larry W.; Weinstock, David M.; Forman, Stephen J.; Weisenburger, Dennis D.; Kim, Young; Rodig, Scott J.; Krishnan, Amrita

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% versus 67% (P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% (P = .013), and 4-year OS was 25% versus 61% (P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response (v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT. PMID:28034071

Aggressive B cell Lymphoma: Optimal Therapy for MYC-positive, Double-Hit, and Triple-Hit DLBCL.

PubMed

Dunleavy, Kieron

2015-12-01

Approximately 10% of cases of diffuse large B cell lymphoma (DLBCL) harbor a MYC rearrangement and this has been associated with an inferior outcome following standard therapy across many different studies. Double-hit and triple-hit lymphomas harbor concurrent rearrangements of MYC and BCL2 and/or BCL6 and are also associated with a very aggressive course and poor clinical outcome. It is unclear and there is lack of consensus on how these diseases should be approached therapeutically. They are characterized typically by high tumor proliferation and likely require Burkitt lymphoma-type strategies and several retrospective studies suggest that more intensive approaches than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) may be beneficial. One challenge in this respect is that most patients with these diseases are older than 60 years and generally have poor tolerability of regimens typically used in Burkitt lymphoma. Dose-adjusted EPOCH-R is an alternative effective immunochemotherapy platform for DLBCL and is effective in Burkitt lymphoma, and retrospective studies suggest that it is effective and feasible in patients with DLBCL that harbors a MYC rearrangement with or without a BCL-2 translocation (double-hit). A multicenter study of this approach in MYC-rearranged DLBCL is ongoing and preliminary results are very encouraging. There is a lack of consensus on the role of consolidation stem cell transplantation in patients who achieve a good response to initial therapy but at this point in time, no (retrospective) studies have demonstrated any benefit. These diseases are also associated with a high rate of CNS involvement and progression and checking for cerebrospinal fluid by cytology and flow cytometry at initial diagnosis should be considered. In summary, based on retrospective data and preliminary prospective data (as more mature data is awaited), while Burkitt-type regimens may be feasible in young patients, DA-EPOCH-R is a reasonable approach for patients with these diseases, particularly for those over the age of 60 years. CNS prophylaxis is a reasonable consideration (depending on clinical characteristics) given that the rate of CNS progression is high. Many exciting new small molecule inhibitors such as BCL-2 and MYC inhibitors are in development and are exciting for these diseases and attempts are underway to combine them with effective immunochemotherapy platforms.

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.

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.

[Doublehit lymphomas -  review of the literature and case report].

PubMed

Smardová, J; Moulis, M; Lišková, K; Koptíková, J; Hrabálková, R; Klusáková, J

2014-01-01

Blymphocytes are cells of the immune system responsible for the antibody  mediated immune response. As estimated, a human body can produce as much as 1011 specific antibodies. There are no specific genes coding for every individual antibody in the human genome. Discrepancy between the huge diversity of antibodies and limited coding capacity of the genome is solved by combination of unique arrangement of genetic information for immunoglobulin and unique genetic and somatic processes providing this wide spectrum of antibodies. On one side, these mechanisms represent a life protecting source of a wide spectrum of antibodies but at the same time, they can be life threatening by raising the risk of a serious tumor disease, the B cell lymphoma. Double hit lymphomas represent a specific group of B cell lymphomas often featuring concurrent rearrangements of BCL2 and MYC genes. Activation of the MYC oncogene, typical for Burkitt lymphoma (BL), causes strong stimulation of cell proliferation. High activity of BCL 2, typical for follicular lymphoma, induces resistance to apoptosis. Concurrent damage of regulation of apoptosis and proliferation is probably responsible for the typical clinical manifestation of double hit lymphomas - aggressive course, resistance to conventional chemotherapy, high-risk of early relapse, short overall survival, frequent extranodal and central nervous system involvement. Recently, these lymphomas have attracted a strong attention of researchers as they provide sharp insights into processes of lymphocytes maturing and lymphomas development and highlight the double edged nature of mechanisms allowing the antibody broad diversity. Fifty  three year  old man was diagnosed with B cell lymphoma unclassifiable with features intermediate between diffuse large B cell lymphoma (DLBCL) and BL, based on morphology and immunophenotype. Fluorescent in situ hybridization analysis revealed double hit lymphoma diagnosis as the tumor cells bear t(14;18) translocation concurrently with the MYC gene rearrangement. The patient died five months after dia-gnosis.

A "double hit" murine model for schizophrenia shows alterations in the structure and neurochemistry of the medial prefrontal cortex and the hippocampus.

PubMed

Gilabert-Juan, Javier; Belles, Maria; Saez, Ana Rosa; Carceller, Hector; Zamarbide-Fores, Sara; Moltó, Maria Dolores; Nacher, Juan

2013-11-01

Both alterations in neurodevelopment and aversive experiences during childhood and adolescence seem important risk factors for schizophrenia. Animal models reproducing these alterations mimic some of the symptoms, constituting a valid approach to study the etiopathology of this disorder. Among these models, the perinatal injection of N-methyl-d-aspartate receptor antagonists and the postweaning social isolation rearing are among the most widely used. Our aim is to combine them in a "double hit" model, which should produce a wider spectrum of alterations. Lister Hooded rats have been subjected to a single injection of MK-801 at postnatal day 7 and socially isolated from postweaning to adulthood. These animals presented increased body weight gain and volume reductions in their medial prefrontal cortex (mPFC) and hippocampus. They also showed an increased number of activated pyramidal neurons and alterations in the numbers of parvalbumin and calbindin expressing interneurons in the mPFC. The expressions of the polysialylated form of the neural cell adhesion molecule and GAD67 are decreased in the mPFC. The mRNA level of calbindin was decreased, while that of calretinin was increased in the mPFC. The mRNA level of ERbB4, a gene associated to schizophrenia, was also altered in this region. All these structural and neurochemical alterations, specially in cortical inhibitory circuits, are similar to those found in schizophrenic patients and are more numerous than in each of the single models. Consequently, the present "double hit" model may be a better tool to study the neurobiological basis of schizophrenia and to explore new therapeutic approaches. © 2013.

Double-hit lymphoma demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-hit translocations, MYC/BCL-2 and IRF4/BCL-2.

PubMed

Tabata, Rie; Yasumizu, Ryoji; Tabata, Chiharu; Kojima, Masaru

2013-01-01

Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.

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.

OLDER ADULTS: AN ENVIRONMENTALLY SUSCEPTIBLE POPULATION

EPA Science Inventory

The baby boom generation is quickly becoming the geriatric generation. The over-65 age bracket hit 13% of Americans in 1997, and is expected to reach 20% by 2030 accounting for 73 million Americans. World-wide the total number of older people (>60years) is expected to double from...

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.

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.

75 FR 62820 - Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-13

... I. Summary Synthetic biology, the developing interdisciplinary field that focuses on both the design and fabrication of novel biological components and systems as well as the re-design and fabrication of... develop, maintain, and document protocols to determine if a sequence ``hit'' qualifies as a true...

Thrombospondin 1 Wages a Double Hit Against Cancer | Center for Cancer Research

Cancer.gov

Cancer is the result of a complex series of molecular steps that promote uncontrolled growth and erode the body’s ability to fight the resulting tumor. Generating a more complete picture of these molecular events should help identify strategies to prevent and treat the disease.

Carrier transport and sensitivity issues in heterojunction with intrinsic thin layer solar cells on N-type crystalline silicon: A computer simulation study

NASA Astrophysics Data System (ADS)

Rahmouni, M.; Datta, A.; Chatterjee, P.; Damon-Lacoste, J.; Ballif, C.; Roca i Cabarrocas, P.

2010-03-01

Heterojunction with intrinsic thin layer or "HIT" solar cells are considered favorable for large-scale manufacturing of solar modules, as they combine the high efficiency of crystalline silicon (c-Si) solar cells, with the low cost of amorphous silicon technology. In this article, based on experimental data published by Sanyo, we simulate the performance of a series of HIT cells on N-type crystalline silicon substrates with hydrogenated amorphous silicon (a-Si:H) emitter layers, to gain insight into carrier transport and the general functioning of these devices. Both single and double HIT structures are modeled, beginning with the initial Sanyo cells having low open circuit voltages but high fill factors, right up to double HIT cells exhibiting record values for both parameters. The one-dimensional numerical modeling program "Amorphous Semiconductor Device Modeling Program" has been used for this purpose. We show that the simulations can correctly reproduce the electrical characteristics and temperature dependence for a set of devices with varying I-layer thickness. Under standard AM1.5 illumination, we show that the transport is dominated by the diffusion mechanism, similar to conventional P/N homojunction solar cells, and tunneling is not required to describe the performance of state-of-the art devices. Also modeling has been used to study the sensitivity of N-c-Si HIT solar cell performance to various parameters. We find that the solar cell output is particularly sensitive to the defect states on the surface of the c-Si wafer facing the emitter, to the indium tin oxide/P-a-Si:H front contact barrier height and to the band gap and activation energy of the P-a-Si:H emitter, while the I-a-Si:H layer is necessary to achieve both high Voc and fill factor, as it passivates the defects on the surface of the c-Si wafer. Finally, we describe in detail for most parameters how they affect current transport and cell properties.

Impact of normalization methods on high-throughput screening data with high hit rates and drug testing with dose-response data.

PubMed

Mpindi, John-Patrick; Swapnil, Potdar; Dmitrii, Bychkov; Jani, Saarela; Saeed, Khalid; Wennerberg, Krister; Aittokallio, Tero; Östling, Päivi; Kallioniemi, Olli

2015-12-01

Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-response experiments, which pose a more stringent requirement for data quality and for intra- and inter-plate variation. Here, we compared common plate normalization and noise-reduction methods, including the B-score and the Loess a local polynomial fit method under high hit-rate scenarios of drug sensitivity testing. We generated simulated 384-well plate HTS datasets, each with 71 plates having a range of 20 (5%) to 160 (42%) hits per plate, with controls placed either at the edge of the plates or in a scattered configuration. We identified 20% (77/384) as the critical hit-rate after which the normalizations started to perform poorly. Results from real drug testing experiments supported this estimation. In particular, the B-score resulted in incorrect normalization of high hit-rate plates, leading to poor data quality, which could be attributed to its dependency on the median polish algorithm. We conclude that a combination of a scattered layout of controls per plate and normalization using a polynomial least squares fit method, such as Loess helps to reduce column, row and edge effects in HTS experiments with high hit-rates and is optimal for generating accurate dose-response curves. john.mpindi@helsinki.fi. Supplementary information: R code and Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Double-hit mouse model of cigarette smoke priming for acute lung injury.

PubMed

Sakhatskyy, Pavlo; Wang, Zhengke; Borgas, Diana; Lomas-Neira, Joanne; Chen, Yaping; Ayala, Alfred; Rounds, Sharon; Lu, Qing

2017-01-01

Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals.

Double-hit mouse model of cigarette smoke priming for acute lung injury

PubMed Central

Sakhatskyy, Pavlo; Wang, Zhengke; Borgas, Diana; Lomas-Neira, Joanne; Chen, Yaping; Ayala, Alfred; Rounds, Sharon

2016-01-01

Epidemiological studies indicate that cigarette smoking (CS) increases the risk and severity of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The mechanism is not understood, at least in part because of lack of animal models that reproduce the key features of the CS priming process. In this study, using two strains of mice, we characterized a double-hit mouse model of ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6 and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before intratracheal instillation of LPS and ALI was assessed 18 h after LPS administration by measuring lung static compliance, lung edema, vascular permeability, inflammation, and alveolar apoptosis. We found that as little as 3 h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar exacerbating effects were observed after 3 wk of preexposure to CS. However, there was a strain difference in susceptibility to CS priming for ALI, with a greater effect in AKR mice. The key features we observed suggest that 3 wk of CS preexposure of AKR mice is a reproducible, clinically relevant animal model that is useful for studying mechanisms and treatment of CS priming for a second-hit-induced ALI. Our data also support the concept that increased susceptibility to ALI/ARDS is an important adverse health consequence of CS exposure that needs to be taken into consideration when treating critically ill individuals. PMID:27864287

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.

Clustered DNA damages induced by high and low LET radiation, including heavy ions

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

2001-01-01

Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

Interventional Catheterization Combined with Staphylococcin Aureus Injection in 112 Cases of Ischemic Necrosis of Femoral Heads.

PubMed

Liang, Junkui; Jiang, Xiliang; Zhang, Xiulin; Cao, Wendong; Wang, Yong; Han, Jie

2015-11-01

The objective of this study was to investigate the effectiveness of interventional catheterization with staphylococcin aureus injection on ischemic necrosis of the femoral heads. By percutaneous catheterization of the femoral artery, papaverine, urokinase, compound Danshen, and anisodamine were injected intravenously into the arteries of the femoral head. Staphylococcin aureus injection was injected into the hit joint capsule on the side of the lesion to compare the conditions before and after surgery. The patients did the rehabilitation exercises of the hit joint 48 h after the surgery and had double crutches for 3-6 months. Of the 112 cases, 39 cases (34.8 %) were cured, 51 cases (45.6 %) were markedly effective, and 22 cases (19.6 %) were effective. Interventional catheterization combined with staphylococcin aureus injection given into the hit joint capsule is an effective way to treat ischemic necrosis of the femoral head by influencing the internal and external environments of the femoral head.

Effects of 12 weeks high-intensity & reduced-volume training in elite athletes.

PubMed

Kilen, Anders; Larsson, Tanja Hultengren; Jørgensen, Majke; Johansen, Lars; Jørgensen, Susanne; Nordsborg, Nikolai B

2014-01-01

It was investigated if high-intensity interval training (HIT) at the expense of total training volume improves performance, maximal oxygen uptake and swimming economy. 41 elite swimmers were randomly allocated to a control (CON) or HIT group. For 12 weeks both groups trained ∼12 h per week. HIT comprised ∼5 h vs. 1 h and total distance was ∼17 km vs. 35 km per week for HIT and CON, respectively. HIT was performed as 6-10×10-30 s maximal effort interspersed by 2-4 minutes of rest. Performance of 100 m all-out freestyle and 200 m freestyle was similar before and after the intervention in both HIT (60.4±4.0 vs. 60.3±4.0 s; n = 13 and 133.2±6.4 vs. 132.6±7.7 s; n = 14) and CON (60.2±3.7 vs. 60.6±3.8 s; n = 15 and 133.5±7.0 vs. 133.3±7.6 s; n = 15). Maximal oxygen uptake during swimming was similar before and after the intervention in both the HIT (4.0±0.9 vs. 3.8±1.0 l O2×min-1; n = 14) and CON (3.8±0.7 vs. 3.8±0.7 l O2×min-1; n = 11) group. Oxygen uptake determined at fixed submaximal speed was not significantly affected in either group by the intervention. Body fat % tended to increase (P = 0.09) in the HIT group (15.4±1.6% vs. 16.3±1.6%; P = 0.09; n = 16) and increased (P<0.05) in the CON group (13.9±1.5% vs. 14.9±1.5%; n = 17). A distance reduction of 50% and a more than doubled HIT amount for 12 weeks did neither improve nor compromise performance or physiological capacity in elite swimmers.

Effects of 12 Weeks High-Intensity & Reduced-Volume Training in Elite Athletes

PubMed Central

Kilen, Anders; Larsson, Tanja Hultengren; Jørgensen, Majke; Johansen, Lars; Jørgensen, Susanne; Nordsborg, Nikolai B.

2014-01-01

It was investigated if high-intensity interval training (HIT) at the expense of total training volume improves performance, maximal oxygen uptake and swimming economy. 41 elite swimmers were randomly allocated to a control (CON) or HIT group. For 12 weeks both groups trained ∼12 h per week. HIT comprised ∼5 h vs. 1 h and total distance was ∼17 km vs. 35 km per week for HIT and CON, respectively. HIT was performed as 6-10×10-30 s maximal effort interspersed by 2–4 minutes of rest. Performance of 100 m all-out freestyle and 200 m freestyle was similar before and after the intervention in both HIT (60.4±4.0 vs. 60.3±4.0 s; n = 13 and 133.2±6.4 vs. 132.6±7.7 s; n = 14) and CON (60.2±3.7 vs. 60.6±3.8 s; n = 15 and 133.5±7.0 vs. 133.3±7.6 s; n = 15). Maximal oxygen uptake during swimming was similar before and after the intervention in both the HIT (4.0±0.9 vs. 3.8±1.0 l O2×min−1; n = 14) and CON (3.8±0.7 vs. 3.8±0.7 l O2×min−1; n = 11) group. Oxygen uptake determined at fixed submaximal speed was not significantly affected in either group by the intervention. Body fat % tended to increase (P = 0.09) in the HIT group (15.4±1.6% vs. 16.3±1.6%; P = 0.09; n = 16) and increased (P<0.05) in the CON group (13.9±1.5% vs. 14.9±1.5%; n = 17). A distance reduction of 50% and a more than doubled HIT amount for 12 weeks did neither improve nor compromise performance or physiological capacity in elite swimmers. PMID:24736598

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

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

PubMed

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

2016-09-22

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

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

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.

Enhanced HTS hit selection via a local hit rate analysis.

PubMed

Posner, Bruce A; Xi, Hualin; Mills, James E J

2009-10-01

The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however, this approach is insensitive to both false positives and false negatives. An alternative method that can minimize the occurrence of these artifacts will increase the efficiency of hit selection and therefore lead discovery. In this work, rather than merely using the activity of a given compound, we look at the presence and absence of activity among all compounds in its "chemical space neighborhood" to give a degree of confidence in its activity. We demonstrate that this local hit rate (LHR) analysis method outperforms hit selection based on ranking by primary screen activity values across ten diverse high throughput screens, spanning both cell-based and biochemical assay formats of varying biology and robustness. On average, the local hit rate analysis method was approximately 2.3-fold and approximately 1.3-fold more effective in identifying active compounds and active chemical series, respectively, than selection based on primary activity alone. Moreover, when applied to finding false negatives, this method was 2.3-fold better than ranking by primary activity alone. In most cases, novel hit series were identified that would have otherwise been missed. Additional uses of and observations regarding this HTS analysis approach are also discussed.

Sex Differences in Internalizing Problems during Adolescence in Autism Spectrum Disorder

ERIC Educational Resources Information Center

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

2016-01-01

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

South Korean Students, Hit Hard by Currency Decline, Opt to Stay Home

ERIC Educational Resources Information Center

McNeill, David

2009-01-01

It is too early to predict enrollment numbers for international students in the United States this fall, but universities in Asia are already seeing big declines among South Koreans studying abroad. The value of South Korea's currency has dropped sharply in recent months, almost doubling the cost of living abroad for South Korean students and…

Effects of sweet flavorings and nicotine on the appeal and sensory properties of e-cigarettes among young adult vapers: Application of a novel methodology.

PubMed

Goldenson, Nicholas I; Kirkpatrick, Matthew G; Barrington-Trimis, Jessica L; Pang, Raina D; McBeth, Julia F; Pentz, Mary Ann; Samet, Jonathan M; Leventhal, Adam M

2016-11-01

Product characteristics that impact e-cigarette appeal by altering the sensory experience of vaping need to be identified to formulate evidence-based regulatory policies. While products that contain sweet flavorings and produce a "throat hit" (i.e., desirable airway irritation putatively caused by nicotine) are anecdotally cited as desirable reasons for vaping among young adults, experimental evidence of their impact on user appeal is lacking. This experiment applied a novel laboratory protocol to assess whether: (1) sweet flavorings and nicotine affect e-cigarette appeal; (2) sweet flavorings increase perceived sweetness; (3) nicotine increases throat hit; and (4) perceived sweetness and throat hit are associated with appeal. Young adult vapers (N=20; age 19-34) self-administered 20 standardized doses of aerosolized e-cigarette solutions varied according to a 3 flavor (sweet [e.g., cotton candy] vs. non-sweet [e.g., tobacco-flavored] vs. flavorless)×2 nicotine (6mg/mL nicotine vs. 0mg/mL [placebo]) double-blind, cross-over design. Participants rated appeal (liking, willingness to use again and perceived monetary value), perceived sweetness and throat hit strength after each administration. Sweet-flavored (vs. non-sweet and flavorless) solutions produced greater appeal and perceived sweetness ratings. Nicotine produced greater throat hit ratings than placebo, but did not significantly increase appeal nor interact with flavor effects on appeal. Controlling for flavor and nicotine, perceived sweetness was positively associated with appeal ratings; throat hit was not positively associated with appeal. Further identification of compounds in e-cigarette solutions that enhance sensory perceptions of sweetness, appeal, and utilization of e-cigarettes are warranted to inform evidence-based regulatory policies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Suicide and the Internet: Changes in the accessibility of suicide-related information between 2007 and 2014.

PubMed

Biddle, Lucy; Derges, Jane; Mars, Becky; Heron, Jon; Donovan, Jenny L; Potokar, John; Piper, Martyn; Wyllie, Clare; Gunnell, David

2016-01-15

Following the ongoing concerns about cyber-suicide, we investigate changes between 2007 and 2014 in material likely to be accessed by suicidal individuals searching for methods of suicide. 12 search terms relating to suicide methods were applied to four search engines and the top ten hits from each were categorised and analysed for content. The frequency of each category of site across all searches, using particular search terms and engines, was counted. Key changes: growth of blogs and discussion forums (from 3% of hits, 2007 to 18.5% of hits, 2014); increase in hits linking to general information sites - especially factual sites that detail and evaluate suicide methods (from 9%, 2007 to 21.7%, 2014). Hits for dedicated suicide sites increased (from 19% to 23%), while formal help sites were less visible (from 13% to 6.5%). Overall, 54% of hits contained information about new high-lethality methods. We did not search for help sites so cannot assess the balance of suicide promoting versus preventing sites available online. Social media was beyond the scope of this study. Working with ISPs and search engines would help optimise support sites. Better site moderation and implementation of suicide reporting guidelines should be encouraged. Copyright © 2015 Elsevier B.V. All rights reserved.

Differentiating between child protection and family support in the Canadian child welfare system's response to intimate partner violence, corporal punishment, and child neglect.

PubMed

Trocmé, Nico; Fallon, Barbara; Sinha, Vandna; Van Wert, Melissa; Kozlowski, Anna; Maclaurin, Bruce

2013-01-01

Rates of reported child maltreatment nearly doubled in Canada over the period 1998-2003, an increase that reflects growing awareness of the harmful effects of an expanding array of parental behaviors, including corporal punishment, lack of supervision, and exposure to intimate partner violence (IPV). Some of these situations may benefit from voluntary family support programs outside of the child welfare system. Analyzing a sample of 11,807 investigations, this paper compares cases where the sole concern is exposure to IPV, or hitting a child, or neglect, or other forms of investigated maltreatment. Situations where exposure to IPV or potentially abusive hitting were the sole reason for investigation presented with fewer risk factors and were less likely to lead to ongoing child welfare interventions compared to other maltreatment investigations. While situations involving alleged neglect presented a higher risk profile and elicited a more intensive child welfare response than did exposure to IPV or hitting, opportunities for alternative services were nevertheless identified. The study also found that visible minority families were overrepresented in cases involving hitting and that Aboriginal families were overrepresented in cases involving neglect. Overall the findings support the development of alternative response programs in Canada.

Monte Carlo-based parametrization of the lateral dose spread for clinical treatment planning of scanned proton and carbon ion beams.

PubMed

Parodi, Katia; Mairani, Andrea; Sommerer, Florian

2013-07-01

Ion beam therapy using state-of-the-art pencil-beam scanning offers unprecedented tumour-dose conformality with superior sparing of healthy tissue and critical organs compared to conventional radiation modalities for external treatment of deep-seated tumours. For inverse plan optimization, the commonly employed analytical treatment-planning systems (TPSs) have to meet reasonable compromises in the accuracy of the pencil-beam modelling to ensure good performances in clinically tolerable execution times. In particular, the complex lateral spreading of ion beams in air and in the traversed tissue is typically approximated with ideal Gaussian-shaped distributions, enabling straightforward superimposition of several scattering contributions. This work presents the double Gaussian parametrization of scanned proton and carbon ion beams in water that has been introduced in an upgraded version of the worldwide first commercial ion TPS for clinical use at the Heidelberg Ion Beam Therapy Center (HIT). First, the Monte Carlo results obtained from a detailed implementation of the HIT beamline have been validated against available experimental data. Then, for generating the TPS lateral parametrization, radial beam broadening has been calculated in a water target placed at a representative position after scattering in the beamline elements and air for 20 initial beam energies for each ion species. The simulated profiles were finally fitted with an idealized double Gaussian distribution that did not perfectly describe the nature of the data, thus requiring a careful choice of the fitting conditions. The obtained parametrization is in clinical use not only at the HIT center, but also at the Centro Nazionale di Adroterapia Oncologica.

Monte Carlo-based parametrization of the lateral dose spread for clinical treatment planning of scanned proton and carbon ion beams

PubMed Central

Parodi, Katia; Mairani, Andrea; Sommerer, Florian

2013-01-01

Ion beam therapy using state-of-the-art pencil-beam scanning offers unprecedented tumour-dose conformality with superior sparing of healthy tissue and critical organs compared to conventional radiation modalities for external treatment of deep-seated tumours. For inverse plan optimization, the commonly employed analytical treatment-planning systems (TPSs) have to meet reasonable compromises in the accuracy of the pencil-beam modelling to ensure good performances in clinically tolerable execution times. In particular, the complex lateral spreading of ion beams in air and in the traversed tissue is typically approximated with ideal Gaussian-shaped distributions, enabling straightforward superimposition of several scattering contributions. This work presents the double Gaussian parametrization of scanned proton and carbon ion beams in water that has been introduced in an upgraded version of the worldwide first commercial ion TPS for clinical use at the Heidelberg Ion Beam Therapy Center (HIT). First, the Monte Carlo results obtained from a detailed implementation of the HIT beamline have been validated against available experimental data. Then, for generating the TPS lateral parametrization, radial beam broadening has been calculated in a water target placed at a representative position after scattering in the beamline elements and air for 20 initial beam energies for each ion species. The simulated profiles were finally fitted with an idealized double Gaussian distribution that did not perfectly describe the nature of the data, thus requiring a careful choice of the fitting conditions. The obtained parametrization is in clinical use not only at the HIT center, but also at the Centro Nazionale di Adroterapia Oncologica. PMID:23824133

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.

Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

PubMed Central

2015-01-01

Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets. PMID:25189630

Building a Future: Interim Impact Findings from the YouthBuild Evaluation

ERIC Educational Resources Information Center

Miller, Cynthia; Millenky, Megan; Schwartz, Lisa; Goble, Lisbeth; Stein, Jillian

2016-01-01

Young people have been hit especially hard by changes in the labor market over the past decades. Unemployment among 16- to 24-year-olds increased the most of any age group during the recent recession, and remains more than double that among older adults. The unemployment rate is especially high for young people without high school diplomas.…

Aggressive B-cell lymphomas in the update of the 4th edition of the World Health Organization classification of haematopoietic and lymphatic tissues: refinements of the classification, new entities and genetic findings.

PubMed

Ott, German

2017-09-01

The update of the 4th edition of the World Health Organization Classification of Haematopoietic and Lymphatic Tissues portends important new findings and concepts in the diagnosis, classification and biology of lymphomas. This review summarizes the basic concepts and cornerstones of the classification of aggressive B-cell lymphomas and details the major changes. Of importance, there is a new concept of High-grade B-cell lymphomas (HGBL), partly replacing the provisional entity of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, the so-called grey zone lymphomas. They either harbour MYC translocations together with a BCL2 and/or a BCL6 rearrangement (HGBL-Double Hit) or HGBL, not otherwise specified (NOS), lacking a double or triple hit constellation. In addition, the requirement for providing the cell-of-origin classification in the diagnostic work-up of DLBCLs, the role of MYC alterations in DLBCL subtypes, and newer findings in the specific variants/subtypes are highlighted. © 2017 John Wiley & Sons Ltd.

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

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.

Scintillating fibres coupled to silicon photomultiplier prototypes for fast beam monitoring and thin timing detectors

NASA Astrophysics Data System (ADS)

Papa, A.; Kettle, P.-R.; Ripiccini, E.; Rutar, G.

2016-07-01

Several scintillating fibre prototypes (single- and double-layers) made of 250 μm multi-clad square fibres coupled to silicon photomultiplier have been studied using electrons, positrons and muons at different energies. Current measurements show promising results: already for a single fibre layer and minimum ionizing particles we obtain a detection efficiency ≥ 95 % (mean collected light/fibre ≈ 8 phe), a timing resolution of 550 ps/fibre and a foreseen spatial resolution < 100 μm, based on the achieved negligible optical cross-talk between fibres (< 1 %). We will also discuss the performances of a double-layer staggered prototype configuration, for which a full detection efficiency (≥ 99 %) has been measured together with a timing resolution of ≈ 400 ps for double hit events.

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

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

Dimensional measurement of micro parts with high aspect ratio in HIT-UOI

NASA Astrophysics Data System (ADS)

Dang, Hong; Cui, Jiwen; Feng, Kunpeng; Li, Junying; Zhao, Shiyuan; Zhang, Haoran; Tan, Jiubin

2016-11-01

Micro parts with high aspect ratios have been widely used in different fields including aerospace and defense industries, while the dimensional measurement of these micro parts becomes a challenge in the field of precision measurement and instrument. To deal with this contradiction, several probes for the micro parts precision measurement have been proposed by researchers in Center of Ultra-precision Optoelectronic Instrument (UOI), Harbin Institute of Technology (HIT). In this paper, optical fiber probes with structures of spherical coupling(SC) with double optical fibers, micro focal-length collimation (MFL-collimation) and fiber Bragg grating (FBG) are described in detail. After introducing the sensing principles, both advantages and disadvantages of these probes are analyzed respectively. In order to improve the performances of these probes, several approaches are proposed. A two-dimensional orthogonal path arrangement is propounded to enhance the dimensional measurement ability of MFL-collimation probes, while a high resolution and response speed interrogation method based on differential method is used to improve the accuracy and dynamic characteristics of the FBG probes. The experiments for these special structural fiber probes are given with a focus on the characteristics of these probes, and engineering applications will also be presented to prove the availability of them. In order to improve the accuracy and the instantaneity of the engineering applications, several techniques are used in probe integration. The effectiveness of these fiber probes were therefore verified through both the analysis and experiments.

Symmetric vs. Asymmetric Stem Cell Divisions: An Adaptation against Cancer?

PubMed Central

Shahriyari, Leili; Komarova, Natalia L.

2013-01-01

Traditionally, it has been held that a central characteristic of stem cells is their ability to divide asymmetrically. Recent advances in inducible genetic labeling provided ample evidence that symmetric stem cell divisions play an important role in adult mammalian homeostasis. It is well understood that the two types of cell divisions differ in terms of the stem cells' flexibility to expand when needed. On the contrary, the implications of symmetric and asymmetric divisions for mutation accumulation are still poorly understood. In this paper we study a stochastic model of a renewing tissue, and address the optimization problem of tissue architecture in the context of mutant production. Specifically, we study the process of tumor suppressor gene inactivation which usually takes place as a consequence of two “hits”, and which is one of the most common patterns in carcinogenesis. We compare and contrast symmetric and asymmetric (and mixed) stem cell divisions, and focus on the rate at which double-hit mutants are generated. It turns out that symmetrically-dividing cells generate such mutants at a rate which is significantly lower than that of asymmetrically-dividing cells. This result holds whether single-hit (intermediate) mutants are disadvantageous, neutral, or advantageous. It is also independent on whether the carcinogenic double-hit mutants are produced only among the stem cells or also among more specialized cells. We argue that symmetric stem cell divisions in mammals could be an adaptation which helps delay the onset of cancers. We further investigate the question of the optimal fraction of stem cells in the tissue, and quantify the contribution of non-stem cells in mutant production. Our work provides a hypothesis to explain the observation that in mammalian cells, symmetric patterns of stem cell division seem to be very common. PMID:24204602

Acute Effects of Mecamylamine and Varenicline on Cognitive Performance in Non-smokers With and Without Schizophrenia

PubMed Central

Roh, Sungwon; Hoeppner, Susanne S.; Schoenfeld, David; Fullerton, Catherine A.; Stoeckel, Luke E.; Evins, A. Eden

2013-01-01

Rationale Nicotinic acetylcholine receptors (nAChRs) have been implicated in the pathophysiology of cognitive deficits in the domains of attention and memory in schizophrenia. While nicotinic agonists and antagonists have been proposed as smoking cessation aids, few comparisons have been made of these agents on cognitive performance in individuals with schizophrenia. Objectives This study investigated the acute effects of a nAChR antagonist, mecamylamine, and partial agonist, varenicline, on cognitive function in non-smokers with and without schizophrenia. Methods Single oral doses of mecamylamine, 10 mg, varenicline, 1 mg, and placebo were administered, one week apart, in random order to adults with schizophrenia (n=30) and to healthy volunteers (n=41) in a double-blind, crossover design. The primary outcome of interest was sustained attention as assessed with hit reaction time variability (HRT-SD) on the identical pairs continuous performance test (CPT-IP). Results Mecamylamine worsened performance on CPT-IP HRT-SD, a measure of attention, compared to varenicline in both groups. Performance on mecamylamine was worse than performance on both placebo and varenicline on several additional measures of attention, including CPT-IP hit reaction time (HRT) and random errors at various levels of task difficulty. There was a treatment by diagnosis interaction, such that mecamylamine worsened performance on CPT-IP 2-digit HRT, 3-digit random errors, and 4-digit hit rate compared to placebo and varenicline in participants with schizophrenia, effects not observed in controls. Conclusions These findings support a role for nAChR’s in attention and suggest that those with schizophrenia may be particularly sensitive to nAChR blockade. PMID:24114425

Hitting the Goalpost: Calculating the Fine Line Between Winning and Losing a Penalty Shootout

ERIC Educational Resources Information Center

Widenhorn, Ralf

2016-01-01

The Portland Timbers won their first Major League Soccer (MLS) Cup Championship in December 2015. However, if it had not been for a kind double goalpost miss during a penalty shootout a few weeks earlier, the Timbers would never have been in the finals. On Oct. 30th, after what has been called "the greatest penalty kick shootout in MLS…

Public Debt: Private Asset. Government Debt and Its Role in the Economy.

ERIC Educational Resources Information Center

Schilling, Tim

In 1981, the United States reached a dubious economic milestone--the federal debt surpassed one trillion dollars for the first time. It took more than 200 years to build up that much debt. The federal debt doubled to two trillion by 1986, hit the three trillion level in 1990, and stands at an estimated five-and-a-half trillion for 1998. Just as…

Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel

PubMed Central

Pietrofesa, Ralph A.; Velalopoulou, Anastasia; Lehman, Stacey L.; Arguiri, Evguenia; Solomides, Pantelis; Koch, Cameron J.; Mishra, Om P.; Koumenis, Constantinos; Goodwin, Thomas J.; Christofidou-Solomidou, Melpo

2016-01-01

Spaceflight occasionally requires multiple extravehicular activities (EVA) that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10) were exposed to >95% O2 for 8 h only (O2), 0.25 Gy ionizing γ-radiation (IR) only, or a double-hit combination of both challenges (O2 + IR) followed by 16 h of normoxia (ambient air containing 21% O2 and 5% CO2) (1 cycle = 24 h, 2 cycles = 48 h). Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05) decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP), apoptotic (cleaved caspase-3 and BAX), and antioxidant (HO-1 and Nqo1) proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O2 + IR exacerbated cell death and DNA damage compared to individual exposures O2 or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia exposure that leads to oxidative lung cell injury, DNA damage, apoptosis, and cell cycle arrest. PMID:27322243

Novel Double-Hit Model of Radiation and Hyperoxia-Induced Oxidative Cell Damage Relevant to Space Travel.

PubMed

Pietrofesa, Ralph A; Velalopoulou, Anastasia; Lehman, Stacey L; Arguiri, Evguenia; Solomides, Pantelis; Koch, Cameron J; Mishra, Om P; Koumenis, Constantinos; Goodwin, Thomas J; Christofidou-Solomidou, Melpo

2016-06-16

Spaceflight occasionally requires multiple extravehicular activities (EVA) that potentially subject astronauts to repeated changes in ambient oxygen superimposed on those of space radiation exposure. We thus developed a novel in vitro model system to test lung cell damage following repeated exposure to radiation and hyperoxia. Non-tumorigenic murine alveolar type II epithelial cells (C10) were exposed to >95% O₂ for 8 h only (O₂), 0.25 Gy ionizing γ-radiation (IR) only, or a double-hit combination of both challenges (O₂ + IR) followed by 16 h of normoxia (ambient air containing 21% O₂ and 5% CO₂) (1 cycle = 24 h, 2 cycles = 48 h). Cell survival, DNA damage, apoptosis, and indicators of oxidative stress were evaluated after 1 and 2 cycles of exposure. We observed a significant (p < 0.05) decrease in cell survival across all challenge conditions along with an increase in DNA damage, determined by Comet analysis and H2AX phosphorylation, and apoptosis, determined by Annexin-V staining, relative to cells unexposed to hyperoxia or radiation. DNA damage (GADD45α and cleaved-PARP), apoptotic (cleaved caspase-3 and BAX), and antioxidant (HO-1 and Nqo1) proteins were increased following radiation and hyperoxia exposure after 1 and 2 cycles of exposure. Importantly, exposure to combination challenge O₂ + IR exacerbated cell death and DNA damage compared to individual exposures O₂ or IR alone. Additionally levels of cell cycle proteins phospho-p53 and p21 were significantly increased, while levels of CDK1 and Cyclin B1 were decreased at both time points for all exposure groups. Similarly, proteins involved in cell cycle arrest was more profoundly changed with the combination challenges as compared to each stressor alone. These results correlate with a significant 4- to 6-fold increase in the ratio of cells in G2/G1 after 2 cycles of exposure to hyperoxic conditions. We have characterized a novel in vitro model of double-hit, low-level radiation and hyperoxia exposure that leads to oxidative lung cell injury, DNA damage, apoptosis, and cell cycle arrest.

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

DOE PAGES

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

2017-09-01

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

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

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

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

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

Multiple-hit parameter estimation in monolithic detectors.

PubMed

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

2013-02-01

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

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…

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.

Bridging the Digital Divide in Diabetes: Family Support and Implications for Health Literacy

PubMed Central

Mayberry, Lindsay S.; Kripalani, Sunil; Rothman, Russell L.

2011-01-01

Abstract Background Patient web portals (PWPs) offer patients remote access to their medical record and communication with providers. Adults with health literacy limitations are less likely to access and use health information technology (HIT), including PWPs. In diabetes, PWP use has been associated with patient satisfaction, patient–provider communication, and glycemic control. Methods Using mixed methods, we explored the relationships between health literacy, numeracy, and computer literacy and the usage of a PWP and HIT. Participants (N=61 adults with type 2 diabetes) attended focus groups and completed surveys, including measures of health literacy, numeracy, and computer anxiety (an indicator of computer literacy) and frequency of PWP and HIT use. Results Computer literacy was positively associated with health literacy (r=0.41, P<0.001) and numeracy (r=0.35, P<0.001), but health literacy was not associated with numeracy. Participants with limited health literacy (23%), numeracy (43%), or computer literacy (25%) were no less likely to access PWPs or HIT, but lower health literacy was associated with less frequent use of a computer to research diabetes medications or treatments. In focus groups, participants spontaneously commented on family support when accessing and using PWPs or HIT for diabetes management. Conclusions Participants reported family members facilitated access and usage of HIT, taught them usage skills, and acted as online delegates. Participant statements suggest family members may bridge the HIT “digital divide” in diabetes by helping adults access a PWP or HIT for diabetes management. PMID:21718098

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).

