Sample records for double hit method

  1. How I treat double-hit lymphoma.

    PubMed

    Friedberg, Jonathan W

    2017-08-03

    The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

  2. Rare transformation to double hit lymphoma in Waldenstrom's macroglobulinemia.

    PubMed

    Okolo, Onyemaechi N; Johnson, Ariel C; Yun, Seongseok; Arnold, Stacy J; Anwer, Faiz

    2017-08-01

    Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL. The paper also broadens to include discussions on current topics in the classification, diagnosis, possible causes of transformation, and treatment of WM, including transformation to double hit lymphoma. The significance of this case lies in that the presence of double hit lymphoma-like genetic mutations in WM have not been previously described in the literature and potentially such changes are harbinger of extra-nodal presentation, aggressive growth, and possibly poor prognosis, if data from other double-hit lymphoma are extrapolated.

  3. A comparison of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the endoscopic treatment of primary vesicoureteral reflux.

    PubMed

    Akin, Melih; Erginel, Basak; Karadag, Cetin Ali; Yildiz, Abdullah; Ozçelik, Gül Sumru; Sever, Nihat; Genc, Nimetullah Mete; Dokucu, Ali Ihsan

    2014-11-01

    We aimed to compare the success rates of the double hydrodistention implantation technique (HIT) and the HIT with a polyacrylate/polyalcohol copolymer (PPC) for the treatment of primary vesicoureteral reflux (VUR) with a new nonbiodegradable tissue-augmenting substance (Vantris, Promedon, Cordoba, Argentina). Between January 2011 and December 2012, fifty-two children who underwent subureteric injection for primary VUR are included. The children were randomly separated into two groups, the HIT and the double HIT groups, according to the type of injection. Success was defined as no reflux on a follow-up voiding cystourethrogram (VCUG) after 6 months. The patients were evaluated according to sex, age, grade of reflux, number of injections, and injected volume, and the radiological success rates were compared. Fifty-two patients underwent an endoscopic injection for primary grade III-V VUR. The HIT group consisted of 26 patients with 33 ureters, and the double HIT group consisted of 26 patients with 35 ureters. There were no significant differences in terms of the sex, ages, VUR grades, bilaterality between the two groups. The mean injected volumes were ml 1.12 (1.02-1.22) in the HIT group and 1.24 ml (95 % CI 1.10-1.38) in the double HIT group. The reflux was resolved in 21/33 (63.6 %) ureters in the HIT group and in 30/35 (85.7 %) ureters in the double HIT group, (p < 0.05). We had only one complication. This patient in the double HIT group, developed bilateral hydronephrosis and oliguric renal failure requiring open reimplantation at the sixth month. We observed successful results double HIT method with PPC in Grade III-V reflux, but the long-term follow-up of patients is needed for hydronephrosis. As the double HIT treatment leads to a higher success rate, its use is preferable.

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

    PubMed

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

    2018-05-21

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

  5. Evaluation of new Deflux administration techniques: intraureteric HIT and Double HIT for the endoscopic correction of vesicoureteral reflux.

    PubMed

    Kirsch, Andrew J; Arlen, Angela M

    2014-09-01

    Vesicoureteral reflux (VUR) is one of the most common urologic diagnoses affecting children, and optimal treatment requires an individualized approach that considers potential risks. Management options include observation with or without continuous antibiotic prophylaxis and surgical correction via endoscopic, open or laparoscopic/robotic approaches. Endoscopic correction of VUR is an outpatient procedure associated with decreased morbidity compared with ureteral reimplantation. The concept of ureteral hydrodistention and intraluminal submucosal injection (Hydrodistention Implantation Technique [HIT]) has led to improved success rates in eliminating VUR compared with the subureteral transurethral injection technique. Further modifications now include use of proximal and distal intraluminal injections (Double HIT) that result in coaptation of both the ureteral tunnel and orifice. Endoscopic injection of dextranomer/hyaluronic acid copolymer, via the HIT and Double HIT, has emerged as a highly successful, minimally invasive alternative to open surgical correction, with minimal associated morbidity.

  6. Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

    PubMed

    Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

    2012-11-01

    The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

  7. Clinical Significance of "Double-hit" and "Double-protein" expression in Primary Gastric B-cell Lymphomas.

    PubMed

    He, Miaoxia; Chen, Keting; Li, Suhong; Zhang, Shimin; Zheng, Jianming; Hu, Xiaoxia; Gao, Lei; Chen, Jie; Song, Xianmin; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin

    2016-01-01

    Primary gastric B-cell lymphoma is the second most common malignancy of the stomach. There are many controversial issues about its diagnosis, treatment and clinical management. "Double-hit" and "double-protein" involving gene rearrangement and protein expression of c-Myc and bcl2/bcl6 are the most used terms to describe DLBCL poor prognostic factors in recent years. However, very little is known about the role of these prognostic factors in primary gastric B-cell lymphomas. This study aims to obtain a molecular pathology prognostic model of gastric B-cell lymphoma for clinical stratified management by evaluating how the "double-hit" and "double-protein" in tumor cells as well as microenvironmental reaction of tumor stromal tissue affect clinical outcome in primary gastric B-cell lymphomas. Data and tissues of 188 cases diagnosed with gastric B-cell lymphomas were used in this study. Tumor tissue microarray (TMA) of formalin fixed and paraffin embedded (FFPE) tissues was constructed for fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analysis with a serial of biomarkers containing MYC, BCL2, BCL6, CD31, SPARC, CD10, MUM1 and Ki-67. Modeled period analysis was used to estimate 3-year and 5-year overall survival (OS) and disease-free survival (DFS) distributions. There was no definite "double-hit" case though the gene rearrangement of c-Myc (5.9%), bcl2 (0.1%) and bcl6 (7.4%) was found in gastric B-cell lymphomas. The gene amplification or copy gains of c-Myc (10.1%), bcl-2 (17.0%) and bcl-6 (0.9%) were present in these lymphomas. There were 12 cases of the lymphomas with the "double-protein" expression of MYC and BCL2/BCL6. All patients with "double-protein" gastric B-cell lymphomas had poor outcome compared with those without. More importantly, "MYC-BCL2-BCL6" negative group of gastric B-cell lymphoma patients had favorable clinical outcome regardless clinical stage, pathological types and therapeutic modalities. And the similar better