Multiple-Hit Parameter Estimation in Monolithic Detectors

PubMed Central

Barrett, Harrison H.; Lewellen, Tom K.; Miyaoka, Robert S.

2014-01-01

We examine a maximum-a-posteriori method for estimating the primary interaction position of gamma rays with multiple interaction sites (hits) in a monolithic detector. In assessing the performance of a multiple-hit estimator over that of a conventional one-hit estimator, we consider a few different detector and readout configurations of a 50-mm-wide square cerium-doped lutetium oxyorthosilicate block. For this study, we use simulated data from SCOUT, a Monte-Carlo tool for photon tracking and modeling scintillation- camera output. With this tool, we determine estimate bias and variance for a multiple-hit estimator and compare these with similar metrics for a one-hit maximum-likelihood estimator, which assumes full energy deposition in one hit. We also examine the effect of event filtering on these metrics; for this purpose, we use a likelihood threshold to reject signals that are not likely to have been produced under the assumed likelihood model. Depending on detector design, we observe a 1%–12% improvement of intrinsic resolution for a 1-or-2-hit estimator as compared with a 1-hit estimator. We also observe improved differentiation of photopeak events using a 1-or-2-hit estimator as compared with the 1-hit estimator; more than 6% of photopeak events that were rejected by likelihood filtering for the 1-hit estimator were accurately identified as photopeak events and positioned without loss of resolution by a 1-or-2-hit estimator; for PET, this equates to at least a 12% improvement in coincidence-detection efficiency with likelihood filtering applied. PMID:23193231

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.

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

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.

Added value of double reading in diagnostic radiology,a systematic review.

PubMed

Geijer, Håkan; Geijer, Mats

2018-06-01

Double reading in diagnostic radiology can find discrepancies in the original report, but a systematic program of double reading is resource consuming. There are conflicting opinions on the value of double reading. The purpose of the current study was to perform a systematic review on the value of double reading. A systematic review was performed to find studies calculating the rate of misses and overcalls with the aim of establishing the added value of double reading by human observers. The literature search resulted in 1610 hits. After abstract and full-text reading, 46 articles were selected for analysis. The rate of discrepancy varied from 0.4 to 22% depending on study setting. Double reading by a sub-specialist, in general, led to high rates of changed reports. The systematic review found rather low discrepancy rates. The benefit of double reading must be balanced by the considerable number of working hours a systematic double-reading scheme requires. A more profitable scheme might be to use systematic double reading for selected, high-risk examination types. A second conclusion is that there seems to be a value of sub-specialisation for increased report quality. A consequent implementation of this would have far-reaching organisational effects. • In double reading, two or more radiologists read the same images. • A systematic literature review was performed. • The discrepancy rates varied from 0.4 to 22% in various studies. • Double reading by sub-specialists found high discrepancy rates.

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.

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.

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

When does adoption of health information technology by physician practices lead to use by physicians within the practice?

PubMed Central

McClellan, Sean R; Casalino, Lawrence P; Shortell, Stephen M; Rittenhouse, Diane R

2013-01-01

Objective We sought to determine the extent to which adoption of health information technology (HIT) by physician practices may differ from the extent of use by individual physicians, and to examine factors associated with adoption and use. Materials and methods Using cross-sectional survey data from the National Study of Small and Medium-Sized Physician Practices (July 2007–March 2009), we examined the extent to which organizational capabilities and external incentives were associated with the adoption of five key HIT functionalities by physician practices and with use of those functionalities by individual physicians. Results The rate of physician practices adopting any of the five HIT functionalities was 34.1%. When practices adopted HIT functionalities, on average, about one in seven physicians did not use those functionalities. One physician in five did not use prompts and reminders following adoption by their practice. After controlling for other factors, both adoption of HIT by practices and use of HIT by individual physicians were higher in primary care practices and larger practices. Practices reporting an emphasis on patient-centered management were not more likely than others to adopt, but their physicians were more likely to use HIT. Discussion Larger practices were most likely to have adopted HIT, but other factors, including specialty mix and self-reported patient-centered management, had a stronger influence on the use of HIT once adopted. Conclusions Adoption of HIT by practices does not mean that physicians will use the HIT. PMID:23396512

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

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.

Using Eye Trackers for Usability Evaluation of Health Information Technology: A Systematic Literature Review

PubMed Central

Yang, Yushi

2015-01-01

Background Eye-tracking technology has been used to measure human cognitive processes and has the potential to improve the usability of health information technology (HIT). However, it is still unclear how the eye-tracking method can be integrated with other traditional usability methodologies to achieve its full potential. Objective The objective of this study was to report on HIT evaluation studies that have used eye-tracker technology, and to envision the potential use of eye-tracking technology in future research. Methods We used four reference databases to initially identify 5248 related papers, which resulted in only 9 articles that met our inclusion criteria. Results Eye-tracking technology was useful in finding usability problems in many ways, but is still in its infancy for HIT usability evaluation. Limited types of HITs have been evaluated by eye trackers, and there has been a lack of evaluation research in natural settings. Conclusions More research should be done in natural settings to discover the real contextual-based usability problems of clinical and mobile HITs using eye-tracking technology with more standardized methodologies and guidance. PMID:27026079

A Pixel Correlation Technique for Smaller Telescopes to Measure Doubles

NASA Astrophysics Data System (ADS)

Wiley, E. O.

2013-04-01

Pixel correlation uses the same reduction techniques as speckle imaging but relies on autocorrelation among captured pixel hits rather than true speckles. A video camera operating at speeds (8-66 milliseconds) similar to lucky imaging to capture 400-1,000 video frames. The AVI files are converted to bitmap images and analyzed using the interferometric algorithms in REDUC using all frames. This results in a series of corellograms from which theta and rho can be measured. Results using a 20 cm (8") Dall-Kirkham working at f22.5 are presented for doubles with separations between 1" to 5.7" under average seeing conditions. I conclude that this form of visualizing and analyzing visual double stars is a viable alternative to lucky imaging that can be employed by telescopes that are too small in aperture to capture a sufficient number of speckles for true speckle interferometry.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target.

PubMed

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M Michael; Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A Mary; Velmurugan, D; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-11-26

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.

Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target

PubMed Central

Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M. Michael; Taguchi, Y-h.; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A. Mary; Velmurugan, D.; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu

2015-01-01

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective. PMID:26607293

Comparison of two hardware-based hit filtering methods for trackers in high-pileup environments

NASA Astrophysics Data System (ADS)

Gradin, J.; Mårtensson, M.; Brenner, R.

2018-04-01

As experiments in high energy physics aim to measure increasingly rare processes, the experiments continually strive to increase the expected signal yields. In the case of the High Luminosity upgrade of the LHC, the luminosity is raised by increasing the number of simultaneous proton-proton interactions, so-called pile-up. This increases the expected yields of signal and background processes alike. The signal is embedded in a large background of processes that mimic that of signal events. It is therefore imperative for the experiments to develop new triggering methods to effectively distinguish the interesting events from the background. We present a comparison of two methods for filtering detector hits to be used for triggering on particle tracks: one based on a pattern matching technique using Associative Memory (AM) chips and the other based on the Hough transform. Their efficiency and hit rejection are evaluated for proton-proton collisions with varying amounts of pile-up using a simulation of a generic silicon tracking detector. It is found that, while both methods are feasible options for a track trigger with single muon efficiencies around 98–99%, the AM based pattern matching produces a lower number of hit combinations with respect to the Hough transform whilst keeping more of the true signal hits. We also present the effect on the two methods of increasing the amount of support material in the detector and of introducing inefficiencies by deactivating detector modules. The increased support material has negligable effects on the efficiency for both methods, while dropping 5% (10%) of the available modules decreases the efficiency to about 95% (87%) for both methods, irrespective of the amount of pile-up.

Volitional and Real-Time Control Cursor Based on Eye Movement Decoding Using a Linear Decoding Model

PubMed Central

Zhang, Cheng

2016-01-01

The aim of this study is to build a linear decoding model that reveals the relationship between the movement information and the EOG (electrooculogram) data to online control a cursor continuously with blinks and eye pursuit movements. First of all, a blink detection method is proposed to reject a voluntary single eye blink or double-blink information from EOG. Then, a linear decoding model of time series is developed to predict the position of gaze, and the model parameters are calibrated by the RLS (Recursive Least Square) algorithm; besides, the assessment of decoding accuracy is assessed through cross-validation procedure. Additionally, the subsection processing, increment control, and online calibration are presented to realize the online control. Finally, the technology is applied to the volitional and online control of a cursor to hit the multiple predefined targets. Experimental results show that the blink detection algorithm performs well with the voluntary blink detection rate over 95%. Through combining the merits of blinks and smooth pursuit movements, the movement information of eyes can be decoded in good conformity with the average Pearson correlation coefficient which is up to 0.9592, and all signal-to-noise ratios are greater than 0. The novel system allows people to successfully and economically control a cursor online with a hit rate of 98%. PMID:28058044

High Levels of S100A8/A9 Proteins Aggravate Ventilator-Induced Lung Injury via TLR4 Signaling

PubMed Central

Aslami, Hamid; Jongsma, Geartsje; van den Berg, Elske; Vlaar, Alexander P. J.; Roelofs, Joris J. T. H.; Juffermans, Nicole P.; Schultz, Marcus J.; van der Poll, Tom; Roth, Johannes; Wieland, Catharina W.

2013-01-01

Background Bacterial products add to mechanical ventilation in enhancing lung injury. The role of endogenous triggers of innate immunity herein is less well understood. S100A8/A9 proteins are released by phagocytes during inflammation. The present study investigates the role of S100A8/A9 proteins in ventilator-induced lung injury. Methods Pulmonary S100A8/A9 levels were measured in samples obtained from patients with and without lung injury. Furthermore, wild-type and S100A9 knock-out mice, naive and with lipopolysaccharide-induced injured lungs, were randomized to 5 hours of spontaneously breathing or mechanical ventilation with low or high tidal volume (VT). In addition, healthy spontaneously breathing and high VT ventilated mice received S100A8/A9, S100A8 or vehicle intratracheal. Furthermore, the role of Toll-like receptor 4 herein was investigated. Results S100A8/A9 protein levels were elevated in patients and mice with lung injury. S100A8/A9 levels synergistically increased upon the lipopolysaccharide/high VT MV double hit. Markers of alveolar barrier dysfunction, cytokine and chemokine levels, and histology scores were attenuated in S100A9 knockout mice undergoing the double-hit. Exogenous S100A8/A9 and S100A8 induced neutrophil influx in spontaneously breathing mice. In ventilated mice, these proteins clearly amplified inflammation: neutrophil influx, cytokine, and chemokine levels were increased compared to ventilated vehicle-treated mice. In contrast, administration of S100A8/A9 to ventilated Toll-like receptor 4 mutant mice did not augment inflammation. Conclusion S100A8/A9 proteins increase during lung injury and contribute to inflammation induced by HVT MV combined with lipopolysaccharide. In the absence of lipopolysaccharide, high levels of extracellular S100A8/A9 still amplify ventilator-induced lung injury via Toll-like receptor 4. PMID:23874727

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

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.

Health Information Technology Systems profoundly impact users: a case study in a dental school.

PubMed

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

2010-04-01

The purpose of this study was to increase our understanding of the impact of Health Information Technology Systems (HITS) on dental school users when the systems are integrated into chair-side patient care. We used qualitative research methods, including interviews, focus groups, and observations, to capture the experiences of HITS users at a single institution. Users included administrators, clinical faculty members, predoctoral students, support staff, and residents. The data were analyzed using a grounded theory approach, and nine themes emerged: 1) HITS benefits were disproportionate among users; 2) communicating about the HITS was challenging; 3) users experienced a range of strong emotions; 4) the instructor persona diminished; 5) there were shifts in the school's power structure; 6) allocation of end-users' time shifted; 7) the training and support needs of end-users were significant; 8) perceived lack of HITS usability made documentation cumbersome for clinicians; and 9) clinicians' workflow was disrupted. HITS integration into patient care impacts the work of all system users, especially end-users. The themes highlight areas of potential concern for implementers and users in integrating a HITS into patient care.

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.

What is the extent of research on the characteristics, behaviors, and impacts of health information technology champions? A scoping review.

PubMed

Shea, Christopher Michael; Belden, Charles M

2016-01-12

Although champions are commonly employed in health information technology (HIT) implementations, the state of empirical literature on HIT champions' is unclear. The purpose of our review was to synthesize quantitative and qualitative studies to identify the extent of research on the characteristics, behaviors, and impacts of HIT champions. Ultimately, our goal was to identify gaps in the literature and inform implementation science. Our review employed a broad search strategy using multiple databases-Embase, Pubmed, Cinahl, PsychInfo, Web of Science, and the Cochrane library. We identified 1728 candidate articles, of which 42 were retained for full-text review. Of the 42 studies included, fourteen studies employed a multiple-case study design (33 %), 12 additional articles employed a single-case study design (29 %), five used quantitative methods (12 %), two used mixed-methods (5 %), and one used a Delphi methodology (2 %). Our review revealed multiple categories and characteristics of champions as well as influence tactics they used to promote an HIT project. Furthermore, studies have assessed three general types of HIT champion impacts: (1) impacts on the implementation process of a specific HIT; (2) impacts on usage behavior or overall success of a specific HIT; and (3) impacts on general organizational-level innovativeness. However the extent to which HIT projects fail even with a champion and why such failures occur is not clear. Also unclear is whether all organizations require a champion for successful HIT project implementation. In other words, we currently do not know enough about the conditions under which (1) a health IT champion is needed, (2) multiple champions are needed, and (3) an appointed champion-as opposed to an emergent champion-can be successful. Although champions appear to have contributed to successful implementation of HIT projects, simply measuring the presence or absence of a champion is not sufficient for assessing impacts. Future research should aim for answers to questions about who champions should be, when they should be engaged, what they should do, how management can support their efforts, and what their impact is given the organizational context.

Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

PubMed

Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford J

2017-12-01

Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect sizes were moderate to large. Comparisons with untreated controls (n = 14) revealed greater improvement for epilepsy patients on omissions and commissions, with improvement trends on d' and hits. Seizure frequency did not increase with methylphenidate treatment (2.8/month vs. 2.4/month). Methylphenidate may be an effective and safe option for improving cognition and quality of life in epilepsy. Larger and longer double-blind, placebo-controlled clinical trials are needed. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

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.

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.

Approved Methods and Algorithms for DoD Risk-Based Explosives Siting

DTIC Science & Technology

2009-07-21

Parameter used in determining probability of hit ( Phit ) by debris. [Table 31, Table 32, Table 33, Eq. (157), Eq. (158)] CCa Variable “Actual...being in the glass hazard area”. [Eq. (60), Eq. (78)] Phit Variable “Probability of hit”. An array value indexed by consequence and mass bin...Eq. (156), Eq. (157)] Phit (f) Variable “Probability of hit for fatality”. [Eq. (157), Eq. (158)] Phit (maji) Variable “Probability of hit for major

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.

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

PubMed

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

2011-07-01

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

The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

NASA Technical Reports Server (NTRS)

Ponomarev, Artem; Cucinotta, F.

2011-01-01

To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantization of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiments using proteins that detect DNA damage. An automated image segmentaiton software can prove useful in a faster and more precise object counting for colocolized foci images.

Therapeutic synergy between tigecycline and venetoclax in a preclinical model of MYC/BCL2 double-hit B cell lymphoma.

PubMed

Ravà, Micol; D'Andrea, Aleco; Nicoli, Paola; Gritti, Ilaria; Donati, Giulio; Doni, Mirko; Giorgio, Marco; Olivero, Daniela; Amati, Bruno

2018-01-31

High-grade B cell lymphomas with concurrent activation of the MYC and BCL2 oncogenes, also known as double-hit lymphomas (DHL), show dismal prognosis with current therapies. MYC activation sensitizes cells to inhibition of mitochondrial translation by the antibiotic tigecycline, and treatment with this compound provides a therapeutic window in a mouse model of MYC -driven lymphoma. We now addressed the utility of this antibiotic for treatment of DHL. BCL2 activation in mouse Eμ- myc lymphomas antagonized tigecycline-induced cell death, which was specifically restored by combined treatment with the BCL2 inhibitor venetoclax. In line with these findings, tigecycline and two related antibiotics, tetracycline and doxycycline, synergized with venetoclax in killing human MYC/BCL2 DHL cells. Treatment of mice engrafted with either DHL cell lines or a patient-derived xenograft revealed strong antitumoral effects of the tigecycline/venetoclax combination, including long-term tumor eradication with one of the cell lines. This drug combination also had the potential to cooperate with rituximab, a component of current front-line regimens. Venetoclax and tigecycline are currently in the clinic with distinct indications: Our preclinical results warrant the repurposing of these drugs for combinatorial treatment of DHL. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

PubMed

Petrich, Adam M; Gandhi, Mitul; Jovanovic, Borko; Castillo, Jorge J; Rajguru, Saurabh; Yang, David T; Shah, Khushboo A; Whyman, Jeremy D; Lansigan, Frederick; Hernandez-Ilizaliturri, Francisco J; Lee, Lisa X; Barta, Stefan K; Melinamani, Shruthi; Karmali, Reem; Adeimy, Camille; Smith, Scott; Dalal, Neil; Nabhan, Chadi; Peace, David; Vose, Julie; Evens, Andrew M; Shah, Namrata; Fenske, Timothy S; Zelenetz, Andrew D; Landsburg, Daniel J; Howlett, Christina; Mato, Anthony; Jaglal, Michael; Chavez, Julio C; Tsai, Judy P; Reddy, Nishitha; Li, Shaoying; Handler, Caitlin; Flowers, Christopher R; Cohen, Jonathon B; Blum, Kristie A; Song, Kevin; Sun, Haowei Linda; Press, Oliver; Cassaday, Ryan; Jaso, Jesse; Medeiros, L Jeffrey; Sohani, Aliyah R; Abramson, Jeremy S

2014-10-09

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed. © 2014 by The American Society of Hematology.

The Impact of the Geometrical Structure of the DNA on Parameters of the Track-Event Theory for Radiation Induced Cell Kill.

PubMed

Schneider, Uwe; Vasi, Fabiano; Besserer, Jürgen

2016-01-01

When fractionation schemes for hypofractionation and stereotactic body radiotherapy are considered, a reliable cell survival model at high dose is needed for calculating doses of similar biological effectiveness. An alternative to the LQ-model is the track-event theory which is based on the probabilities for one- and two two-track events. A one-track-event (OTE) is always represented by at least two simultaneous double strand breaks. A two-track-event (TTE) results in one double strand break. Therefore at least two two-track-events on the same or different chromosomes are necessary to produce an event which leads to cell sterilization. It is obvious that the probabilities of OTEs and TTEs must somehow depend on the geometrical structure of the chromatin. In terms of the track-event theory the ratio ε of the probabilities of OTEs and TTEs includes the geometrical dependence and is obtained in this work by simple Monte Carlo simulations. For this work it was assumed that the anchors of loop forming chromatin are most sensitive to radiation induced cell deaths. Therefore two adjacent tetranucleosomes representing the loop anchors were digitized. The probability ratio ε of OTEs and TTEs was factorized into a radiation quality dependent part and a geometrical part: ε = εion ∙ εgeo. εgeo was obtained for two situations, by applying Monte Carlo simulation for DNA on the tetranucleosomes itself and for linker DNA. Low energy electrons were represented by randomly distributed ionizations and high energy electrons by ionizations which were simulated on rays. εion was determined for electrons by using results from nanodosimetric measurements. The calculated ε was compared to the ε obtained from fits of the track event model to 42 sets of experimental human cell survival data. When the two tetranucleosomes are in direct contact and the hits are randomly distributed εgeo and ε are 0.12 and 0.85, respectively. When the hits are simulated on rays εgeo and ε are 0.10 and 0.71. For the linker-DNA εgeo and ε for randomly distributed hits are 0.010 and 0.073, and for hits on rays 0.0058 and 0.041, respectively. The calculated ε fits the experimentally obtained ε = 0.64±0.32 best for hits on the tetranucleosome when they are close to each other both, for high and low energy electrons. The parameter εgeo of the track event model was obtained by pure geometrical considerations of the chromatin structure and is 0.095 ± 0.022. It can be used as a fixed parameter in the track-event theory.

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.

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

PubMed Central

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

2014-01-01

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

Evaluation and application of multiple scoring functions for a virtual screening experiment

NASA Astrophysics Data System (ADS)

Xing, Li; Hodgkin, Edward; Liu, Qian; Sedlock, David

2004-05-01

In order to identify novel chemical classes of factor Xa inhibitors, five scoring functions (FlexX, DOCK, GOLD, ChemScore and PMF) were engaged to evaluate the multiple docking poses generated by FlexX. The compound collection was composed of confirmed potent factor Xa inhibitors and a subset of the LeadQuest® screening compound library. Except for PMF the other four scoring functions succeeded in reproducing the crystal complex (PDB code: 1FAX). During virtual screening the highest hit rate (80%) was demonstrated by FlexX at an energy cutoff of -40 kJ/mol, which is about 40-fold over random screening (2.06%). Limited results suggest that presenting more poses of a single molecule to the scoring functions could deteriorate their enrichment factors. A series of promising scaffolds with favorable binding scores was retrieved from LeadQuest. Consensus scoring by pair-wise intersection failed to enrich the hit rate yielded by single scorings (i.e. FlexX). We note that reported successes of consensus scoring in hit rate enrichment could be artificial because their comparisons were based on a selected subset of single scoring and a markedly reduced subset of double or triple scoring. The findings presented in this report are based upon a single biological system and support further studies.

Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study.

PubMed

Naber, Marnix; Hommel, Bernhard; Colzato, Lorenza S

2015-08-14

Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate's diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest that it serves as a cognitive enhancer. As choline is important for the communication between motor neurons and the control of skeletal muscles, we assumed that choline supplementation may have positive effects on action coordination in humans. A group of twenty-eight individuals ingested two grams of choline bitartrate or a placebo in two separate sessions. Seventy minutes post ingestion, participants performed a visuomotor aiming task in which they had to rapidly hit the centers of targets. Results showed that participants hit targets more centrally after choline supplementation. Pupil size (a cognition-sensitive biomarker) also significantly decreased after choline intake and correlated positively with the hit distance to the targets and the number of target misses, and negatively with reaction times. These findings point to a choline-induced bias towards action precision in the trade-off between speed and accuracy. The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system.

Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study

PubMed Central

Naber, Marnix; Hommel, Bernhard; Colzato, Lorenza S.

2015-01-01

Only few nutrients are known to enhance cognition. Here we explore whether visuomotor performance can be improved through the intake of the nutrient choline, an essential chemical compound in a vertebrate’s diet. Choline is abundant in for example eggs and shrimps and many animal studies suggest that it serves as a cognitive enhancer. As choline is important for the communication between motor neurons and the control of skeletal muscles, we assumed that choline supplementation may have positive effects on action coordination in humans. A group of twenty-eight individuals ingested two grams of choline bitartrate or a placebo in two separate sessions. Seventy minutes post ingestion, participants performed a visuomotor aiming task in which they had to rapidly hit the centers of targets. Results showed that participants hit targets more centrally after choline supplementation. Pupil size (a cognition-sensitive biomarker) also significantly decreased after choline intake and correlated positively with the hit distance to the targets and the number of target misses, and negatively with reaction times. These findings point to a choline-induced bias towards action precision in the trade-off between speed and accuracy. The changes in pupil size suggest that choline uptake alters cholinergic functions in the nervous system. PMID:26271904

[Fragment-based drug discovery: concept and aim].

PubMed

Tanaka, Daisuke

2010-03-01

Fragment-Based Drug Discovery (FBDD) has been recognized as a newly emerging lead discovery methodology that involves biophysical fragment screening and chemistry-driven fragment-to-lead stages. Although fragments, defined as structurally simple and small compounds (typically <300 Da), have not been employed in conventional high-throughput screening (HTS), the recent significant progress in the biophysical screening methods enables fragment screening at a practical level. The intention of FBDD primarily turns our attention to weakly but specifically binding fragments (hit fragments) as the starting point of medicinal chemistry. Hit fragments are then promoted to more potent lead compounds through linking or merging with another hit fragment and/or attaching functional groups. Another positive aspect of FBDD is ligand efficiency. Ligand efficiency is a useful guide in screening hit selection and hit-to-lead phases to achieve lead-likeness. Owing to these features, a number of successful applications of FBDD to "undruggable targets" (where HTS and other lead identification methods failed to identify useful lead compounds) have been reported. As a result, FBDD is now expected to complement more conventional methodologies. This review, as an introduction of the following articles, will summarize the fundamental concepts of FBDD and will discuss its advantages over other conventional drug discovery approaches.

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.

Synthesis and screening of one-bead-one-compound cyclic peptide libraries.

PubMed

Qian, Ziqing; Upadhyaya, Punit; Pei, Dehua

2015-01-01

Cyclic peptides have been a rich source of biologically active molecules. Herein we present a method for the combinatorial synthesis and screening of large one-bead-one-compound (OBOC) libraries of cyclic peptides against biological targets such as proteins. Up to ten million different cyclic peptides are rapidly synthesized on TentaGel microbeads by the split-and-pool synthesis method and subjected to a multistage screening protocol which includes magnetic sorting, on-bead enzyme-linked and fluorescence-based assays, and in-solution binding analysis of cyclic peptides selectively released from single beads by fluorescence anisotropy. Finally, the most active hit(s) is identified by the partial Edman degradation-mass spectrometry (PED-MS) method. This method allows a single researcher to synthesize and screen up to ten million cyclic peptides and identify the most active ligand(s) in ~1 month, without the time-consuming and expensive hit resynthesis or the use of any special equipment.

The lattice Boltzmann method and the problem of turbulence

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

Djenidi, L.

2015-03-10

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

HIT or miss: the application of health care information technology to managing uncertainty in clinical decision making.

PubMed

Kazandjian, Vahé A; Lipitz-Snyderman, Allison

2011-12-01

To discuss the usefulness of health care information technology (HIT) in assisting care providers minimize uncertainty while simultaneously increasing efficiency of the care provided. An ongoing study of HIT, performance measurement (clinical and production efficiency) and their implications to the payment for care represents the design of this study. Since 2006, all Maryland hospitals have embarked on a multi-faceted study of performance measures and HIT adoption surveys, which will shape the health care payment model in Maryland, the last of the all-payor states, in 2011. This paper focuses on the HIT component of the Maryland care payment initiative. While the payment model is still under review and discussion, 'appropriateness' of care has been discussed as an important dimension of measurement. Within this dimension, the 'uncertainty' concept has been identified as associated with variation in care practices. Hence, the methods of this paper define how HIT can assist care providers in addressing the concept of uncertainty, and then provides findings from the first HIT survey in Maryland to infer the readiness of Maryland hospital in addressing uncertainty of care in part through the use of HIT. Maryland hospitals show noteworthy variation in their adoption and use of HIT. While computerized, electronic patient records are not commonly used among and across Maryland hospitals, many of the uses of HIT internally in each hospital could significantly assist in better communication about better practices to minimize uncertainty of care and enhance the efficiency of its production. © 2010 Blackwell Publishing Ltd.

Efficient hit-finding approaches for histone methyltransferases: the key parameters.

PubMed

Ahrens, Thomas; Bergner, Andreas; Sheppard, David; Hafenbradl, Doris

2012-01-01

For many novel epigenetics targets the chemical ligand space and structural information were limited until recently and are still largely unknown for some targets. Hit-finding campaigns are therefore dependent on large and chemically diverse libraries. In the specific case of the histone methyltransferase G9a, the authors have been able to apply an efficient process of intelligent selection of compounds for primary screening, rather than screening the full diverse deck of 900 000 compounds to identify hit compounds. A number of different virtual screening methods have been applied for the compound selection, and the results have been analyzed in the context of their individual success rates. For the primary screening of 2112 compounds, a FlashPlate assay format and full-length histone H3.1 substrate were employed. Validation of hit compounds was performed using the orthogonal fluorescence lifetime technology. Rated by purity and IC(50) value, 18 compounds (0.9% of compound screening deck) were finally considered validated primary G9a hits. The hit-finding approach has led to novel chemotypes being identified, which can facilitate hit-to-lead projects. This study demonstrates the power of virtual screening technologies for novel, therapeutically relevant epigenetics protein targets.

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

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

Experimental design and statistical methods for improved hit detection in high-throughput screening.

PubMed

Malo, Nathalie; Hanley, James A; Carlile, Graeme; Liu, Jing; Pelletier, Jerry; Thomas, David; Nadon, Robert

2010-09-01

Identification of active compounds in high-throughput screening (HTS) contexts can be substantially improved by applying classical experimental design and statistical inference principles to all phases of HTS studies. The authors present both experimental and simulated data to illustrate how true-positive rates can be maximized without increasing false-positive rates by the following analytical process. First, the use of robust data preprocessing methods reduces unwanted variation by removing row, column, and plate biases. Second, replicate measurements allow estimation of the magnitude of the remaining random error and the use of formal statistical models to benchmark putative hits relative to what is expected by chance. Receiver Operating Characteristic (ROC) analyses revealed superior power for data preprocessed by a trimmed-mean polish method combined with the RVM t-test, particularly for small- to moderate-sized biological hits.

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

PubMed Central

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

2015-01-01

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

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.

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

Applications of Biophysics in High-Throughput Screening Hit Validation.

PubMed

Genick, Christine Clougherty; Barlier, Danielle; Monna, Dominique; Brunner, Reto; Bé, Céline; Scheufler, Clemens; Ottl, Johannes

2014-06-01

For approximately a decade, biophysical methods have been used to validate positive hits selected from high-throughput screening (HTS) campaigns with the goal to verify binding interactions using label-free assays. By applying label-free readouts, screen artifacts created by compound interference and fluorescence are discovered, enabling further characterization of the hits for their target specificity and selectivity. The use of several biophysical methods to extract this type of high-content information is required to prevent the promotion of false positives to the next level of hit validation and to select the best candidates for further chemical optimization. The typical technologies applied in this arena include dynamic light scattering, turbidometry, resonance waveguide, surface plasmon resonance, differential scanning fluorimetry, mass spectrometry, and others. Each technology can provide different types of information to enable the characterization of the binding interaction. Thus, these technologies can be incorporated in a hit-validation strategy not only according to the profile of chemical matter that is desired by the medicinal chemists, but also in a manner that is in agreement with the target protein's amenability to the screening format. Here, we present the results of screening strategies using biophysics with the objective to evaluate the approaches, discuss the advantages and challenges, and summarize the benefits in reference to lead discovery. In summary, the biophysics screens presented here demonstrated various hit rates from a list of ~2000 preselected, IC50-validated hits from HTS (an IC50 is the inhibitor concentration at which 50% inhibition of activity is observed). There are several lessons learned from these biophysical screens, which will be discussed in this article. © 2014 Society for Laboratory Automation and Screening.

A novel microseeding method for the crystallization of membrane proteins in lipidic cubic phase.

PubMed

Kolek, Stefan Andrew; Bräuning, Bastian; Stewart, Patrick Douglas Shaw

2016-04-01

Random microseed matrix screening (rMMS), in which seed crystals are added to random crystallization screens, is an important breakthrough in soluble protein crystallization that increases the number of crystallization hits that are available for optimization. This greatly increases the number of soluble protein structures generated every year by typical structural biology laboratories. Inspired by this success, rMMS has been adapted to the crystallization of membrane proteins, making LCP seed stock by scaling up LCP crystallization conditions without changing the physical and chemical parameters that are critical for crystallization. Seed crystals are grown directly in LCP and, as with conventional rMMS, a seeding experiment is combined with an additive experiment. The new method was used with the bacterial integral membrane protein OmpF, and it was found that it increased the number of crystallization hits by almost an order of magnitude: without microseeding one new hit was found, whereas with LCP-rMMS eight new hits were found. It is anticipated that this new method will lead to better diffracting crystals of membrane proteins. A method of generating seed gradients, which allows the LCP seed stock to be diluted and the number of crystals in each LCP bolus to be reduced, if required for optimization, is also demonstrated.

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.

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.

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.

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.

Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine

PubMed Central

Yang, Min; Rendas-Baum, Regina; Varon, Sepideh F; Kosinski, Mark

2011-01-01

Objective: The purpose of this study was to assess psychometric properties of the six-item Headache Impact Text (HIT-6™) across episodic and chronic migraine. Methods: Using a migraine screener and number of headache days per month (HDPM), participants from the National Survey of Headache Impact (NSHI) study and the HIT-6 validation study (HIT6-V) were selected for this study. Eligible participants were categorized into three groups: chronic migraine (CM: ≥ 15 HDPM); episodic migraine (EM: < 15 HDPM); non-migraine headaches. Reliability and validity of the HIT-6 were evaluated. Results: A total of 2,049 survey participants met the inclusion/exclusion criteria for this study. Participants were identified as 6.4% CM; 42.1% EM; 51.5% non-migraine, with respective mean HIT-6 scores: 62.5 ± 7.8; 60.2 ± 6.8; and 49.1 ± 8.7. High reliability was demonstrated with internal consistency (time1/time2) of 0.83/0.87 in NSHI, and 0.82/0.92 in HIT6-V. Intra-class correlation for test-retest reliability was very good at 0.77. HIT-6 scores correlated significantly (p < .0001) with total Migraine Disability Assessment Scale scores (r = 0.56), headache pain severity (r = 0.46), and HDPM (r = 0.29). Discriminant validity analysis showed significantly different HIT-6 scores (F = 488.02, p < .0001) across the groups. Conclusion: Results from these analyses confirm that the HIT-6 is a reliable and valid tool for discriminating headache impact across episodic and chronic migraine. PMID:20819842

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

Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: Subset analysis of randomized trial intergroup SWOG S9704

PubMed Central

Puvvada, Soham D.; Stiff, Patrick J.; Leblanc, Michael; Cook, James R.; Couban, Stephen; Leonard, John P.; Kahl, Brad; Marcellus, Deborah; Shea, Thomas C.; Winter, Jane N.; Li, Hongli; Rimsza, Lisa M.; Friedberg, Jonathan W.; Smith, Sonali M.

2016-01-01

Summary Double hit lymphoma (DHL) and double protein-expressing (MYC and BCL2) lymphomas (DPL) fare poorly with R-CHOP; consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/−R with or without ASCT allows evaluation of intensive consolidation. Immunohistochemical analysis identified 27 of 198 patients (13.6%) with MYC IHC overexpression and 20 (74%) harboring concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median follow-up 127 months, there is a trend favoring outcomes after consolidative ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT. PMID:27072903

Hitting the Goalpost: Calculating the Fine Line Between Winning and Losing a Penalty Shootout

NASA Astrophysics Data System (ADS)

Widenhorn, Ralf

2016-10-01

The Portland Timbers won their first Major League Soccer (MLS) Cup Championship in December 2015. However, if it had not been for a kind double goalpost miss during a penalty shootout a few weeks earlier, the Timbers would never have been in the finals. On Oct. 30th, after what has been called "the greatest penalty kick shootout in MLS history," featuring a combined 22 penalties that included penalties by both goalkeepers, the Timbers won their first-round playoff against Sporting Kansas City. During the thrilling shootout, which can be watched, for example, for example on the MLS website, Sporting had two potentially game-winning penalties miss by the smallest of margins. One penalty bounced off the goalpost back into the field and another was an improbable double post miss. For a physicist, this prompts an interesting research question. Could we find an estimate by what distance the double post penalty shown in Fig. 1 failed to be the game winning shot?

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

Human Factors and Ergonomics in the Design of Health Information Technology: Trends and Progress in 2014

PubMed Central

Ong, MS.

2015-01-01

Summary Objective To summarize significant contributions to the research on human factors and organizational issues in medical informatics. Methods An extensive search using PubMed/Medline and Web of Science® was conducted to identify the scientific contributions, published in 2014, to human factors and organizational issues in medical informatics, with a focus on health information technology (HIT) usability. The selection process comprised three steps: (i) 15 candidate best papers were selected by the two section editors, (ii) external reviewers from a pool of international experts reviewed each candidate best paper, and (iii) the final selection of three best papers was made by the editorial board of the IMIA Yearbook. Results Noteworthy papers published in 2014 describe an efficient, easy to implement, and useful process for detecting and mitigating human factors and ergonomics (HFE) issues of HIT. They contribute to promote the HFE approach with interventions based on rigorous and well-conducted methods when designing and implementing HIT. Conclusion The application of HFE in the design and implementation of HIT remains limited, and the impact of incorporating HFE principles on patient safety is understudied. Future works should be conducted to advance this field of research, so that the safety and quality of patient care are not compromised by the increasing adoption of HIT. PMID:26293852

Development of ultra-precision micro-cavity measurement technique in HIT-UOI

NASA Astrophysics Data System (ADS)

Cui, Jiwen; Li, Lei; Tan, Jiubin

2010-08-01

Micro cavities with high aspect ratio are widely used in different fields including aerospace and defense industries with the development of manufacturing technology. So how to measure the dimension of these cavities has become one of the major research subjects in the field of measurement and instrument. This paper describes some activities of the precision micro cavity measurement technique in Center of Ultra-precision Optoelectronic Instrument (UOI), Harbin Institute of Technology (HIT). The key issue of micro cavity measurement in UOI is called touch-trigger measurement method. The first scheme is double optical fiber coupling, in which light coming from the incident optical fiber is transmitted in the reversal direction via the optical fiber coupling into the effluent optical fiber, the lateral displacement of the touch-trigger sensor is transformed into the deflexion of light coming out from the effluent optical fiber, and the deflexion is transformed into an image signal by the object lens and CCD capturing system. And the second scheme is micro focal-length collimation, in which a fiber stem with a ball mounted on its end is used as a probe and a small segment of it is used as a cylindrical lens to collimate a point light source and image it to a camera, the deflection of the fiber stem can be inferred from the change in image acquired by the camera with ultrahigh displacement sensitivity. Experiments for these activities will be given with a focus on the measurement results and repeatability uncertainty.

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

HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.

PubMed

Favaloro, Emmanuel J; McCaughan, Georgia; Mohammed, Soma; Lau, Kun Kan Edwin; Gemmell, Rosalie; Cavanaugh, Lauren; Donikian, Dea; Kondo, Mayuko; Brighton, Timothy; Pasalic, Leonardo

2018-04-17

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG (PF4-H) ), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

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.

Effect of Soft Tissue Techniques on Headache Impact, Disability, and Quality of Life in Migraine Sufferers: A Pilot Study.

PubMed

Espí-López, Gemma-Victoria; Ruescas-Nicolau, Maria-Arantzazu; Nova-Redondo, Cristina; Benítez-Martínez, Josep C; Dugailly, Pierre-Michel; Falla, Deborah

2018-04-30

To determine the efficacy of suboccipital inhibitory techniques in people with migraine compared with a control treatment based on myofascial trigger point (MTrP) therapy and stretching. A randomized, double-blind controlled pilot trial was conducted. University research laboratory. Forty-six adults diagnosed with migraine with over 6 months duration. Participants were randomized to receive either combined MTrP therapy and stretching (control group) or the control treatment plus suboccipital soft tissue inhibition (experimental group). Treatment was applied on four occasions over 8 weeks (one every 15 days), with a duration of 30 minutes per session in the experimental group and 20 min in the control group. The impact of headache was assessed with the Headache Impact Test (HIT-6), disability by the migraine disability assessment (MIDAS), and quality of life by the Short Form Health Survey (SF-36). Both groups were assessed at baseline and 1 week immediately after the end of treatment. The amount of change of the HIT-6 score and MIDAS scores were significantly different between groups (p < 0.05), although the SF-36 scores were not. The change in the HIT-6 score and MIDAS scores was greater in the experimental group. Both groups showed a reduction on the HIT-6 score (p < 0.001), MIDAS scores (p < 0.05), and SF-36 physical subscale, whereas the SF-36 mental subscale improved only in the experimental group (p < 0.001). Soft tissue techniques based on MTrP therapy and stretching were helpful for improving certain aspects of migraine, such as the impact and disability caused by the headache, and the frequency and intensity of headache; however, when combined with suboccipital soft tissue inhibition, the treatment effect was larger.

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

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.

Profiling Cholinesterase Adduction: A High-Throughput Prioritization Method for Organophosphate Exposure Samples

PubMed Central

Carter, Melissa D.; Crow, Brian S.; Pantazides, Brooke G.; Watson, Caroline M.; deCastro, B. Rey; Thomas, Jerry D.; Blake, Thomas A.; Johnson, Rudolph C.

2017-01-01

A high-throughput prioritization method was developed for use with a validated confirmatory method detecting organophosphorus nerve agent exposure by immunomagnetic separation-HPLC-MS/MS. A ballistic gradient was incorporated into this analytical method in order to profile unadducted butyrylcholinesterase (BChE) in clinical samples. With Zhang, et al. 1999’s Z′-factor of 0.88 ± 0.01 (SD) of control analytes and Z-factor of 0.25 ± 0.06 (SD) of serum samples, the assay is rated an “excellent assay” for the synthetic peptide controls used and a “double assay” when used to prioritize clinical samples. Hits, defined as samples containing BChE Ser-198 adducts or no BChE present, were analyzed in a confirmatory method for identification and quantitation of the BChE adduct, if present. The ability to prioritize samples by highest exposure for confirmatory analysis is of particular importance in an exposure to cholinesterase inhibitors such as organophosphorus nerve agents where a large number of clinical samples may be collected. In an initial blind screen, 67 out of 70 samples were accurately identified giving an assay accuracy of 96% and yielded no false negatives. The method is the first to provide a high-throughput prioritization assay for profiling adduction of Ser-198 BChE in clinical samples. PMID:23954929

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

A leukemic double-hit follicular lymphoma associated with a complex variant translocation, t(8;14;18)(q24;q32;q21), involving BCL2, MYC, and IGH.

PubMed

Minakata, Daisuke; Sato, Kazuya; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Umino, Kento; Nakano, Hirofumi; Yamasaki, Ryoko; Morita, Kaoru; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Oh, Iekuni; Fujiwara, Shin-Ichiro; Ohmine, Ken; Kawata, Hirotoshi; Muroi, Kazuo; Miura, Ikuo; Kanda, Yoshinobu

2018-01-01

Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes. Based on a combination of fluorescence in situ hybridization (FISH), using BCL2, MYC and IGH, and spectral karyotyping (SKY), the karyotype was interpreted as being the result of a multistep mechanism in which the precursor B-cell gained t(14;18) in the bone marrow and acquired a translocation between der(14)t(14;18) and chromosome 8 in the germinal center, resulting in t(8;14;18). The pathological diagnosis was consistently FL, not only at presentation but even after a second relapse. The patient responded well to standard chemotherapies but relapsed after a short remission. This patient is a unique case of leukemic DH-FL with t(8;14;18) that remained in FL even at a second relapse. Copyright © 2017 Elsevier Inc. All rights reserved.

Double Hits in Schizophrenia.

PubMed

Vorstman, Jacob A S; Olde Loohuis, Loes M; Kahn, René S; Ophoff, Roel A

2018-05-14

The co-occurrence of a Copy Number Variant (CNV) and a functional variant on the other allele may be a relevant genetic mechanism in schizophrenia. We hypothesized that the cumulative burden of such double hits - in particular those composed of a deletion and a coding single nucleotide variation (SNV) - is increased in patients with schizophrenia.We combined CNV data with coding variants data in 795 patients with schizophrenia and 474 controls. To limit false CNV-detection, only CNVs called only by two algorithms we included. CNV-affected genes were subsequently examined for coding SNVs, which we termed "CNV-SNVs". Correcting for total queried sequence, we assessed the CNV-SNV-burden and the combined predicted deleterious effect. We estimated p-values by permutation of the phenotype.We detected 105 CNV-SNVs; 67 in duplicated and 38 in deleted genic sequence. While the difference in CNV-SNVs rates was not significant, the combined deleteriousness inferred by CNV-SNVs in deleted sequence was almost fourfold higher in cases compared to controls (nominal p = 0.009). This effect may be driven by a higher number of CNV-SNVs and/or by a higher degree of predicted deleteriousness of CNV-SNVs. No such effect was observed for duplications.We provide early evidence that deletions co-occurring with a functional variant may be relevant, albeit of modest impact, for the genetic etiology of schizophrenia. Large-scale consortium studies are required to validate our findings. Sequence-based analyses would provide the best resolution for detection of CNVs as well as coding variants genome-wide.

Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment Induce Changes in the Structure and Neurochemistry of Inhibitory Neurons of the Adult Amygdala and Prefrontal Cortex.

PubMed

Castillo-Gómez, Esther; Pérez-Rando, Marta; Bellés, María; Gilabert-Juan, Javier; Llorens, José Vicente; Carceller, Héctor; Bueno-Fernández, Clara; García-Mompó, Clara; Ripoll-Martínez, Beatriz; Curto, Yasmina; Sebastiá-Ortega, Noelia; Moltó, María Dolores; Sanjuan, Julio; Nacher, Juan

2017-01-01

The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia.

Structure-function analysis of rotavirus NSP2 octamer by using a novel complementation system.

PubMed

Taraporewala, Zenobia F; Jiang, Xiaofang; Vasquez-Del Carpio, Rodrigo; Jayaram, Hariharan; Prasad, B V Venkataram; Patton, John T

2006-08-01

Viral inclusion bodies, or viroplasms, that form in rotavirus-infected cells direct replication and packaging of the segmented double-stranded RNA (dsRNA) genome. NSP2, one of two rotavirus proteins needed for viroplasm assembly, possesses NTPase, RNA-binding, and helix-unwinding activities. NSP2 of the rotavirus group causing endemic infantile diarrhea (group A) was shown to self-assemble into large doughnut-shaped octamers with circumferential grooves and deep clefts containing nucleotide-binding histidine triad (HIT)-like motifs. Here, we demonstrate that NSP2 of group C rotavirus, a group that fails to reassort with group A viruses, retains the unique architecture of the group A octamer but differs in surface charge distribution. By using an NSP2-dependent complementation system, we show that the HIT-dependent NTPase activity of NSP2 is necessary for dsRNA synthesis, but not for viroplasm formation. The complementation system also showed that despite the retention of the octamer structure and the HIT-like fold, group C NSP2 failed to rescue replication and viroplasm formation in NSP2-deficient cells infected with group A rotavirus. The distinct differences in the surface charges on the Bristol and SA11 NSP2 octamers suggest that charge complementarity of the viroplasm-forming proteins guides the specificity of viroplasm formation and, possibly, reassortment restriction between rotavirus groups.

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

PubMed Central

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

2013-01-01

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

Composing compound libraries for hit discovery--rationality-driven preselection or random choice by structural diversity?

PubMed

Weidel, Elisabeth; Negri, Matthias; Empting, Martin; Hinsberger, Stefan; Hartmann, Rolf W

2014-01-01

In order to identify new scaffolds for drug discovery, surface plasmon resonance is frequently used to screen structurally diverse libraries. Usually, hit rates are low and identification processes are time consuming. Hence, approaches which improve hit rates and, thus, reduce the library size are required. In this work, we studied three often used strategies for their applicability to identify inhibitors of PqsD. In two of them, target-specific aspects like inhibition of a homologous protein or predicted binding determined by virtual screening were used for compound preselection. Finally, a fragment library, covering a large chemical space, was screened and served as comparison. Indeed, higher hit rates were observed for methods employing preselected libraries indicating that target-oriented compound selection provides a time-effective alternative.

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…

Measuring the Impact of Technology on Nurse Workflow: A Mixed Methods Approach

ERIC Educational Resources Information Center

Cady, Rhonda Guse

2012-01-01

Background. Investment in health information technology (HIT) is rapidly accelerating. The absence of contextual or situational analysis of the environment in which HIT is incorporated makes it difficult to measure success or failure. The methodology introduced in this paper combines observational research with time-motion study to measure the…

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.

[Preliminary application of video head impulse test in the diagnosis of vertigo].

PubMed

Zhang, Yanmei; Chen, Siqi; Zhong, Zhen; Chen, Li; Wu, Yuanding; Zhao, Guiping; Liu, Yuhe

2015-06-01

To investigate clinical application of head impulse test with video recording eye movements in the diagnosis of vertigo. The video head impulse test(vHIT) was used to measure the eye saccades and velocity gain in 95 patients with vertigo which were divided into two groups, peripheral vertigo (47 cases) and central vertigo(48 cases); the characteristics of eye saccades and velocity gain of six semicircular canals in different patients with vertigo were analyzed, and were compared between the two groups. The vHIT result in patients with peripheral vertigo: in 22 patients (23 affected ears) with Meniere's disease, 21 ears were abnormal (91. 3%); the vHIT results in 4 patients with vestibular schwannoma, 2 patients with vestibular neuritis, 5 patients with delayed endolymphatic hydrops, 6 patients with sudden hearing loss accompanied vertigo, and 8 patients with vestibular dysfunction, were abnormal with correct saccades and/or lower velocity gain of vHIT. The abnormal vHIT results were also found in 35 of 48 patients (72. 9%) with central vertigo, which including posterior cerebral circulation ischemia(7 patients), cerebral infarction/stroke(6 patients), and dizziness with vertigo(17 patients) and others(18 patients). Abnormal rate of vHIT in patients with peripheral vertigo was 95. 7% (45/47), which was significantly higher than that (72. 9%) in patients with central vertigo. It is easy to perform the vHIT which without adverse reactions. We can record high-frequency characteristics of vestibular-ocular reflex among six semicircular canals through vHIT. The vHIT results which show the function of vestibular ocular reflex in different diseases with vertigo, can help discriminate peripheral vertigo from central vertigo, and it is a practical assessment method for vertigo.

Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.

PubMed

Kobayashi, Masakazu; Retra, Kim; Figaroa, Francis; Hollander, Johan G; Ab, Eiso; Heetebrij, Robert J; Irth, Hubertus; Siegal, Gregg

2010-09-01

Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the first stage of the process be optimized. Here the authors compare the 3 most commonly used methods for hit discovery in FBDD: high concentration screening (HCS), solution ligand-observed nuclear magnetic resonance (NMR), and surface plasmon resonance (SPR). They selected the commonly used saturation transfer difference (STD) NMR spectroscopy and the proprietary target immobilized NMR screening (TINS) as representative of the array of possible NMR methods. Using a target typical of FBDD campaigns, the authors find that HCS and TINS are the most sensitive to weak interactions. They also find a good correlation between TINS and STD for tighter binding ligands, but the ability of STD to detect ligands with affinity weaker than 1 mM K(D) is limited. Similarly, they find that SPR detection is most suited to ligands that bind with K(D) better than 1 mM. However, the good correlation between SPR and potency in a bioassay makes this a good method for hit validation and characterization studies.

Trends in Health Information Technology Safety: From Technology-Induced Errors to Current Approaches for Ensuring Technology Safety

PubMed Central

2013-01-01

Objectives Health information technology (HIT) research findings suggested that new healthcare technologies could reduce some types of medical errors while at the same time introducing classes of medical errors (i.e., technology-induced errors). Technology-induced errors have their origins in HIT, and/or HIT contribute to their occurrence. The objective of this paper is to review current trends in the published literature on HIT safety. Methods A review and synthesis of the medical and life sciences literature focusing on the area of technology-induced error was conducted. Results There were four main trends in the literature on technology-induced error. The following areas were addressed in the literature: definitions of technology-induced errors; models, frameworks and evidence for understanding how technology-induced errors occur; a discussion of monitoring; and methods for preventing and learning about technology-induced errors. Conclusions The literature focusing on technology-induced errors continues to grow. Research has focused on the defining what an error is, models and frameworks used to understand these new types of errors, monitoring of such errors and methods that can be used to prevent these errors. More research will be needed to better understand and mitigate these types of errors. PMID:23882411

No Additional Benefits of Block- Over Evenly-Distributed High-Intensity Interval Training within a Polarized Microcycle

PubMed Central

McGawley, Kerry; Juudas, Elisabeth; Kazior, Zuzanna; Ström, Kristoffer; Blomstrand, Eva; Hansson, Ola; Holmberg, Hans-Christer

2017-01-01

Introduction: The current study aimed to investigate the responses to block- versus evenly-distributed high-intensity interval training (HIT) within a polarized microcycle. Methods: Twenty well-trained junior cross-country skiers (10 males, age 17.6 ± 1.5 and 10 females, age 17.3 ± 1.5) completed two, 3-week periods of training (EVEN and BLOCK) in a randomized, crossover-design study. In EVEN, 3 HIT sessions (5 × 4-min of diagonal-stride roller-skiing) were completed at a maximal sustainable intensity each week while low-intensity training (LIT) was distributed evenly around the HIT. In BLOCK, the same 9 HIT sessions were completed in the second week while only LIT was completed in the first and third weeks. Heart rate (HR), session ratings of perceived exertion (sRPE), and perceived recovery (pREC) were recorded for all HIT and LIT sessions, while distance covered was recorded for each HIT interval. The recovery-stress questionnaire for athletes (RESTQ-Sport) was completed weekly. Before and after EVEN and BLOCK, resting saliva and muscle samples were collected and an incremental test and 600-m time-trial (TT) were completed. Results: Pre- to post-testing revealed no significant differences between EVEN and BLOCK for changes in resting salivary cortisol, testosterone, or IgA, or for changes in muscle capillary density, fiber area, fiber composition, enzyme activity (CS, HAD, and PFK) or the protein content of VEGF or PGC-1α. Neither were any differences observed in the changes in skiing economy, V˙O2max or 600-m time-trial performance between interventions. These findings were coupled with no significant differences between EVEN and BLOCK for distance covered during HIT, summated HR zone scores, total sRPE training load, overall pREC or overall recovery-stress state. However, 600-m TT performance improved from pre- to post-training, irrespective of intervention (P = 0.003), and a number of hormonal and muscle biopsy markers were also significantly altered post-training (P < 0.05). Discussion: The current study shows that well-trained junior cross-country skiers are able to complete 9 HIT sessions within 1 week without compromising total work done and without experiencing greater stress or reduced recovery over a 3-week polarized microcycle. However, the findings do not support block-distributed HIT as a superior method to a more even distribution of HIT in terms of enhancing physiological or performance adaptions. PMID:28659826

No Additional Benefits of Block- Over Evenly-Distributed High-Intensity Interval Training within a Polarized Microcycle.

PubMed

McGawley, Kerry; Juudas, Elisabeth; Kazior, Zuzanna; Ström, Kristoffer; Blomstrand, Eva; Hansson, Ola; Holmberg, Hans-Christer

2017-01-01

Introduction: The current study aimed to investigate the responses to block- versus evenly-distributed high-intensity interval training (HIT) within a polarized microcycle. Methods: Twenty well-trained junior cross-country skiers (10 males, age 17.6 ± 1.5 and 10 females, age 17.3 ± 1.5) completed two, 3-week periods of training (EVEN and BLOCK) in a randomized, crossover-design study. In EVEN, 3 HIT sessions (5 × 4-min of diagonal-stride roller-skiing) were completed at a maximal sustainable intensity each week while low-intensity training (LIT) was distributed evenly around the HIT. In BLOCK, the same 9 HIT sessions were completed in the second week while only LIT was completed in the first and third weeks. Heart rate (HR), session ratings of perceived exertion (sRPE), and perceived recovery (pREC) were recorded for all HIT and LIT sessions, while distance covered was recorded for each HIT interval. The recovery-stress questionnaire for athletes (RESTQ-Sport) was completed weekly. Before and after EVEN and BLOCK, resting saliva and muscle samples were collected and an incremental test and 600-m time-trial (TT) were completed. Results: Pre- to post-testing revealed no significant differences between EVEN and BLOCK for changes in resting salivary cortisol, testosterone, or IgA, or for changes in muscle capillary density, fiber area, fiber composition, enzyme activity (CS, HAD, and PFK) or the protein content of VEGF or PGC-1α. Neither were any differences observed in the changes in skiing economy, [Formula: see text] or 600-m time-trial performance between interventions. These findings were coupled with no significant differences between EVEN and BLOCK for distance covered during HIT, summated HR zone scores, total sRPE training load, overall pREC or overall recovery-stress state. However, 600-m TT performance improved from pre- to post-training, irrespective of intervention ( P = 0.003), and a number of hormonal and muscle biopsy markers were also significantly altered post-training ( P < 0.05). Discussion: The current study shows that well-trained junior cross-country skiers are able to complete 9 HIT sessions within 1 week without compromising total work done and without experiencing greater stress or reduced recovery over a 3-week polarized microcycle. However, the findings do not support block-distributed HIT as a superior method to a more even distribution of HIT in terms of enhancing physiological or performance adaptions.

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

NASA Astrophysics Data System (ADS)

Rosenberg, D. E.; Alafifi, A.

2016-12-01

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

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.

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

Overview of the HIT-SI3 spheromak experiment

NASA Astrophysics Data System (ADS)

Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Everson, C. J.; Penna, J. M.; Nelson, B. A.

2017-10-01

The HIT-SI and HIT-SI3 spheromak experiments (a = 23 cm) study efficient, steady-state current drive for magnetic confinement plasmas using a novel method which is ideal for low aspect ratio, toroidal geometries. Sustained spheromaks show coherent, imposed plasma motion and low plasma-generated mode activity, indicating stability. Analysis of surface magnetic fields in HIT-SI indicates large n = 0 and 1 mode amplitudes and little energy in higher modes. Within measurement uncertainties all the n = 1 energy is imposed by the injectors, rather than being plasma-generated. The fluctuating field imposed by the injectors is sufficient to sustain the toroidal current through dynamo action whereas the plasma-generated field is not (Hossack et al., Phys. Plasmas, 2017). Ion Doppler spectroscopy shows coherent, imposed plasma motion inside r 10 cm in HIT-SI and a smaller volume of coherent motion in HIT-SI3. Coherent motion indicates the spheromak is stable and a lack of plasma-generated n = 1 energy indicates the maximum q is maintained below 1 for stability during sustainment. In HIT-SI3, the imposed mode structure is varied to test the plasma response (Hossack et al., Nucl. Fusion, 2017). Imposing n = 2, n = 3, or large, rotating n = 1 perturbations is correlated with transient plasma-generated activity. Work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences, under Award Number DE-FG02-96ER54361.

Biophysics: for HTS hit validation, chemical lead optimization, and beyond.

PubMed

Genick, Christine C; Wright, S Kirk

2017-09-01

There are many challenges to the drug discovery process, including the complexity of the target, its interactions, and how these factors play a role in causing the disease. Traditionally, biophysics has been used for hit validation and chemical lead optimization. With its increased throughput and sensitivity, biophysics is now being applied earlier in this process to empower target characterization and hit finding. Areas covered: In this article, the authors provide an overview of how biophysics can be utilized to assess the quality of the reagents used in screening assays, to validate potential tool compounds, to test the integrity of screening assays, and to create follow-up strategies for compound characterization. They also briefly discuss the utilization of different biophysical methods in hit validation to help avoid the resource consuming pitfalls caused by the lack of hit overlap between biophysical methods. Expert opinion: The use of biophysics early on in the drug discovery process has proven crucial to identifying and characterizing targets of complex nature. It also has enabled the identification and classification of small molecules which interact in an allosteric or covalent manner with the target. By applying biophysics in this manner and at the early stages of this process, the chances of finding chemical leads with novel mechanisms of action are increased. In the future, focused screens with biophysics as a primary readout will become increasingly common.

Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial.

PubMed

Beiderlinden, Martin; Werner, Patrick; Bahlmann, Astrid; Kemper, Johann; Brezina, Tobias; Schäfer, Maximilian; Görlinger, Klaus; Seidel, Holger; Kienbaum, Peter; Treschan, Tanja A

2018-02-09

Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients. This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor. To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] μg/ml argatroban and 0.17 [0.1-0.32] μg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs. In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT. ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.

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 high-performance liquid chromatography method for the serotonin release assay is equivalent to the radioactive method.

PubMed

Sono-Koree, N K; Crist, R A; Frank, E L; Rodgers, G M; Smock, K J

2016-02-01

The serotonin release assay (SRA) is considered the gold standard laboratory test for heparin-induced thrombocytopenia (HIT). The historic SRA method uses platelets loaded with radiolabeled serotonin to evaluate platelet activation by HIT immune complexes. However, a nonradioactive method is desirable. We report the performance characteristics of a high-performance liquid chromatography (HPLC) SRA method. We validated the performance characteristics of an HPLC-SRA method, including correlation with a reference laboratory using the radioactive method. Serotonin released from reagent platelets was quantified by HPLC using fluorescent detection. Results were expressed as % release and classified as positive, negative, or indeterminate based on previously published cutoffs. Serum samples from 250 subjects with suspected HIT were tested in the HPLC-SRA and with the radioactive method. Concordant classifications were observed in 230 samples (92%). Sera from 41 healthy individuals tested negative. Between-run imprecision studies showed standard deviation of <6 (% release) for positive, weak positive, and negative serum pools. Stability studies demonstrated stability after two freeze-thaw cycles or up to a week of refrigeration. The HPLC-SRA has robust performance characteristics, equivalent to the historic radioactive method, but avoids the complexities of working with radioactivity. © 2015 John Wiley & Sons Ltd.

The Probability of Hitting a Polygonal Target

DTIC Science & Technology

1981-04-01

required for the use of this method for coalputing the probability of hitting d polygonal target. These functions are 1. PHIT (called by user’s main progran...2. FIJ (called by PHIT ) 3. FUN (called by FIJ) The user must include all three of these in his main program, but needs only to call PHIT . The

Transition to Double Mach Stem for Nuclear Explosion at 104 ft Height of Burst.

DTIC Science & Technology

1981-11-17

P ROIS, 0 L BOOK UNCLASS II D NP.l--4630Mhhnnmmmnmhunm *uunummmummuuuu EllllIhllllllIIIIIIIII VA . L, BOK -- Wotk~ ~ ~ hit ftIlum Zsm Noe4be 01 NOV1...resolved on the mesh. By the time it occupies a region of 15 cells high and 35 cells wide, the peak pressures are in good agreement with the HE data and...2800 3220 2800 32 RADIUS- cm RADIUS -cm 35 1 kt AT 104 f t HOB TIME =5.47 nisec CYCLE= 5400 PRESSURE VELOC IT Y 350

Results from the HARP Experiment

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

Borghi, Silvia

2006-07-11

The HARP experiment at CERN performed extensive measurements of hadronic cross-sections and secondary particle yields in the momentum range 1.5-15 GeV/c aiming at full angular coverage and full particle identification. We report about the double-differential production cross-section for positive pions, for incident protons of 12.9 GeV/c momentum hitting an aluminum target of 5% nuclear interaction length. The measurement of this cross-section has direct application to the prediction of the neutrino flux of K2K experiment and in particular on the far-near neutrino flux ratio.

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.

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.

[Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens].

PubMed

Yin, W J; Zhu, X; Yang, H Y; Sun, W Y; Wu, M J

2018-01-08

Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

Changes in mitochondrial function and mitochondria associated protein expression in response to 2-weeks of high intensity interval training

PubMed Central

Vincent, Grace; Lamon, Séverine; Gant, Nicholas; Vincent, Peter J.; MacDonald, Julia R.; Markworth, James F.; Edge, Johann A.; Hickey, Anthony J. R.

2015-01-01

Purpose: High-intensity short-duration interval training (HIT) stimulates functional and metabolic adaptation in skeletal muscle, but the influence of HIT on mitochondrial function remains poorly studied in humans. Mitochondrial metabolism as well as mitochondrial-associated protein expression were tested in untrained participants performing HIT over a 2-week period. Methods: Eight males performed a single-leg cycling protocol (12 × 1 min intervals at 120% peak power output, 90 s recovery, 4 days/week). Muscle biopsies (vastus lateralis) were taken pre- and post-HIT. Mitochondrial respiration in permeabilized fibers, citrate synthase (CS) activity and protein expression of peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and respiratory complex components were measured. Results: HIT training improved peak power and time to fatigue. Increases in absolute oxidative phosphorylation (OXPHOS) capacities and CS activity were observed, but not in the ratio of CCO to the electron transport system (CCO/ETS), the respiratory control ratios (RCR-1 and RCR-2) or mitochondrial-associated protein expression. Specific increases in OXPHOS flux were not apparent after normalization to CS, indicating that gross changes mainly resulted from increased mitochondrial mass. Conclusion: Over only 2 weeks HIT significantly increased mitochondrial function in skeletal muscle independently of detectable changes in mitochondrial-associated and mitogenic protein expression. PMID:25759671

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.

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.

Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors.

PubMed

Varnes, Jeffrey G; Geschwindner, Stefan; Holmquist, Christopher R; Forst, Janet; Wang, Xia; Dekker, Niek; Scott, Clay W; Tian, Gaochao; Wood, Michael W; Albert, Jeffrey S

2016-01-01

Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's ∼500μM), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4μM hit, which, after preparation of a small number of analogs, was elaborated into a 16nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Just-in-Time Compound Pooling Increases Primary Screening Capacity without Compromising Screening Quality.

PubMed

Elkin, L L; Harden, D G; Saldanha, S; Ferguson, H; Cheney, D L; Pieniazek, S N; Maloney, D P; Zewinski, J; O'Connell, J; Banks, M

2015-06-01

Compound pooling, or multiplexing more than one compound per well during primary high-throughput screening (HTS), is a controversial approach with a long history of limited success. Many issues with this approach likely arise from long-term storage of library plates containing complex mixtures of compounds at high concentrations. Due to the historical difficulties with using multiplexed library plates, primary HTS often uses a one-compound-one-well approach. However, as compound collections grow, innovative strategies are required to increase the capacity of primary screening campaigns. Toward this goal, we have developed a novel compound pooling method that increases screening capacity without compromising data quality. This method circumvents issues related to the long-term storage of complex compound mixtures by using acoustic dispensing to enable "just-in-time" compound pooling directly in the assay well immediately prior to assay. Using this method, we can pool two compounds per well, effectively doubling the capacity of a primary screen. Here, we present data from pilot studies using just-in-time pooling, as well as data from a large >2-million-compound screen using this approach. These data suggest that, for many targets, this method can be used to vastly increase screening capacity without significant reduction in the ability to detect screening hits. © 2015 Society for Laboratory Automation and Screening.

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

Do L5 and s1 nerve root compressions produce radicular pain in a dermatomal pattern?

PubMed

Taylor, Christopher S; Coxon, Andrew J; Watson, Paul C; Greenough, Charles G

2013-05-20

Observational case series. To compare the pattern of distribution of radicular pain with published dermatome charts. Dermatomal charts vary and previous studies have demonstrated significant individual subject variation. Patients with radiologically and surgically proven nerve root compression (NRC) caused by prolapsed intervertebral disc completed computerized diagrams of the distribution of pain and pins and needles. Ninety-eight patients had L5 compressions and 83 had S1 compressions. The distribution of pain and pins and needles did not correspond well with dermatomal patterns. Of those patients with L5 NRC, only 22 (22.4%) recorded any hits on the L5 dermatome on the front, and only 60 (61.2%) on the back with only 13 (13.3%) on both. Only 1 (1.0%) patient placed more than 50% of their hits within the L5 dermatome. Of those patients with S1 NRC, only 3 (3.6%) recorded any hits on the S1 dermatome on the front, and only 64 (77.1%) on the back with only 15 (18.1%) on both. No patients placed more than 50% of their hits within the S1 dermatome. Regarding pins and needles, 27 (29.7%) patients with L5 NRC recorded hits on the front alone, 27 (29.7%) on the back alone, and 14 (15.4%) on both. Nineteen (20.9%) recorded more than 50% of hits within the L5 dermatome. Three (3.6%) patients with S1 NRC recorded hits on the front alone, 44 (53.0%) on the back alone, and 18 (21.7%) on both. Twelve (14.5%) recorded more than 50% of hits within the S1 dermatome. Patient report is an unreliable method of identifying the anatomical source of pain or paresthesia caused by nerve root compression. 4.

Effects of high-intensity interval training on central haemodynamics and skeletal muscle oxygenation during exercise in patients with chronic heart failure.

PubMed

Spee, Ruud F; Niemeijer, Victor M; Wijn, Pieter F; Doevendans, Pieter A; Kemps, Hareld M

2016-12-01

Background High-intensity interval training (HIT) improves exercise capacity in patients with chronic heart failure (CHF). Moreover, HIT was associated with improved resting cardiac function. However, the extent to which these improvements actually contribute to training-induced changes in exercise capacity remains to be elucidated. Therefore, we evaluated the effects of HIT on exercising central haemodynamics and skeletal muscle oxygenation. Methods Twenty-six CHF patients were randomised to a 12-week 4 × 4 minute HIT program at 85-95% of peak VO 2 or usual care. Patients performed maximal and submaximal cardiopulmonary exercise testing with simultaneous assessment of cardiac output and skeletal muscle oxygenation by near infrared spectroscopy, using the amplitude of the tissue saturation index (TSIamp). Results Peak workload increased by 11% after HIT ( p between group = 0.01) with a non-significant increase in peak VO 2 (+7%, p between group = 0.19). Cardiac reserve increased by 37% after HIT ( p within group = 0.03, p between group = 0.08); this increase was not related to improvements in peak workload. Oxygen uptake recovery kinetics after submaximal exercise were accelerated by 20% ( p between group = 0.02); this improvement was related to a decrease in TSIamp ( r = 0.71, p = 0.03), but not to changes in cardiac output kinetics. Conclusion HIT induced improvements in maximal exercise capacity and exercising haemodynamics at peak exercise. Improvements in recovery after submaximal exercise were associated with attenuated skeletal muscle deoxygenation during submaximal exercise, but not with changes in cardiac output kinetics, suggesting that the effect of HIT on submaximal exercise capacity is mediated by improved microvascular oxygen delivery-to-utilisation matching.

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.

Hurst exponent and prediction based on weak-form efficient market hypothesis of stock markets

NASA Astrophysics Data System (ADS)

Eom, Cheoljun; Choi, Sunghoon; Oh, Gabjin; Jung, Woo-Sung

2008-07-01

We empirically investigated the relationships between the degree of efficiency and the predictability in financial time-series data. The Hurst exponent was used as the measurement of the degree of efficiency, and the hit rate calculated from the nearest-neighbor prediction method was used for the prediction of the directions of future price changes. We used 60 market indexes of various countries. We empirically discovered that the relationship between the degree of efficiency (the Hurst exponent) and the predictability (the hit rate) is strongly positive. That is, a market index with a higher Hurst exponent tends to have a higher hit rate. These results suggested that the Hurst exponent is useful for predicting future price changes. Furthermore, we also discovered that the Hurst exponent and the hit rate are useful as standards that can distinguish emerging capital markets from mature capital markets.

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

Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment Induce Changes in the Structure and Neurochemistry of Inhibitory Neurons of the Adult Amygdala and Prefrontal Cortex

PubMed Central

Bellés, María; Gilabert-Juan, Javier; Llorens, José Vicente; Bueno-Fernández, Clara; Ripoll-Martínez, Beatriz; Curto, Yasmina; Sebastiá-Ortega, Noelia; Sanjuan, Julio

2017-01-01

Abstract The exposure to aversive experiences during early life influences brain development and leads to altered behavior. Moreover, the combination of these experiences with subtle alterations in neurodevelopment may contribute to the emergence of psychiatric disorders, such as schizophrenia. Recent hypotheses suggest that imbalances between excitatory and inhibitory (E/I) neurotransmission, especially in the prefrontal cortex and the amygdala, may underlie their etiopathology. In order to understand better the neurobiological bases of these alterations, we studied the impact of altered neurodevelopment and chronic early-life stress on these two brain regions. Transgenic mice displaying fluorescent excitatory and inhibitory neurons, received a single injection of MK801 (NMDAR antagonist) or vehicle solution at postnatal day 7 and/or were socially isolated from the age of weaning until adulthood (3 months old). We found that anxiety-related behavior, brain volume, neuronal structure, and the expression of molecules related to plasticity and E/I neurotransmission in adult mice were importantly affected by early-life stress. Interestingly, many of these effects were potentiated when the stress paradigm was applied to mice perinatally injected with MK801 ("double-hit" model). These results clearly show the impact of early-life stress on the adult brain, especially on the structure and plasticity of inhibitory networks, and highlight the double-hit model as a valuable tool to study the contribution of early-life stress in the emergence of neurodevelopmental psychiatric disorders, such as schizophrenia. PMID:28466069

"Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.

PubMed

Chapiro, Elise; Lesty, Claude; Gabillaud, Clémentine; Durot, Eric; Bouzy, Simon; Armand, Marine; Le Garff-Tavernier, Magali; Bougacha, Nadia; Struski, Stéphanie; Bidet, Audrey; Laharanne, Elodie; Barin, Carole; Veronese, Lauren; Prié, Nolwen; Eclache, Virginie; Gaillard, Baptiste; Michaux, Lucienne; Lefebvre, Christine; Gaillard, Jean-Baptiste; Terré, Christine; Penther, Dominique; Bastard, Christian; Nadal, Nathalie; Fert-Ferrer, Sandra; Auger, Nathalie; Godon, Catherine; Sutton, Laurent; Tournilhac, Olivier; Susin, Santos A; Nguyen-Khac, Florence

2018-03-01

Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL. © 2017 Wiley Periodicals, Inc.

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.

Spectroscopic studies of Cr VI species in a laser produced plasma

NASA Astrophysics Data System (ADS)

Klemke, Nicolai; Nadarajan, Smijesh; Laban, Dane; Wood, James; Chetty, Dashavir; Kielpinski, David; Litvinyuk, Igor; Sang, Robert

2015-09-01

We present measurements characterizing a laser generated, highly ionized microplasma suitable to extend the cut-off energy of High Harmonic Generation (HHG) to energies up to 5 keV. The HHG process occurs when a strong ultrafast laser hits a gaseous target producing coherent radiation with a much higher photon energy than the driving laser. Commonly, noble gases are used and typical photon energies of several 100 eV are obtained. We plan to use Cr5+ species as the target for HHG as generated by a double pulse method: the first pulse creates the plasma, the second pulse is used to obtain the temperature required for Cr5+. Here, we present results on the optimization of plasma parameters such as the plasma temperature, the number density and the dynamics of Cr5+ by means of spectroscopic techniques in the optical and the XUV regime. This research is supported by Lockheed Martin and the Australian Research Council.

Leakage current-induced effects in the silicon microstrip and gas electron multiplier readout chain and their compensation method

NASA Astrophysics Data System (ADS)

Zubrzycka, W.; Kasinski, K.

2018-04-01

Leakage current flowing into the charge sensitive amplifier (CSA) is a common issue in many radiation detection systems as it can increase overall system noise, shift a DC baseline or even lead a recording channel to instability. The commonly known leakage current contributor is a detector, however other system components like wires or an input protection circuit may become a serious problem. Compensation of the leakage current resulting from the electrostatic discharge (ESD) protection circuit by properly sizing its components is possible only for a narrow temperature range. Moreover, the leakage current from external sources can be significantly larger. Many applications, especially High Energy Physics (HEP) experiments, require a fast baseline restoration for high input hit rates by applying either a low-value feedback resistor or a high feedback resistance combined with a pulsed reset circuit. Leakage current flowing in the feedback in conjunction with a large feedback resistance supplied with a pulsed reset results in a significant voltage offset between the CSA input and output which can cause problems (e.g. fake hits or instability). This paper shows an issue referred to the leakage current of the ESD protection circuit flowing into the input amplifier. The following analysis and proposed solution is a result of the time and energy readout ASIC project realization for the Compressed Baryonic Matter (CBM) experiment at FAIR (Facility for Antiproton and Ion Research) in Darmstadt, Germany. This chip is purposed to work with microstrip and gaseous detectors, with high average input pulses frequencies (250 kHit/s per channel) and the possibility to process input charge of both polarities. We present measurements of the test structure fabricated in UMC 180 nm technology and propose a solution addressing leakage current related issues. This work combines the leakage current compensation capabilities at the CSA level with high, controllable value of the amplifier feedback resistor independent of the leakage current level and polarity. The simulation results of the double, switchable, Krummenacher circuit-based feedback application in the CSA with a pulsed reset functionality are presented.

Functional genomics platform for pooled screening and mammalian genetic interaction maps

PubMed Central

Kampmann, Martin; Bassik, Michael C.; Weissman, Jonathan S.

2014-01-01

Systematic genetic interaction maps in microorganisms are powerful tools for identifying functional relationships between genes and defining the function of uncharacterized genes. We have recently implemented this strategy in mammalian cells as a two-stage approach. First, genes of interest are robustly identified in a pooled genome-wide screen using complex shRNA libraries. Second, phenotypes for all pairwise combinations of hit genes are measured in a double-shRNA screen and used to construct a genetic interaction map. Our protocol allows for rapid pooled screening under various conditions without a requirement for robotics, in contrast to arrayed approaches. Each stage of the protocol can be implemented in ~2 weeks, with additional time for analysis and generation of reagents. We discuss considerations for screen design, and present complete experimental procedures as well as a full computational analysis suite for identification of hits in pooled screens and generation of genetic interaction maps. While the protocols outlined here were developed for our original shRNA-based approach, they can be applied more generally, including to CRISPR-based approaches. PMID:24992097

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration

PubMed Central

Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

2013-01-01

Background Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Methods Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Results Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis (p<0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. Conclusion We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration. PMID:24358450

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

High intensity training in obesity: a Meta‐analysis

PubMed Central

Theel, W.; Kasteleyn, M. J.; Franssen, F. M. E.; Hiemstra, P. S.; Rudolphus, A.; Taube, C.; Braunstahl, G. J.

2017-01-01

Summary Introduction High Intensity training (HIT) is a time‐effective alternative to traditional exercise programs in adults with obesity, but the superiority in terms of improving cardiopulmonary fitness and weight loss has not been demonstrated. Objective to determine the effectiveness of HIT on cardiopulmonary fitness and body composition in adults with obesity compared to traditional (high volume continuous) exercise. Methods A systematic search of the main health science databases was conducted for randomized controlled trials comparing HIT with traditional forms of exercise in people with obesity. Eighteen studies were included in the meta‐analysis. The (unstandardized) mean difference of each outcome parameters was calculated and pooled with the random effects model. Results HIT resulted in greater improvement of cardiopulmonary fitness (VO2max) (MD 1.83, 95% CI 0.70, 2.96, p<0.005; I2=31%) and a greater reduction of %body fat (MD ‐1.69, 95% CI ‐3.10, ‐0.27, p=0.02, I2=30%) compared to traditional exercise. Overall effect for BMI was not different between HIT and traditional exercise. Conclusion Training at high intensity is superior to improve cardiopulmonary fitness and to reduce %body fat in adults with obesity compared to traditional exercise. Future studies are needed to design specific HIT programs for the obese with regard to optimal effect and long‐term adherence. PMID:29071102

5-week block periodization increases aerobic power in elite cross-country skiers.