  8. EBV-associated but HHV8-unrelated double-hit effusion-based lymphoma.

    PubMed

    Chen, Bo-Jung; Chen, David Yen-Ting; Kuo, Chun-Chi; Chuang, Shih-Sung

    2017-03-01

    Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion. He has no HIV, HBV or HCV infection and no mass lesion by CT scans. Cytology of both pleural effusion and ascites show large lymphoma cells with plasmablastic morphology characterized by pleomorphic and eccentric nuclei, prominent nucleoli and frequent mitoses. Immunohistochemical study with cell block shows that the lymphoma cells express plasma cell-related markers (CD138, MUM-1 and EMA), but not CD3, CD30, CD45, B-cell markers (CD19, CD20, CD79a, and PAX5), HHV8, ALK or cytokeratin. EBER is positive in most lymphoma cells. Fluorescence in situ hybridization reveals rearrangement at the IGH, BCL2, and MYC loci, but not at BCL6. It is diagnosed as an EBV-associated but HHV8-unrelated double hit effusion-based lymphoma with plasmablastic features. The patient passed away soon after diagnosis without chemotherapy. This is the first reported case of double-hit effusion-based lymphoma with MYC and BCL2 rearrangement. This case illustrates the importance of integrating clinical, cytological, immunophenotypical, and molecular findings to reach a correct diagnosis. Diagn. Cytopathol. 2017;45:257-261. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. 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

    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

  10. 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

  11. 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.

  12. 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.

  13. Clinicopathological and genomic analysis of double-hit follicular lymphoma: comparison with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.

    PubMed

    Miyaoka, Masashi; Kikuti, Yara Y; Carreras, Joaquim; Ikoma, Haruka; Hiraiwa, Shinichiro; Ichiki, Akifumi; Kojima, Minoru; Ando, Kiyoshi; Yokose, Tomoyuki; Sakai, Rika; Hoshikawa, Masahiro; Tomita, Naoto; Miura, Ikuo; Takata, Katsuyoshi; Yoshino, Tadashi; Takizawa, Jun; Bea, Silvia; Campo, Elias; Nakamura, Naoya

    2018-02-01

    Most high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are aggressive B-cell lymphomas. Occasional double-hit follicular lymphomas have been described but the clinicopathological features of these tumors are not well known. To clarify the characteristics of double-hit follicular lymphomas, we analyzed 10 cases of double-hit follicular lymphomas and 15 cases of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements for clinicopathological and genome-wide copy-number alterations and copy-neutral loss-of-heterozygosity profiles. For double-hit follicular lymphomas, the median age was 67.5 years (range: 48-82 years). The female/male ratio was 2.3. Eight patients presented with advanced clinical stage. The median follow-up time was 20 months (range: 1-132 months). At the end of the follow-up, 8 patients were alive, 2 patients were dead including 1 patient with diffuse large B-cell lymphoma transformation. Rearrangements of MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6 were seen in 8, 1, and 1 cases, respectively. The partner of MYC was IGH in 6 cases. There were no cases of histological grade 1, 4 cases of grade 2, 5 cases of grade 3a, and 1 case of grade 3b. Two cases of grade 3a exhibited immunoblast-like morphology. Immunohistochemistry demonstrated 9 cases with ≥50% MYC-positive cells. There was significant difference in MYC intensity (P=0.00004) and MIB-1 positivity (P=0.001) between double-hit follicular lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. The genome profile of double-hit follicular lymphomas was comparable with conventional follicular lymphomas (GSE67385, n=198) with characteristic gains of 2p25.3-p11.1, 7p22.3-q36.3, 12q11-q24.33, and loss of 18q21.32-q23 (P<0.05). In comparison with high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements, double-hit follicular lymphomas had fewer copy-number alterations and minimal common region of gain at 2p16.1 (70%), locus

  14. Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

    PubMed

    Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

    2018-03-26

    In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with

  15. 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.

  16. 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.

  17. Formulation of the Multi-Hit Model With a Non-Poisson Distribution of Hits

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

    Vassiliev, Oleg N., E-mail: Oleg.Vassiliev@albertahealthservices.ca

    2012-07-15

    Purpose: We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target. Methods and Materials: Poisson distribution is well justified for the first of the two processes. The second distribution depends on howmore » a hit is defined. To test our approach, we assumed that the second distribution was also a Poisson distribution. The two distributions combined resulted in a non-Poisson distribution. We tested the proposed model by comparing it with previously reported data for DNA single- and double-strand breaks induced by protons and electrons, for survival of a range of cell lines, and variation of the initial slopes of survival curves with radiation quality for heavy-ion beams. Results: Analysis of cell survival equations for this new model showed that they had realistic properties overall, such as the initial and high-dose slopes of survival curves, the shoulder, and relative biological effectiveness (RBE) In most cases tested, a better fit of survival curves was achieved with the new model than with the linear-quadratic model. The results also suggested that the proposed approach may extend the multi-hit model beyond its traditional role in analysis of survival curves to predicting effects of radiation quality and analysis of DNA strand breaks. Conclusions: Our model, although conceptually simple, performed well in all tests. The model was able to consistently fit data for both cell survival and DNA single- and double-strand breaks. It correctly predicted the dependence of radiation effects on parameters of radiation quality.« less

  18. 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.

  19. 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

  20. Double-hit follicular lymphoma with MYC and BCL2 translocations: a study of 7 cases with a review of literature.

    PubMed

    Miao, Yuan; Hu, Shimin; Lu, Xinyan; Li, Shaoying; Wang, Wei; Medeiros, L Jeffrey; Lin, Pei

    2016-12-01

    Follicular lymphoma with MYC and BCL2 translocations, so-called double-hit follicular lymphoma (DH-FL), is rare. Here, we report the clinicopathological features of 7 cases of DH-FL. All neoplasms had a follicular pattern (1 partially diffuse). Five cases were predominantly low grade, 4 of which had focal (≤20%) grade 3A areas, and 2 cases were of grade 3. All cases were positive for pan-B-cell antigens, CD10, and BCL6; 6 cases were positive for BCL2. Ki-67 was less than or equal to 50% in 6 cases and 90% in 1 grade 3 case. Three patients presented with stage IV disease and 3 had a Follicular Lymphoma International Prognostic Index score of greater than 2. Six patients received immunochemotherapy, and 1 is still under induction therapy with rituximab, ibrutinib, and lenalidomide. Four achieved complete remission and two had a partial response with persistent or refractory disease. The median follow-up time was 25 months (range, 8.5-53.7 months). Two patients treated with standard regimen for follicular lymphoma had relapsed or refractory disease, and 1 died from complications of allogeneic stem cell transplant administered for relapse. In contrast, all 4 patients treated with more intensive regimen for double-hit lymphoma achieved complete remission. In summary, despite predominantly low-grade histology, cases of DH-FL in this study were aggressive and responded better to more intensive than standard treatment regimens, suggesting DH-FL is part of the spectrum of double-hit high-grade lymphoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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

  3. 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.

  4. Triple Hit Lymphoma: Rare Cases With Less Dire Than Usual Prognosis.

    PubMed

    Kallen, Michael E; Alexanian, Serge; Said, Jonathan; Quintero-Rivera, Fabiola

    2016-12-01

    Triple hit lymphomas are a subset of so-called double hit non-Hodgkin lymphomas exhibiting simultaneous gene translocations/disruption of MYC, BCL2, and BCL6; however, their overlapping morphologic features and complex genetic rearrangements can render classification and prognostication vexing. Clinically triple hit lymphomas are thought to demonstrate aggressive behavior, similar to or worse than that of double hit lymphomas. Only rare reports of long term survivors exist and raise the possibility that unidentified morphologic, immunologic, or cytogenetic differences may impart a less adverse prognosis than current literature and opinion may suggest. Here we report 3 such cases with less aggressive behavior. Cases such as these may prove useful in comparing outcomes, and underlying mechanisms of tumor progression, in aggressive non-Hodgkin lymphomas. © The Author(s) 2016.

  5. 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.

  6. The prognosis of MYC translocation positive diffuse large B-cell lymphoma depends on the second hit.

    PubMed

    Clipson, Alexandra; Barrans, Sharon; Zeng, Naiyan; Crouch, Simon; Grigoropoulos, Nicholas F; Liu, Hongxiang; Kocialkowski, Sylvia; Wang, Ming; Huang, Yuanxue; Worrillow, Lisa; Goodlad, John; Buxton, Jenny; Neat, Michael; Fields, Paul; Wilkins, Bridget; Grant, John W; Wright, Penny; Ei-Daly, Hesham; Follows, George A; Roman, Eve; Watkins, A James; Johnson, Peter W M; Jack, Andrew; Du, Ming-Qing

    2015-07-01

    A proportion of MYC translocation positive diffuse large B-cell lymphomas (DLBCL) harbour a BCL2 and/or BCL6 translocation, known as double-hit DLBCL, and are clinically aggressive. It is unknown whether there are other genetic abnormalities that cooperate with MYC translocation and form double-hit DLBCL, and whether there is a difference in clinical outcome between the double-hit DLBCL and those with an isolated MYC translocation. We investigated TP53 gene mutations along with BCL2 and BCL6 translocations in a total of 234 cases of DLBCL, including 81 with MYC translocation. TP53 mutations were investigated by PCR and sequencing, while BCL2 and BCL6 translocation was studied by interphase fluorescence in situ hybridization. The majority of MYC translocation positive DLBCLs (60/81 = 74%) had at least one additional genetic hit. In MYC translocation positive DLBCL treated by R-CHOP ( n  = 67), TP53 mutation and BCL2, but not BCL6 translocation had an adverse effect on patient overall survival. In comparison with DLBCL with an isolated MYC translocation, cases with MYC/TP53 double-hits had the worst overall survival, followed by those with MYC/BCL2 double-hits. In MYC translocation negative DLBCL treated by R-CHOP ( n  = 101), TP53 mutation, BCL2 and BCL6 translocation had no impact on patient survival. The prognosis of MYC translocation positive DLBCL critically depends on the second hit, with TP53 mutations and BCL2 translocation contributing to an adverse prognosis. It is pivotal to investigate both TP53 mutations and BCL2 translocations in MYC translocation positive DLBCL, and to distinguish double-hit DLBCLs from those with an isolated MYC translocation.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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...

  18. Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

    PubMed

    Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

    2018-06-01

    Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

  19. 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/hit.html>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/hit.html>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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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…

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. "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…

  16. 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.

  17. 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...

  18. Advanced Doubling Adding Method for Radiative Transfer in Planetary Atmospheres

    NASA Astrophysics Data System (ADS)

    Liu, Quanhua; Weng, Fuzhong

    2006-12-01

    The doubling adding method (DA) is one of the most accurate tools for detailed multiple-scattering calculations. The principle of the method goes back to the nineteenth century in a problem dealing with reflection and transmission by glass plates. Since then the doubling adding method has been widely used as a reference tool for other radiative transfer models. The method has never been used in operational applications owing to tremendous demand on computational resources from the model. This study derives an analytical expression replacing the most complicated thermal source terms in the doubling adding method. The new development is called the advanced doubling adding (ADA) method. Thanks also to the efficiency of matrix and vector manipulations in FORTRAN 90/95, the advanced doubling adding method is about 60 times faster than the doubling adding method. The radiance (i.e., forward) computation code of ADA is easily translated into tangent linear and adjoint codes for radiance gradient calculations. The simplicity in forward and Jacobian computation codes is very useful for operational applications and for the consistency between the forward and adjoint calculations in satellite data assimilation.