PubMed

Rønnestad, B R; Hansen, J; Thyli, V; Bakken, T A; Sandbakk, Ø

2016-02-01

The purpose of this study was to compare the effect of two different methods of organizing endurance training in elite cross-country skiers approaching the competition period. During the 5-week intervention period, one group performed block periodization (BP; n = 10) with 5 and 3 high-intensity sessions (HIT) during the first and third training week. One HIT was performed during the remaining weeks in BP, while the group performing traditional training organization (TRAD, n = 9) performed two weekly HIT except during the third week where they performed three HIT. HIT were interspersed with low-intensity training (LIT) and both groups performed similar total amount of both HIT and LIT during the intervention. BP achieved a larger relative increase in peak power output and power output at a blood lactate concentration of 4 mmol/L than TRAD (4 ± 4 vs -3 ± 6% and 11 ± 10 vs 2 ± 4%, respectively, both P < 0.01). BP also increased maximal oxygen uptake by 2 ± 2% (P < 0.05), while no changes occurred in TRAD. The effect sizes of the relative improvement in these measurements revealed moderate effects of BP vs TRAD training. The present study suggests that block periodization of endurance training have superior effects on several endurance and performance indices compared with traditional organization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Incorporating interaction networks into the determination of functionally related hit genes in genomic experiments with Markov random fields

PubMed Central

Robinson, Sean; Nevalainen, Jaakko; Pinna, Guillaume; Campalans, Anna; Radicella, J. Pablo; Guyon, Laurent

2017-01-01

Abstract Motivation: Incorporating gene interaction data into the identification of ‘hit’ genes in genomic experiments is a well-established approach leveraging the ‘guilt by association’ assumption to obtain a network based hit list of functionally related genes. We aim to develop a method to allow for multivariate gene scores and multiple hit labels in order to extend the analysis of genomic screening data within such an approach. Results: We propose a Markov random field-based method to achieve our aim and show that the particular advantages of our method compared with those currently used lead to new insights in previously analysed data as well as for our own motivating data. Our method additionally achieves the best performance in an independent simulation experiment. The real data applications we consider comprise of a survival analysis and differential expression experiment and a cell-based RNA interference functional screen. Availability and implementation: We provide all of the data and code related to the results in the paper. Contact: sean.j.robinson@utu.fi or laurent.guyon@cea.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28881978

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.

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.

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.

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.

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

PubMed Central

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

2011-01-01

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

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.

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.

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.

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.

Let’s Get Healthy! Health Awareness Through Public Participation in an Education and Research Exhibit

PubMed Central

Marriott, Lisa K.; Cameron, William E.; Purnell, Jonathan Q.; Cetola, Stephano; Ito, Matthew K.; Williams, Craig D.; Newcomb, Kenneth C.; Randall, Joan A.; Messenger, Wyatt B.; Lipus, Adam C.; Shannon, Jackilen

2013-01-01

Background Health information technology (HIT) offers a resource for public empowerment through tailored information. Objective Use interactive community health events to improve awareness of chronic disease risk factors while collecting data to improve health. Methods Let’s Get Healthy! is an education and research program in which participants visit interactive research stations to learn about their own health (diet, body composition, blood chemistry). HIT enables computerized data collection that presents participants with immediate results and tailored educational feedback. An anonymous wristband number links collected data in a population database. Results and Lessons Learned Communities tailor events to meet community health needs with volunteers trained to conduct research. Participants experience being a research participant and contribute to an anonymous population database for both traditional research purposes and open-source community use. Conclusions By integrating HIT with community involvement, health fairs become an interactive method for engaging communities in research and raising health awareness. PMID:22982846

An Automatic Quality Control Pipeline for High-Throughput Screening Hit Identification.

PubMed

Zhai, Yufeng; Chen, Kaisheng; Zhong, Yang; Zhou, Bin; Ainscow, Edward; Wu, Ying-Ta; Zhou, Yingyao

2016-09-01

The correction or removal of signal errors in high-throughput screening (HTS) data is critical to the identification of high-quality lead candidates. Although a number of strategies have been previously developed to correct systematic errors and to remove screening artifacts, they are not universally effective and still require fair amount of human intervention. We introduce a fully automated quality control (QC) pipeline that can correct generic interplate systematic errors and remove intraplate random artifacts. The new pipeline was first applied to ~100 large-scale historical HTS assays; in silico analysis showed auto-QC led to a noticeably stronger structure-activity relationship. The method was further tested in several independent HTS runs, where QC results were sampled for experimental validation. Significantly increased hit confirmation rates were obtained after the QC steps, confirming that the proposed method was effective in enriching true-positive hits. An implementation of the algorithm is available to the screening community. © 2016 Society for Laboratory Automation and Screening.

CHI during an ohmic discharge in HIT-II

NASA Astrophysics Data System (ADS)

Mueller, Dennis; Nelson, Brian A.; Redd, Aaron J.; Hamp, William T.

2004-11-01

Coaxial Helicity Injection (CHI) has been used on the National Spherical Torus Experiment (NSTX), the Helicity Injected Torus (HIT) and HIT-II to initiate plasma and to drive up to 400 kA of toroidal current. The primary goal of the CHI systems is to provide a start-up plasma with substantial toroidal current that can be heated and sustained with other methods. We have investigated the use of CHI systems to add current to an established, inductively driven plasma. This may be an attractive method to add edge current that may modify the stability characteristics of the discharge or modify the particle and energy transport in a spherical torus. For example, divertor biasing experiments have been successful in modifying particle and energy transport in the scrape-off layer of tokamaks. Use of IGBT power supplies to modulate the injector current makes analysis of current penetration feasible by comparisons of before and after CHI using EFIT analysis of the data.

A Bayesian taxonomic classification method for 16S rRNA gene sequences with improved species-level accuracy.

PubMed

Gao, Xiang; Lin, Huaiying; Revanna, Kashi; Dong, Qunfeng

2017-05-10

Species-level classification for 16S rRNA gene sequences remains a serious challenge for microbiome researchers, because existing taxonomic classification tools for 16S rRNA gene sequences either do not provide species-level classification, or their classification results are unreliable. The unreliable results are due to the limitations in the existing methods which either lack solid probabilistic-based criteria to evaluate the confidence of their taxonomic assignments, or use nucleotide k-mer frequency as the proxy for sequence similarity measurement. We have developed a method that shows significantly improved species-level classification results over existing methods. Our method calculates true sequence similarity between query sequences and database hits using pairwise sequence alignment. Taxonomic classifications are assigned from the species to the phylum levels based on the lowest common ancestors of multiple database hits for each query sequence, and further classification reliabilities are evaluated by bootstrap confidence scores. The novelty of our method is that the contribution of each database hit to the taxonomic assignment of the query sequence is weighted by a Bayesian posterior probability based upon the degree of sequence similarity of the database hit to the query sequence. Our method does not need any training datasets specific for different taxonomic groups. Instead only a reference database is required for aligning to the query sequences, making our method easily applicable for different regions of the 16S rRNA gene or other phylogenetic marker genes. Reliable species-level classification for 16S rRNA or other phylogenetic marker genes is critical for microbiome research. Our software shows significantly higher classification accuracy than the existing tools and we provide probabilistic-based confidence scores to evaluate the reliability of our taxonomic classification assignments based on multiple database matches to query sequences. Despite its higher computational costs, our method is still suitable for analyzing large-scale microbiome datasets for practical purposes. Furthermore, our method can be applied for taxonomic classification of any phylogenetic marker gene sequences. Our software, called BLCA, is freely available at https://github.com/qunfengdong/BLCA .

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.

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

PubMed Central

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

2017-01-01

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

Health information technology 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

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

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.

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

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.

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.

The FLIGHT Drosophila RNAi database

PubMed Central

Bursteinas, Borisas; Jain, Ekta; Gao, Qiong; Baum, Buzz; Zvelebil, Marketa

2010-01-01

FLIGHT (http://flight.icr.ac.uk/) is an online resource compiling data from high-throughput Drosophila in vivo and in vitro RNAi screens. FLIGHT includes details of RNAi reagents and their predicted off-target effects, alongside RNAi screen hits, scores and phenotypes, including images from high-content screens. The latest release of FLIGHT is designed to enable users to upload, analyze, integrate and share their own RNAi screens. Users can perform multiple normalizations, view quality control plots, detect and assign screen hits and compare hits from multiple screens using a variety of methods including hierarchical clustering. FLIGHT integrates RNAi screen data with microarray gene expression as well as genomic annotations and genetic/physical interaction datasets to provide a single interface for RNAi screen analysis and datamining in Drosophila. PMID:20855970

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.

Non-Alcoholic Fatty Liver Disease.

PubMed

Engin, Atilla

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/Non-alcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with rising saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in liver tissue of patients with NASH. Furthermore, hepatocyte lipoapoptosis is a critical feature of NASH. In "second hit" reduced glutathione levels due to oxidative stress lead to overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused by the ineffectual cycling of the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and Kelch like-ECH-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries.

PubMed

Han, Bucong; Ma, Xiaohua; Zhao, Ruiying; Zhang, Jingxian; Wei, Xiaona; Liu, Xianghui; Liu, Xin; Zhang, Cunlong; Tan, Chunyan; Jiang, Yuyang; Chen, Yuzong

2012-11-23

Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

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

Functional Assays to Screen and Dissect Genomic Hits: Doubling Down on the National Investment in Genomic Research.

PubMed

Musunuru, Kiran; Bernstein, Daniel; Cole, F Sessions; Khokha, Mustafa K; Lee, Frank S; Lin, Shin; McDonald, Thomas V; Moskowitz, Ivan P; Quertermous, Thomas; Sankaran, Vijay G; Schwartz, David A; Silverman, Edwin K; Zhou, Xiaobo; Hasan, Ahmed A K; Luo, Xiao-Zhong James

2018-04-01

The National Institutes of Health have made substantial investments in genomic studies and technologies to identify DNA sequence variants associated with human disease phenotypes. The National Heart, Lung, and Blood Institute has been at the forefront of these commitments to ascertain genetic variation associated with heart, lung, blood, and sleep diseases and related clinical traits. Genome-wide association studies, exome- and genome-sequencing studies, and exome-genotyping studies of the National Heart, Lung, and Blood Institute-funded epidemiological and clinical case-control studies are identifying large numbers of genetic variants associated with heart, lung, blood, and sleep phenotypes. However, investigators face challenges in identification of genomic variants that are functionally disruptive among the myriad of computationally implicated variants. Studies to define mechanisms of genetic disruption encoded by computationally identified genomic variants require reproducible, adaptable, and inexpensive methods to screen candidate variant and gene function. High-throughput strategies will permit a tiered variant discovery and genetic mechanism approach that begins with rapid functional screening of a large number of computationally implicated variants and genes for discovery of those that merit mechanistic investigation. As such, improved variant-to-gene and gene-to-function screens-and adequate support for such studies-are critical to accelerating the translation of genomic findings. In this White Paper, we outline the variety of novel technologies, assays, and model systems that are making such screens faster, cheaper, and more accurate, referencing published work and ongoing work supported by the National Heart, Lung, and Blood Institute's R21/R33 Functional Assays to Screen Genomic Hits program. We discuss priorities that can accelerate the impressive but incomplete progress represented by big data genomic research. © 2018 American Heart Association, Inc.

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

PubMed

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains.

Highly Sensitive Detection of Individual HEAT and ARM Repeats with HHpred and COACH

PubMed Central

Kippert, Fred; Gerloff, Dietlind L.

2009-01-01

Background HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Methodology and Principal Findings Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. Significance A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains. PMID:19777061

Health Literacy and Health Information Technology Adoption: The Potential for a New Digital Divide

PubMed Central

Mabry-Flynn, Amanda; Champlin, Sara; Donovan, Erin E; Pounders, Kathrynn

2016-01-01

Background Approximately one-half of American adults exhibit low health literacy and thus struggle to find and use health information. Low health literacy is associated with negative outcomes including overall poorer health. Health information technology (HIT) makes health information available directly to patients through electronic tools including patient portals, wearable technology, and mobile apps. The direct availability of this information to patients, however, may be complicated by misunderstanding of HIT privacy and information sharing. Objective The purpose of this study was to determine whether health literacy is associated with patients’ use of four types of HIT tools: fitness and nutrition apps, activity trackers, and patient portals. Additionally, we sought to explore whether health literacy is associated with patients’ perceived ease of use and usefulness of these HIT tools, as well as patients’ perceptions of privacy offered by HIT tools and trust in government, media, technology companies, and health care. This study is the first wide-scale investigation of these interrelated concepts. Methods Participants were 4974 American adults (n=2102, 42.26% male, n=3146, 63.25% white, average age 43.5, SD 16.7 years). Participants completed the Newest Vital Sign measure of health literacy and indicated their actual use of HIT tools, as well as the perceived ease of use and usefulness of these applications. Participants also answered questions regarding information privacy and institutional trust, as well as demographic items. Results Cross-tabulation analysis indicated that adequate versus less than adequate health literacy was significantly associated with use of fitness apps (P=.02), nutrition apps (P<.001), activity trackers (P<.001), and patient portals (P<.001). Additionally, greater health literacy was significantly associated with greater perceived ease of use and perceived usefulness across all HIT tools after controlling for demographics. Regarding privacy perceptions of HIT and institutional trust, patients with greater health literacy often demonstrated decreased privacy perceptions for HIT tools including fitness apps (P<.001) and nutrition apps (P<.001). Health literacy was negatively associated with trust in government (P<.001), media (P<.001), and technology companies (P<.001). Interestingly, health literacy score was positively associated with trust in health care (P=.03). Conclusions Patients with low health literacy were less likely to use HIT tools or perceive them as easy or useful, but they perceived information on HIT as private. Given the fast-paced evolution of technology, there is a pressing need to further the understanding of how health literacy is related to HIT app adoption and usage. This will ensure that all users receive the full health benefits from these technological advances, in a manner that protects health information privacy, and that users engage with organizations and providers they trust. PMID:27702738

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

PubMed

Feldman, Howard J; Hogue, Christopher W V

2002-01-01

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

Safe use of electronic health records and health information technology systems: trust but verify.

PubMed

Denham, Charles R; Classen, David C; Swenson, Stephen J; Henderson, Michael J; Zeltner, Thomas; Bates, David W

2013-12-01

We will provide a context to health information technology systems (HIT) safety hazards discussions, describe how electronic health record-computer prescriber order entry (EHR-CPOE) simulation has already identified unrecognized hazards in HIT on a national scale, helping make EHR-CPOE systems safer, and we make the case for all stakeholders to leverage proven methods and teams in HIT performance verification. A national poll of safety, quality improvement, and health-care administrative leaders identified health information technology safety as the hazard of greatest concern for 2013. Quality, HIT, and safety leaders are very concerned about technology performance risks as addressed in the Health Information Technology and Patient Safety report of the Institute of Medicine; and these are being addressed by the Office of the National Coordinator of HIT of the U.S. Dept. of Human Services in their proposed plans. We describe the evolution of postdeployment testing of HIT performance, including the results of national deployment of Texas Medical Institute of Technology's electronic health record computer prescriber order entry (TMIT EHR-CPOE) Flight Simulator verification test that is addressed in these 2 reports, and the safety hazards of concern to leaders. A global webinar for health-care leaders addressed the top patient safety hazards in the areas of leadership, practices, and technologies. A poll of 76 of the 221 organizations participating in the webinar revealed that HIT hazards were the participants' greatest concern of all 30 hazards presented. Of those polled, 89% rated HIT patient/data mismatches in EHRs and HIT systems as a 9 or 10 on a scale of 1 to 10 as a hazard of great concern. Review of a key study of postdeployment testing of the safety performance of operational EHR systems with CPOE implemented in 62 hospitals, using the TMIT EHR-CPOE simulation tool, showed that only 53% of the medication orders that could have resulted in fatalities were detected. The study also showed significant variability in the performance of specific EHR vendor systems, with the same vendor product scoring as high as a 75% detection score in one health-care organization, and the same vendor system scoring below 10% in another health-care organization. HIT safety hazards should be taken very seriously, and the need for proven, robust, and regular postdeployment performance verification measurement of EHR system operations in every health-care organization is critical to ensure that these systems are safe for every patient. The TMIT EHR-CPOE flight simulator is a well-tested and scalable tool that can be used to identify performance gaps in EHR and other HIT systems. It is critical that suppliers, providers, and purchasers of health-care partner with HIT stakeholders and leverage the existing body of work, as well as expert teams and collaborative networks to make care safer; and public-private partnerships to accelerate safety in HIT. A global collaborative is already underway incorporating a "trust but verify" philosophy.

Hit detection in serial femtosecond crystallography using X-ray spectroscopy of plasma emission.

PubMed

Jönsson, H Olof; Caleman, Carl; Andreasson, Jakob; Tîmneanu, Nicuşor

2017-11-01

Serial femtosecond crystallography is an emerging and promising method for determining protein structures, making use of the ultrafast and bright X-ray pulses from X-ray free-electron lasers. The upcoming X-ray laser sources will produce well above 1000 pulses per second and will pose a new challenge: how to quickly determine successful crystal hits and avoid a high-rate data deluge. Proposed here is a hit-finding scheme based on detecting photons from plasma emission after the sample has been intercepted by the X-ray laser. Plasma emission spectra are simulated for systems exposed to high-intensity femtosecond pulses, for both protein crystals and the liquid carrier systems that are used for sample delivery. The thermal radiation from the glowing plasma gives a strong background in the XUV region that depends on the intensity of the pulse, around the emission lines from light elements (carbon, nitrogen, oxygen). Sample hits can be reliably distinguished from the carrier liquid based on the characteristic emission lines from heavier elements present only in the sample, such as sulfur. For buffer systems with sulfur present, selenomethionine substitution is suggested, where the selenium emission lines could be used both as an indication of a hit and as an aid in phasing and structural reconstruction of the protein.

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

Syndromic surveillance for health information system failures: a feasibility study

PubMed Central

Ong, Mei-Sing; Magrabi, Farah; Coiera, Enrico

2013-01-01

Objective To explore the applicability of a syndromic surveillance method to the early detection of health information technology (HIT) system failures. Methods A syndromic surveillance system was developed to monitor a laboratory information system at a tertiary hospital. Four indices were monitored: (1) total laboratory records being created; (2) total records with missing results; (3) average serum potassium results; and (4) total duplicated tests on a patient. The goal was to detect HIT system failures causing: data loss at the record level; data loss at the field level; erroneous data; and unintended duplication of data. Time-series models of the indices were constructed, and statistical process control charts were used to detect unexpected behaviors. The ability of the models to detect HIT system failures was evaluated using simulated failures, each lasting for 24 h, with error rates ranging from 1% to 35%. Results In detecting data loss at the record level, the model achieved a sensitivity of 0.26 when the simulated error rate was 1%, while maintaining a specificity of 0.98. Detection performance improved with increasing error rates, achieving a perfect sensitivity when the error rate was 35%. In the detection of missing results, erroneous serum potassium results and unintended repetition of tests, perfect sensitivity was attained when the error rate was as small as 5%. Decreasing the error rate to 1% resulted in a drop in sensitivity to 0.65–0.85. Conclusions Syndromic surveillance methods can potentially be applied to monitor HIT systems, to facilitate the early detection of failures. PMID:23184193

An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening.

PubMed

Chen, Haining; Li, Sijia; Hu, Yajiao; Chen, Guo; Jiang, Qinglin; Tong, Rongsheng; Zang, Zhihe; Cai, Lulu

2016-01-01

Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is an important regulator of focal adhesion, actomyosin contraction and cell motility. In this manuscript, a combination of the multi-complex-based pharmacophore (MCBP), molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of multipharmacophore- based virtual screening (PBVS) and ensemble docking-based virtual screening (DBVS) methods were used for retrieving novel ROCK1 inhibitors from the natural products database embedded in the ZINC database. Ten hit compounds were selected from the hit compounds, and five compounds were tested experimentally. Thus, these results may provide valuable information for further discovery of more novel ROCK1 inhibitors.

Avalanche for shape and feature-based virtual screening with 3D alignment

NASA Astrophysics Data System (ADS)

Diller, David J.; Connell, Nancy D.; Welsh, William J.

2015-11-01

This report introduces a new ligand-based virtual screening tool called Avalanche that incorporates both shape- and feature-based comparison with three-dimensional (3D) alignment between the query molecule and test compounds residing in a chemical database. Avalanche proceeds in two steps. The first step is an extremely rapid shape/feature based comparison which is used to narrow the focus from potentially millions or billions of candidate molecules and conformations to a more manageable number that are then passed to the second step. The second step is a detailed yet still rapid 3D alignment of the remaining candidate conformations to the query conformation. Using the 3D alignment, these remaining candidate conformations are scored, re-ranked and presented to the user as the top hits for further visualization and evaluation. To provide further insight into the method, the results from two prospective virtual screens are presented which show the ability of Avalanche to identify hits from chemical databases that would likely be missed by common substructure-based or fingerprint-based search methods. The Avalanche method is extended to enable patent landscaping, i.e., structural refinements to improve the patentability of hits for deployment in drug discovery campaigns.

Destination bedside: using research findings to visualize optimal unit layouts and health information technology in support of bedside care.

PubMed

Watkins, Nicholas; Kennedy, Mary; Lee, Nelson; O'Neill, Michael; Peavey, Erin; Ducharme, Maria; Padula, Cynthia

2012-05-01

This study explored the impact of unit design and healthcare information technology (HIT) on nursing workflow and patient-centered care (PCC). Healthcare information technology and unit layout-related predictors of nursing workflow and PCC were measured during a 3-phase study involving questionnaires and work sampling methods. Stepwise multiple linear regressions demonstrated several HIT and unit layout-related factors that impact nursing workflow and PCC.

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

PubMed Central

Hutchins, James R. A.

2014-01-01

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

Plasma response to sustainment with imposed-dynamo current drive in HIT-SI and HIT-SI3

NASA Astrophysics Data System (ADS)

Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Penna, J. M.; Everson, C. J.; Nelson, B. A.

2017-07-01

The helicity injected torus—steady inductive (HIT-SI) program studies efficient, steady-state current drive for magnetic confinement plasmas using a novel experimental method. Stable, high-beta spheromaks have been sustained using steady, inductive current drive. Externally induced loop voltage and magnetic flux are oscillated together so that helicity and power injection are always positive, sustaining the edge plasma current indefinitely. Imposed-dynamo current drive (IDCD) theory further shows that the entire plasma current is sustained. The method is ideal for low aspect ratio, toroidal geometries with closed flux surfaces. Experimental studies of spheromak plasmas sustained with IDCD have shown stable magnetic profiles with evidence of pressure confinement. New measurements show coherent motion of a stable spheromak in response to the imposed perturbations. On the original device two helicity injectors were mounted on either side of the spheromak and the injected mode spectrum was predominantly n  =  1. Coherent, rigid motion indicates that the spheromak is stable and a lack of plasma-generated n  =  1 energy indicates that the maximum q is maintained below 1 during sustainment. Results from the HIT-SI3 device are also presented. Three inductive helicity injectors are mounted on one side of the spheromak flux conserver. Varying the relative injector phasing changes the injected mode spectrum which includes n  =  2, 3, and higher modes.

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...

Health information technology needs help from primary care researchers.

PubMed

Krist, Alex H; Green, Lee A; Phillips, Robert L; Beasley, John W; DeVoe, Jennifer E; Klinkman, Michael S; Hughes, John; Puro, Jon; Fox, Chester H; Burdick, Tim

2015-01-01

While health information technology (HIT) efforts are beginning to yield measurable clinical benefits, more is needed to meet the needs of patients and clinicians. Primary care researchers are uniquely positioned to inform the evidence-based design and use of technology. Research strategies to ensure success include engaging patient and clinician stakeholders, working with existing practice-based research networks, and using established methods from other fields such as human factors engineering and implementation science. Policies are needed to help support primary care researchers in evaluating and implementing HIT into everyday practice, including expanded research funding, strengthened partnerships with vendors, open access to information systems, and support for the Primary Care Extension Program. Through these efforts, the goal of improved outcomes through HIT can be achieved. © Copyright 2015 by the American Board of Family Medicine.

Sleeping beauties in psychology: comparisons of "hits" and "missed signals" in psychological journals.

PubMed

Lange, Lydia L

2005-05-01

Scientific publications tend to be forgotten quickly. A few works, however, are still cited 100 years and more after their publication. The author used bibliometric methods to compare "hits" (works noticed by the scientific community soon after their publication) with "missed signals" (works that went unnoticed until much later) by investigating 2 psychological journals founded in the 1890s: Zeitschrift für Psychologie and Psychological Review. All articles that were published in either of these journals up to 1920 and cited more than 25 times in the Web of Science up to the year 2000 were considered for inclusion in the analysis. It emerged that hits corresponded more closely to the focus of scientific attention at the time of the publications than missed signals.

Binding of radiation-induced phenylalanine radicals to DNA: influence on the biological activity of the DNA and on its sensitivity to the induction of breaks by gamma rays

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

Vanderschans, G.P.; Vanrijn, C.J.S.; Bleichrodt, J.F.

1975-11-01

When an aqueous solution of double-stranded deoxyribonucleic acid (DNA) of bacteriophage PM2 containing phenylalanine and saturated with N2O is irradiated with gamma rays, radiation induced phenylalanine radicals are bound covalently. Under the conditions used about 25 phenylalanine molecules may be bound per lethal hit. Also for single-stranded PM2 DNA most of the phenylalanine radicals bound are nonlethal. Evidence is presented that in double-stranded DNA an appreciable fraction of the single-strand breaks is induced by phenylalanine radicals. Radiation products of phenylalanine and the phenylalanine bound to the DNA decrease the sensitivity of the DNA to the induction of single-strand breaks. Theremore » are indications that the high efficiency of protection by radiation products of phenylalanine is due to their positive charge, which will result in a relatively high concentration of these compounds in the vicinity of the negatively charged DNA molecules. (Author) (GRA)« less

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.

Why do women justify violence against wives more often than do men in Vietnam?

PubMed Central

Krause, Kathleen Helen; Gordon-Roberts, Rachel; VanderEnde, Kristin; Schuler, Sidney Ruth; Yount, Kathryn Mary

2015-01-01

Background Intimate partner violence (IPV) harms the health of women and their children. In Vietnam, 31% of women report lifetime exposure to physical IPV, and surprisingly, women justify physical IPV against wives more often than do men. Objective We compare men’s and women’s rates of finding good reason for wife hitting and assess whether differences in childhood experiences and resources and constraints in adulthood account for observed differences. Methods Probability samples of married men (N = 522) and women (N = 533) were surveyed in Vietnam. Ordered logit models assessed the proportional odds for women versus men of finding more “good reasons” to hit a wife (never, 1–3 situations, 4–6 situations). Results In all situations, women found good reason to hit a wife more often than did men. The unadjusted odds for women versus men of reporting more good reasons to hit a wife were 6.55 (95% CI 4.82 – 8.91). This gap disappeared in adjusted models that included significant interactions of gender with age, number of children ever born, and experience of physical IPV as an adult. Discussion Having children was associated with justifying wife hitting among women but not men. Exposure to IPV in adulthood was associated with justifying wife hitting among men but was negatively associated with justification of IPV among women. Further study of the gendered effects of resources and constraints in adulthood on attitudes about IPV against women will clarify women’s more frequent reporting than men’s that IPV against women is justified. PMID:25948647

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.

A combination of 19F NMR and surface plasmon resonance for site-specific hit selection and validation of fragment molecules that bind to the ATP-binding site of a kinase.

PubMed

Nagatoishi, Satoru; Yamaguchi, Sou; Katoh, Etsuko; Kajita, Keita; Yokotagawa, Takane; Kanai, Satoru; Furuya, Toshio; Tsumoto, Kouhei

2018-05-01

19 F NMR has recently emerged as an efficient, sensitive tool for analyzing protein binding to small molecules, and surface plasmon resonance (SPR) is also a popular tool for this purpose. Herein a combination of 19 F NMR and SPR was used to find novel binders to the ATP-binding pocket of MAP kinase extracellular regulated kinase 2 (ERK2) by fragment screening with an original fluorinated-fragment library. The 19 F NMR screening yielded a high primary hit rate of binders to the ERK2 ATP-binding pocket compared with the rate for the SPR screening. Hit compounds were evaluated and categorized according to their ability to bind to different binding sites in the ATP-binding pocket. The binding manner was characterized by using isothermal titration calorimetry and docking simulation. Combining 19 F NMR with other biophysical methods allows the identification of multiple types of hit compounds, thereby increasing opportunities for drug design using preferred fragments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using a Regression Method for Estimating Performance in a Rapid Serial Visual Presentation Target-Detection Task

DTIC Science & Technology

2017-12-01

values designating each stimulus as a target ( true ) or nontarget (false). Both stim_time and stim_label should have length equal to the number of...position unless so designated by other authorized documents. Citation of manufacturer’s or trade names does not constitute an official endorsement or...depend strongly on the true values of hit rate and false-alarm rate. Based on its better estimation of hit rate and false-alarm rate, the regression

A comparison of two search methods for determining the scope of systematic reviews and health technology assessments.

PubMed

Forsetlund, Louise; Kirkehei, Ingvild; Harboe, Ingrid; Odgaard-Jensen, Jan

2012-01-01

This study aims to compare two different search methods for determining the scope of a requested systematic review or health technology assessment. The first method (called the Direct Search Method) included performing direct searches in the Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessments (HTA). Using the comparison method (called the NHS Search Engine) we performed searches by means of the search engine of the British National Health Service, NHS Evidence. We used an adapted cross-over design with a random allocation of fifty-five requests for systematic reviews. The main analyses were based on repeated measurements adjusted for the order in which the searches were conducted. The Direct Search Method generated on average fewer hits (48 percent [95 percent confidence interval {CI} 6 percent to 72 percent], had a higher precision (0.22 [95 percent CI, 0.13 to 0.30]) and more unique hits than when searching by means of the NHS Search Engine (50 percent [95 percent CI, 7 percent to 110 percent]). On the other hand, the Direct Search Method took longer (14.58 minutes [95 percent CI, 7.20 to 21.97]) and was perceived as somewhat less user-friendly than the NHS Search Engine (-0.60 [95 percent CI, -1.11 to -0.09]). Although the Direct Search Method had some drawbacks such as being more time-consuming and less user-friendly, it generated more unique hits than the NHS Search Engine, retrieved on average fewer references and fewer irrelevant results.

The Helicity Injected Torus (HIT) Program

NASA Astrophysics Data System (ADS)

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

2000-10-01

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

Superior Effects of High-Intensity Interval Training vs. Moderate Continuous Training on Arterial Stiffness in Episodic Migraine: A Randomized Controlled Trial.

PubMed

Hanssen, Henner; Minghetti, Alice; Magon, Stefano; Rossmeissl, Anja; Papadopoulou, Athina; Klenk, Christopher; Schmidt-Trucksäss, Arno; Faude, Oliver; Zahner, Lukas; Sprenger, Till; Donath, Lars

2017-01-01

Background: Migraine is associated with increased cardiovascular risk and vascular dysfunction. Since aerobic exercise can reduce cardiovascular risk, the present randomized controlled trail aimed at investigating the effects of high-intensity interval training (HIT) vs. moderate continuous exercise training (MCT) on arterial stiffness in migraine patients. Methods: Forty-eight episodic migraineurs were initially enrolled in the study. 37 patients [female: 30; age: 37 ( SD : 10); BMI: 23.1 (5.2); Migraine days per month: 3.7 (2.5)] completed the intervention. Central blood pressure, pulse wave reflection, and aortic pulse wave velocity (PWV) were obtained by an oscillometric monitor. Incremental treadmill exercise testing yielded maximal and submaximal fitness parameters. Participants were randomly assigned to either HIT, MCT, or a control group (CON). The intervention groups trained twice a week over a 12-week intervention period. Results: After adjustment for between-group baseline differences, a moderate meaningful overall reduction of the augmentation index at 75 min -1 heart rate (AIx@75) was observed [partial eta squared ([Formula: see text]) = 0.16; p = 0.06]. With 91% likely beneficial effects, HIT was more effective in reducing AIx@75 than MCT [HIT: pre 22.0 (9.7), post 14.9 (13.0), standardized mean difference (SMD) = 0.62; MCT: pre 16.6 (8.5), post 21.3 (10.4), SMD -0.49]. HIT induced a relevant reduction in central systolic blood pressure [cSBP: pre 118 (23) mmHg, post 110 (16) mmHg, SMD = 0.42] with a 59% possibly beneficial effect compared to CON, while MCT showed larger effects in lowering central diastolic blood pressure [pre 78 (7) mmHg, post 74 (7) mmHg, SMD = 0.61], presenting 60% possibly beneficial effects compared to CON. Central aortic PWV showed no changes in any of the three groups. Migraine days were reduced more successfully by HIT than MCT (HIT: SMD = 1.05; MCT: SMD = 0.43). Conclusion: HIT but not MCT reduces AIx@75 as a measure of pulse wave reflection and indirect marker of systemic arterial stiffness. Both exercise modalities beneficially affect central blood pressure. HIT proved to be an effective complementary treatment option to reduce vascular dysfunction and blood pressure in migraineurs.

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

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.

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.

Effects of Sprint versus High-Intensity Aerobic Interval Training on Cross-Country Mountain Biking Performance: A Randomized Controlled Trial

PubMed Central

Inoue, Allan; Impellizzeri, Franco M.; Pires, Flávio O.; Pompeu, Fernando A. M. S.; Deslandes, Andrea C.; Santos, Tony M.

2016-01-01

Objectives The current study compared the effects of high-intensity aerobic training (HIT) and sprint interval training (SIT) on mountain biking (MTB) race simulation performance and physiological variables, including peak power output (PPO), lactate threshold (LT) and onset of blood lactate accumulation (OBLA). Methods Sixteen mountain bikers (mean ± SD: age 32.1 ± 6.4 yr, body mass 69.2 ± 5.3 kg and VO2max 63.4 ± 4.5 mL∙kg-1∙min-1) completed graded exercise and MTB performance tests before and after six weeks of training. The HIT (7–10 x [4–6 min—highest sustainable intensity / 4–6 min—CR100 10–15]) and SIT (8–12 x [30 s—all-out intensity / 4 min—CR100 10–15]) protocols were included in the participants’ regular training programs three times per week. Results Post-training analysis showed no significant differences between training modalities (HIT vs. SIT) in body mass, PPO, LT or OBLA (p = 0.30 to 0.94). The Cohen’s d effect size (ES) showed trivial to small effects on group factor (p = 0.00 to 0.56). The interaction between MTB race time and training modality was almost significant (p = 0.08), with a smaller ES in HIT vs. SIT training (ES = -0.43). A time main effect (pre- vs. post-phases) was observed in MTB race performance and in several physiological variables (p = 0.001 to 0.046). Co-variance analysis revealed that the HIT (p = 0.043) group had significantly better MTB race performance measures than the SIT group. Furthermore, magnitude-based inferences showed HIT to be of likely greater benefit (83.5%) with a lower probability of harmful effects (0.8%) compared to SIT. Conclusion The results of the current study suggest that six weeks of either HIT or SIT may be effective at increasing MTB race performance; however, HIT may be a preferable strategy. Trial Registration ClinicalTrials.gov NCT01944865 PMID:26789124

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.

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.

Phosphoproteome and transcriptome analyses of ErbB ligand-stimulated MCF-7 cells.

PubMed

Nagashima, Takeshi; Oyama, Masaaki; Kozuka-Hata, Hiroko; Yumoto, Noriko; Sakaki, Yoshiyuki; Hatakeyama, Mariko

2008-01-01

Cellular signal transduction pathways and gene expression are tightly regulated to accommodate changes in response to physiological environments. In the current study, molecules were identified that are activated as a result of intracellular signaling and immediately expressed as mRNA in MCF-7 breast cancer cells shortly after stimulation of ErbB receptor ligands, epidermal growth factor (EGF) or heregulin (HRG). For the identification of tyrosine-phosphorylated proteins and expressed genes, a SILAC (stable isotopic labeling using amino acids in cell culture) method and Affymetrix gene expression array system, respectively, were used. Unexpectedly, the overlapping of genes appeared in two experimental datasets was very low for HRG (43 hits in the proteome data, 1,655 in the transcriptome data, and 5 hits common to both datasets), while no overlapping gene was detected for EGF (15 hits in the proteome data, 211 hits in the transcriptome data, and no hits common to both datasets). The HRG overlapping genes included ERBB2, NEDD9, MAPK3, JUP and EPHA2. Biological pathway analysis indicated that HRG-stimulated molecular activation is significantly related to cancer pathways including bladder cancer, chronic myeloid leukemia and pancreatic cancer (p < 0.05). The proteome datasets of EGF and HRG contain molecules that are related to Axon guidance, ErbB signaling and VEGF signaling at a high rate.

Hitting Is Contagious in Baseball: Evidence from Long Hitting Streaks

PubMed Central

Bock, Joel R.; Maewal, Akhilesh; Gough, David A.

2012-01-01

Data analysis is used to test the hypothesis that “hitting is contagious”. A statistical model is described to study the effect of a hot hitter upon his teammates’ batting during a consecutive game hitting streak. Box score data for entire seasons comprising streaks of length games, including a total observations were compiled. Treatment and control sample groups () were constructed from core lineups of players on the streaking batter’s team. The percentile method bootstrap was used to calculate confidence intervals for statistics representing differences in the mean distributions of two batting statistics between groups. Batters in the treatment group (hot streak active) showed statistically significant improvements in hitting performance, as compared against the control. Mean for the treatment group was found to be to percentage points higher during hot streaks (mean difference increased points), while the batting heat index introduced here was observed to increase by points. For each performance statistic, the null hypothesis was rejected at the significance level. We conclude that the evidence suggests the potential existence of a “statistical contagion effect”. Psychological mechanisms essential to the empirical results are suggested, as several studies from the scientific literature lend credence to contagious phenomena in sports. Causal inference from these results is difficult, but we suggest and discuss several latent variables that may contribute to the observed results, and offer possible directions for future research. PMID:23251507

Validation of a rapid DNA process with the RapidHIT® ID system using GlobalFiler® Express chemistry, a platform optimized for decentralized testing environments.

PubMed

Salceda, Susana; Barican, Arnaldo; Buscaino, Jacklyn; Goldman, Bruce; Klevenberg, Jim; Kuhn, Melissa; Lehto, Dennis; Lin, Frank; Nguyen, Phong; Park, Charles; Pearson, Francesca; Pittaro, Rick; Salodkar, Sayali; Schueren, Robert; Smith, Corey; Troup, Charles; Tsou, Dean; Vangbo, Mattias; Wunderle, Justus; King, David

2017-05-01

The RapidHIT ® ID is a fully automated sample-to-answer system for short tandem repeat (STR)-based human identification. The RapidHIT ID has been optimized for use in decentralized environments and processes presumed single source DNA samples, generating Combined DNA Index System (CODIS)-compatible DNA profiles in less than 90min. The system is easy to use, requiring less than one minute of hands-on time. Profiles are reviewed using centralized linking software, RapidLINK™ (IntegenX, Pleasanton, CA), a software tool designed to collate DNA profiles from single or multiple RapidHIT ID systems at different geographic locations. The RapidHIT ID has been designed to employ GlobalFiler ® Express and AmpFLSTR ® NGMSElect™, Thermo Fisher Scientific (Waltham, MA) STR chemistries. The Developmental Validation studies were performed using GlobalFiler ® Express with single source reference samples according to Scientific Working Group for DNA Analysis Methods guidelines. These results show that multiple RapidHIT ID systems networked with RapidLINK software form a highly reliable system for wide-scale deployment in locations such as police booking stations and border crossings enabling real-time testing of arrestees, potential human trafficking victims, and other instances where rapid turnaround is essential. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Effectiveness of a Treatment Involving Soft Tissue Techniques and/or Neural Mobilization Techniques in the Management of Tension-Type Headache: A Randomized Controlled Trial.