  19. 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...

  20. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis.

    PubMed

    Padmanabhan, Anand; Jones, Curtis G; Bougie, Daniel W; Curtis, Brian R; McFarland, Janice G; Wang, Demin; Aster, Richard H

    2015-01-01

    Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P < .0001). Binding of SRA-positive antibodies to platelets was inhibited by chondroitinase ABC digestion (P < .05) and by the addition of chondroitin-4-sulfate (CS) or heparin in excess quantities. The findings suggest that although all HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain "delayed HIT" seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. © 2015 by The American Society of Hematology.

  1. 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.

  2. Computational Physics' Greatest Hits

    NASA Astrophysics Data System (ADS)

    Bug, Amy

    2011-03-01

    The digital computer, has worked its way so effectively into our profession that now, roughly 65 years after its invention, it is virtually impossible to find a field of experimental or theoretical physics unaided by computational innovation. It is tough to think of another device about which one can make that claim. In the session ``What is computational physics?'' speakers will distinguish computation within the field of computational physics from this ubiquitous importance across all subfields of physics. This talk will recap the invited session ``Great Advances...Past, Present and Future'' in which five dramatic areas of discovery (five of our ``greatest hits'') are chronicled: The physics of many-boson systems via Path Integral Monte Carlo, the thermodynamic behavior of a huge number of diverse systems via Monte Carlo Methods, the discovery of new pharmaceutical agents via molecular dynamics, predictive simulations of global climate change via detailed, cross-disciplinary earth system models, and an understanding of the formation of the first structures in our universe via galaxy formation simulations. The talk will also identify ``greatest hits'' in our field from the teaching and research perspectives of other members of DCOMP, including its Executive Committee.

  3. "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.

  4. 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.

  5. Study report on a double isotope method of calcium absorption

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Some of the pros and cons of three methods to study gastrointestinal calcium absorption are briefly discussed. The methods are: (1) a balance study; (2) a single isotope method; and (3) a double isotope method. A procedure for the double isotope method is also included.

  6. 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.

  7. 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.

  8. 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.

  9. Method for double-sided processing of thin film transistors

    DOEpatents

    Yuan, Hao-Chih; Wang, Guogong; Eriksson, Mark A.; Evans, Paul G.; Lagally, Max G.; Ma, Zhenqiang

    2008-04-08

    This invention provides methods for fabricating thin film electronic devices with both front- and backside processing capabilities. Using these methods, high temperature processing steps may be carried out during both frontside and backside processing. The methods are well-suited for fabricating back-gate and double-gate field effect transistors, double-sided bipolar transistors and 3D integrated circuits.

  10. Optical Diagnostics on HIT-SI3

    NASA Astrophysics Data System (ADS)

    Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

    2016-10-01

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

  11. 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

  12. 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.

  13. 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...

  14. Cyclone Chris Hits Australia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This false-color image shows Cyclone Chris shortly after it hit Australia's northwestern coast on February 6, 2002. This scene was acquired by the Moderate-resolution Imaging Spectroradiometer (MODIS), flying aboard NASA's Terra satellite. (Please note that this scene has not been reprojected.) Cyclone Chris is one of the most powerful storms ever to hit Australia. Initially, the storm contained wind gusts of up to 200 km per hour (125 mph), but shortly after making landfall it weakened to a Category 4 storm. Meteorologists expect the cyclone to weaken quickly as it moves further inland.

  15. 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

  16. 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/hit.html>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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. HIT: time to end behavioral health discrimination.

    PubMed

    Rosenberg, Linda

    2012-10-01

    While the Health Information Technology for Economic and Clinical Health Act, enacted as part of the American Recovery and Reinvestment Act of 2009, provided $20.6 billion for incentive payments to support the adoption and meaningful use of health information technology (HIT), behavioral health organizations were not eligible to receive facility payments. The consequences of excluding behavioral health from HIT incentive payments are found in the results of the "HIT Adoption and Meaningful Use Readiness in Community Behavioral Health" survey. The survey found that only 2% of community behavioral health organizations are able to meet federal meaningful use (MU) requirements-compare this to the 27% of Federally Qualified Health Centers and 20% of hospitals that already meet some level of MU requirements. Behavioral health organizations, serving more than eight million adults, children, and families with mental illnesses and addiction disorders, are ready and eager to adopt HIT to meet the goals of better healthcare, better health, and lower costs. But reaching these goals may prove impossible unless behavioral health achieves "parity" within healthcare and receives resources for the adoption of HIT.

  4. 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.

  5. 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.

  6. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

    PubMed Central

    Jones, Curtis G.; Bougie, Daniel W.; Curtis, Brian R.; McFarland, Janice G.; Wang, Demin; Aster, Richard H.

    2015-01-01

    Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P < .0001). Binding of SRA-positive antibodies to platelets was inhibited by chondroitinase ABC digestion (P < .05) and by the addition of chondroitin-4-sulfate (CS) or heparin in excess quantities. The findings suggest that although all HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain “delayed HIT” seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. PMID:25342714

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. A double-correlation tremor-location method

    NASA Astrophysics Data System (ADS)

    Li, Ka Lok; Sgattoni, Giulia; Sadeghisorkhani, Hamzeh; Roberts, Roland; Gudmundsson, Olafur

    2017-02-01

    A double-correlation method is introduced to locate tremor sources based on stacks of complex, doubly-correlated tremor records of multiple triplets of seismographs back projected to hypothetical source locations in a geographic grid. Peaks in the resulting stack of moduli are inferred source locations. The stack of the moduli is a robust measure of energy radiated from a point source or point sources even when the velocity information is imprecise. Application to real data shows how double correlation focuses the source mapping compared to the common single correlation approach. Synthetic tests demonstrate the robustness of the method and its resolution limitations which are controlled by the station geometry, the finite frequency of the signal, the quality of the used velocity information and noise level. Both random noise and signal or noise correlated at time shifts that are inconsistent with the assumed velocity structure can be effectively suppressed. Assuming a surface wave velocity, we can constrain the source location even if the surface wave component does not dominate. The method can also in principle be used with body waves in 3-D, although this requires more data and seismographs placed near the source for depth resolution.

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

    PubMed Central

    Picci, Giorgia; Scherf, K. Suzanne

    2015-01-01

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

  13. 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.

  14. Concerning the Video Drift Method to Measure Double Stars

    NASA Astrophysics Data System (ADS)

    Nugent, Richard L.; Iverson, Ernest W.

    2015-05-01

    Classical methods to measure position angles and separations of double stars rely on just a few measurements either from visual observations or photographic means. Visual and photographic CCD observations are subject to errors from the following sources: misalignments from eyepiece/camera/barlow lens/micrometer/focal reducers, systematic errors from uncorrected optical distortions, aberrations from the telescope system, camera tilt, magnitude and color effects. Conventional video methods rely on calibration doubles and graphically calculating the east-west direction plus careful choice of select video frames stacked for measurement. Atmospheric motion is one of the larger sources of error in any exposure/measurement method which is on the order of 0.5-1.5. Ideally, if a data set from a short video can be used to derive position angle and separation, with each data set self-calibrating independent of any calibration doubles or star catalogues, this would provide measurements of high systematic accuracy. These aims are achieved by the video drift method first proposed by the authors in 2011. This self calibrating video method automatically analyzes 1,000's of measurements from a short video clip.

  15. 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…

  16. 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.

  17. Do pigeons prefer alternatives that include near-hit outcomes?

    PubMed

    Stagner, Jessica P; Case, Jacob P; Sticklen, Mary F; Duncan, Amanda K; Zentall, Thomas R

    2015-07-01

    Pigeons show suboptimal choice on a gambling-like task similar to that shown by humans. Humans also show a preference for gambles in which there are near hits (losses that come close to winning). In the present research, we asked if pigeons would show a preference for alternatives with near-hit-like trials. In Experiment 1, we included an alternative that presented a near hit, in which a stimulus associated with reinforcement (a presumed conditioned reinforcer) changed to a stimulus associated with the absence of reinforcement (a presumed conditioned inhibitor). The pigeons tended to avoid this alternative. In Experiment 2, we varied the duration of the presumed conditioned reinforcer (2 vs. 8 s) that changed to a presumed conditioned inhibitor (8 vs. 2 s) and found that the longer the conditioned reinforcer was presented, the more the pigeons avoided it. In Experiment 3, the near-hit alternative involved an ambiguous stimulus for 8 s that changed to a presumed conditioned reinforcer (or a presumed conditioned inhibitor) for 2 s, but the pigeons still avoided it. In Experiment 4, we controlled for the duration of the conditioned reinforcer by presenting it first for 2 s followed by the ambiguous stimulus for 8 s. Once again, the pigeons avoided the alternative with the near-hit trials. In all 4 experiments, the pigeons tended to avoid alternatives that provided near-hit-like trials. We concluded that humans may be attracted to near-hit trials because near-hit trials give them the illusion of control, whereas this does not appear to be a factor for pigeons. (c) 2015 APA, all rights reserved).

  18. 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.

  19. A hemispherical imaging and tracking (HIT) system

    NASA Astrophysics Data System (ADS)

    Gilbert, John A.; Fair, Sara B.; Caldwell, Scott E.; Gronner, Sally J.

    1992-05-01

    A hemispherical imaging and tracking (HIT) system is described which is used for an interceptor designed to acquire, select, home, and hit-to-kill reentry vehicle targets from intercontinental ballistic missiles. The system provides a sizable field of view, over which a target may be tracked and yields a unique and distinctive optical signal when the system is 'on target'. The system has an infinite depth of focus and no moving parts are required for imaging within a hemisphere. Critical alignment of the HIT system is based on the comparison of signals captured through different points on an annular window. Assuming that the perturbations are radially symmetric, errors may be eliminated during the subtraction.

  20. Hitting Is Contagious: Experience and Action Induction

    ERIC Educational Resources Information Center

    Gray, Rob; Beilock, Sian L.

    2011-01-01

    In baseball, it is believed that "hitting is contagious," that is, probability of success increases if the previous few batters get a hit. Could this effect be partially explained by action induction--that is, the tendency to perform an action related to one that has just been observed? A simulation was used to investigate the effect of inducing…

  1. 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

  2. Laboratory Testing Protocols for Heparin-Induced Thrombocytopenia (HIT) Testing.

    PubMed

    Lau, Kun Kan Edwin; Mohammed, Soma; Pasalic, Leonardo; Favaloro, Emmanuel J

    2017-01-01

    Heparin-induced thrombocytopenia (HIT) represents a significant high morbidity complication of heparin therapy. The clinicopathological diagnosis of HIT remains challenging for many reasons; thus, laboratory testing represents an important component of an accurate diagnosis. Although there are many assays available to assess HIT, these essentially fall into two categories-(a) immunological assays, and (b) functional assays. The current chapter presents protocols for several HIT assays, being those that are most commonly performed in laboratory practice and have the widest geographic distribution. These comprise a manual lateral flow-based system (STiC), a fully automated latex immunoturbidimetric assay, a fully automated chemiluminescent assay (CLIA), light transmission aggregation (LTA), and whole blood aggregation (Multiplate).

  3. 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.

  4. [Successful treatment of a patient with two hematologic tumors: double-hit lymphoma and acute myelomonoblastic leukemia].