PubMed

Ferragut-Garcías, Alejandro; Plaza-Manzano, Gustavo; Rodríguez-Blanco, Cleofás; Velasco-Roldán, Olga; Pecos-Martín, Daniel; Oliva-Pascual-Vaca, Jesús; Llabrés-Bennasar, Bartomeu; Oliva-Pascual-Vaca, Ángel

2017-02-01

To evaluate the effects of a protocol involving soft tissue techniques and/or neural mobilization techniques in the management of patients with frequent episodic tension-type headache (FETTH) and those with chronic tension-type headache (CTTH). Randomized, double-blind, placebo-controlled before and after trial. Rehabilitation area of the local hospital and a private physiotherapy center. Patients (N=97; 78 women, 19 men) diagnosed with FETTH or CTTH were randomly assigned to groups A, B, C, or D. (A) Placebo superficial massage; (B) soft tissue techniques; (C) neural mobilization techniques; (D) a combination of soft tissue and neural mobilization techniques. The pressure pain threshold (PPT) in the temporal muscles (points 1 and 2) and supraorbital region (point 3), the frequency and maximal intensity of pain crisis, and the score in the Headache Impact Test-6 (HIT-6) were evaluated. All variables were assessed before the intervention, at the end of the intervention, and 15 and 30 days after the intervention. Groups B, C, and D had an increase in PPT and a reduction in frequency, maximal intensity, and HIT-6 values in all time points after the intervention as compared with baseline and group A (P<.001 for all cases). Group D had the highest PPT values and the lowest frequency and HIT-6 values after the intervention. The application of soft tissue and neural mobilization techniques to patients with FETTH or CTTH induces significant changes in PPT, the characteristics of pain crisis, and its effect on activities of daily living as compared with the application of these techniques as isolated interventions. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Prenatal cannabis exposure - The "first hit" to the endocannabinoid system.

PubMed

Richardson, Kimberlei A; Hester, Allison K; McLemore, Gabrielle L

As more states and countries legalize medical and/or adult recreational marijuana use, the incidences of prenatal cannabis exposure (PCE) will likely increase. While young people increasingly view marijuana as innocuous, marijuana preparations have been growing in potency in recent years, potentially creating global clinical, public health, and workforce concerns. Unlike fetal alcohol spectrum disorder, there is no phenotypic syndrome associated with PCE. There is also no preponderance of evidence that PCE causes lifelong cognitive, behavioral, or functional abnormalities, and/or susceptibility to subsequent addiction. However, there is compelling circumstantial evidence, based on the principles of teratology and fetal malprogramming, suggesting that pregnant women should refrain from smoking marijuana. The usage of marijuana during pregnancy perturbs the fetal endogenous cannabinoid signaling system (ECSS), which is present and active from the early embryonic stage, modulating neurodevelopment and continuing this role into adulthood. The ECSS is present in virtually every brain structure and organ system, and there is also evidence that this system is important in the regulation of cardiovascular processes. Endocannabinoids (eCBs) undergird a broad spectrum of processes, including the early stages of fetal neurodevelopment and uterine implantation. Delta-9-tetrahydrocannabinol (THC), the psychoactive chemical in cannabis, enters maternal circulation, and readily crosses the placental membrane. THC binds to CB receptors of the fetal ECSS, altering neurodevelopment and possibly rewiring ECSS circuitry. In this review, we discuss the Double-Hit Hypothesis as it relates to PCE. We contend that PCE, similar to a neurodevelopmental teratogen, delivers the first hit to the ECSS, which is compromised in such a way that a second hit (i.e., postnatal stressors) will precipitate the emergence of a specific phenotype. In summary, we conclude that perturbations of the intrauterine milieu via the introduction of exogenous CBs alter the fetal ECSS, predisposing the offspring to abnormalities in cognition and altered emotionality. Based on recent experimental evidence that we will review here, we argue that young women who become pregnant should immediately take a "pregnant pause" from using marijuana. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-03-06

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

Assessing HTS Performance Using BioAssay Ontology: Screening and Analysis of a Bacterial Phospho-N-Acetylmuramoyl-Pentapeptide Translocase Campaign

PubMed Central

Moberg, Andreas; Hansson, Eva; Boyd, Helen

2014-01-01

Abstract With the public availability of biochemical assays and screening data constantly increasing, new applications for data mining and method analysis are evolving in parallel. One example is BioAssay Ontology (BAO) for systematic classification of assays based on screening setup and metadata annotations. In this article we report a high-throughput screening (HTS) against phospho-N-acetylmuramoyl-pentapeptide translocase (MraY), an attractive antibacterial drug target involved in peptidoglycan synthesis. The screen resulted in novel chemistry identification using a fluorescence resonance energy transfer assay. To address a subset of the false positive hits, a frequent hitter analysis was performed using an approach in which MraY hits were compared with hits from similar assays, previously used for HTS. The MraY assay was annotated according to BAO and three internal reference assays, using a similar assay design and detection technology, were identified. Analyzing the assays retrospectively, it was clear that both MraY and the three reference assays all showed a high false positive rate in the primary HTS assays. In the case of MraY, false positives were efficiently identified by applying a method to correct for compound interference at the hit-confirmation stage. Frequent hitter analysis based on the three reference assays with similar assay method identified additional false actives in the primary MraY assay as frequent hitters. This article demonstrates how assays annotated using BAO terms can be used to identify closely related reference assays, and that analysis based on these assays clearly can provide useful data to influence assay design, technology, and screening strategy. PMID:25415593

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.

Automated recycling of chemistry for virtual screening and library design.

PubMed

Vainio, Mikko J; Kogej, Thierry; Raubacher, Florian

2012-07-23

An early stage drug discovery project needs to identify a number of chemically diverse and attractive compounds. These hit compounds are typically found through high-throughput screening campaigns. The diversity of the chemical libraries used in screening is therefore important. In this study, we describe a virtual high-throughput screening system called Virtual Library. The system automatically "recycles" validated synthetic protocols and available starting materials to generate a large number of virtual compound libraries, and allows for fast searches in the generated libraries using a 2D fingerprint based screening method. Virtual Library links the returned virtual hit compounds back to experimental protocols to quickly assess the synthetic accessibility of the hits. The system can be used as an idea generator for library design to enrich the screening collection and to explore the structure-activity landscape around a specific active compound.

Syndromic surveillance for health information system failures: a feasibility study.

PubMed

Ong, Mei-Sing; Magrabi, Farah; Coiera, Enrico

2013-05-01

To explore the applicability of a syndromic surveillance method to the early detection of health information technology (HIT) system failures. A syndromic surveillance system was developed to monitor a laboratory information system at a tertiary hospital. Four indices were monitored: (1) total laboratory records being created; (2) total records with missing results; (3) average serum potassium results; and (4) total duplicated tests on a patient. The goal was to detect HIT system failures causing: data loss at the record level; data loss at the field level; erroneous data; and unintended duplication of data. Time-series models of the indices were constructed, and statistical process control charts were used to detect unexpected behaviors. The ability of the models to detect HIT system failures was evaluated using simulated failures, each lasting for 24 h, with error rates ranging from 1% to 35%. In detecting data loss at the record level, the model achieved a sensitivity of 0.26 when the simulated error rate was 1%, while maintaining a specificity of 0.98. Detection performance improved with increasing error rates, achieving a perfect sensitivity when the error rate was 35%. In the detection of missing results, erroneous serum potassium results and unintended repetition of tests, perfect sensitivity was attained when the error rate was as small as 5%. Decreasing the error rate to 1% resulted in a drop in sensitivity to 0.65-0.85. Syndromic surveillance methods can potentially be applied to monitor HIT systems, to facilitate the early detection of failures.

HitPredict version 4: comprehensive reliability scoring of physical protein-protein interactions from more than 100 species.

PubMed

López, Yosvany; Nakai, Kenta; Patil, Ashwini

2015-01-01

HitPredict is a consolidated resource of experimentally identified, physical protein-protein interactions with confidence scores to indicate their reliability. The study of genes and their inter-relationships using methods such as network and pathway analysis requires high quality protein-protein interaction information. Extracting reliable interactions from most of the existing databases is challenging because they either contain only a subset of the available interactions, or a mixture of physical, genetic and predicted interactions. Automated integration of interactions is further complicated by varying levels of accuracy of database content and lack of adherence to standard formats. To address these issues, the latest version of HitPredict provides a manually curated dataset of 398 696 physical associations between 70 808 proteins from 105 species. Manual confirmation was used to resolve all issues encountered during data integration. For improved reliability assessment, this version combines a new score derived from the experimental information of the interactions with the original score based on the features of the interacting proteins. The combined interaction score performs better than either of the individual scores in HitPredict as well as the reliability score of another similar database. HitPredict provides a web interface to search proteins and visualize their interactions, and the data can be downloaded for offline analysis. Data usability has been enhanced by mapping protein identifiers across multiple reference databases. Thus, the latest version of HitPredict provides a significantly larger, more reliable and usable dataset of protein-protein interactions from several species for the study of gene groups. Database URL: http://hintdb.hgc.jp/htp. © The Author(s) 2015. Published by Oxford University Press.

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.

Effects of detector dead-time on quantitative analyses involving boron and multi-hit detection events in atom probe tomography.

PubMed

Meisenkothen, Frederick; Steel, Eric B; Prosa, Ty J; Henry, Karen T; Prakash Kolli, R

2015-12-01

In atom probe tomography (APT), some elements tend to field evaporate preferentially in multi-hit detection events. Boron (B) is one such element. It is thought that a large fraction of the B signal may be lost during data acquisition and is not reported in the mass spectrum or in the 3-D APT reconstruction. Understanding the relationship between the field evaporation behavior of B and the limitations for detecting multi-hit events can provide insight into the signal loss mechanism for B and may suggest ways to improve B detection accuracy. The present work reports data for nominally pure B and for B-implanted silicon (Si) (NIST-SRM2137) at dose levels two-orders of magnitude lower than previously studied by Da Costa, et al. in 2012. Boron concentration profiles collected from SRM2137 specimens qualitatively confirmed a signal loss mechanism is at work in laser pulsed atom probe measurements of B in Si. Ion correlation analysis was used to graphically demonstrate that the detector dead-time results in few same isotope, same charge-state (SISCS) ion pairs being properly recorded in the multi-hit data, explaining why B is consistently under-represented in quantitative analyses. Given the important role of detector dead-time as a signal loss mechanism, the results from three different methods of estimating the detector dead-time are presented. The findings of this study apply to all quantitative analyses that involve multi-hit data, but the dead-time will have the greatest effect on the elements that have a significant quantity of ions detected in multi-hit events. Published by Elsevier B.V.

Increasing Human Papillomavirus Vaccine Initiation among Publically-Insured Florida Adolescents

PubMed Central

Staras, Stephanie A. S.; Vadaparampil, Susan T.; Livingston, Melvin D.; Thompson, Lindsay A.; Sanders, Ashley H.; Shenkman, Elizabeth A.

2014-01-01

Purpose We evaluated the feasibility of a multi-level intervention to increase HPV vaccine initiation among adolescents. Methods We used a four-arm factorial quasi-experimental trial to assess feasibility and short-term, preliminary effectiveness of a health system-level, gender-specific postcard campaign and an in-clinic health information technology (HIT) system. Between August to November 2013, we tested the intervention among 11–17 year olds without prior HPV vaccine claims in Florida Medicaid or Children’s Health Insurance Program encounters (2773 girls and 3350 boys) who attended or were assigned to primary care clinics in North Central Florida. Results At least one postcard was deliverable to 95% of parents. Most parents (91% boys’ and 80% girls’) who participated in the process evaluation survey (n=162) reported seeking additional information about the vaccine after receiving the postcard. Only 8% (57 of the 1062) of adolescents assigned to a HIT provider with an office visit during the study used the HIT system. When compared with arms not containing that component, HPV vaccine initiation increased with the postcard campaign [girls Odds Ratio (OR) = 1.6, 95% Confidence Interval (CI) = 1.1–2.3 and boys = not significant], the HIT system (girls OR = 1.5, 95% CI =1.0–2.3 and boys OR = 1.4, 95% CI=1.0–2.0), and the combined HIT and postcard intervention (girls OR = 2.4, 95% CI =1.4–4.3 and boys OR = 1.6, 95% CI=1.0–2.5). Conclusions A system-level postcard campaign was feasible. Despite low recruitment to the inclinic HIT system, the intervention demonstrated short-term, preliminary effectiveness similar to prior HPV vaccine interventions. PMID:25863554

High-intensity Interval Training Dosage for Heart Failure and Coronary Artery Disease Cardiac Rehabilitation. A Systematic Review and Meta-analysis.

PubMed

Ballesta García, Ismael; Rubio Arias, Jacobo Ángel; Ramos Campo, Domingo Jesús; Martínez González-Moro, Ignacio; Carrasco Poyatos, María

2018-04-09

High-interval intensity training (HIT) has been suggested to improve peak VO 2 in cardiac rehabilitation programs. However, the optimal HIT protocol is unknown. The objective of this study was to identify the most effective doses of HIT to optimize peak VO 2 in coronary artery disease (CAD) and heart failure (HF) patients. A search was conducted in 6 databases (MEDLINE, Web of Science, LILACS, CINAHL, Academic Search Complete, and SportDiscus). Studies using a HIT protocol in CAD or HF patients and measuring peak VO 2 were included. The PEDro Scale and Cochrane Collaboration tools were used. Analyses reported significant improvements in peak VO 2 after HIT in both diseases (P = .000001), with a higher increase in HF patients (P = .03). Nevertheless, in HF patients, there were no improvements when the intensity recovery was ≤ 40% of peak VO 2 (P = .19) and the frequency of training was ≤ 2 d/wk (P = .07). There were significant differences regarding duration in CAD patients, with greater improvements in peak VO 2 when the duration was < 12 weeks (P = .05). In HF, programs lasting < 12 weeks did not significantly improve peak VO 2 (P = .1). The HIT is an effective method for improving peak VO 2 in HF and CAD, with a significantly greater increase in HF patients. The recovery intervals should be active and be between 40% and 60% of peak VO 2 in HF patients. Training frequency should be ≥ 2 d/wk for CAD patients and ≥ 3 d/wk for HF patients. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. 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.

Assessing the level of healthcare information technology adoption in the United States: a snapshot

PubMed Central

Poon, Eric G; Jha, Ashish K; Christino, Melissa; Honour, Melissa M; Fernandopulle, Rushika; Middleton, Blackford; Newhouse, Joseph; Leape, Lucian; Bates, David W; Blumenthal, David; Kaushal, Rainu

2006-01-01

Background Comprehensive knowledge about the level of healthcare information technology (HIT) adoption in the United States remains limited. We therefore performed a baseline assessment to address this knowledge gap. Methods We segmented HIT into eight major stakeholder groups and identified major functionalities that should ideally exist for each, focusing on applications most likely to improve patient safety, quality of care and organizational efficiency. We then conducted a multi-site qualitative study in Boston and Denver by interviewing key informants from each stakeholder group. Interview transcripts were analyzed to assess the level of adoption and to document the major barriers to further adoption. Findings for Boston and Denver were then presented to an expert panel, which was then asked to estimate the national level of adoption using the modified Delphi approach. We measured adoption level in Boston and Denver was graded on Rogers' technology adoption curve by co-investigators. National estimates from our expert panel were expressed as percentages. Results Adoption of functionalities with financial benefits far exceeds adoption of those with safety and quality benefits. Despite growing interest to adopt HIT to improve safety and quality, adoption remains limited, especially in the area of ambulatory electronic health records and physician-patient communication. Organizations, particularly physicians' practices, face enormous financial challenges in adopting HIT, and concerns remain about its impact on productivity. Conclusion Adoption of HIT is limited and will likely remain slow unless significant financial resources are made available. Policy changes, such as financial incentivesto clinicians to use HIT or pay-for-performance reimbursement, may help health care providers defray upfront investment costs and initial productivity loss. PMID:16396679

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

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries

PubMed Central

2012-01-01

Background Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. Results We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. Conclusions SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates. PMID:23173901

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.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

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

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

DTIC Science & Technology

2007-01-01

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

Review of Social and Organizational Issues in Health Information Technology.

PubMed

Kuziemsky, Craig E

2015-07-01

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

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

PubMed

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

2017-01-01

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

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.

Bias Adjusted Precipitation Threat Scores

NASA Astrophysics Data System (ADS)

Mesinger, F.

2008-04-01

Among the wide variety of performance measures available for the assessment of skill of deterministic precipitation forecasts, the equitable threat score (ETS) might well be the one used most frequently. It is typically used in conjunction with the bias score. However, apart from its mathematical definition the meaning of the ETS is not clear. It has been pointed out (Mason, 1989; Hamill, 1999) that forecasts with a larger bias tend to have a higher ETS. Even so, the present author has not seen this having been accounted for in any of numerous papers that in recent years have used the ETS along with bias "as a measure of forecast accuracy". A method to adjust the threat score (TS) or the ETS so as to arrive at their values that correspond to unit bias in order to show the model's or forecaster's accuracy in placing precipitation has been proposed earlier by the present author (Mesinger and Brill, the so-called dH/dF method). A serious deficiency however has since been noted with the dH/dF method in that the hypothetical function that it arrives at to interpolate or extrapolate the observed value of hits to unit bias can have values of hits greater than forecast when the forecast area tends to zero. Another method is proposed here based on the assumption that the increase in hits per unit increase in false alarms is proportional to the yet unhit area. This new method removes the deficiency of the dH/dF method. Examples of its performance for 12 months of forecasts by three NCEP operational models are given.

Effectiveness and cost-effectiveness of double reading in digital mammography screening: A systematic review and meta-analysis.

PubMed

Posso, Margarita; Puig, Teresa; Carles, Misericòrdia; Rué, Montserrat; Canelo-Aybar, Carlos; Bonfill, Xavier

2017-11-01

Double reading is the strategy of choice for mammogram interpretation in screening programmes. It remains, however, unknown whether double reading is still the strategy of choice in the context of digital mammography. Our aim was to determine the effectiveness and cost-effectiveness of double reading versus single reading of digital mammograms in screening programmes. We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases up to April 2017. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist to assess the methodological quality of the diagnostic studies and economic evaluations, respectively. A proportion's meta-analysis approach, 95% Confidence Intervals (95% CI) and test of heterogeneity (P values) were used for pooled results. Costs are expressed US$ PPP (United States Dollar purchasing power parities). The PROSPERO ID of this Systematic Review's protocol is CRD42014013804. Of 1473 potentially relevant hits, four high-quality studies were included. The pooled cancer detection rate of double reading was 6.01 per 1000 screens (CI: 4.47‰-7.77‰), and it was 5.65 per 1000 screens (CI: 3.95‰-7.65‰) for single reading (P=0.76). The pooled proportion of false-positives of double reading was 47.03 per 1000 screens (CI: 39.13‰-55.62‰) and it was 40.60 per 1000 screens (CI: 38.58‰-42.67‰) for single reading (P=0.12). One study reported, for double reading, an ICER (Incremental Cost-Effectiveness Ratio) of 16,684 Euros (24,717 US$ PPP; 2015 value) per detected cancer. Single reading+CAD (computer-aided-detection) was cost-effective in Japan. The evidence of benefit for double reading compared to single reading for digital mammography interpretation is scarce. Double reading seems to increase operational costs, have a not significantly higher false-positive rate, and a similar cancer detection rate. Copyright © 2017 Elsevier B.V. All rights reserved.

Obesity Prevalence in Nepal: Public Health Challenges in a Low-Income Nation during an Alarming Worldwide Trend

PubMed Central

Vaidya, Abhinav; Shakya, Suraj; Krettek, Alexandra

2010-01-01

The future toll of the obesity epidemic will likely hit hardest in low- and middle-income countries. Ongoing urbanization promotes risk factors including sedentary lifestyle and fat- and sugar-laden diets. Low-income countries like Nepal experience a double disease burden: infectious diseases as well as rising incidence of noncommunicable diseases (e.g., cardiovascular disease and diabetes mellitus) frequently characterized by obesity. Nepal currently directs efforts towards curing disease but pays little attention to preventive actions. This article highlights obesity prevalence in Nepal, delineates the challenges identified by our pilot study (including low health literacy rates), and suggests strategies to overcome this trend. PMID:20644698

Obesity prevalence in Nepal: public health challenges in a low-income nation during an alarming worldwide trend.

PubMed

Vaidya, Abhinav; Shakya, Suraj; Krettek, Alexandra

2010-06-01

The future toll of the obesity epidemic will likely hit hardest in low- and middle-income countries. Ongoing urbanization promotes risk factors including sedentary lifestyle and fat- and sugar-laden diets. Low-income countries like Nepal experience a double disease burden: infectious diseases as well as rising incidence of noncommunicable diseases (e.g., cardiovascular disease and diabetes mellitus) frequently characterized by obesity. Nepal currently directs efforts towards curing disease but pays little attention to preventive actions. This article highlights obesity prevalence in Nepal, delineates the challenges identified by our pilot study (including low health literacy rates), and suggests strategies to overcome this trend.

[Diffuse large B-cell lymphoma with concomitant c-MYC and BCL6 gene rearrangements with primary skin involvement: A case report and a review of literature].

PubMed

Gabeeva, N G; Koroleva, D A; Belyaeva, A V; Chernova, N G; Kuzmina, L A; Sudarikov, A B; Obukhova, T N; Kovrigina, A M; Zvonkov, E E; Savchenko, V G

Double-hit lymphoma (DHL) is a rare aggressive B-cell lymphoma with concomitant c-MYC, BCL2 or BCL6 gene rearrangements, which is characterized by the high frequency of extranodal lesions and by resistance to chemotherapy. The median survival does not exceed 18 months in patients with this disease. The majority of DHL is represented by с-MYC/BCL2 cases. The combination of c-MYC/BCL6 occurs rarely (5-8%). The paper describes a case of DHL with concomitant c-MYC and BCL6 gene rearrangements, which mimics diffuse large B-cell lymphoma, leg-type.

A highly optimized vectorized code for Monte Carlo simulations of SU(3) lattice gauge theories

NASA Technical Reports Server (NTRS)

Barkai, D.; Moriarty, K. J. M.; Rebbi, C.

1984-01-01

New methods are introduced for improving the performance of the vectorized Monte Carlo SU(3) lattice gauge theory algorithm using the CDC CYBER 205. Structure, algorithm and programming considerations are discussed. The performance achieved for a 16(4) lattice on a 2-pipe system may be phrased in terms of the link update time or overall MFLOPS rates. For 32-bit arithmetic, it is 36.3 microsecond/link for 8 hits per iteration (40.9 microsecond for 10 hits) or 101.5 MFLOPS.

The Effects of Aging on Clinical Vestibular Evaluations

PubMed Central

Maheu, Maxime; Houde, Marie-Soleil; Landry, Simon P.; Champoux, François

2015-01-01

Balance disorders are common issues for aging populations due to the effects of normal aging on peripheral vestibular structures. These changes affect the results of vestibular function evaluations and make the interpretation of these results more difficult. The objective of this article is to review the current state of knowledge of clinically relevant vestibular measures. We will first focus on otolith function assessment methods cervical-VEMP (cVEMP) and ocular-VEMP (oVEMP), then the caloric and video-head impulse test (vHIT) methods for semicircular canals assessment. cVEMP and oVEMP are useful methods, though research on the effects of age for some parameters are still inconclusive. vHIT results are largely independent of age as compared to caloric stimulation and should therefore be preferred for the evaluation of the semicircular canals function. PMID:26441824

HITTING THE BULL'S-EYE IN GROUNDWATER SAMPLING

EPA Science Inventory

Many of the commonly-used groundwater sampling techniques and procedures have resulted from methods developed for water supply investigations. These methods have persisted, even though the monitoring goals may have changed from water supply development to contaminant source and ...

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.

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

PubMed

Van Hoecke, F; Devreese, K

2012-08-01

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

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

PubMed

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

2017-07-01

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

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

PubMed

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

2017-10-05

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

Computational Methods Used in Hit-to-Lead and Lead Optimization Stages of Structure-Based Drug Discovery.

PubMed

Heifetz, Alexander; Southey, Michelle; Morao, Inaki; Townsend-Nicholson, Andrea; Bodkin, Mike J

2018-01-01

GPCR modeling approaches are widely used in the hit-to-lead (H2L) and lead optimization (LO) stages of drug discovery. The aims of these modeling approaches are to predict the 3D structures of the receptor-ligand complexes, to explore the key interactions between the receptor and the ligand and to utilize these insights in the design of new molecules with improved binding, selectivity or other pharmacological properties. In this book chapter, we present a brief survey of key computational approaches integrated with hierarchical GPCR modeling protocol (HGMP) used in hit-to-lead (H2L) and in lead optimization (LO) stages of structure-based drug discovery (SBDD). We outline the differences in modeling strategies used in H2L and LO of SBDD and illustrate how these tools have been applied in three drug discovery projects.

Readiness for Meaningful Use of Health Information Technology and Patient Centered Medical Home Recognition Survey Results

PubMed Central

Shin, Peter; Sharac, Jessica

2013-01-01

Objective Determine the factors that impact HIT use and MU readiness for community health centers (CHCs). Background The HITECH Act allocates funds to Medicaid and Medicare providers to encourage the adoption of electronic health records (EHR), in an effort to improve health care quality and patient outcomes, and to reduce health care costs. Methods We surveyed CHCs on their Readiness for Meaningful Use (MU) of Health Information Technology (HIT) and Patient Centered Medical Home (PCMH) Recognition, then we combined responses with 2009 Uniform Data System data to determine which factors impact use of HIT and MU readiness. Results Nearly 70% of CHCs had full or partial EHR adoption at the time of survey. Results are presented for centers with EHR adoption, by the length of time that their EHR systems have been in operation. PMID:24834365

How Can Information and Communication Technology Improve Healthcare Inequalities and Healthcare Inequity? The Concept of Context Driven Care.

PubMed

Yee, Kwang Chien; Bettiol, Silvana; Nash, Rosie; Macintyrne, Kate; Wong, Ming Chao; Nøhr, Christian

2018-01-01

Advances in medicine have improved health and healthcare for many around the world. The challenge is achieving the best outcomes of health via healthcare delivery to every individual. Healthcare inequalities exist within a country and between countries. Health information technology (HIT) has provided a mean to deliver equal access to healthcare services regardless of social context and physical location. In order to achieve better health outcomes for every individual, socio-cultural factors, such as literacy and social context need to consider. This paper argues that HIT while improves healthcare inequalities by providing access, might worsen healthcare inequity. In order to improve healthcare inequity using HIT, this paper argues that we need to consider patients and context, and hence the concept of context driven care. To improve healthcare inequity, we need to conceptually consider the patient's view and methodologically consider design methods that achieve participatory outcomes.

Tracking down quirks at the Large Hadron Collider

NASA Astrophysics Data System (ADS)

Knapen, Simon; Lou, Hou Keong; Papucci, Michele; Setford, Jack

2017-12-01

Nonhelical tracks are the smoking gun signature of charged and/or colored quirks, which are pairs of particles bound by a new, long-range confining force. We propose a method to efficiently search for these nonhelical tracks at the LHC, without the need to fit their trajectories. We show that the hits corresponding to quirky trajectories can be selected efficiently by searching for coplanar hits in the inner layers of the ATLAS and CMS trackers, even in the presence of on average 50 pile-up vertices. We further argue that backgrounds from photon conversions and unassociated pile-up hits can be removed almost entirely, while maintaining a signal reconstruction efficiency as high as ˜70 % . With the 300 fb-1 dataset, this implies a discovery potential for string tension between 100 eV and 30 keV, and colored (electroweak charged) quirks as heavy as 1600 (650) GeV may be discovered.

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.

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.

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

PubMed

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

2012-01-01

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

Staff Responses When Parents Hit Children in a Hospital Setting

PubMed Central

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

2016-01-01

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

Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

PubMed Central

Hernández, Antonio F.; Menéndez, Pablo

2016-01-01

Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events. PMID:27043530

Effects of transdermally administered nicotine on aspects of attention, task load, and mood in women and men.

PubMed

Trimmel, Michael; Wittberger, Susanne

2004-07-01

This double-blind placebo-controlled study was conducted to determine nicotine effects on diverse types of attentional performance, task load, and mood considering sex effects as suggested by animal studies. Twelve smokers, 12 deprived smokers and 12 nonsmokers (6 females, 6 males in each group) were investigated. Participants were treated either by 5 mg/16 h nicotine patches (Nicorette) or placebo. Effects of treatment were examined by a computerized attention-test battery; mood was assessed by the Berliner-Alltagssprachliches-Stimmungs-Inventar and task load by the NASA Task Load Index (NASA-TLX). Results showed that nicotine significantly increased the number of hits and decreased reaction time (RT) in the vigilance task. In the selective attention task combined with irrelevant speech as background noise, nicotine enhanced rate of hits. Although it was indicated that nicotine leads to a generally higher accuracy in attention tasks, response time of visual search was prolonged, contradicting a universal facilitation by nicotine. Participants experienced mental demand and temporal demand lower and rated alertness higher when in the nicotine condition. These effects were independent of smoking status, indicating "true" nicotine effects. Females took significant advantage of nicotine in the vigilance task, reaching the performance level of males, accompanied by a higher rated alertness. Results indicate task- and sex-dependent nicotine effects.

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.

MetaPhinder—Identifying Bacteriophage Sequences in Metagenomic Data Sets

PubMed Central

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

2016-01-01

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

MetaPhinder-Identifying Bacteriophage Sequences in Metagenomic Data Sets.

PubMed

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

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

Developing Health Information Technology (HIT) Programs and HIT Curriculum: The Southern Polytechnic State University Experience

ERIC Educational Resources Information Center

Zhang, Chi; Reichgelt, Han; Rutherfoord, Rebecca H.; Wang, Andy Ju An

2014-01-01

Health Information Technology (HIT) professionals are in increasing demand as healthcare providers need help in the adoption and meaningful use of Electronic Health Record (EHR) systems while the HIT industry needs workforce skilled in HIT and EHR development. To respond to this increasing demand, the School of Computing and Software Engineering…

Lead discovery for mammalian elongation of long chain fatty acids family 6 using a combination of high-throughput fluorescent-based assay and RapidFire mass spectrometry assay

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

Takamiya, Mari; Discovery Technology Laboratories, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Kawagishi, Toda-shi, Saitama; Sakurai, Masaaki

A high-throughput RapidFire mass spectrometry assay is described for elongation of very long-chain fatty acids family 6 (Elovl6). Elovl6 is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 may be a new therapeutic target for fat metabolism disorders such as obesity, type 2 diabetes, and nonalcoholic steatohepatitis. To identify new Elovl6 inhibitors, we developed a high-throughput fluorescence screening assay in 1536-well format. However, a number of false positives caused by fluorescent interference have been identified. To pick up the real active compounds among the primary hits from the fluorescence assay, we developed amore » RapidFire mass spectrometry assay and a conventional radioisotope assay. These assays have the advantage of detecting the main products directly without using fluorescent-labeled substrates. As a result, 276 compounds (30%) of the primary hits (921 compounds) in a fluorescence ultra-high-throughput screening method were identified as common active compounds in these two assays. It is concluded that both methods are very effective to eliminate false positives. Compared with the radioisotope method using an expensive {sup 14}C-labeled substrate, the RapidFire mass spectrometry method using unlabeled substrates is a high-accuracy, high-throughput method. In addition, some of the hit compounds selected from the screening inhibited cellular fatty acid elongation in HEK293 cells expressing Elovl6 transiently. This result suggests that these compounds may be promising lead candidates for therapeutic drugs. Ultra-high-throughput fluorescence screening followed by a RapidFire mass spectrometry assay was a suitable strategy for lead discovery against Elovl6. - Highlights: • A novel assay for elongation of very-long-chain fatty acids 6 (Elovl6) is proposed. • RapidFire mass spectrometry (RF-MS) assay is useful to select real screening hits. • RF-MS assay is proved to be beneficial because of its high-throughput and accuracy. • A combination of fluorescent and RF-MS assays is effective for Elovl6 inhibitors.« less

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.

Improving the Raster Scanning Methods used with X-ray Fluorescence to See the Ancient Greek Text of Archimedes (SULI Paper)

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

Griffin, Isabella B.; /Norfolk State U. /SLAC, SSRL

2006-01-04

X-ray fluorescence is being used to detect the ancient Greek copy of Archimedes work. The copy of Archimedes text was erased with a weak acid and written over to make a prayer book in the Middle Ages. The ancient parchment, made of goat skin, has on it some of Archimedes most valuable writings. The ink in the text contains iron which will fluoresce under x-ray radiation. My research project deals with the scanning and imaging process. The palimpsest is put in a stage that moves in a raster format. As the beam hits the parchment, a germanium detector detects themore » iron atoms and discriminates against other elements. Since the computer scans in both forwards and backwards directions, it is imperative that each row of data lines up exactly on top of the next row. There are several parameters to consider when scanning the parchment. These parameters include: speed, count time, shutter time, x-number of points, and acceleration. Formulas were made to relate these parameters together. During the actual beam time of this project, the scanning was very slow going; it took 30 hours to scan 1/2 of a page. Using the formulas, the scientists doubled distance and speed to scan the parchment faster; however, the grey scaled data was not lined up properly causing the images to look blurred. My project was is to find out why doubling the parameters caused blurred images, and to fix the problem if it is fixable.« less

Health information technology and physicians' perceptions of healthcare quality.

PubMed

Fang, Hai; Peifer, Karen L; Chen, Jie; Rizzo, John A

2011-03-01

To investigate the relationship between the use of health information technology (HIT) and physician perceptions of providing high-quality care and to determine whether this relationship has changed over time. We used 2 waves of longitudinal data from the Community Tracking Study Physician Surveys, 2000-2001 and 2004-2005. Three measures of HIT were examined: a binary variable measuring the use of at least 1 type of HIT, a continuous variable measuring the total number of HIT types, and a binary variable measuring use of all 5 HIT types related to "meaningful use" of HIT as defined by Centers for Medicare and Medicaid Services. Three multivariate models were estimated to study the effect of each HIT measure on physicians' perception of providing high-quality care. Individual fixed-effects estimation also was used to control for individual time-invariant factors. Using at least 1 type of HIT significantly enhanced physicians' perception of providing high-quality care in 2000-2001, but not in 2004-2005. The marginal effect of adding 1 extra HIT type was positive and statistically significant in both periods. The association between using all 5 HIT types related to meaningful use and perceived quality was statistically significant in 2000-2001, but not in 2004-2005. Health information technology has become a multifunctional system and appears to have enhanced physicians' perception of providing high-quality care. Physicians' perceptions of medical care quality improved as the number of HIT types used increased. This study supports more extensive use of HIT in physician practices.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes.

PubMed

Carlson, Hanqian L; Quinn, Jeffrey J; Yang, Yul W; Thornburg, Chelsea K; Chang, Howard Y; Stadler, H Scott

2015-12-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage.

LncRNA-HIT Functions as an Epigenetic Regulator of Chondrogenesis through Its Recruitment of p100/CBP Complexes

PubMed Central

Carlson, Hanqian L.; Quinn, Jeffrey J.; Yang, Yul W.; Thornburg, Chelsea K.; Chang, Howard Y.; Stadler, H. Scott

2015-01-01

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage. PMID:26633036

Differences in head impulse test results due to analysis techniques.

PubMed

Cleworth, Taylor W; Carpenter, Mark G; Honegger, Flurin; Allum, John H J

2017-01-01

Different analysis techniques are used to define vestibulo-ocular reflex (VOR) gain between eye and head angular velocity during the video head impulse test (vHIT). Comparisons would aid selection of gain techniques best related to head impulse characteristics and promote standardisation. Compare and contrast known methods of calculating vHIT VOR gain. We examined lateral canal vHIT responses recorded from 20 patients twice within 13 weeks of acute unilateral peripheral vestibular deficit onset. Ten patients were tested with an ICS Impulse system (GN Otometrics) and 10 with an EyeSeeCam (ESC) system (Interacoustics). Mean gain and variance were computed with area, average sample gain, and regression techniques over specific head angular velocity (HV) and acceleration (HA) intervals. Results for the same gain technique were not different between measurement systems. Area and average sample gain yielded equally lower variances than regression techniques. Gains computed over the whole impulse duration were larger than those computed for increasing HV. Gain over decreasing HV was associated with larger variances. Gains computed around peak HV were smaller than those computed around peak HA. The median gain over 50-70 ms was not different from gain around peak HV. However, depending on technique used, the gain over increasing HV was different from gain around peak HA. Conversion equations between gains obtained with standard ICS and ESC methods were computed. For low gains, the conversion was dominated by a constant that needed to be added to ESC gains to equal ICS gains. We recommend manufacturers standardize vHIT gain calculations using 2 techniques: area gain around peak HA and peak HV.

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.

Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

PubMed

Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

2017-08-31

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT).

PubMed

Sachs, Ulrich J; von Hesberg, Jakob; Santoso, Sentot; Bein, Gregor; Bakchoul, Tamam

2011-12-01

Heparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid single-sample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT.

Elevated circulating IGF-I promotes mammary gland development and proliferation.

PubMed

Cannata, Dara; Lann, Danielle; Wu, Yingjie; Elis, Sebastien; Sun, Hui; Yakar, Shoshana; Lazzarino, Deborah A; Wood, Teresa L; Leroith, Derek

2010-12-01

Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.

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.

Non-targeted analysis of unexpected food contaminants using LC-HRMS.

PubMed

Kunzelmann, Marco; Winter, Martin; Åberg, Magnus; Hellenäs, Karl-Erik; Rosén, Johan

2018-03-29

A non-target analysis method for unexpected contaminants in food is described. Many current methods referred to as "non-target" are capable of detecting hundreds or even thousands of contaminants. However, they will typically still miss all other possible contaminants. Instead, a metabolomics approach might be used to obtain "true non-target" analysis. In the present work, such a method was optimized for improved detection capability at low concentrations. The method was evaluated using 19 chemically diverse model compounds spiked into milk samples to mimic unknown contamination. Other milk samples were used as reference samples. All samples were analyzed with UHPLC-TOF-MS (ultra-high-performance liquid chromatography time-of-flight mass spectrometry), using reversed-phase chromatography and electrospray ionization in positive mode. Data evaluation was performed by the software TracMass 2. No target lists of specific compounds were used to search for the contaminants. Instead, the software was used to sort out all features only occurring in the spiked sample data, i.e., the workflow resembled a metabolomics approach. Procedures for chemical identification of peaks were outside the scope of the study. Method, study design, and settings in the software were optimized to minimize manual evaluation and faulty or irrelevant hits and to maximize hit rate of the spiked compounds. A practical detection limit was established at 25 μg/kg. At this concentration, most compounds (17 out of 19) were detected as intact precursor ions, as fragments or as adducts. Only 2 irrelevant hits, probably natural compounds, were obtained. Limitations and possible practical use of the approach are discussed.

Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis.

PubMed

Howlett, Christina; Snedecor, Sonya J; Landsburg, Daniel J; Svoboda, Jakub; Chong, Elise A; Schuster, Stephen J; Nasta, Sunita Dwivedy; Feldman, Tatyana; Rago, Allison; Walsh, Kristy M; Weber, Scott; Goy, Andre; Mato, Anthony

2015-08-01

'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or, alternatively, BCL6) rearrangements, have a very poor outcome compared to standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently, dose-intensive (DI) therapies and/or consolidation with high-dose therapy and transplant have been explored in DHL, although benefit has been debated. This meta-analysis compared survival outcomes in DHL patients receiving dose-escalated regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens (R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in the first-line setting. Data were synthesized to estimate hazard ratios of dose-escalated treatments versus R-CHOP using a Weibull proportional hazards model within a Bayesian meta-analysis framework. Eleven studies examining 394 patients were included. Patients were treated with either front-line R-CHOP (n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine (R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was 12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH significantly reduced the risk of a progression compared with R-CHOP (relative risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not significantly different across treatment approaches. A subset of patients might benefit from intensive induction with/without transplant. Further investigation into the role of transplant and novel therapy combinations is necessary. © 2015 John Wiley & Sons Ltd.

Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: distinct early response compared with single trauma or "double-hit" injury.

PubMed

Weckbach, Sebastian; Hohmann, Christoph; Braumueller, Sonja; Denk, Stephanie; Klohs, Bettina; Stahel, Philip F; Gebhard, Florian; Huber-Lang, Markus S; Perl, Mario

2013-02-01

The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries. Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx). After 2 hours or 6 hours, animals were sacrificed, and the systemic as well as the local pulmonary immune response (bronchoalveolar lavage [BAL]/plasma cytokines, lung myeloperoxidase [MPO] activity, and alveolocapillary barrier dysfunction) were evaluated along with lung/brain apoptosis (lung caspase 3 Western blotting, immunohistochemistry, and polymorphonuclear leukocytes [PMN] Annexin V). Hemoglobin, PO2 saturation, and pH did not differ between the experimental groups. Local BAL cytokines/chemokines were significantly increased in almost all groups, which included Tx. There was no further enhancement of this local inflammatory response in the lungs in case of PTx. At 2 hours, all groups except sham and closed head injury alone revealed an increased activity of lung MPO. However, 6 hours after injury, lung MPO remained increased only in the PTx group. Increased BAL protein levels were found, reflecting enhanced lung leakage in all groups with Tx 6 hours after trauma. Only after PTx was neutrophil apoptosis significantly decreased, whereas lung caspase 3 and plasma interleukin 6/keratinocyte chemoattractant (KC) were substantially increased. The combination of different injuries leads to an earlier systemic inflammatory response when compared with the single insults. Interestingly, only after PTx but not after single or double hits was lung apoptosis increased, and PMN apoptosis was decreased along with a prolonged presence of neutrophils in the lungs, which may therefore represent a possible pathomechanism for lung injury after polytrauma.

Pre- and Neonatal Exposure to Lipopolysaccharide or the Enteric Metabolite, Propionic Acid, Alters Development and Behavior in Adolescent Rats in a Sexually Dimorphic Manner

PubMed Central

Foley, Kelly A.; Ossenkopp, Klaus-Peter; Kavaliers, Martin; MacFabe, Derrick F.

2014-01-01

Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD). The current study examined the effects of prenatal and early life administration of lipopolysaccharide (LPS), a bacterial mimetic, and the short chain fatty acid, propionic acid (PPA), a metabolic fermentation product of enteric bacteria, on developmental milestones, locomotor activity, and anxiety-like behavior in adolescent male and female offspring. Pregnant Long-Evans rats were subcutaneously injected once a day with PPA (500 mg/kg) on gestation days G12–16, LPS (50 µg/kg) on G15–16, or vehicle control on G12–16 or G15–16. Male and female offspring were injected with PPA (500 mg/kg) or vehicle twice a day, every second day from postnatal days (P) 10–18. Physical milestones and reflexes were monitored in early life with prenatal PPA and LPS inducing delays in eye opening. Locomotor activity and anxiety were assessed in adolescence (P40–42) in the elevated plus maze (EPM) and open-field. Prenatal and postnatal treatments altered behavior in a sex-specific manner. Prenatal PPA decreased time spent in the centre of the open-field in males and females while prenatal and postnatal PPA increased anxiety behavior on the EPM in female rats. Prenatal LPS did not significantly influence those behaviors. Evidence for the double hit hypothesis was seen as females receiving a double hit of PPA (prenatal and postnatal) displayed increased repetitive behavior in the open-field. These results provide evidence for the hypothesis that by-products of enteric bacteria metabolism such as PPA may contribute to ASD, altering development and behavior in adolescent rats similar to that observed in ASD and other neurodevelopmental disorders. PMID:24466331

Subchronic MK-801 treatment and post-weaning social isolation in rats: differential effects on locomotor activity and hippocampal long-term potentiation.

PubMed

Ashby, Donovan M; Habib, Diala; Dringenberg, Hans C; Reynolds, James N; Beninger, Richard J

2010-09-01

Subchronic NMDA receptor antagonist treatment and post-weaning social isolation are two animal models of schizophrenia symptoms. However, behavioral and physiological changes following a combination of these two procedures have not been investigated. Thus, we examined effects of a novel, "double hit" model combining these two treatments, comparing them to standard models involving only NMDA antagonist treatment or social isolation. Male, Sprague-Dawley rats were either group-housed or maintained in social isolation (starting at postnatal day [PD] 21 and continuing throughout the study). Each housing condition was further subdivided into two groups, receiving either subchronic treatment with either saline or MK-801 (0.5mg/kg, i.p., 2xday for seven days starting at PD 56). Post-weaning social isolation increased locomotor activity (assessed at PD 70) in response to a novel environment and an acute amphetamine injection, while subchronic MK-801 increased only amphetamine induced locomotor activity. Subsequent electrophysiological experiments (under urethane anesthesia) assessing changes in plasticity of hippocampal synapses showed that subchronic MK-801 treatment resulted in an increase in long-term potentiation in area CA1 in response to high frequency stimulation of the contralateral CA3 area, while housing condition had no effect. No other changes in hippocampal electrophysiology (input-output curves, paired-pulse facilitation) were observed. These data are the first to demonstrate an enhancement in hippocampal long-term plasticity in vivo following subchronic MK-801 administration, an effect that may be related to the well-characterized changes in glutamatergic and GABAergic systems seen after subchronic NMDA receptor blockade. That lack of additive or synergistic effects in the "double hit model" suggests that combining isolation and subchronic MK-801 treatment does not necessarily produce greater behavioral or physiological dysfunction than that seen with either treatment alone. Copyright 2010 Elsevier B.V. All rights reserved.

Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study.

PubMed

Ashina, Messoud; Dodick, David; Goadsby, Peter J; Reuter, Uwe; Silberstein, Stephen; Zhang, Feng; Gage, Julia R; Cheng, Sunfa; Mikol, Daniel D; Lenz, Robert A

2017-09-19

To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM). Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without imputation for missing data. Of 472 patients enrolled in the parent study, 383 continued in the OLE with a median exposure to erenumab of 575 days (range 28-822 days). Mean (SD) MMD were 8.8 (2.6) at parent study baseline, 6.3 (4.2) at week 12 (beginning of OLE), and 3.7 (4.0) at week 64 (mean change from baseline [reduction] of 5.0 days). At week 64, 65%, 42%, and 26% achieved ≥50%, ≥75%, and 100% reduction in MMD, respectively. Mean HIT-6 scores were 60.2 (6.3) at baseline and 51.7 (9.2) at week 64. MSQ and MIDAS improvements from baseline were maintained through week 64. Safety profiles during the OLE were similar to those in the double-blind phase, which overall were similar to placebo. One-year efficacy, supported by functional improvements and favorable safety and tolerability profiles, supports further investigation of erenumab as a preventive treatment in patients with EM. NCT01952574. This study provides Class IV evidence that for patients with episodic migraine, erenumab reduces long-term MMD and improves headache-related disability and migraine-specific quality of life. © 2017 American Academy of Neurology.

Calculation of the number of Monte Carlo histories for a planetary protection probability of impact estimation

NASA Astrophysics Data System (ADS)

Barengoltz, Jack

2016-07-01

Monte Carlo (MC) is a common method to estimate probability, effectively by a simulation. For planetary protection, it may be used to estimate the probability of impact P{}_{I} by a launch vehicle (upper stage) of a protected planet. The object of the analysis is to provide a value for P{}_{I} with a given level of confidence (LOC) that the true value does not exceed the maximum allowed value of P{}_{I}. In order to determine the number of MC histories required, one must also guess the maximum number of hits that will occur in the analysis. This extra parameter is needed because a LOC is desired. If more hits occur, the MC analysis would indicate that the true value may exceed the specification value with a higher probability than the LOC. (In the worst case, even the mean value of the estimated P{}_{I} might exceed the specification value.) After the analysis is conducted, the actual number of hits is, of course, the mean. The number of hits arises from a small probability per history and a large number of histories; these are the classic requirements for a Poisson distribution. For a known Poisson distribution (the mean is the only parameter), the probability for some interval in the number of hits is calculable. Before the analysis, this is not possible. Fortunately, there are methods that can bound the unknown mean for a Poisson distribution. F. Garwoodfootnote{ F. Garwood (1936), ``Fiduciary limits for the Poisson distribution.'' Biometrika 28, 437-442.} published an appropriate method that uses the Chi-squared function, actually its inversefootnote{ The integral chi-squared function would yield probability α as a function of the mean µ and an actual value n.} (despite the notation used): This formula for the upper and lower limits of the mean μ with the two-tailed probability 1-α depends on the LOC α and an estimated value of the number of "successes" n. In a MC analysis for planetary protection, only the upper limit is of interest, i.e., the single-tailed distribution. (Smaller actual P{}_{I }is no problem.) {}_{ } One advantage of this method is that this function is available in EXCEL. Note that care must be taken with the definition of the CHIINV function (the inverse of the integral chi-squared distribution). The equivalent inequality in EXCEL is μ < CHIINV[1-α, 2(n+1)] In practice, one calculates this upper limit for a specified LOC, α , and a guess of how many hits n will be found after the MC analysis. Then the estimate of the number of histories required is this upper limit divided by the specification for the allowed P{}_{I} (rounded up). However, if the number of hits actually exceeds the guess, the P{}_{I} requirement will be met only with a smaller LOC. A disadvantage is that the intervals about the mean are "in general too wide, yielding coverage probabilities much greater than 1- α ." footnote{ G. Casella and C. Robert (1988), Purdue University-Technical Report #88-7 or Cornell University-Technical Report BU-903-M.} For planetary protection, this technical issue means that the upper limit of the interval and the probability associated with the interval (i.e., the LOC) are conservative.

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

PubMed

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

2016-01-01

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

[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.

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.

Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor.

PubMed

Li, Guo-Bo; Yang, Ling-Ling; Feng, Shan; Zhou, Jian-Ping; Huang, Qi; Xie, Huan-Zhang; Li, Lin-Li; Yang, Sheng-Yong

2011-03-15

Development of glutamate non-competitive antagonists of mGluR1 (Metabotropic glutamate receptor subtype 1) has increasingly attracted much attention in recent years due to their potential therapeutic application for various nervous disorders. Since there is no crystal structure reported for mGluR1, ligand-based virtual screening (VS) methods, typically pharmacophore-based VS (PB-VS), are often used for the discovery of mGluR1 antagonists. Nevertheless, PB-VS usually suffers a lower hit rate and enrichment factor. In this investigation, we established a multistep ligand-based VS approach that is based on a support vector machine (SVM) classification model and a pharmacophore model. Performance evaluation of these methods in virtual screening against a large independent test set, M-MDDR, show that the multistep VS approach significantly increases the hit rate and enrichment factor compared with the individual SB-VS and PB-VS methods. The multistep VS approach was then used to screen several large chemical libraries including PubChem, Specs, and Enamine. Finally a total of 20 compounds were selected from the top ranking compounds, and shifted to the subsequent in vitro and in vivo studies, which results will be reported in the near future. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

A simple procedure for parallel sequence analysis of both strands of 5'-labeled DNA.

PubMed

Razvi, F; Gargiulo, G; Worcel, A

1983-08-01

Ligation of a 5'-labeled DNA restriction fragment results in a circular DNA molecule carrying the two 32Ps at the reformed restriction site. Double digestions of the circular DNA with the original enzyme and a second restriction enzyme cleavage near the labeled site allows direct chemical sequencing of one 5'-labeled DNA strand. Similar double digestions, using an isoschizomer that cleaves differently at the 32P-labeled site, allows direct sequencing of the now 3'-labeled complementary DNA strand. It is possible to directly sequence both strands of cloned DNA inserts by using the above protocol and a multiple cloning site vector that provides the necessary restriction sites. The simultaneous and parallel visualization of both DNA strands eliminates sequence ambiguities. In addition, the labeled circular molecules are particularly useful for single-hit DNA cleavage studies and DNA footprint analysis. As an example, we show here an analysis of the micrococcal nuclease-induced breaks on the two strands of the somatic 5S RNA gene of Xenopus borealis, which suggests that the enzyme may recognize and cleave small AT-containing palindromes along the DNA helix.

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.

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.

Detecting non-orthology in the COGs database and other approaches grouping orthologs using genome-specific best hits.

PubMed

Dessimoz, Christophe; Boeckmann, Brigitte; Roth, Alexander C J; Gonnet, Gaston H

2006-01-01

Correct orthology assignment is a critical prerequisite of numerous comparative genomics procedures, such as function prediction, construction of phylogenetic species trees and genome rearrangement analysis. We present an algorithm for the detection of non-orthologs that arise by mistake in current orthology classification methods based on genome-specific best hits, such as the COGs database. The algorithm works with pairwise distance estimates, rather than computationally expensive and error-prone tree-building methods. The accuracy of the algorithm is evaluated through verification of the distribution of predicted cases, case-by-case phylogenetic analysis and comparisons with predictions from other projects using independent methods. Our results show that a very significant fraction of the COG groups include non-orthologs: using conservative parameters, the algorithm detects non-orthology in a third of all COG groups. Consequently, sequence analysis sensitive to correct orthology assignments will greatly benefit from these findings.

Childhood and adolescent animal cruelty methods and their possible link to adult violent crimes.

PubMed

Hensley, Christopher; Tallichet, Suzanne E

2009-01-01

Few researchers have investigated the potentially predictive power of childhood and adolescent animal cruelty methods as they are associated with subsequent interpersonal violence in adulthood. Based on a sample of 261 inmates at medium- and maximum-security prisons in a southern state, the present study examines the relationship between several retrospectively reported animal cruelty methods (drowned, hit or kicked, shot, choked, burned, and had sex) and violent criminal acts committed against humans (assault, rape, and murder). More than half of the sample reported they had shot animals, and almost half had either kicked or hit them. About one in five said they had choked animals, and about one in seven said they had either drowned, burned, or had sex with them. Regression analyses revealed that drowning and having sex with an animal was predictive of later interpersonal violence as adults.

External validation of the HIT Expert Probability (HEP) score.

PubMed

Joseph, Lee; Gomes, Marcelo P V; Al Solaiman, Firas; St John, Julie; Ozaki, Asuka; Raju, Manjunath; Dhariwal, Manoj; Kim, Esther S H

2015-03-01

The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The HIT Expert Probability (HEP) Score has recently been proposed to aid in the diagnosis of HIT. We sought to externally and prospectively validate the HEP score. We prospectively assessed pre-test probability of HIT for 51 consecutive patients referred to our Consultative Service for evaluation of possible HIT between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows independently applied the 4T and HEP scores for each patient. Two independent HIT expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median (interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5), respectively. There were no significant differences between area under receiver-operating characteristic curves of 4T and HEP scores against the gold standard, confirmed HIT [defined as positive serotonin release assay and positive anti-PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score ≥ 2 was 100 % sensitive and 16 % specific for determining the presence of confirmed HIT while a 4T score > 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores are excellent screening pre-test probability models for HIT, however, in this prospective validation study, test characteristics for the diagnosis of HIT based on confirmatory laboratory testing and expert opinion are similar. Given the complexity of the HEP scoring model compared to that of the 4T score, further validation of the HEP score is warranted prior to widespread clinical acceptance.

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

PubMed Central

Bakchoul, Tamam

2012-01-01

Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. PMID:23606934

Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

PubMed

Klinkhammer, Brent; Gruchalla, Michael

2018-03-01

Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P < 0.001). In disease-specific analyses, patients with a diagnosis of HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P < 0.001), systemic lupus erythematous (8.5% vs 0.4%, P = 0.001), rheumatoid arthritis (5.1% vs 0.0%, P = 0.007), Hashimoto's thyroiditis (13.6% vs 3.6%, P = 0.006), or nonischemic cardiomyopathy (5.1% vs 0.0%, P = 0.007). Patients diagnosed with HIT were significantly older than controls ( P < 0.001). This novel study gives evidence to suggest an association between HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

PubMed

Marler, Jacob L; Jones, G Morgan; Wheeler, Brian J; Alshaya, Abdulrahman; Hartmann, Jonathan L; Oliphant, Carrie S

2018-06-01

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

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.

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.

Azimuthal correlations between directed and elliptic flow in heavy ion collisions

NASA Astrophysics Data System (ADS)

Wu, Feng-Juan; Shan, Lian-Qiang; Zhang, Jing-Bo; Tang, Gui-Xin; Huo, Lei

2008-12-01

A method for investigating the azimuthal correlations between directed and elliptic flow in heavy ion collisions is described. The transverse anisotropy of particle emission at AGS energies is investigated within the RQMD model. It is found that the azimuthal correlations between directed and elliptic flow are sensitive to the incident energy and impact parameter. The fluctuations in the initial stage and dynamical evolution of heavy ion collisions are not negligible. Supported by Natural Science Foundation of Heilongjiang Province (A0208) and Science Foundation of Harbin Institute of Technology (HIT.2002.47, HIT.2003.33)

Determination of time zero from a charged particle detector

DOEpatents

Green, Jesse Andrew [Los Alamos, NM

2011-03-15

A method, system and computer program is used to determine a linear track having a good fit to a most likely or expected path of charged particle passing through a charged particle detector having a plurality of drift cells. Hit signals from the charged particle detector are associated with a particular charged particle track. An initial estimate of time zero is made from these hit signals and linear tracks are then fit to drift radii for each particular time-zero estimate. The linear track having the best fit is then searched and selected and errors in fit and tracking parameters computed. The use of large and expensive fast detectors needed to time zero in the charged particle detectors can be avoided by adopting this method and system.

Use of health information technology to advance evidence-based care: lessons from the VA QUERI program.

PubMed

Hynes, Denise M; Weddle, Timothy; Smith, Nina; Whittier, Erika; Atkins, David; Francis, Joseph

2010-01-01

As the Department of Veterans Affairs (VA) Health Services Research and Development Service's Quality Enhancement Research Initiative (QUERI) has progressed, health information technology (HIT) has occupied a crucial role in implementation research projects. We evaluated the role of HIT in VA QUERI implementation research, including HIT use and development, the contributions implementation research has made to HIT development, and HIT-related barriers and facilitators to implementation research. Key informants from nine disease-specific QUERI Centers. Documentation analysis of 86 implementation project abstracts followed up by semi-structured interviews with key informants from each of the nine QUERI centers. We used qualitative and descriptive analyses. We found: (1) HIT provided data and information to facilitate implementation research, (2) implementation research helped to further HIT development in a variety of uses including the development of clinical decision support systems (23 of 86 implementation research projects), and (3) common HIT barriers to implementation research existed but could be overcome by collaborations with clinical and administrative leadership. Our review of the implementation research progress in the VA revealed interdependency on an HIT infrastructure and research-based development. Collaboration with multiple stakeholders is a key factor in successful use and development of HIT in implementation research efforts and in advancing evidence-based practice.

WE-H-BRA-06: Experimental Investigation of RBE for Lung Cancer Cell Lines as a Function of Dose and LET in Proton, Helium and Carbon Beams

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

Patel, D; Titt, U; Bronk, L

2016-06-15

Purpose: Investigate and quantify the effect of dose and LET on the RBE of protons, helium and carbon ions. Methods: High throughput, high accuracy experimental setups were custom designed to investigate the Relative Biological Effectiveness (RBE) dependence on the dose and Linear Energy Transfer (LET) values for proton, helium and carbon ion beams. The experiment was conducted at the HIT facility in collaboration with the DKFZ in Heidelberg/Germany. Clonogenic assays of two human lung cancer cell lines, H460 and H1437, were investigated in this study. γH2AX foci staining on the H460 cell line was also undertaken to facilitate the studymore » of differential DNA double-strand break induction and repair between low-design available at the HIT facility. Specific points along the Bragg curve corresponding to well-defined doses and LET values were chosen by appropriate selection of the pre-absorber thicknesses. With a setup design for horizontal beam lines we were able to minimize ion scattering in the cell plate, resulting in narrower energy spectra and hence LET distributions in the Bragg peak and in the distal falloff regions, compared to the earlier experiments. Results: Approximately 16,000 samples of cancer cells were irradiated during 23 hours of beam time. The preliminary results of the survival curves for both cell lines show a distinct dependence on LET for a given dose with decreased survival fractions at increasing LET values, encountered at the Bragg peak and in the distal falloff. Conclusion: Our preliminary findings are indicative of the importance of novel variable-RBE models for proton therapy and provide insight into the RBE of heavy ions for possible future heavy ion therapy facilities in the US. Funding support: SINF 2015/16.« less

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.

Factors affecting reproducibility between genome-scale siRNA-based screens

PubMed Central

Barrows, Nicholas J.; Le Sommer, Caroline; Garcia-Blanco, Mariano A.; Pearson, James L.

2011-01-01

RNA interference-based screening is a powerful new genomic technology which addresses gene function en masse. To evaluate factors influencing hit list composition and reproducibility, we performed two identically designed small interfering RNA (siRNA)-based, whole genome screens for host factors supporting yellow fever virus infection. These screens represent two separate experiments completed five months apart and allow the direct assessment of the reproducibility of a given siRNA technology when performed in the same environment. Candidate hit lists generated by sum rank, median absolute deviation, z-score, and strictly standardized mean difference were compared within and between whole genome screens. Application of these analysis methodologies within a single screening dataset using a fixed threshold equivalent to a p-value ≤ 0.001 resulted in hit lists ranging from 82 to 1,140 members and highlighted the tremendous impact analysis methodology has on hit list composition. Intra- and inter-screen reproducibility was significantly influenced by the analysis methodology and ranged from 32% to 99%. This study also highlighted the power of testing at least two independent siRNAs for each gene product in primary screens. To facilitate validation we conclude by suggesting methods to reduce false discovery at the primary screening stage. In this study we present the first comprehensive comparison of multiple analysis strategies, and demonstrate the impact of the analysis methodology on the composition of the “hit list”. Therefore, we propose that the entire dataset derived from functional genome-scale screens, especially if publicly funded, should be made available as is done with data derived from gene expression and genome-wide association studies. PMID:20625183

Development of surgical skill with singular neurectomy using human cadaveric temporal bones.

PubMed

Feigl, Georg; Kos, Izabel; Anderhuber, Friedrich; Guyot, Jean Phillippe; Fasel, Jean

2008-01-01

Profound anatomical knowledge and surgical experience are essential for safe otological surgery. The surgeon's learning curve is evaluated in performing Gacek's singular neurectomy on cadaveric specimens. One otological surgeon performed Gacek's approach on 96 halves of human heads embalmed according to Thiel's method, divided into four groups (24 halves per group) and evaluated them concurrent to the evaluation of an anatomist after a first surgical attempt. Successful operations were subdivided into "direct hits" of the osseous canal of the posterior ampullary nerve also known as the singular nerve and "indirect hits" with access to the posterior ampullary recess. Unsuccessful operations showed "no hit" of the nerve without lesion of the membranous labyrinth. "Indirect" or "no hits" were reinvestigated in a second attempt to evaluate possible reclassifications due to a learning process of the surgeon. The order of dissection, the rate of success and the changes of results in correlation with the numbers of dissected specimens were documented. The success rate significantly increased from 54.2% direct hits after the first group to 87.36% in the fourth group after the first attempt. Successful operations were performed in 86.5% after completion of the first attempt and 97.9% after the second attempt. The number of new allocations decreased from 11 cases in the first group of dissected specimens to zero in the fourth group. This paper strengthens the value of cadaveric training for surgeons and the crucial role of dissection of a large number of specimens in improvement of the surgeon's experience and success rate.

Engineering and Design of the Steady Inductive Helicity Injected Torus (HIT--SI)

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Jarboe, T. R.; Nelson, B. A.; Rogers, J. A.; Shumlak, U.

1999-11-01

Steady Inductive Helicity Injection (SIHI) is an inductive helicity injection method that injects helicity at a nearly constant rate, without open field lines, and without removing any helicity or magnetic energy from the plasma.(T.R. Jarboe, Fusion Technology, 36) (1), p. 85, 1999 SIHI directly produces a rotating magnetic field structure, and in the frame of the rotating field the current profile is nearly time independent. The Steady Inductive Helicity Injected Torus (HIT--SI) is a spheromak designed to implement SIHI so that the current profile in the rotating frame is optimized. The geometry of HIT--SI will be presented, including the manufacturing techniques and metallurgical processes planned for construction of the close-fitting flux conserver. The flux conserver is made of aged chromium copper with 80% the conductivity of pure copper. The detailed electrical insulation requirements in the helicity injector design lead to a complex o-ring seal and a plasma-sprayed alumina insulation coating. This has prompted the construction of an o-ring prototype test fixture having the main features of the o-ring design and the alumina coating. The design and evaluation of this fixture will also be presented with vacuum and voltage test results.

Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines

PubMed Central

2011-01-01

Introduction The pan-HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) has previously shown to be a radio-sensitizer to conventional photon radiotherapy (XRT) in pediatric sarcoma cell lines. Here, we investigate its effect on the response of two sarcoma cell lines and a normal tissue cell line to heavy ion irradiation (HIT). Materials and methods Clonogenic assays after different doses of heavy ions were performed. DNA damage and repair were evaluated by measuring γH2AX via flow-cytometry. Apoptosis and cell cycle analysis were also measured via flow cytometry. Protein expression of repair proteins, p53 and p21 were measured using immunoblot analysis. Changes of nuclear architecture after treatment with SAHA and HIT were observed in one of the sarcoma cell lines via light microscopy after staining towards chromatin and γH2AX. Results Corresponding with previously reported photon data, SAHA lead to an increase of sensitivity to heavy ions along with an increase of DSB and apoptosis in the two sarcoma cell lines. In contrast, in the osteoblast cell line (hFOB 1.19), the combination of SAHA and HIT showed a significant radio-protective effect. Laser scanning microscopy revealed no significant morphologic changes after HIT compared to the combined treatment with SAHA. Immunoblot analysis revealed no significant up or down regulation of p53. However, p21 was significantly increased by SAHA and combination treatment as compared to HIT only in the two sarcoma cell lines - again in contrast to the osteoblast cell line. Changes in the repair kinetics of DSB p53-independent apoptosis with p21 involvement may be part of the underlying mechanisms for radio-sensitization by SAHA. Conclusion Our in vitro data suggest an increase of the therapeutic ratio by the combination of SAHA with HIT in infantile sarcoma cell lines. PMID:21933400

Development of a Health Information Technology Acceptance Model Using Consumers’ Health Behavior Intention

PubMed Central

2012-01-01

Background For effective health promotion using health information technology (HIT), it is mandatory that health consumers have the behavioral intention to measure, store, and manage their own health data. Understanding health consumers’ intention and behavior is needed to develop and implement effective and efficient strategies. Objective To develop and verify the extended Technology Acceptance Model (TAM) in health care by describing health consumers’ behavioral intention of using HIT. Methods This study used a cross-sectional descriptive correlational design. We extended TAM by adding more antecedents and mediating variables to enhance the model’s explanatory power and to make it more applicable to health consumers’ behavioral intention. Additional antecedents and mediating variables were added to the hypothetical model, based on their theoretical relevance, from the Health Belief Model and theory of planned behavior, along with the TAM. We undertook structural equation analysis to examine the specific nature of the relationship involved in understanding consumers’ use of HIT. Study participants were 728 members recruited from three Internet health portals in Korea. Data were collected by a Web-based survey using a structured self-administered questionnaire. Results The overall fitness indices for the model developed in this study indicated an acceptable fit of the model. All path coefficients were statistically significant. This study showed that perceived threat, perceived usefulness, and perceived ease of use significantly affected health consumers’ attitude and behavioral intention. Health consumers’ health status, health belief and concerns, subjective norm, HIT characteristics, and HIT self-efficacy had a strong indirect impact on attitude and behavioral intention through the mediators of perceived threat, perceived usefulness, and perceived ease of use. Conclusions An extended TAM in the HIT arena was found to be valid to describe health consumers’ behavioral intention. We categorized the concepts in the extended TAM into 3 domains: health zone, information zone, and technology zone. PMID:23026508

Assessment of the 4Ts pretest clinical scoring system as a predictor of heparin-induced thrombocytopenia.

PubMed

Strutt, Jaclyn K; Mackey, Jennifer E; Johnson, Stephen M; Sylvia, Lynne M

2011-02-01

To evaluate the utility of the 4Ts clinical scoring system as a pretest probability method for the detection of heparin-induced thrombocytopenia (HIT). Prospective observational study. Medical and surgical inpatients at a tertiary care medical center. Eighty consecutive patients with suspicion of HIT who had a polyspecific enzyme-linked immunosorbent assay (ELISA) performed between December 1, 2008, and April 1, 2009, for detection of platelet factor 4 (PF4)-heparin antibodies. The predictive value of the 4Ts scoring system as determined by using a standard laboratory marker of HIT--the ELISA--and the interrater reliability of the scoring system were assessed. Sixty-seven (84%) of the 80 patients had low clinical probability of HIT based on the calculated 4Ts score. The ELISA result was negative for PF4-heparin antibodies in 74 patients (93%). Based on the results of the ELISA, the negative predictive value of the 4Ts score was 91%. Each 4Ts score was calculated by two independent investigators and adjudicated by a third investigator when necessary. The interrater reliability of the scoring system was fair (Cohen κ coefficient 0.362, 95% confidence interval [CI] 0.222-0.502; weighted κ coefficient 0.554 (95% CI 0.441-0.667). Determination of the timing of HIT was associated with the largest number of discrepancies (16) between evaluators, followed by other causes of thrombocytopenia (15), degree of decline in platelet count (14), and the presence of thrombosis or other sequelae (2). A low 4Ts score supports a low probability of HIT based on the results of the polyspecific ELISA. Overall, the interrater reliability of the scoring system was fair. Components of the 4Ts scoring system need to be further clarified or modified in order to improve interrater reliability and thereby increase the clinical utility of this pretest probability model.

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

PubMed

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

2013-09-01

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

A path analysis study of retention of healthcare professionals in urban India using health information technology.

PubMed

Bhattacharya, Indrajit; Ramachandran, Anandhi

2015-07-31

Healthcare information technology (HIT) applications are being ubiquitously adopted globally and have been indicated to have effects on certain dimensions of recruitment and retention of healthcare professionals. Retention of healthcare professionals is affected by their job satisfaction (JS), commitment to the organization and intention to stay (ITS) that are interlinked with each other and influenced by many factors related to job, personal, organization, etc. The objectives of the current study were to determine if HIT was one among the factors and, if so, propose a probable retention model that incorporates implementation and use of HIT as a strategy. This was a cross-sectional survey study covering 20 hospitals from urban areas of India. The sample (n = 586) consisted of doctors, nurses, paramedics and hospital administrators. Data was collected through a structured questionnaire. Factors affecting job satisfaction were determined. Technology acceptance by the healthcare professionals was also determined. Interactions between the factors were predicted using a path analysis model. The overall satisfaction rate of the respondents was 51 %. Based on factor analysis method, 10 factors were identified for JS and 9 factors for ITS. Availability and use of information technology was one factor that affected JS. The need for implementing technology influenced ITS through work environment and career growth. Also, the study indicated that nearly 70 % of the respondents had awareness of HIT, but only 40 % used them. The importance of providing training for HIT applications was stressed by many respondents. The results are in agreement with literature studies exploring job satisfaction and retention among healthcare professionals. Our study documented a relatively medium level of job satisfaction among the healthcare professionals in the urban area. Information technology was found to be one among the factors that can plausibly influence their job satisfaction and intention to stay. Based on the results of the study, a retention strategy has been suggested that utilizes implementation of HIT and provision of training to influence the retention of healthcare workers.

Repealing Federal Health Reform: Economic and Employment Consequences for States.

PubMed

Ku, Leighton; Steinmetz, Erika; Brantley, Erin; Bruen, Brian

2017-01-01

Issue: The incoming Trump administration and Republicans in Congress are seeking to repeal the Affordable Care Act (ACA), likely beginning with the law’s insurance premium tax credits and expansion of Medicaid eligibility. Research shows that the loss of these two provisions would lead to a doubling of the number of uninsured, higher uncompensated care costs for providers, and higher taxes for low-income Americans. Goal: To determine the state-by-state effect of repeal on employment and economic activity. Methods: A multistate economic forecasting model (PI+ from Regional Economic Models, Inc.) was used to quantify for each state the effects of the federal spending cuts. Findings and Conclusions: Repeal results in a $140 billion loss in federal funding for health care in 2019, leading to the loss of 2.6 million jobs (mostly in the private sector) that year across all states. A third of lost jobs are in health care, with the majority in other industries. If replacement policies are not in place, there will be a cumulative $1.5 trillion loss in gross state products and a $2.6 trillion reduction in business output from 2019 to 2023. States and health care providers will be particularly hard hit by the funding cuts.

HIT-6 and MIDAS as measures of headache disability in a headache referral population.

PubMed

Sauro, Khara M; Rose, Marianne S; Becker, Werner J; Christie, Suzanne N; Giammarco, Rose; Mackie, Gordon F; Eloff, Arnoldas G; Gawel, Marek J

2010-03-01

The objective of this study was to compare the headache impact test (HIT-6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache-related disability. The degree of headache-related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. We compared HIT-6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT-6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI-II) scores. A positive correlation was found between HIT-6 and MIDAS scores (r = 0.52). The BDI-II scores correlated equally with the HIT-6 and the MIDAS (r = 0.42). There was a non-monotonic relationship between headache frequency and the MIDAS, and a non-linear monotonic relationship between headache frequency and the HIT-6 (r = 0.24). The correlation was higher between the intensity and the HIT-6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy-nine percent of patients fell into the most severe HIT-6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT-6 than with the MIDAS (McNemar chi-square = 191 on 6 d.f., P < .0001). The HIT-6 and MIDAS appear to measure headache-related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT-6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT-6 and MIDAS together may give a more accurate assessment of a patient's headache-related disability.

78 FR 29135 - HIT Standards Committee Advisory Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting AGENCY: Office of...: HIT Standards Committee. General Function of the Committee: To provide recommendations to the National... Federal Health IT Strategic Plan, and in accordance with policies developed by the HIT Policy Committee...

76 FR 25355 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations AGENCY: Office of the National Coordinator for Health Information... Committee regarding health information technology standards, implementation specifications, and/or...

Post-hit dynamics of price limit hits in the Chinese stock markets

NASA Astrophysics Data System (ADS)

Wu, Ting; Wang, Yue; Li, Ming-Xia

2017-01-01

Price limit trading rules are useful to cool off traders short-term trading mania on individual stocks. The price dynamics approaching the limit boards are known as the magnet effect. However, the price dynamics after opening price limit hits are not well investigated. Here, we provide a detailed analysis on the price dynamics after the hits of up-limit or down-limit is open based on all A-share stocks traded in the Chinese stock markets. A "W" shape is found in the expected return, which reveals high probability of a continuous price limit hit on the following day. We also find that price dynamics after opening limit hits are dependent on the market trends. The time span of continuously hitting the price limit is found to an influence factor of the expected profit after the limit hit is open. Our analysis provides a better understanding of the price dynamics around the limit boards and contributes potential practical values for investors.

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

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.

A Divergent SAR Study Allows Optimization of a Potent 5-HT2c Inhibitor to a Promising Antimalarial Scaffold.

PubMed

Calderón, Félix; Vidal-Mas, Jaume; Burrows, Jeremy; de la Rosa, Juan Carlos; Jiménez-Díaz, María Belén; Mulet, Teresa; Prats, Sara; Solana, Jorge; Witty, Michael; Gamo, Francisco Javier; Fernández, Esther

2012-05-10

From the 13 533 chemical structures published by GlaxoSmithKline in 2010, we identified 47 quality starting points for lead optimization. One of the most promising hits was the TCMDC-139046, a molecule presenting an indoline core, which is well-known for its anxiolytic properties by interacting with serotonin antagonist receptors 5-HT2. The inhibition of this target will complicate the clinical development of these compounds as antimalarials. Herein, we present the antimalarial profile of this series and our efforts to avoid interaction with this receptor, while maintaining a good antiparasitic potency. By using a double-divergent structure-activity relationship analysis, we have obtained a novel lead compound harboring an indoline core.

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.

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.

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

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.

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.

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.

Emerging Issues and Opportunities in Health Information Technology.

PubMed

Nardi, Elizabeth A; Lentz, Lisa Korin; Winckworth-Prejsnar, Katherine; Abernethy, Amy P; Carlson, Robert W

2016-10-01

When used effectively, health information technology (HIT) can transform clinical care and contribute to new research discoveries. Despite advances in HIT and increased electronic health record adoption, many challenges to optimal use, interoperability, and data sharing exist. Data standardization across systems is limited, and scanned medical note documents result in unstructured data that make reporting on quality measures for reimbursement burdensome. Different policies and initiatives, including the Health Information Technology for Economic and Clinical Health Act, the Medicare Access and CHIP Reauthorization Act, and the National Cancer Moonshot initiative, among others, all recognize the impact that HIT can have on cancer care. Given the growing role HIT plays in health care, it is vital to have effective and efficient HIT systems that can exchange information, collect credible data that is analyzable at the point of care, and improves the patient-provider relationship. In June 2016, NCCN hosted the Emerging Issues and Opportunities in Health Information Technology Policy Summit. The summit addressed challenges, issues, and opportunities in HIT as they relate to cancer care. Keynote presentations and panelists discussed moving beyond Meaningful Use, HIT readiness to support and report on quality care, the role of HIT in precision medicine, the role of HIT in the National Cancer Moonshot initiative, and leveraging HIT to improve quality of clinical care. Copyright © 2016 by the National Comprehensive Cancer Network.

Comparison of Health Information Technology Use Between American Adults With and Without Chronic Health Conditions: Findings From The National Health Interview Survey 2012.

PubMed

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.

Short branches lead to systematic artifacts when BLAST searches are used as surrogate for phylogenetic reconstruction.