    PubMed

    Lukina, A E; Bariakh, E A; Kravchenko, S K; Nareĭko, M V; Kuz'mina, L A; Parovichnikova, E N; Obukhova, T N; Kovrigina, A M; Magomedova, A U

    2014-01-01

    Double-hit (DH) lymphoma, an extremely aggressive variant of B-cell lymphoma, is accompanied by chromosomal abnormalities leading to the activation of a few oncogenes, one of which is the c-MYC gene in conjunction with BCL2 or BCL6 gene rearrangements. There are most common cases of MYC/8q24 and BCL2/18q21 gene rearrangements (MYC/BCL-2 DH lymphoma). The tumor is characterized by an aggressive clinical course and a poor response to chemotherapy (CT). The median survival in patients with DH lymphomas varies from 4.5 to 18 months. Such patients are generally resistant to CHOP-21 and R-CHOP-21 therapy regimens. For the treatment of patients with DH lymphoma, the Hematology Research Center, Ministry of Health of the Russian Federation, chose an original BL-M-04 polychemotherapy (PCT) protocol in combination with rituximab, followed by autologous stem cell transplantation (allo-SCT). The paper describes the experience in successfully treating a patient with two hematologic tumors: 1) MYC/BCL-2 DH lymphoma with high-dose PCT cycles, followed by allo-SCT, and 2) a metachronously developed second tumor (acute myelomonoblastic leukemia (AMML)) with CT cycles, followed by auto-SCT. The incidence of tumors induced by the previous high-dose CT for aggressive lymphomas for 10 years is 0.7 to 10%. As a rule, the development of secondary AMML is preceded by a history of myelodysplastic syndrome (MDS); characteristic chromosomal abnormalities (deletions of the long arm of chromosomes 5 and 7) are detectable. In this case, the follow-up was 3 months before the development of AMML, during this period the patient was not found to have laboratory signs of MDS (anemia, thrombocytopenia) or chromosomal abnormalities associated with secondary MDS/AML. The presence of a leukemic stem cell is associated with the occurrence and development of hemoblastosis; that of the similar cell populations that may cause B-cell lymphomas remains uncertain. The described case may have defect in a

  5. 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.

  6. Geometric Hitting Set for Segments of Few Orientations

    DOE PAGES

    Fekete, Sandor P.; Huang, Kan; Mitchell, Joseph S. B.; ...

    2016-01-13

    Here we study several natural instances of the geometric hitting set problem for input consisting of sets of line segments (and rays, lines) having a small number of distinct slopes. These problems model path monitoring (e.g., on road networks) using the fewest sensors (the \\hitting points"). We give approximation algorithms for cases including (i) lines of 3 slopes in the plane, (ii) vertical lines and horizontal segments, (iii) pairs of horizontal/vertical segments. Lastly, we give hardness and hardness of approximation results for these problems. We prove that the hitting set problem for vertical lines and horizontal rays is polynomially solvable.

  7. Overview of HIT-SI Results and Plans

    NASA Astrophysics Data System (ADS)

    Ennis, D. A.; Akcay, C.; Hansen, C. J.; Hicks, N. K.; Hossack, A. C.; Jarboe, T. R.; Marklin, G. J.; Nelson, B. A.; Victor, B. S.

    2011-10-01

    Experiments in the Helicity Injected Torus-Steady Inductive (HIT-SI) device have achieved record spheromak current amplification during operations in deuterium plasmas. HIT-SI investigates steady inductive helicity injection with the aim of forming and sustaining a high-beta equilibrium in a spheromak geometry using two semi-toroidal injectors. Recent operations in deuterium plasmas have produced toroidal plasma currents greater than 50 kA, with current amplifications (Itor / Iinj) > 3 , and poloidal flux amplifications (ψpol /ψinj) > 10 . High performance deuterium discharges are achieved by initially conditioning the plasma-facing alumina surface of the HIT-SI confinement volume with helium plasmas. During subsequent deuterium operation the alumina surface strongly pumps deuterium, thereby limiting the density in the confinement volume. Additional measurements during high current deuterium discharges demonstrate reduced current and electron density fluctuations, impurity O III ion temperatures up to 50 eV and a toroidal current persistence for 0.6 ms after the injectors are shut off. Progress and plans for the HIT-SI3 configuration, with three injectors mounted on the same side of the confinement volume, will also be presented. Work supported by USDoE and ARRA.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Data Independent Acquisition analysis in ProHits 4.0.

    PubMed

    Liu, Guomin; Knight, James D R; Zhang, Jian Ping; Tsou, Chih-Chiang; Wang, Jian; Lambert, Jean-Philippe; Larsen, Brett; Tyers, Mike; Raught, Brian; Bandeira, Nuno; Nesvizhskii, Alexey I; Choi, Hyungwon; Gingras, Anne-Claude

    2016-10-21

    Affinity purification coupled with mass spectrometry (AP-MS) is a powerful technique for the identification and quantification of physical interactions. AP-MS requires careful experimental design, appropriate control selection and quantitative workflows to successfully identify bona fide interactors amongst a large background of contaminants. We previously introduced ProHits, a Laboratory Information Management System for interaction proteomics, which tracks all samples in a mass spectrometry facility, initiates database searches and provides visualization tools for spectral counting-based AP-MS approaches. More recently, we implemented Significance Analysis of INTeractome (SAINT) within ProHits to provide scoring of interactions based on spectral counts. Here, we provide an update to ProHits to support Data Independent Acquisition (DIA) with identification software (DIA-Umpire and MSPLIT-DIA), quantification tools (through DIA-Umpire, or externally via targeted extraction), and assessment of quantitative enrichment (through mapDIA) and scoring of interactions (through SAINT-intensity). With additional improvements, notably support of the iProphet pipeline, facilitated deposition into ProteomeXchange repositories and enhanced export and viewing functions, ProHits 4.0 offers a comprehensive suite of tools to facilitate affinity proteomics studies. It remains challenging to score, annotate and analyze proteomics data in a transparent manner. ProHits was previously introduced as a LIMS to enable storing, tracking and analysis of standard AP-MS data. In this revised version, we expand ProHits to include integration with a number of identification and quantification tools based on Data-Independent Acquisition (DIA). ProHits 4.0 also facilitates data deposition into public repositories, and the transfer of data to new visualization tools. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. 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.

  15. 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

  16. 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.

  17. Verbs in the lexicon: Why is hitting easier than breaking?

    PubMed

    McKoon, Gail; Love, Jessica

    2011-11-01

    Adult speakers use verbs in syntactically appropriate ways. For example, they know implicitly that the boy hit at the fence is acceptable but the boy broke at the fence is not. We suggest that this knowledge is lexically encoded in semantic decompositions. The decomposition for break verbs (e.g. crack, smash) is hypothesized to be more complex than that for hit verbs (e.g. kick, kiss). Specifically, the decomposition of a break verb denotes that "an entity changes state as the result of some external force" whereas the decomposition for a hit verb denotes only that "an entity potentially comes in contact with another entity." In this article, verbs of the two types were compared in a lexical decision experiment - Experiment 1 - and they were compared in sentence comprehension experiments with transitive sentences (e.g. the car hit the bicycle and the car broke the bicycle) - Experiments 2 and 3. In Experiment 1, processing times were shorter for the hit than the break verbs and in Experiments 2 and 3, processing times were shorter for the hit sentences than the break sentences, results that are in accord with the complexities of the postulated semantic decompositions.

  18. 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.

  19. 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

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Single-hit mechanism of tumour cell killing by radiation.

    PubMed

    Chapman, J D

    2003-02-01

    To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells

  7. Assessing the lipophilicity of fragments and early hits

    NASA Astrophysics Data System (ADS)

    Mortenson, Paul N.; Murray, Christopher W.

    2011-07-01

    A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLEAT) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLEAT should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation.

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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).

  15. 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.

  16. HIT collaborative base project at APS of Argonne

    NASA Astrophysics Data System (ADS)

    Liu, H.; Wang, L.

    2012-12-01

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

  17. Double power series method for approximating cosmological perturbations

    NASA Astrophysics Data System (ADS)

    Wren, Andrew J.; Malik, Karim A.

    2017-04-01

    We introduce a double power series method for finding approximate analytical solutions for systems of differential equations commonly found in cosmological perturbation theory. The method was set out, in a noncosmological context, by Feshchenko, Shkil' and Nikolenko (FSN) in 1966, and is applicable to cases where perturbations are on subhorizon scales. The FSN method is essentially an extension of the well known Wentzel-Kramers-Brillouin (WKB) method for finding approximate analytical solutions for ordinary differential equations. The FSN method we use is applicable well beyond perturbation theory to solve systems of ordinary differential equations, linear in the derivatives, that also depend on a small parameter, which here we take to be related to the inverse wave-number. We use the FSN method to find new approximate oscillating solutions in linear order cosmological perturbation theory for a flat radiation-matter universe. Together with this model's well-known growing and decaying Mészáros solutions, these oscillating modes provide a complete set of subhorizon approximations for the metric potential, radiation and matter perturbations. Comparison with numerical solutions of the perturbation equations shows that our approximations can be made accurate to within a typical error of 1%, or better. We also set out a heuristic method for error estimation. A Mathematica notebook which implements the double power series method is made available online.

  18. 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.

  19. 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.

  20. The Rock that Hit New York

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

    Meade, Roger Allen; Keksis, August Lawrence

    On January 12, 1975, a rock seemed to fall from the sky over New York State’s Schoharie County hitting the tractor of a local farmer, who was “preparing his fields for spring planting.” As the farmer later described the event to a reporter from the UFO INVESTIGATOR, the object glanced off the tractor, fell to the ground, and melted its way through a patch of ice that was two and one half inches thick. The farmer, Leonard Tillapaugh, called the county sheriff, Harvey Stoddard, who recovered the rock, noting that it “was still warm.” Why and how a sample ofmore » the rock came to Los Alamos is not known. However, it captivated a wide Laboratory audience, was subjected to rigorous testing and evaluation. Los Alamos used the scientific method in the manner promoted by Hynek. Did Los Alamos solve the mystery of the rock’s origin? Not definitively. Although the exact origin could not be determined, it was shown conclusively that the rock was not from outer space. With that said, the saga of Rock that hit New York came to an end. Nothing more was said or written about it. The principals involved have long since passed from the scene. The NICAP ceased operations in 1980. And, the rock, itself, has disappeared.« less

  1. 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.

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

    PubMed

    Chuartzman, Silvia G; Schuldiner, Maya

    2018-03-25

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

  3. Double wall vacuum tubing and method of manufacture

    DOEpatents

    Stahl, Charles R.; Gibson, Michael A.; Knudsen, Christian W.

    1989-01-01

    An evacuated double wall tubing is shown together with a method for the manufacture of such tubing which includes providing a first pipe of predetermined larger diameter and a second pipe having an O.D. substantially smaller than the I.D. of the first pipe. An evacuation opening is then in the first pipe. The second pipe is inserted inside the first pipe with an annular space therebetween. The pipes are welded together at one end. A stretching tool is secured to the other end of the second pipe after welding. The second pipe is then prestressed mechanically with the stretching tool an amount sufficient to prevent substantial buckling of the second pipe under normal operating conditions of the double wall pipe. The other ends of the first pipe and the prestressed second pipe are welded together, preferably by explosion welding, without the introduction of mechanical spacers between the pipes. The annulus between the pipes is evacuated through the evacuation opening, and the evacuation opening is finally sealed. The first pipe is preferably of steel and the second pipe is preferably of titanium. The pipes may be of a size and wall thickness sufficient for the double wall pipe to be structurally load bearing or may be of a size and wall thickness insufficient for the double wall pipe to be structurally load bearing, and the double wall pipe positioned with a sliding fit inside a third pipe of a load-bearing size.