PubMed

Dick, Amanda A; Harlow, Timothy J; Gogarten, J Peter

2017-02-01

Long Branch Attraction (LBA) is a well-known artifact in phylogenetic reconstruction when dealing with branch length heterogeneity. Here we show another phenomenon, Short Branch Attraction (SBA), which occurs when BLAST searches, a phenetic analysis, are used as a surrogate method for phylogenetic analysis. This error also results from branch length heterogeneity, but this time it is the short branches that are attracting. The SBA artifact is reciprocal and can be returned 100% of the time when multiple branches differ in length by a factor of more than two. SBA is an intended feature of BLAST searches, but becomes an issue, when top scoring BLAST hit analyses are used to infer Horizontal Gene Transfers (HGTs), assign taxonomic category with environmental sequence data in phylotyping, or gather homologous sequences for building gene families. SBA can lead researchers to believe that there has been a HGT event when only vertical descent has occurred, cause slowly evolving taxa to be over-represented and quickly evolving taxa to be under-represented in phylotyping, or systematically exclude quickly evolving taxa from analyses. SBA also contributes to the changing results of top scoring BLAST hit analyses as the database grows, because more slowly evolving taxa, or short branches, are added over time, introducing more potential for SBA. SBA can be detected by examining reciprocal best BLAST hits among a larger group of taxa, including the known closest phylogenetic neighbors. Therefore, one should look for this phenomenon when conducting best BLAST hit analyses as a surrogate method to identify HGTs, in phylotyping, or when using BLAST to gather homologous sequences. Copyright © 2016 Elsevier Inc. All rights reserved.

VOR Gain Is Related to Compensatory Saccades in Healthy Older Adults

PubMed Central

Anson, Eric R.; Bigelow, Robin T.; Carey, John P.; Xue, Qian-Li; Studenski, Stephanie; Schubert, Michael C.; Agrawal, Yuri

2016-01-01

Objective: Vestibulo-ocular reflex (VOR) gain is well-suited for identifying rotational vestibular dysfunction, but may miss partial progressive decline in age-related vestibular function. Since compensatory saccades might provide an alternative method for identifying subtle vestibular decline, we describe the relationship between VOR gain and compensatory saccades in healthy older adults. Methods: Horizontal VOR gain was measured in 243 subjects age 60 and older from the Baltimore Longitudinal Study of Aging using video head impulse testing (HIT). Saccades in each HIT were identified as either “compensatory” or “compensatory back-up,” i.e., same or opposite direction as the VOR response respectively. Saccades were also classified as “covert” (occurring during head movement) and “overt” (occurring after head movement). The relationship between VOR gain and percentage of HITs with saccades, as well as the relationship between VOR gain and saccade latency and amplitude, were evaluated using regression analyses adjusting for age, gender, and race. Results: In adjusted analyses, the percentage of HITs with compensatory saccades increased 4.5% for every 0.1 decrease in VOR gain (p < 0.0001). Overt compensatory saccade amplitude decreased 0.6° (p < 0.005) and latency increased 90 ms (p < 0.001) for every 0.1 increase in VOR gain. Covert back-up compensatory saccade amplitude increased 0.4° for every 0.1 increase in VOR gain. Conclusion: We observed significant relationships between VOR gain and compensatory saccades in healthy older adults. Lower VOR gain was associated with larger amplitude, shorter latency compensatory saccades. Compensatory saccades reflect underlying rotational vestibular hypofunction, and may be particularly useful at identifying partial vestibular deficits as occur in aging adults. PMID:27445793

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.

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.

IA-Regional-Radio - Social Network for Radio Recommendation

NASA Astrophysics Data System (ADS)

Dziczkowski, Grzegorz; Bougueroua, Lamine; Wegrzyn-Wolska, Katarzyna

This chapter describes the functions of a system proposed for the music hit recommendation from social network data base. This system carries out the automatic collection, evaluation and rating of music reviewers and the possibility for listeners to rate musical hits and recommendations deduced from auditor's profiles in the form of regional Internet radio. First, the system searches and retrieves probable music reviews from the Internet. Subsequently, the system carries out an evaluation and rating of those reviews. From this list of music hits, the system directly allows notation from our application. Finally, the system automatically creates the record list diffused each day depending on the region, the year season, the day hours and the age of listeners. Our system uses linguistics and statistic methods for classifying music opinions and data mining techniques for recommendation part needed for recorded list creation. The principal task is the creation of popular intelligent radio adaptive on auditor's age and region - IA-Regional-Radio.

78 FR 29134 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... quality, clinical operations, implementation, consumer technology, nationwide health information networks and privacy and security. Other groups will be convened to address specific issues as needed. HIT...) Direct the appropriate workgroup or other special group to develop a report for the HIT Standards...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

77 FR 37408 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... be open to the public. Name of Committee: HIT Standards Committee. General Function of the Committee... with policies developed by the HIT Policy Committee. Date and Time: The meeting will be held on July 19...

77 FR 65691 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on November 13, 2012, from 9...

76 FR 70455 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 14, 2011, from 9...

76 FR 79684 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on January 25, 2012, from 9 a...

77 FR 65690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on December 19, 2012, from 9...

77 FR 45353 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on August 15, 2012, from 9:00...

77 FR 2727 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on February 29, 2012, from 9...

77 FR 73661 - HIT Standards Committee Advisory Meetings; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meetings; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: These meetings will be held on the following dates and...

77 FR 60438 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on October 17, 2012, from 9 a...

77 FR 50690 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on September 19, 2012, from 9...

42 CFR 495.332 - State Medicaid health information technology (HIT) plan requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false State Medicaid health information technology (HIT... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.332 State Medicaid health information technology (HIT) plan requirements. Each State Medicaid HIT plan must include...

75 FR 62399 - Office of the National Coordinator for Health Information Technology; HIT Standards Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-08

..., implementation, and privacy and security. HIT Standards Committee Schedule for the Assessment of HIT Policy... recommendations received from the HIT Policy Committee regarding health information technology standards...), section 3003. Erin Poetter, Office of Policy and Planning, Office of the National Coordinator for Health...

A Systolic Array-Based FPGA Parallel Architecture for the BLAST Algorithm

PubMed Central

Guo, Xinyu; Wang, Hong; Devabhaktuni, Vijay

2012-01-01

A design of systolic array-based Field Programmable Gate Array (FPGA) parallel architecture for Basic Local Alignment Search Tool (BLAST) Algorithm is proposed. BLAST is a heuristic biological sequence alignment algorithm which has been used by bioinformatics experts. In contrast to other designs that detect at most one hit in one-clock-cycle, our design applies a Multiple Hits Detection Module which is a pipelining systolic array to search multiple hits in a single-clock-cycle. Further, we designed a Hits Combination Block which combines overlapping hits from systolic array into one hit. These implementations completed the first and second step of BLAST architecture and achieved significant speedup comparing with previously published architectures. PMID:25969747

Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

PubMed

Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

2017-08-24

High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

77 FR 15760 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: to provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on April 18, 2012, from 9 a.m...

77 FR 27459 - HIT Standards Committee Advisory Meeting; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of... public. Name of Committee: HIT Standards Committee. General Function of the Committee: To provide... developed by the HIT Policy Committee. Date and Time: The meeting will be held on June 20, 2012, from 9 a.m...

Prospective virtual screening for novel p53-MDM2 inhibitors using ultrafast shape recognition

NASA Astrophysics Data System (ADS)

Patil, Sachin P.; Ballester, Pedro J.; Kerezsi, Cassidy R.

2014-02-01

The p53 protein, known as the guardian of genome, is mutated or deleted in approximately 50 % of human tumors. In the rest of the cancers, p53 is expressed in its wild-type form, but its function is inhibited by direct binding with the murine double minute 2 (MDM2) protein. Therefore, inhibition of the p53-MDM2 interaction, leading to the activation of tumor suppressor p53 protein presents a fundamentally novel therapeutic strategy against several types of cancers. The present study utilized ultrafast shape recognition (USR), a virtual screening technique based on ligand-receptor 3D shape complementarity, to screen DrugBank database for novel p53-MDM2 inhibitors. Specifically, using 3D shape of one of the most potent crystal ligands of MDM2, MI-63, as the query molecule, six compounds were identified as potential p53-MDM2 inhibitors. These six USR hits were then subjected to molecular modeling investigations through flexible receptor docking followed by comparative binding energy analysis. These studies suggested a potential role of the USR-selected molecules as p53-MDM2 inhibitors. This was further supported by experimental tests showing that the treatment of human colon tumor cells with the top USR hit, telmisartan, led to a dose-dependent cell growth inhibition in a p53-dependent manner. It is noteworthy that telmisartan has a long history of safe human use as an approved anti-hypertension drug and thus may present an immediate clinical potential as a cancer therapeutic. Furthermore, it could also serve as a structurally-novel lead molecule for the development of more potent, small-molecule p53-MDM2 inhibitors against variety of cancers. Importantly, the present study demonstrates that the adopted USR-based virtual screening protocol is a useful tool for hit identification in the domain of small molecule p53-MDM2 inhibitors.

Preventive effect of α-lipoic acid on prepulse inhibition deficits in a juvenile two-hit model of schizophrenia.

PubMed

Deslauriers, J; Racine, W; Sarret, P; Grignon, S

2014-07-11

Some pathophysiological models of schizophrenia posit that prenatal inflammation sensitizes the developing brain to second insults in early life and enhances brain vulnerability, thereby increasing the risk of developing the disorder during adulthood. We previously developed a two-hit animal model, based on the well-established prenatal immune challenge with poly-inosinic/cytidylic acid (polyI:C), followed by juvenile restraint stress (RS). We observed an additive disruption of prepulse inhibition (PPI) of acoustic startle in juvenile mice submitted to both insults. Previous studies have also reported that oxidative stress is associated with pathophysiological mechanisms of psychiatric disorders, including schizophrenia. We report here that PPI disruption in our two-hit animal model of schizophrenia is associated with an increase in oxidative stress. These findings led us to assess whether α-lipoic acid, an antioxidant, can prevent both increase in oxidative status and PPI deficits in our juvenile in vivo model of schizophrenia. In the offspring submitted to prenatal injection of polyI:C and to RS, treatment with α-lipoic acid prevented the development of PPI deficits 24h after the last period of RS. α-Lipoic acid also improved PPI performance in control mice. The reversal effect of α-lipoic acid pretreatment on these behavioral alterations was further accompanied by a normalization of the associated oxidative status and dopaminergic and GABAergic abnormalities in the prefrontal cortex. Based on our double insult paradigm, these results support the hypothesis that oxidative stress plays an important role in the development of PPI deficits, a well-known behavior associated with schizophrenia. These findings form the basis of future studies aiming to unravel mechanistic insights of the putative role of antioxidants in the treatment of schizophrenia, especially during the prodromal stage. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Amphetamine improves mouse and human attention in the 5-choice continuous performance test.

PubMed

MacQueen, David A; Minassian, Arpi; Kenton, Johnny A; Geyer, Mark A; Perry, William; Brigman, Jonathan L; Young, Jared W

2018-05-31

Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5-choice continuous performance test (5C-CPT) of attention in healthy young adult humans and mice. A mixed gender sample received placebo (n = 29), 10 (n = 17) or 20 mg D-amp (n = 25) in a double-blind fashion before 5C-CPT testing. In addition, male C57BL/6J mice were trained on a touchscreen adaptation of the 5C-CPT and tested after receiving saline or D-amp (0.1, 0.3, 1.0 mg/kg; n = 8/dose). In humans, D-amp significantly improved 5C-CPT performance. Both doses improved signal detection driven by increased hit rate (reduced omissions). Both doses also improved response accuracy and reduced hit reaction time (HRT) variability. In mice, similar effects (improved signal detection, hit rate, and response accuracy) were observed at the moderate dose (0.3 mg/kg). In contrast to human participants however, no effect on HRT variability was detected in mice, with no effect on HRT in either species. Human 5C-CPT performance was consistent with prior studies and consistent with alternative CPT paradigms. The performance of C57BL/6J mice on the touchscreen 5C-CPT mirrored performance of this strain on 5-hole operant chambers. Importantly, comparable facilitation of attention with D-amp was observed in both species. The 5C-CPT provides a cross-species paradigm by which the cognitive enhancing properties of stimulants and the neural underpinnings of attention can be assessed. Copyright © 2018. Published by Elsevier Ltd.

The impact of health information technology adoption by outpatient facilities on pregnancy outcomes.

PubMed

Deily, Mary E; Hu, Tianyan; Terrizzi, Sabrina; Chou, Shin-Yi; Meyerhoefer, Chad D

2013-02-01

Examine whether health information technology (HIT) at nonhospital facilities (NHFs) improves health outcomes and decreases resource use at hospitals within the same heath care network, and whether the impact of HIT varies as providers gain experience using the technologies. Administrative claims data on 491,832 births in Pennsylvania during 1998-2004 from the Pennsylvania Health Care Cost Containment Council and HIT applications data from the Dorenfest Institute. Fixed-effects regression analysis of the impact of HIT at NHFs on adverse birth outcomes and resource use. Greater use of clinical HIT applications by NHFs is associated with reduced incidence of obstetric trauma and preventable complications, as well as longer lengths of stay. In addition, the beneficial effects of HIT increase the longer that technologies have been in use. However, we find no consistent evidence on whether or how nonclinical HIT in NHFs affects either resource use or health outcomes. Clinical HIT applications at NHFs may reduce the likelihood of adverse birth outcomes, particularly after physicians and staff gain experience using the technologies. © Health Research and Educational Trust.

The Impact of Health Information Technology Adoption by Outpatient Facilities on Pregnancy Outcomes

PubMed Central

Deily, Mary E; Hu, Tianyan; Terrizzi, Sabrina; Chou, Shin-Yi; Meyerhoefer, Chad D

2013-01-01

Objective Examine whether health information technology (HIT) at nonhospital facilities (NHFs) improves health outcomes and decreases resource use at hospitals within the same heath care network, and whether the impact of HIT varies as providers gain experience using the technologies. Data Sources Administrative claims data on 491,832 births in Pennsylvania during 1998–2004 from the Pennsylvania Health Care Cost Containment Council and HIT applications data from the Dorenfest Institute. Study Design Fixed-effects regression analysis of the impact of HIT at NHFs on adverse birth outcomes and resource use. Principal Findings Greater use of clinical HIT applications by NHFs is associated with reduced incidence of obstetric trauma and preventable complications, as well as longer lengths of stay. In addition, the beneficial effects of HIT increase the longer that technologies have been in use. However, we find no consistent evidence on whether or how nonclinical HIT in NHFs affects either resource use or health outcomes. Conclusions Clinical HIT applications at NHFs may reduce the likelihood of adverse birth outcomes, particularly after physicians and staff gain experience using the technologies. PMID:22742682

Plasma exchange to remove HIT antibodies: dissociation between enzyme-immunoassay and platelet activation test reactivities.

PubMed

Warkentin, Theodore E; Sheppard, Jo-Ann I; Chu, F Victor; Kapoor, Anil; Crowther, Mark A; Gangji, Azim

2015-01-01

Repeated therapeutic plasma exchange (TPE) has been advocated to remove heparin-induced thrombocytopenia (HIT) IgG antibodies before cardiac/vascular surgery in patients who have serologically-confirmed acute or subacute HIT; for this situation, a negative platelet activation assay (eg, platelet serotonin-release assay [SRA]) has been recommended as the target serological end point to permit safe surgery. We compared reactivities in the SRA and an anti-PF4/heparin IgG-specific enzyme immunoassay (EIA), testing serial serum samples in a patient with recent (subacute) HIT who underwent serial TPE precardiac surgery, as well as for 15 other serially-diluted HIT sera. We observed that post-TPE/diluted HIT sera-when first testing SRA-negative-continue to test strongly positive by EIA-IgG. This dissociation between the platelet activation assay and a PF4-dependent immunoassay for HIT antibodies indicates that patients with subacute HIT undergoing repeated TPE before heparin reexposure should be tested by serial platelet activation assays even when their EIAs remain strongly positive. © 2015 by The American Society of Hematology.

Progress and Plans for the HIT--SI Experiment

NASA Astrophysics Data System (ADS)

Sieck, P. E.; Gu, P.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Redd, A. J.; Rogers, J. A.; Smith, R. J.

2002-11-01

The next step in the Helicity Injected Torus (HIT) program is HIT--SI, a ``bow tie'' spheromak to be formed and sustained by Steady Inductive Helicity Injection (SIHI). SIHI injects helicity at a nearly constant rate with no open field lines intersecting the boundary.(T. R. Jarboe, Fusion Technology 36) (1), p. 85, 1999 HIT--SI has been designed with a bow tie geometry to achieve stable high-β (>10%) spheromak equilibria.(U. Shumlak and T. R. Jarboe, Phys. Plasmas 7) (7), p. 2959, 2000 Injector dynamics depend greatly on reconnection rates in two locations: deep in the injector, and at the edge of the spheromak equilibrium. The first stage of HIT--SI operation concentrates on formation of a spheromak and sustainment for 1 ms, where the injector dynamics can be studied and the formation parameter space can be explored. Once these goals are met, the experiment will move into the second stage of operation, where the discharge duration will be extended and the device will inherit a suite of diagnostics from the existing HIT--II device.

An event-related potential study of memory for words spoken aloud or heard.

PubMed

Wilding, E L; Rugg, M D

1997-09-01

Subjects made old/new recognition judgements to visually presented words, half of which had been encountered in a prior study phase. For each word judged old, subjects made a subsequent source judgement, indicating whether they had pronounced the word aloud at study (spoken words), or whether they had heard the word spoken to them (heard words). Event-related potentials (ERPs) were compared for three classes of test item; words correctly judged to be new (correct rejections), and spoken and heard words that were correctly assigned to source (spoken hit/hit and heard hit/hit response categories). Consistent with previous findings (Wilding, E. L. and Rugg, M. D., Brain, 1996, 119, 889-905), two temporally and topographically dissociable components, with parietal and frontal maxima respectively, differentiated the ERPs to the hit/hit and correct rejection response categories. In addition, there was some evidence that the frontally distributed component could be decomposed into two distinct components, only one of which differentiated the two classes of hit/hit ERPs. The findings suggest that at least three functionally and neurologically dissociable processes can contribute to successful recovery of source information.

Model Checking for Verification of Interactive Health IT Systems

PubMed Central

Butler, Keith A.; Mercer, Eric; Bahrami, Ali; Tao, Cui

2015-01-01

Rigorous methods for design and verification of health IT systems have lagged far behind their proliferation. The inherent technical complexity of healthcare, combined with the added complexity of health information technology makes their resulting behavior unpredictable and introduces serious risk. We propose to mitigate this risk by formalizing the relationship between HIT and the conceptual work that increasingly typifies modern care. We introduce new techniques for modeling clinical workflows and the conceptual products within them that allow established, powerful modeling checking technology to be applied to interactive health IT systems. The new capability can evaluate the workflows of a new HIT system performed by clinicians and computers to improve safety and reliability. We demonstrate the method on a patient contact system to demonstrate model checking is effective for interactive systems and that much of it can be automated. PMID:26958166

Understanding Unintended Consequences and Health Information Technology:

PubMed Central

Randell, R.; Borycki, E. M.

2016-01-01

Summary Objective No framework exists to identify and study unintended consequences (UICs) with a focus on organizational and social issues (OSIs). To address this shortcoming, we conducted a literature review to develop a framework for considering UICs and health information technology (HIT) from the perspective of OSIs. Methods A literature review was conducted for the period 2000-2015 using the search terms “unintended consequences” and “health information technology”. 67 papers were screened, of which 18 met inclusion criteria. Data extraction was focused on the types of technologies studied, types of UICs identified, and methods of data collection and analysis used. A thematic analysis was used to identify themes related to UICs. Results We identified two overarching themes. One was the definition and terminology of how people classify and discuss UICs. Second was OSIs and UICs. For the OSI theme, we also identified four sub-themes: process change and evolution, individual-collaborative interchange, context of use, and approaches to model, study, and understand UICs. Conclusions While there is a wide body of research on UICs, there is a lack of overall consensus on how they should be classified and reported, limiting our ability to understand the implications of UICs and how to manage them. More mixed-methods research and better proactive identification of UICs remain priorities. Our findings and framework of OSI considerations for studying UICs and HIT extend existing work on HIT and UICs by focusing on organizational and social issues. PMID:27830231

Factors associated with hit-and-run pedestrian fatalities and driver identification.

PubMed

MacLeod, Kara E; Griswold, Julia B; Arnold, Lindsay S; Ragland, David R

2012-03-01

As hit-and-run crashes account for a significant proportion of pedestrian fatalities, a better understanding of these crash types will assist efforts to reduce these fatalities. Of the more than 48,000 pedestrian deaths that were recorded in the United States between 1998 and 2007, 18.1% of them were caused by hit-and-run drivers. Using national data on single pedestrian-motor vehicle fatal crashes (1998-2007), logistic regression analyses were conducted to identify factors related to hit-and-run and to identify factors related to the identification of the hit-and-run driver. Results indicate an increased risk of hit-and-run in the early morning, poor light conditions, and on the weekend. There may also be an association between the type of victim and the likelihood of the driver leaving and being identified. Results also indicate that certain driver characteristics, behavior, and driving history are associated with hit-and-run. Alcohol use and invalid license were among the leading driver factor associated with an increased risk of hit-and-run. Prevention efforts that address such issues could substantially reduce pedestrian fatalities as a result of hit-and-run. However, more information about this driver population may be necessary. Copyright © 2011. Published by Elsevier Ltd.

Think of HIT.

PubMed

Warkentin, Theodore E

2006-01-01

Heparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common-isolated thrombocytopenia, venous thromboembolism, acute limb ischemia-to less common but specific presentations-necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 x 10(9)/L, and ranges from 15 to 150 x 10(9)/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin ("delayed-onset HIT") is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin > low-molecular-weight heparin), type of patient (surgical > medical), and gender (female > male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to "think of HIT." Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.

Prospective evaluation of automatized PF4/heparin immunoassays HemosIL HIT-ab (PF4-H) for the diagnosis of heparin-induced thrombocytopenia.

PubMed

Jourdy, Y; Nougier, C; Rugeri, L; Bordet, J C; Sobas, F; Negrier, C

2015-04-01

Recently, rapid immunoassays have been developed to allow the detection of antibodies anti-PF4/heparin. In this prospective study, we evaluated the performances of a automatized immunoassay (HemosIL HIT-Ab) in comparison with an ELISA (Zymutest HIA IgG) used for the diagnosis of heparin-induced thrombocytopenia (HIT) in association with the 4T's score. According to the 4T's score, samples with score ≤3 had no further analysis. Two immunological assays Zymutest HIA IgG and HemosIL HIT-Ab were performed in samples with score ≥4. In patients with at least one positive immunological assay or two negative immunological assays but with high-pretest probability (4T's score ≥6), HIT was screened by one functional assay using washed platelets. The sensitivities of both assays were excellent and comparable (100%). The specificity was 92.3% for ELISA and 91.2% for HemosIL HIT-Ab. The analysis of the operating characteristics showed that both assays have almost identical ROCs (AUROC, 0.9951 and 0.9853, respectively, for ELISA and HemosIL HIT-Ab) and the calculating of the κ coefficient revealed a good agreement (0.67). Performance characteristics of the HemosIL HIT-Ab are comparable to the Zymutest HIA IgG. The HemosIL HIT-Ab can be used in association with the 4T's score to rule out HIT. © 2014 John Wiley & Sons Ltd.

Reliability and Validity of the Persian HIT-6 Questionnaire in Migraine and Tension-type Headache.

PubMed

Zandifar, Alireza; Banihashemi, Mahboobeh; Haghdoost, Faraidoon; Masjedi, Samaneh S; Manouchehri, Navid; Asgari, Fatemeh; Najafi, Mohammad R; Ghorbani, Abbas; Zandifar, Samaneh; Saadatnia, Mohammad; White, Michelle K

2014-09-01

Headache Impact Test (HIT-6) measures the impact headaches in a 1-month period. We validated the Persian translation of HIT-6, compared the HIT-6 psychometric analysis between migraine and tension-type headache (TTH) patients, and evaluated the capability of HIT-6 to differentiate between TTH, chronic migraine, and episodic migraine. Qualified participants, including 274 patients diagnosed with migraine or TTH, were required to complete HIT-6, SF-36v2, and a symptoms questionnaire on their first visit. At 3 and 8 weeks from first visit, participants completed HIT-6. Internal consistency (Cronbach's α) and test-retest reproducibility (Pearson's correlation coefficient) were used to assess reliability. Convergent validity was also assessed. Tension-type headache, episodic, and chronic migraines included 24.5%, 61.9%, and 13.6% of the participants, respectively. Internal consistency among all patients, TTH, and migraine in the first visit were 0.74, 0.77, and 0.73, respectively. Test-retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of correlation (r = 0.50). Convergent validity and also item total correlation were acceptable. There was no significant difference in HIT-6 total score between TTH and migraine. Persian HIT-6 is a valid and reliable questionnaire for the evaluation of headache. However, it cannot differentiate between chronic migraine, episodic migraine, and TTH in Iranian population. © 2013 World Institute of Pain.

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

The role of health information technology in advancing care management and coordination in accountable care organizations.

PubMed

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

To be successful, accountable care organizations (ACOs) must effectively manage patient care. Health information technology (HIT) can support care delivery by providing various degrees of coordination. Few studies have examined the role of HIT functionalities or the role of different levels of coordination enabled by HIT on care management processes. We examine HIT functionalities in ACOs, categorized by the level of coordination they enable in terms of information and work flow, to determine which specific HIT functionalities and levels of coordination are most strongly associated with care management processes. Retrospective cross-sectional analysis was done using 2012 data from the National Survey of Accountable Care Organizations. HIT functionalities are categorized into coordination levels: information capture, the lowest level, which coordinates through standardization; information provision, which supports unidirectional activities; and information exchange, which reflects the highest level of coordination allowing for bidirectional exchange. The Care Management Process index (CMP index) includes 13 questions about the extent to which care is planned, monitored, and supported by providers and patients. Multiple regressions adjusting for organizational and ACO contractual factors are used to assess relationships between HIT functionalities and the CMP index. HIT functionality coordinating the most complex interdependences (information exchange) was associated with a 0.41 standard deviation change in the CMP index (β = .41, p < .001), but the associations for information capture (β = -.01, p = .97) and information provision (β = .15, p = .48) functionalities were not significant. The current study has shed some light on the relationship between HIT and care management processes by specifying the coordination roles that HIT may play and, in particular, the importance of information exchange functionalities. Although these represent early findings, further research can help policy makers and clinical leaders understand how to prioritize HIT development given resource constraints.

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

PubMed Central

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

2015-01-01

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

Heparin-induced thrombocytopenia: reducing misdiagnosis via collaboration between an inpatient anticoagulation pharmacy service and hospital reference laboratory.

PubMed

Burnett, Allison E; Bowles, Harmony; Borrego, Matthew E; Montoya, Tiffany N; Garcia, David A; Mahan, Charles

2016-11-01

Misdiagnosis of heparin-induced thrombocytopenia (HIT) is common and exposes patients to high-risk therapies and potentially serious adverse events. The primary objective of this study was to evaluate the impact of collaboration between an inpatient pharmacy-driven anticoagulation management service (AMS) and hospital reference laboratory to reduce inappropriate HIT antibody testing via pharmacist intervention and use of the 4T pre-test probability score. Secondary objectives included clinical outcomes and cost-savings realized through reduced laboratory testing and decreased unnecessary treatment of HIT. This was a single center, pre-post, observational study. The hospital reference laboratory contacted the AMS when they received a blood sample for an enzyme-linked immunosorbent HIT antibody (HIT Ab). Trained pharmacists prospectively scored each HIT Ab ordered by using the 4T score with subsequent communication to physicians recommending for or against processing and reporting of lab results. Utilizing retrospective chart review and a database for all patients with a HIT Ab ordered during the study period, we compared the incidence of HIT Ab testing before and after implementation of the pharmacy-driven 4T score intervention. Our intervention significantly reduced the number of inappropriate HIT Ab tests processed (176 vs. 63, p < 0.0001), with no increase in thrombotic or hemorrhagic events. Overall incidence of suspected and confirmed HIT was <3 and <0.005 %, respectively. Overall cost savings were $75,754 (US) or 62 % per patient exposed to heparin between the pre and post intervention groups. Collaboration between inpatient pharmacy AMS and hospital reference laboratories can result in reduction of misdiagnosis of HIT and significant cost savings with similar safety.

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

PubMed

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

2017-10-01

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

Increased Health Information Technology Adoption and Use Among Small Primary Care Physician Practices Over Time: A National Cohort Study.

PubMed

Rittenhouse, Diane R; Ramsay, Patricia P; Casalino, Lawrence P; McClellan, Sean; Kandel, Zosha K; Shortell, Stephen M

2017-01-01

Implementation and meaningful use of health information technology (HIT) has been shown to facilitate delivery system transformation, yet implementation is far from universal. This study examined correlates of greater HIT implementation over time among a national cohort of small primary care practices in the United States. We used data from a 40-minute telephone panel survey of 566 small primary care practices having 8 or fewer physicians to investigate adoption and use of HIT in 2007-2010 and 2012-2013. We used generalized estimating equations (GEE) to estimate the association of practice characteristics and external incentives with the adoption and use of HIT. We studied 18 measures of HIT functionalities, including record keeping, clinical decision support, patient communication, and health information exchange with hospitals and pharmacies. Overall, use of 16 HIT functionalities increased significantly over time, whereas use of 2 decreased significantly. On average, compared with physician-owned practices, hospital-owned practices used 1.48 (95% CI, 1.07-1.88; P <.001) more HIT processes. And relative to smaller practices, practices with 3 to 8 physicians used 2.49 (95% CI, 2.26-2.72; P <.001) more HIT processes. Participation in pay-for-performance programs, participation in public reporting of clinical quality data, and a larger proportion of revenue from Medicare were also associated with greater adoption and use of HIT. The new Medicare Access and CHIP Reauthorization Act (MACRA) will provide payment incentives and technical support to speed HIT adoption and use by small practices. We found that external incentives were, indeed, positively associated with greater adoption and use of HIT. Our findings also support a strategy of targeting assistance to smaller physician practices and those that are physician owned. © 2017 Annals of Family Medicine, Inc.

The costs of heparin-induced thrombocytopenia: a patient-based cost of illness analysis.

PubMed

Wilke, T; Tesch, S; Scholz, A; Kohlmann, T; Greinacher, A

2009-05-01

SUMMARY BACKGROUND AND OBJECTIVES: Due to the complexity of heparin-induced thrombocytopenia (HIT), currently available cost analyses are rough estimates. The objectives of this study were quantification of costs involved in HIT and identification of main cost drivers based on a patient-oriented approach. Patients diagnosed with HIT (1995-2004, University-hospital Greifswald, Germany) based on a positive functional assay (HIPA test) were retrieved from the laboratory records and scored (4T-score) by two medical experts using the patient file. For cost of illness analysis, predefined HIT-relevant cost parameters (medication costs, prolonged in-hospital stay, diagnostic and therapeutic interventions, laboratory tests, blood transfusions) were retrieved from the patient files. The data were analysed by linear regression estimates with the log of costs and a gamma regression model. Mean length of stay data of non-HIT patients were obtained from the German Federal Statistical Office, adjusted for patient characteristics, comorbidities and year of treatment. Hospital costs were provided by the controlling department. One hundred and thirty HIT cases with a 4T-score >or=4 and a positive HIPA test were analyzed. Mean additional costs of a HIT case were 9008 euro. The main cost drivers were prolonged in-hospital stay (70.3%) and costs of alternative anticoagulants (19.7%). HIT was more costly in surgical patients compared with medical patients and in patients with thrombosis. Early start of alternative anticoagulation did not increase HIT costs despite the high medication costs indicating prevention of costly complications. An HIT cost calculator is provided, allowing online calculation of HIT costs based on local cost structures and different currencies.

The use and role of open source software applications in public and not-for-profit hospitals in the United States.

PubMed

Vest, Joshua R; Stephens, James H

2013-01-01

The potential cost savings and customizability of open source software (OSS) may be particularly attractive for hospitals. However, numerous health-care-specific OSS applications exist, the adoption of OSS health information technology (HIT) applications is not widespread in the United States. This disconnect between the availability of promising software and low adoption raises the basic question: If OSS HIT is so advantageous, why are more health care organizations not using it? We interviewed the chief information officer, or equivalent position, at 17 not-for-profit and public hospitals across the United States. Through targeted recruitment, our sample included nine hospitals using OSS HIT and eight hospitals not using OSS HIT. The open-ended interview questions were guided by domains included in the fit-viability theory, an organizational-level innovation adoption framework, and those suggested by a review of the literature. Transcripts were analyzed using an inductive and comparative approach, which involved an open coding for relevant themes. Interviews described the state of OSS use in hospitals. Specifically, general OSS applications were widely used by IT professionals. In addition, hospitals using OSS HIT still relied heavily on vendor support. In terms of why decisions arose to use OSS HIT, several hospitals using OSS HIT noted the cost advantages. In contrast, hospitals avoiding OSS HIT were clear, OSS as a class did not fit with clinical work and posed too much risk. Perceptions of OSS HIT ranged from enthusiastic embracement to resigned adoption, to refusal, to abandonment. Some organizations were achieving success with their OSS HIT choices, but they still relied on vendors for significant support. The decision to adopt OSS HIT was not uniform but contingent upon views of the risk posed by the technology, economic factors, and the hospital's existing capabilities.

Recovery of Vestibulo-Ocular Reflex Symmetry After an Acute Unilateral Peripheral Vestibular Deficit: Time Course and Correlation With Canal Paresis.

PubMed

Allum, John H J; Cleworth, T; Honegger, Flurin

2016-07-01

We investigated how response asymmetries and deficit side response amplitudes for head accelerations used clinically to test the vestibular ocular reflex (VOR) are correlated with caloric canal paresis (CP) values. 30 patients were examined at onset of an acute unilateral peripheral vestibular deficit (aUPVD) and 3, 6, and 13 weeks later with three different VOR tests: caloric, rotating chair (ROT), and video head impulse tests (vHIT). Response changes over time were fitted with an exponential decay model and compared with using linear regression analysis. Recovery times (to within 10% of steady state) were similar for vHIT-asymmetry and CP (>10 weeks) but shorter for ROT asymmetry (<4 weeks). Regressions with CP were similar (vHIT asymmetry, R = 0.68, ROT, R = 0.62). Responses to the deficit side were also equally well correlated with CP values (R = 0.71). Specificity for vHIT and 20 degrees/s ROT deficit side responses was 100% in comparison to CP values, sensitivity was 74% for vHIT, 75% for ROT. A decrease in normal side responses occurred for ROT but not for vHIT at 3 weeks. Normal side responses were weekly correlated with CP for ROT (R = 0.49) but not for vHIT (R = 0.17). These results indicate that vHIT deficit side VOR gains are slightly better correlated with CP values than ROT, probably because of similar recovery time courses of vHIT and caloric responses and the lack of normal side vHIT changes. However, specificity and sensitivity is the same for vHIT and ROT tests.

A mouse model for the cystic fibrosis delta F508 mutation.

PubMed Central

van Doorninck, J H; French, P J; Verbeek, E; Peters, R H; Morreau, H; Bijman, J; Scholte, B J

1995-01-01

Most cystic fibrosis (CF) patients produce a mutant form (delta F508) of the cystic fibrosis transmembrane conductance regulator (CFTR), which is not properly processed in normal cells but is active as a chloride channel in several experimental systems. We used a double homologous recombination ('Hit and Run') procedure to generate a mouse model for the delta F508 mutation. Targeted embryonic stem (ES) cells (Hit clones) were found; of these either 80 or 20% of the clones had lost the delta F508 mutation, depending on the distance between the linearization site in the targeting construct and the delta F508 mutation. Correctly targeted clones underwent a second selection step resulting in ES cell clones (Run clones) heterozygous for the delta F508 mutation with an efficiency of 2-7%. Chimeric mice were generated and offspring homozygous for the delta F508 mutation showed electrophysiological abnormalities in nasal epithelium, gallbladder and in the intestine, and histological abnormalities in the intestine, typical of CF. Our data suggest that the delta F508 mice have residual delta F508 CFTR activity which would explain the mild pathology of the delta F508 mice. The delta F508 mouse may provide a useful model for the study of the processing defect of delta F508 CFTR and for the development of novel therapeutic approaches based on circumvention of the processing block. Images PMID:7556083

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

PubMed

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

2015-01-01

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

High-Intensity Interval Training with Vibration as Rest Intervals Attenuates Fiber Atrophy and Prevents Decreases in Anaerobic Performance

PubMed Central

Mueller, Sandro Manuel; Aguayo, David; Zuercher, Matthias; Fleischmann, Oliver; Boutellier, Urs; Auer, Maria; Jung, Hans H.; Toigo, Marco

2015-01-01

Aerobic high-intensity interval training (HIT) improves cardiovascular capacity but may reduce the finite work capacity above critical power (W′) and lead to atrophy of myosin heavy chain (MyHC)-2 fibers. Since whole-body vibration may enhance indices of anaerobic performance, we examined whether side-alternating whole-body vibration as a replacement for the active rest intervals during a 4x4 min HIT prevents decreases in anaerobic performance and capacity without compromising gains in aerobic function. Thirty-three young recreationally active men were randomly assigned to conduct either conventional 4x4 min HIT, HIT with 3 min of WBV at 18 Hz (HIT+VIB18) or 30 Hz (HIT+VIB30) in lieu of conventional rest intervals, or WBV at 30 Hz (VIB30). Pre and post training, critical power (CP), W′, cellular muscle characteristics, as well as cardiovascular and neuromuscular variables were determined. W′ (−14.3%, P = 0.013), maximal voluntary torque (−8.6%, P = 0.001), rate of force development (−10.5%, P = 0.018), maximal jumping power (−6.3%, P = 0.007) and cross-sectional areas of MyHC-2A fibers (−6.4%, P = 0.044) were reduced only after conventional HIT. CP, V̇O2peak, peak cardiac output, and overall capillary-to-fiber ratio were increased after HIT, HIT+VIB18, and HIT+VIB30 without differences between groups. HIT-specific reductions in anaerobic performance and capacity were prevented by replacing active rest intervals with side-alternating whole-body vibration, notably without compromising aerobic adaptations. Therefore, competitive cyclists (and potentially other endurance-oriented athletes) may benefit from replacing the active rest intervals during aerobic HIT with side-alternating whole-body vibration. Trial Registration ClinicalTrials.gov Identifier: NCT01875146 PMID:25679998

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.

Computer-aided drug discovery research at a global contract research organization

NASA Astrophysics Data System (ADS)

Kitchen, Douglas B.

2017-03-01

Computer-aided drug discovery started at Albany Molecular Research, Inc in 1997. Over nearly 20 years the role of cheminformatics and computational chemistry has grown throughout the pharmaceutical industry and at AMRI. This paper will describe the infrastructure and roles of CADD throughout drug discovery and some of the lessons learned regarding the success of several methods. Various contributions provided by computational chemistry and cheminformatics in chemical library design, hit triage, hit-to-lead and lead optimization are discussed. Some frequently used computational chemistry techniques are described. The ways in which they may contribute to discovery projects are presented based on a few examples from recent publications.

Computer-aided drug discovery research at a global contract research organization.

PubMed

Kitchen, Douglas B

2017-03-01

Computer-aided drug discovery started at Albany Molecular Research, Inc in 1997. Over nearly 20 years the role of cheminformatics and computational chemistry has grown throughout the pharmaceutical industry and at AMRI. This paper will describe the infrastructure and roles of CADD throughout drug discovery and some of the lessons learned regarding the success of several methods. Various contributions provided by computational chemistry and cheminformatics in chemical library design, hit triage, hit-to-lead and lead optimization are discussed. Some frequently used computational chemistry techniques are described. The ways in which they may contribute to discovery projects are presented based on a few examples from recent publications.

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

Flaws in the LNT single-hit model for cancer risk: An historical assessment.

PubMed

Calabrese, Edward J

2017-10-01

The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day. Copyright © 2017 Elsevier Inc. All rights reserved.

Designing small molecules to target cryptic pockets yields both positive and negative allosteric modulators

PubMed Central

Moeder, Katelyn E.; Ho, Chris M. W.; Zimmerman, Maxwell I.; Frederick, Thomas E.; Bowman, Gregory R.

2017-01-01

Allosteric drugs, which bind to proteins in regions other than their main ligand-binding or active sites, make it possible to target proteins considered “undruggable” and to develop new therapies that circumvent existing resistance. Despite growing interest in allosteric drug discovery, rational design is limited by a lack of sufficient structural information about alternative binding sites in proteins. Previously, we used Markov State Models (MSMs) to identify such “cryptic pockets,” and here we describe a method for identifying compounds that bind in these cryptic pockets and modulate enzyme activity. Experimental tests validate our approach by revealing both an inhibitor and two activators of TEM β-lactamase (TEM). To identify hits, a library of compounds is first virtually screened against either the crystal structure of a known cryptic pocket or an ensemble of structures containing the same cryptic pocket that is extracted from an MSM. Hit compounds are then screened experimentally and characterized kinetically in individual assays. We identify three hits, one inhibitor and two activators, demonstrating that screening for binding to allosteric sites can result in both positive and negative modulation. The hit compounds have modest effects on TEM activity, but all have higher affinities than previously identified inhibitors, which bind the same cryptic pocket but were found, by chance, via a computational screen targeting the active site. Site-directed mutagenesis of key contact residues predicted by the docking models is used to confirm that the compounds bind in the cryptic pocket as intended. Because hit compounds are identified from docking against both the crystal structure and structures from the MSM, this platform should prove suitable for many proteins, particularly targets whose crystal structures lack obvious druggable pockets, and for identifying both inhibitory and activating small-molecule modulators. PMID:28570708

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.

Specific Intensity for Peaking: Is Race Pace the Best Option?

PubMed Central

Munoz, Iker; Seiler, Stephen; Alcocer, Alberto; Carr, Natasha; Esteve-Lanao, Jonathan

2015-01-01

Background: The peaking period for endurance competition is characterized for a relative increase of the intensity of training, after a longer period of training relatively dominated by lower intensity and higher volume Objectives: The present study was designed to compare physiological and 10 km performance effects of high intensity training (HIT) versus race pace interval training (RP) during peaking for competition in well-trained runners. Patients and Methods: 13 athletes took part in the study, they were divided into two groups: HIT and RP. HIT performed short intervals at ~105% of the maximal aerobic velocity (MAV), while RP trained longer intervals at a speed of ~90% of the MAV (a speed approximating 10 km race pace). After 12 weeks of baseline training, the athletes trained for 6 weeks under one of the two peaking regimes. Subjects performed 10 km prior to and after the intervention period. The total load of training was matched between groups during the treatment phase. Subjects completed a graded treadmill running test until volitional exhaustion prior to each 10 km race. MAV was determined as the minimal velocity eliciting maximal oxygen consumption (VO2max). Results: Both groups significantly improved their 10 km time (35 minutes 29 seconds ± 1 minutes 41 seconds vs 34 minutes 53 seconds ± 1 minutes 55 seconds, P < 0.01 for HIT; 35 minutes 27 seconds ± 1 minutes 40 seconds vs 34 minutes 53 seconds ± 1 minutes 18 seconds P < 0.01 for RP). VO2max increased after HIT (69 ± 3.6 vs 71.5 ± 4.2 ml.Kg-1.min-1, P < 0.05); while it didn’t for RP (68.4 ± 6 vs 69.8 ± 3 ml.Kg-1.min-1, p>0.05). In contrast, running economy decreased significantly after HIT (210 ± 6 ml.Kg-1.km-1 vs 218 ± 9, P < 0.05). Conclusions: A 6 week period of training at either 105% of MAV or 90% of MAV yielded similar performance gains in a 10km race performed at ~90% MAV. Therefore, the physiological impact of HIT training seems to be positive for VO2max but negative for running economy. PMID:26448854

Teachers' Perspectives on Hitting Back in School: Between Inexcusable Violence and Self-Defense

ERIC Educational Resources Information Center

Fleischmann, Amos

2015-01-01

Israeli schools expressly forbid a student to hit back after being attacked. In semistructured interviews, 71 Israeli educators were asked for their views on the hitting-back tactic. The interviews compared their attitude toward hitting back as teachers with their take on the matter as parents. The results, analyzed using grounded theory, show…

Studying the HIT-Complexity Interchange.

PubMed

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

2016-01-01

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

Saccadic entropy of head impulses in acute unilateral vestibular loss.

PubMed

Hsieh, Li-Chun; Lin, Hung-Ching; Lee, Guo-She

2017-10-01

To evaluate the complexity of vestibular-ocular reflex (VOR) in patients with acute unilateral vestibular loss (AUVL) via entropy analysis of head impulses. Horizontal head impulse test (HIT) with high-velocity alternating directions was used to evaluate 12 participants with AUVL and 16 healthy volunteers. Wireless electro-oculography and electronic gyrometry were used to acquire eye positional signals and head velocity signals. The eye velocity signals were then obtained through differentiation, band-pass filtering. The approximate entropy of eye velocity to head velocity (R ApEn ) was used to evaluate chaos property. VOR gain, gain asymmetry ratio, and R ApEn asymmetry ratio were also used to compare the groups. For the lesion-side HIT of the patient group, the mean VOR gain was significantly lower and the mean R ApEn was significantly greater compared with both nonlesion-side HIT and healthy controls (p < 0.01, one-way analysis of variance). Both the R ApEn asymmetry ratio and gain asymmetry ratio of the AUVL group were significantly greater compared with those of the control group (p < 0.05, independent sample t test). Entropy and gain analysis of HIT using wireless electro-oculography system could be used to detect the VOR dysfunctions of AUVL and may become effective methods for evaluating vestibular disorders. Copyright © 2017. Published by Elsevier B.V.

Identification of novel PfDHODH inhibitors as antimalarial agents via pharmacophore-based virtual screening followed by molecular docking and in vivo antimalarial activity.

PubMed

Vyas, V K; Qureshi, G; Ghate, M; Patel, H; Dalai, S

2016-06-01

Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) catalyses the fourth reaction of de novo pyrimidine biosynthesis in parasites, and represents an important target for the treatment of malaria. In this study, we describe pharmacophore-based virtual screening combined with docking study and biological evaluation as a rational strategy for identification of novel hits as antimalarial agents. Pharmacophore models were established from known PfDHODH inhibitors using the GALAHAD module with IC50 values ranging from 0.033 μM to 142 μM. The best pharmacophore model consisted of three hydrogen bond acceptor, one hydrogen bond donor and one hydrophobic features. The pharmacophore models were validated through receiver operating characteristic and Günere-Henry scoring methods. The best pharmacophore model as a 3D search query was searched against the IBS database. Several compounds with different structures (scaffolds) were retrieved as hit molecules. Among these compounds, those with a QFIT value of more than 81 were docked in the PfDHODH enzyme to further explore the binding modes of these compounds. In silico pharmacokinetic and toxicities were predicted for the best docked molecules. Finally, the identified hits were evaluated in vivo for their antimalarial activity in a parasite inhibition assay. The hits reported here showed good potential to become novel antimalarial agents.

Economic impact due to Cimanuk river flood disaster in Garut district using Cobb-Douglas analysis with least square method

NASA Astrophysics Data System (ADS)

Bestari, T. A. S.; Supian, S.; Purwani, S.

2018-03-01

Cimanuk River, Garut District, West Java which have upper course in Papandayan Mountain have an important purpose in dialy living of Garut people as a water source. But in 2016 flash flood in this river was hitted and there was 26 peple dead and 23 peole gone. Flash flood which hitted last year make the settlement almost align with the ground, soaking school and hospital. BPLHD Jawa Barat saw this condition as a disaster which coused by distroyed upper course of Cimanuk River. Flash Flood which happened on the 2016 had ever made economic sector paralized. Least square method selected to analyze economic condition in residents affected post disaster, after the mathematical equations was determined by Cobb Douglas Method. By searching proportion value of the damage, and the result expected became a view to the stakeholder to know which sector that become a worse and be able to make a priority in development

Childhood animal cruelty methods and their link to adult interpersonal violence.

PubMed

Henderson, Brandy B; Hensley, Christopher; Tallichet, Suzanne E

2011-07-01

Recent research has begun to establish a relationship between childhood acts of animal cruelty and later violence against humans. However, few studies have focused on the influence of animal cruelty methods on later interpersonal violence. In a replication of a study by Hensley and Tallichet (2009) and based on a sample of 180 inmates at medium- and maximum-security prisons in a Southern state, the present study examines the relationship between several retrospectively identified animal cruelty methods (drowned, hit, shot, kicked, choked, burned, and sex) and interpersonal violence committed against humans. Four out of 5 inmates reported hitting animals. Over one third of the sample chose to shoot or kick animals, while 1 in 5 had sex with them. Less then one fifth of the sample drowned or choked animals, while less than one sixth of the inmates burned animals. Regression analyses revealed that the age at which offenders began committing animal cruelty and having sex with animals were predictive of adult interpersonal violence.

False-Positive Head-Impulse Test in Cerebellar Ataxia

PubMed Central

Kremmyda, Olympia; Kirchner, Hanni; Glasauer, Stefan; Brandt, Thomas; Jahn, Klaus; Strupp, Michael

2012-01-01

The objective of this study was to compare the findings of the bedside head-impulse test (HIT), passive head rotation gain, and caloric irrigation in patients with cerebellar ataxia (CA). In 16 patients with CA and bilaterally pathological bedside HIT, vestibuloocular reflex (VOR) gains were measured during HIT and passive head rotation by scleral search coil technique. Eight of the patients had pathologically reduced caloric responsiveness, while the other eight had normal caloric responses. Those with normal calorics showed a slightly reduced HIT gain (mean ± SD: 0.73 ± 0.15). In those with pathological calorics, gains 80 and 100 ms after the HIT as well as the passive rotation VOR gains were significantly lower. The corrective saccade after head turn occurred earlier in patients with pathological calorics (111 ± 62 ms after onset of the HIT) than in those with normal calorics (191 ± 17 ms, p = 0.0064). We identified two groups of patients with CA: those with an isolated moderate HIT deficit only, probably due to floccular dysfunction, and those with combined HIT, passive rotation, and caloric deficit, probably due to a peripheral vestibular deficit. From a clinical point of view, these results show that the bedside HIT alone can be false-positive for establishing a diagnosis of a bilateral peripheral vestibular deficit in patients with CA. PMID:23162531

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.

Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT.

PubMed

Kowalska, M Anna; Krishnaswamy, Sriram; Rauova, Lubica; Zhai, Li; Hayes, Vincent; Amirikian, Karine; Esko, Jeffrey D; Bougie, Daniel W; Aster, Richard H; Cines, Douglas B; Poncz, Mortimer

2011-09-08

Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes between platelet factor 4 (PF4) and heparin or glycosaminoglycan side chains. These antibodies can lead to a limb- and life-threatening prothrombotic state. We now show that HIT antibodies are able to inhibit generation of activated protein C (aPC) by thrombin/thrombomodulin (IIa/TM) in the presence of PF4. Tetrameric PF4 potentiates aPC generation by formation of complexes with chondroitin sulfate (CS) on TM. Formation of these complexes occurs at a specific molar ratio of PF4 to glycosaminoglycan. This observation and the finding that the effect of heparin on aPC generation depends on the concentration of PF4 suggest similarity between PF4/CS complexes and those that bind HIT antibodies. HIT antibodies reduced the ability of PF4 to augment aPC formation. Cationic protamine sulfate, which forms similar complexes with heparin, also enhanced aPC generation, but its activity was not blocked by HIT antibodies. Our studies provide evidence that complexes formed between PF4 and TM's CS may play a physiologic role in potentiating aPC generation. Recognition of these complexes by HIT antibodies reverses the PF4-dependent enhancement in aPC generation and may contribute to the prothrombotic nature of HIT.

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.

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.

Design of the rivaroxaban for heparin-induced thrombocytopenia study.

PubMed

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

2014-11-01

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

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.

Fragment-based virtual screening approach and molecular dynamics simulation studies for identification of BACE1 inhibitor leads.

PubMed

Manoharan, Prabu; Ghoshal, Nanda

2018-05-01

Traditional structure-based virtual screening method to identify drug-like small molecules for BACE1 is so far unsuccessful. Location of BACE1, poor Blood Brain Barrier permeability and P-glycoprotein (Pgp) susceptibility of the inhibitors make it even more difficult. Fragment-based drug design method is suitable for efficient optimization of initial hit molecules for target like BACE1. We have developed a fragment-based virtual screening approach to identify/optimize the fragment molecules as a starting point. This method combines the shape, electrostatic, and pharmacophoric features of known fragment molecules, bound to protein conjugate crystal structure, and aims to identify both chemically and energetically feasible small fragment ligands that bind to BACE1 active site. The two top-ranked fragment hits were subjected for a 53 ns MD simulation. Principle component analysis and free energy landscape analysis reveal that the new ligands show the characteristic features of established BACE1 inhibitors. The potent method employed in this study may serve for the development of potential lead molecules for BACE1-directed Alzheimer's disease therapeutics.

Discovery of potent KIFC1 inhibitors using a method of integrated high-throughput synthesis and screening.

PubMed

Yang, Bin; Lamb, Michelle L; Zhang, Tao; Hennessy, Edward J; Grewal, Gurmit; Sha, Li; Zambrowski, Mark; Block, Michael H; Dowling, James E; Su, Nancy; Wu, Jiaquan; Deegan, Tracy; Mikule, Keith; Wang, Wenxian; Kaspera, Rüdiger; Chuaqui, Claudio; Chen, Huawei

2014-12-11

KIFC1 (HSET), a member of the kinesin-14 family of motor proteins, plays an essential role in centrosomal bundling in cancer cells, but its function is not required for normal diploid cell division. To explore the potential of KIFC1 as a therapeutic target for human cancers, a series of potent KIFC1 inhibitors featuring a phenylalanine scaffold was developed from hits identified through high-throughput screening (HTS). Optimization of the initial hits combined both design-synthesis-test cycles and an integrated high-throughput synthesis and biochemical screening method. An important aspect of this integrated method was the utilization of DMSO stock solutions of compounds registered in the corporate compound collection as synthetic reactants. Using this method, over 1500 compounds selected for structural diversity were quickly assembled in assay-ready 384-well plates and were directly tested after the necessary dilutions. Our efforts led to the discovery of a potent KIFC1 inhibitor, AZ82, which demonstrated the desired centrosome declustering mode of action in cell studies.

Quantum mechanical energy-based screening of combinatorially generated library of tautomers. TauTGen: a tautomer generator program.

PubMed

Harańczyk, Maciej; Gutowski, Maciej

2007-01-01

We describe a procedure of finding low-energy tautomers of a molecule. The procedure consists of (i) combinatorial generation of a library of tautomers, (ii) screening based on the results of geometry optimization of initial structures performed at the density functional level of theory, and (iii) final refinement of geometry for the top hits at the second-order Möller-Plesset level of theory followed by single-point energy calculations at the coupled cluster level of theory with single, double, and perturbative triple excitations. The library of initial structures of various tautomers is generated with TauTGen, a tautomer generator program. The procedure proved to be successful for these molecular systems for which common chemical knowledge had not been sufficient to predict the most stable structures.

What can Space Resources do for Astronomy and Planetary Science?

NASA Astrophysics Data System (ADS)

Elvis, Martin

2016-11-01

The rapid cost growth of flagship space missions has created a crisis for astronomy and planetary science. We have hit the funding wall. For the past 3 decades scientists have not had to think much about how space technology would change within their planning horizon. However, this time around enormous improvements in space infrastructure capabilities and, especially, costs are likely on the 20-year gestation periods for large space telescopes. Commercial space will lower launch and spacecraft costs substantially, enable cost-effective on-orbit servicing, cheap lunar landers and interplanetary cubesats by the early 2020s. A doubling of flagship launch rates is not implausible. On a longer timescale it will enable large structures to be assembled and constructed in space. These developments will change how we plan and design missions.

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration.

PubMed

Pietrofesa, Ralph A; Turowski, Jason B; Arguiri, Evguenia; Milovanova, Tatyana N; Solomides, Charalambos C; Thom, Stephen R; Christofidou-Solomidou, Melpo

2013-09-30

Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O 2 (O 2 ); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O 2 and IR (O 2 +IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O 2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis ( p <0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration.

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.

Characterization of an Opioid-Like Hibernation Induction Trigger

DTIC Science & Technology

1989-07-01

to HIT administration with a dose -reryonse relationship between the amount of adenosina dijphosphate (ADP) added and the extent of aggregation. However...despite the use of high doses of ADP. Our preliminary results suggest that one mechanism of prolonged organ survival following HIT administration may...HIT administration despite high dose ADP to stimulate aggregation . . . . 36 -3- INTRODUCTION A hibernation induction trigger (HIT) molecule derived

Lessons learnt from the Wenchuan earthquake: performance evaluation of treatment of critical injuries in hardest-hit areas.

PubMed

Jiang, Jie; Li, Youping; Huang, Xiaolin; Li, Bing; Su, Lin; Zhong, Dake; Shi, Chenghu; Li, Mingxu; Shan, Juan; Chen, Yin

2012-08-01

Critical injury treatment in the hardest-hit areas after a great earthquake was retrospectively analyzed to determine how best to reduce mortality and disability and increase the rehabilitation rate through postquake medical relief. Retrospective analysis, primary sources, and secondary sources were comprehensively retrieved and analyzed. According to incomplete data, 30,620 injured were rescued by themselves among the hardest-hit areas in the 72 hours immediately following the earthquake. Critically injured patients accounted for 22% of total inpatients. Mortality rates declined with greater distance from the epicenter: rates were 12.21% for municipal healthcare centers in the hardest-hit areas, 4.50% for municipal medical units in peripheral quake-hit areas, 2.50% for provincial medical units in peripheral quake-hit areas, and 2.17% for Ministry of Health-affiliated hospitals in peripheral quake-hit areas. The number of injured with fractures on body, limbs or unknown-parts, severe conditions as well as other kinds of non-traumatic diseases received in second-line hospitals was much more than those treated in first-line hospitals with more severe injuries. Among 10,373 injured in stable condition transferred to third-line hospitals, 99.07% were discharged from hospitals within four months, while the mortality rate was 0.017%. The medical relief model of "supervising body helping subordinate unit, severely stricken areas assisting hardest-hit areas, least-hit areas supporting both hardest-hit and severely stricken areas, and self help and mutual assistance applied between hardest-hit areas" was roughly established for injured from severely stricken areas after the Wenchuan Earthquake. The "four-centralization" treatment principle, which referred to concentrating patients, experts, resources and treatment for those injured in critical condition effectively reduced the mortality from 15.06% to 2.9%. Timely, scientific, and standard on-site triage and postmedical transfer guided by accurate injury information determine rescue effect for the injured, while there is large space to fulfill as for treatment for critical diseases among the hardest-hit areas under extreme conditions after the Wenchuan earthquake. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Effects of Device on Video Head Impulse Test (vHIT) Gain.

PubMed

Janky, Kristen L; Patterson, Jessie N; Shepard, Neil T; Thomas, Megan L A; Honaker, Julie A

2017-10-01

Numerous video head impulse test (vHIT) devices are available commercially; however, gain is not calculated uniformly. An evaluation of these devices/algorithms in healthy controls and patients with vestibular loss is necessary for comparing and synthesizing work that utilizes different devices and gain calculations. Using three commercially available vHIT devices/algorithms, the purpose of the present study was to compare: (1) horizontal canal vHIT gain among devices/algorithms in normal control subjects; (2) the effects of age on vHIT gain for each device/algorithm in normal control subjects; and (3) the clinical performance of horizontal canal vHIT gain between devices/algorithms for differentiating normal versus abnormal vestibular function. Prospective. Sixty-one normal control adult subjects (range 20-78) and eleven adults with unilateral or bilateral vestibular loss (range 32-79). vHIT was administered using three different devices/algorithms, randomized in order, for each subject on the same day: (1) Impulse (Otometrics, Schaumberg, IL; monocular eye recording, right eye only; using area under the curve gain), (2) EyeSeeCam (Interacoustics, Denmark; monocular eye recording, left eye only; using instantaneous gain), and (3) VisualEyes (MicroMedical, Chatham, IL, binocular eye recording; using position gain). There was a significant mean difference in vHIT gain among devices/algorithms for both the normal control and vestibular loss groups. vHIT gain was significantly larger in the ipsilateral direction of the eye used to measure gain; however, in spite of the significant mean differences in vHIT gain among devices/algorithms and the significant directional bias, classification of "normal" versus "abnormal" gain is consistent across all compared devices/algorithms, with the exception of instantaneous gain at 40 msec. There was not an effect of age on vHIT gain up to 78 years regardless of the device/algorithm. These findings support that vHIT gain is significantly different between devices/algorithms, suggesting that care should be taken when making direct comparisons of absolute gain values between devices/algorithms. American Academy of Audiology

Novel Method of Weighting Cumulative Helmet Impacts Improves Correlation with Brain White Matter Changes After One Football Season of Sub-concussive Head Blows.

PubMed

Merchant-Borna, Kian; Asselin, Patrick; Narayan, Darren; Abar, Beau; Jones, Courtney M C; Bazarian, Jeffrey J

2016-12-01

One football season of sub-concussive head blows has been shown to be associated with subclinical white matter (WM) changes on diffusion tensor imaging (DTI). Prior research analyses of helmet-based impact metrics using mean and peak linear and rotational acceleration showed relatively weak correlations to these WM changes; however, these analyses failed to account for the emerging concept that neuronal vulnerability to successive hits is inversely related to the time between hits (TBH). To develop a novel method for quantifying the cumulative effects of sub-concussive head blows during a single season of collegiate football by weighting helmet-based impact measures for time between helmet impacts. We further aim to compare correlations to changes in DTI after one season of collegiate football using weighted cumulative helmet-based impact measures to correlations using non-weighted cumulative helmet-based impact measures and non-cumulative measures. We performed a secondary analysis of DTI and helmet impact data collected on ten Division III collegiate football players during the 2011 season. All subjects underwent diffusion MR imaging before the start of the football season and within 1 week of the end of the football season. Helmet impacts were recorded at each practice and game using helmet-mounted accelerometers, which computed five helmet-based impact measures for each hit: linear acceleration (LA), rotational acceleration (RA), Gadd Severity Index (GSI), Head Injury Criterion (HIC 15 ), and Head Impact Technology severity profile (HITsp). All helmet-based impact measures were analyzed using five methods of summary: peak and mean (non-cumulative measures), season sum-totals (cumulative unweighted measures), and season sum-totals weighted for time between hits (TBH), the interval of time from hit to post-season DTI assessment (TUA), and both TBH and TUA combined. Summarized helmet-based impact measures were correlated to statistically significant changes in fractional anisotropy (FA) using bivariate and multivariable correlation analyses. The resulting R 2 values were averaged in each of the five summary method groups and compared using one-way ANOVA followed by Tukey post hoc tests for multiple comparisons. Total head hits for the season ranged from 431 to 1850. None of the athletes suffered a clinically evident concussion during the study period. The mean R 2 value for the correlations using cumulative helmet-based impact measures weighted for both TUA and TBH combined (0.51 ± 0.03) was significantly greater than the mean R 2 value for correlations using non-cumulative HIMs (vs. 0.19 ± 0.04, p < 0.0001), unweighted cumulative helmet-based impact measures (vs. 0.27 + 0.03, p < 0.0001), and cumulative helmet-based impact measures weighted for TBH alone (vs. 0.34 ± 0.02, p < 0.001). R 2 values for weighted cumulative helmet-based impact measures ranged from 0.32 to 0.77, with 60% of correlations being statistically significant. Cumulative GSI weighted for TBH and TUA explained 77% of the variance in the percent of white matter voxels with statistically significant (PWMVSS) increase in FA from pre-season to post-season, while both cumulative GSI and cumulative HIC 15 weighted for TUA accounted for 75% of the variance in PWMVSS decrease in FA. A novel method for weighting cumulative helmet-based impact measures summed over the course of a football season resulted in a marked improvement in the correlation to brain WM changes observed after a single football season of sub-concussive head blows. Our results lend support to the emerging concept that sub-concussive head blows can result in sub-clinical brain injury, and this may be influenced by the time between hits. If confirmed in an independent data set, our novel method for quantifying the cumulative effects of sub-concussive head blows could be used to develop threshold-based countermeasures to prevent the accumulation of WM changes with multiple seasons of play.

Secondary neutron-production cross sections from heavy-ioninteractions in composite targets.

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

Heilbronn, L.; Iwata, Y.; Iwase,H.

Secondary neutron-production cross-sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 and 80 deg in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion, neutron production experiments; namely, a peak at forward angles near the energy corresponding to the beam velocity, withmore » the remaining spectra generated by pre-equilibrium and equilibrium processes. The double differential cross sections are fitted with a moving-source parameterization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials, and for neutron production in non-target materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well, but, on average, underestimate the magnitudes of the cross sections.« less

Secondary neutron-production cross sections from heavy-ion interactions in composite targets

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

Heilbronn, L.; Iwata, Y.; Murakami, T.

Secondary neutron-production cross sections have been measured from interactions of 290 MeV/nucleon C and 600 MeV/nucleon Ne in a target composed of simulated Martian regolith and polyethylene, and from 400 MeV/nucleon Ne interactions in wall material from the International Space Station. The data were measured between 5 deg. and 80 deg. in the laboratory. We report the double-differential cross sections, angular distributions, and total neutron-production cross sections from all three systems. The spectra from all three systems exhibit behavior previously reported in other heavy-ion neutron-production experiments, namely, a peak at forward angles near the energy corresponding to the beam velocity,more » with the remaining spectra generated by pre-equilibrium and equilibrium processes. The double-differential cross sections are fitted with a moving-source parametrization. Also reported are the data without corrections for neutron flux attenuation in the target and other intervening materials and for neutron production in nontarget materials near the target position. These uncorrected spectra are compared with SHIELD-HIT and PHITS transport model calculations. The transport model calculations reproduce the spectral shapes well but, on average, underestimate the magnitudes of the cross sections.« less

Comparison of large-angle production of charged pions with incident protons on cylindrical long and short targets

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

Apollonio, M.; Chimenti, P.; Giannini, G.

2009-12-15

The HARP Collaboration has presented measurements of the double-differential {pi}{sup {+-}} production cross section in the range of momentum 100 MeV/c{<=}p{<=}800 MeV/c and angle 0.35 rad{<=}{theta}{<=}2.15 rad with proton beams hitting thin nuclear targets. In many applications the extrapolation to long targets is necessary. In this article the analysis of data taken with long (one interaction length) solid cylindrical targets made of carbon, tantalum, and lead is presented. The data were taken with the large-acceptance HARP detector in the T9 beam line of the CERN proton synchrotron. The secondary pions were produced by beams of protons with momenta of 5,more » 8, and 12GeV/c. The tracking and identification of the produced particles were performed using a small-radius cylindrical time projection chamber placed inside a solenoidal magnet. Incident protons were identified by an elaborate system of beam detectors. Results are obtained for the double-differential yields per target nucleon d{sup 2}{sigma}/dpd{theta}. The measurements are compared with predictions of the MARS and GEANT4 Monte Carlo simulations.« less

Rational Design of Novel 1,3-Oxazine Based β-Secretase (BACE1) Inhibitors: Incorporation of a Double Bond To Reduce P-gp Efflux Leading to Robust Aβ Reduction in the Brain.

PubMed

Fuchino, Kouki; Mitsuoka, Yasunori; Masui, Moriyasu; Kurose, Noriyuki; Yoshida, Shuhei; Komano, Kazuo; Yamamoto, Takahiko; Ogawa, Masayoshi; Unemura, Chie; Hosono, Motoko; Ito, Hisanori; Sakaguchi, Gaku; Ando, Shigeru; Ohnishi, Shuichi; Kido, Yasuto; Fukushima, Tamio; Miyajima, Hirofumi; Hiroyama, Shuichi; Koyabu, Kiyotaka; Dhuyvetter, Deborah; Borghys, Herman; Gijsen, Harrie J M; Yamano, Yoshinori; Iso, Yasuyoshi; Kusakabe, Ken-Ichi

2018-05-23

Accumulation of Aβ peptides is a hallmark of Alzheimer's disease (AD) and is considered a causal factor in the pathogenesis of AD. β-Secretase (BACE1) is a key enzyme responsible for producing Aβ peptides, and thus agents that inhibit BACE1 should be beneficial for disease-modifying treatment of AD. Here we describe the discovery and optimization of novel oxazine-based BACE1 inhibitors by lowering amidine basicity with the incorporation of a double bond to improve brain penetration. Starting from a 1,3-dihydrooxazine lead 6 identified by a hit-to-lead SAR following HTS, we adopted a p K a lowering strategy to reduce the P-gp efflux and the high hERG potential leading to the discovery of 15 that produced significant Aβ reduction with long duration in pharmacodynamic models and exhibited wide safety margins in cardiovascular safety models. This compound improved the brain-to-plasma ratio relative to 6 by reducing P-gp recognition, which was demonstrated by a P-gp knockout mouse model.

45 CFR 170.457 - Authorized testing and certification methods.

Code of Federal Regulations, 2010 CFR

2010-10-01

....457 Section 170.457 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT...

45 CFR 170.557 - Authorized certification methods.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 170.557 Public Welfare Department of Health and Human Services HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY ONC HIT Certification Program § 170.557 Authorized certification...

45 CFR 170.557 - Authorized certification methods.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 170.557 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Permanent Certification Program for HIT § 170.557 Authorized...

45 CFR 170.557 - Authorized certification methods.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 170.557 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY ONC HIT Certification Program § 170.557 Authorized certification...

45 CFR 170.457 - Authorized testing and certification methods.

Code of Federal Regulations, 2013 CFR

2013-10-01

....457 Section 170.457 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT...

45 CFR 170.457 - Authorized testing and certification methods.

Code of Federal Regulations, 2012 CFR

2012-10-01

....457 Section 170.457 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT...

45 CFR 170.457 - Authorized testing and certification methods.

Code of Federal Regulations, 2011 CFR

2011-10-01

....457 Section 170.457 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT...

45 CFR 170.457 - Authorized testing and certification methods.

Code of Federal Regulations, 2014 CFR

2014-10-01

....457 Section 170.457 Public Welfare Department of Health and Human Services HEALTH INFORMATION TECHNOLOGY HEALTH INFORMATION TECHNOLOGY STANDARDS, IMPLEMENTATION SPECIFICATIONS, AND CERTIFICATION CRITERIA AND CERTIFICATION PROGRAMS FOR HEALTH INFORMATION TECHNOLOGY Temporary Certification Program for HIT...

Towards novel therapeutics for HIV through fragment-based screening and drug design.

PubMed

Tiefendbrunn, Theresa; Stout, C David

2014-01-01

Fragment-based drug discovery has been applied with varying levels of success to a number of proteins involved in the HIV (Human Immunodeficiency Virus) life cycle. Fragment-based approaches have led to the discovery of novel binding sites within protease, reverse transcriptase, integrase, and gp41. Novel compounds that bind to known pockets within CCR5 have also been identified via fragment screening, and a fragment-based approach to target the TAR-Tat interaction was explored. In the context of HIV-1 reverse transcriptase (RT), fragment-based approaches have yielded fragment hits with mid-μM activity in an in vitro activity assay, as well as fragment hits that are active against drug-resistant variants of RT. Fragment-based drug discovery is a powerful method to elucidate novel binding sites within proteins, and the method has had significant success in the context of HIV proteins.

A multi-method pilot evaluation of an online diabetes exercise system.

PubMed

Schaarup, Clara; Hejlesen, Ole K

2015-01-01

The American Diabetes Association and The European Association of The Study of Diabetes recommend people with Type 2 diabetes to do moderate to vigorous aerobic exercise for 150 min per week to avoid late diabetic complications. However, most people with diabetes do not follow the recommendation. Consumer health information technology (CHIT) might play a role in supporting behavior changes that promote health and well-being. A CHIT prototype of an online diabetes exercise system, which contained the newest research of low volume high-intensity interval training (HIT), was developed. To test the system we used a multi-method pilot evaluation that includes; interviews, paper prototyping, heuristic evaluation, and test with patients. The patients expressed satisfaction with HIT and appreciated that the system was web-based. The findings from this pilot study inspire to further development and evaluation of online CHIT systems to diabetics.

Outlier and target detection in aerial hyperspectral imagery: a comparison of traditional and percentage occupancy hit or miss transform techniques

NASA Astrophysics Data System (ADS)

Young, Andrew; Marshall, Stephen; Gray, Alison

2016-05-01

The use of aerial hyperspectral imagery for the purpose of remote sensing is a rapidly growing research area. Currently, targets are generally detected by looking for distinct spectral features of the objects under surveillance. For example, a camouflaged vehicle, deliberately designed to blend into background trees and grass in the visible spectrum, can be revealed using spectral features in the near-infrared spectrum. This work aims to develop improved target detection methods, using a two-stage approach, firstly by development of a physics-based atmospheric correction algorithm to convert radiance into re ectance hyperspectral image data and secondly by use of improved outlier detection techniques. In this paper the use of the Percentage Occupancy Hit or Miss Transform is explored to provide an automated method for target detection in aerial hyperspectral imagery.

Affective Responses to Repeated Sessions of High-Intensity Interval Training.

PubMed

Saanijoki, Tiina; Nummenmaa, Lauri; Eskelinen, Jari-Joonas; Savolainen, Anna M; Vahlberg, Tero; Kalliokoski, Kari K; Hannukainen, Jarna C

2015-12-01

Vigorous exercise feels unpleasant, and negative emotions may discourage adherence to regular exercise. We quantified the subjective affective responses to short-term high-intensity interval training (HIT) in comparison with moderate-intensity continuous training (MIT). Twenty-six healthy middle-age (mean age, 47 ± 5 yr; mean VO2peak, 34.2 ± 4.1 mL·kg⁻¹·min⁻¹) sedentary men were randomized into HIT (n = 13, 4-6 × 30 s of all-out cycling efforts at approximately 180% of peak workload with 4-min recovery) or MIT (n = 13, 40- to 60-min continuous cycling at 60% of peak workload) groups, performing six sessions within two weeks. Perceived exertion, stress, and affective state were recorded before, during, and after each session. Perceived exertion and arousal were higher, and affective state, more negative during the HIT than that during MIT sessions (P < 0.001). HIT versus MIT exercise acutely increased the experience of stress, tension, and irritation and decreased positive affect (P < 0.05). In addition, satisfaction was lower and pain and negative affect were higher in the HIT than those in the MIT group (P < 0.05). However, perceived exertion and displeasure experienced during exercise alleviated similarly in response to HIT and MIT over the 6 d of training. Peak oxygen consumption increased (P < 0.001) after intervention (HIT, 34.7 ± 3.9 vs 36.7 ± 4.5; MIT, 33.9 ± 4.6 vs 35.0 ± 4.6) and was not different between HIT and MIT (P = 0.28 for group × training). Short-term HIT and MIT are equally effective in improving aerobic fitness, but HIT increases experience of negative emotions and exertion in sedentary middle-age men. This may limit the adherence to this time-effective training mode, even though displeasure lessens over time and suggests similar mental adaptations to both MIT and HIT.

Performance characteristics of an automated latex immunoturbidimetric assay [HemosIL® HIT-Ab(PF4-H)] for the diagnosis of immune heparin-induced thrombocytopenia.

PubMed

Warkentin, Theodore E; Sheppard, Jo-Ann I; Linkins, Lori-Ann; Arnold, Donald M; Nazy, Ishac

2017-05-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating anti-PF4/heparin antibodies. Given time-sensitive treatment considerations, a rapid and accurate laboratory test for HIT antibodies is needed. To determine operating characteristics for the HemosIL ® HIT-Ab (PF4/H) , a rapid, on-demand, fully-automated, latex immunoturbidimetric assay (LIA), for diagnosis of HIT. We evaluated LIA sensitivity, specificity, negative (NPV) and positive predictive value (PPV), negative (LR-) and positive likelihood ratio (LR+), using citrated-plasma from 429 patients (prospective cohort study of 4Ts scoring; HIT, n=31), and from consecutive HIT patients (n=125), using reference standard serotonin-release assay (SRA). Comparators included two PF4-dependent enzyme-immunoassays (EIAs). We used stratum-specific likelihood ratios (SSLRs) to determine how differing magnitudes of LIA-positivity influenced post-test probability of HIT. LIA operating characteristics were: sensitivity=97.4% (152/156); specificity=94.0% (374/398); PPV=55.6% (30/54); and NPV=99.7% (374/375). At manufacturers' cutoffs, LIA specificity and PPV were superior to the EIAs. Although a negative LIA pointed strongly against HIT (LR-, 0.034), the post-test probability was ~2% with high 4Ts score. The LIA's LR+ was high (16.0), with SSLRs rising substantially with greater LIA-positivity: 5.7 (1.0-4.9U/mL), 31 (5.0-15.9U/mL), and 128 (≥16U/mL). A LIA-positive result (at 1.0 cutoff) indicated at least 24% HIT probability (low 4Ts score), rising to 90% with high 4Ts score. Although approximately 1 in 40 SRA-positive patients tested LIA-negative, the LIA's high NPV and PPV indicate that this rapid assay is useful for the diagnostic evaluation of HIT, including in low pre-test situations. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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.

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

PubMed

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

2011-01-01

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

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.

Throat hit in users of the electronic cigarette: An exploratory study.

PubMed

Etter, Jean-François

2016-02-01

A cross-sectional survey on the Internet in 2012-2014 was used to study the "throat hit," the specific sensation in the throat felt by users of e-cigarettes. Participants were 1672 current users of e-cigarettes, visitors of Websites dedicated to e-cigarettes and to smoking cessation. It was assessed whether the strength of the throat hit was associated with the characteristics of e-cigarettes and e-liquids, modifications of the devices, patterns of use, reasons for use, satisfaction with e-cigarettes, dependence on e-cigarettes, smoking behavior, and perceived effects on smoking. The strongest throat hit was obtained by using better-quality models and liquids with high nicotine content. Those who reported a "very strong" throat hit used liquids with 17.3 mg/mL nicotine, versus 7.1 mg/mL for those reporting a "very weak" hit (p < .001). The strength of the throat hit was also associated with ratings of dependence on e-cigarettes, and with the perceived efficacy of e-cigarettes to relieve craving for tobacco and to facilitate smoking cessation. All the variables assessing satisfaction with e-cigarettes were associated with a stronger throat hit. From a public health perspective, there is a trade-off between e-cigarette models that provide high levels of nicotine, a strong throat hit, high satisfaction, and more effects on smoking, but may also be addictive, and models than contain less nicotine and are less addictive, but produce a weaker throat hit, are less satisfactory, and are possibly less efficient at helping people quit smoking. This trade-off must be kept in mind when regulating e-cigarettes. (c) 2016 APA, all rights reserved).

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

PubMed Central

Aronson, Jeffrey K

2016-01-01

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