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  5. Interferometric Methods of Measuring Refractive Indices and Double-Refraction of Fibres.

    ERIC Educational Resources Information Center

    Hamza, A. A.; El-Kader, H. I. Abd

    1986-01-01

    Presents two methods used to measure the refractive indices and double-refraction of fibers. Experiments are described, with one involving the use of Pluta microscope in the double-beam interference technique, the other employing the multiple-beam technique. Immersion liquids are discussed that can be used in the experiments. (TW)

  6. The rationale and design of the national familial hypercholesterolemia registries in Turkey: A-HIT1 and A-HIT2 studies.

    PubMed

    Kayıkçıoğlu, Meral; Tokgözoğlu, Lale

    2017-04-01

    Familial hypercholesterolemia (FH) is a genetic disease characterized by extremely high levels of cholesterol, leading to premature atherosclerosis. Although many countries have already addressed the burden of FH by means of national registries, Turkey has no national FH registry or national screening program to detect FH. Creation of a series of FH registries is planned as part of Turkish FH Initiative endorsed by the Turkish Society of Cardiology to meet this need. This article provides detailed information on the rationale and design of the first 2 FH registries (A-HIT1 and A-HIT2). A-HIT1 is a nationwide survey of adult homozygous FH (HoFH) patients undergoing low-density lipoprotein (LDL) apheresis (LA) in Turkey. A-HIT1 will provide insight into the clinical status of HoFH patients undergoing LA. Primary objective of this cross-sectional study is to identify how HoFH patients on LA are managed. Inclusion criteria are age >12 years, diagnosis of HoFH, and regular LA treatment. All available apheresis centers were electronically invited to participate in the study. The principal physicians of each center will respond to a questionnaire regarding their attitude toward LA. For each patient, another questionnaire will be used to collect data on clinical status, medication use, and disease data. In addition, patients will be asked to complete self-report questionnaires that provide information on quality of life, disease-related anxiety, and depression. A-HIT2 is a registry of adult FH patients presenting at outpatient clinics. At least 1000 FH patients will be recruited from 30 outpatient clinics representing the 12 statistical regions in Turkey based on the EU NUTS classification. Sites specializing in cardiology, internal medicine, and endocrinology were invited to participate. The primary objective of this cross-sectional study is to determine clinical status and management of patients in Turkey diagnosed with FH. Eligibility for screening was defined as having

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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.

  13. HIT: a new approach for hiding multimedia information in text

    NASA Astrophysics Data System (ADS)

    El-Kwae, Essam A.; Cheng, Li

    2002-04-01

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

  14. Examining the use of HIT functions among physicians serving minority populations.

    PubMed

    Tarver, Will; Menachemi, Nir

    2014-02-01

    The Institute of Medicine highlighted the fact that the U.S. health care system does not provide consistent, high quality medical care to all people. The routine use of health information technology (HIT) that includes certain key functions may be critical in reducing such disparities. We used logistic regression analyses to examine differences when it comes to the routine use of key HIT functions that are linked to improvements in clinical care. Physicians predominantly serving Black patients were more likely than physicians predominantly serving White patients to routinely use HIT to generate reminders for clinicians and patients about preventive services. Similarly, physicians predominantly serving Hispanic patients were more likely than physicians predominantly serving White patients to routinely use HIT to access patients' preferred language. Importantly, although minority-serving institutions have lower adoption rates overall, differences exist in the routine use of key HIT functions that have the potential to reduce health disparities.

  15. Estimating residual fault hitting rates by recapture sampling

    NASA Technical Reports Server (NTRS)

    Lee, Larry; Gupta, Rajan

    1988-01-01

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

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

    PubMed

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

    2015-06-01

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

  17. Universal Hitting Time Statistics for Integrable Flows

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  18. Optoelectronic hit/miss transform for screening cervical smear slides

    NASA Astrophysics Data System (ADS)

    Narayanswamy, R.; Turner, R. M.; McKnight, D. J.; Johnson, K. M.; Sharpe, J. P.

    1995-06-01

    An optoelectronic morphological processor for detecting regions of interest (abnormal cells) on a cervical smear slide using the hit/miss transform is presented. Computer simulation of the algorithm tested on 184 Pap-smear images provided 95% detection and 5% false alarm. An optoelectronic implementation of the hit/miss transform is presented, along with preliminary experimental results.

  19. [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.

  20. "Hit-and-Run" leaves its mark: catalyst transcription factors and chromatin modification.

    PubMed

    Varala, Kranthi; Li, Ying; Marshall-Colón, Amy; Para, Alessia; Coruzzi, Gloria M

    2015-08-01

    Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome-wide evidence for a "Hit-and-Run" model of transcription. In this model, a master TF "hits" a target promoter to initiate a rapid response to a signal. As the "hit" is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the "run", the master TF "hits" other targets to propagate the response genome-wide. As such, a TF may act as a "catalyst" to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long-term adaptive behavior in the whole organism. This "Hit-and-Run" model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF-regulated and TF-bound genes, implicating transient TF-target binding. Here, we explore this "Hit-and-Run" model to suggest molecular mechanisms and its biological relevance. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

  1. 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.

  2. 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

  3. 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.

  4. Overview of the Helicity Injected Torus (HIT) Program

    NASA Astrophysics Data System (ADS)

    Redd, A. J.; Jarboe, T. R.; Hamp, W. T.; Nelson, B. A.; O'Neill, R. G.; Sieck, P. E.; Smith, R. J.; Sutphin, G. L.; Wrobel, J. S.

    2007-06-01

    The Helicity Injected Torus with Steady Inductive Helicity Injection (HIT-SI) consists of a "bowtie"-shaped axisymmetric confinement region, with two half-torus helicity injectors mounted on each side of the axisymmetric flux conserver [Sieck et al, IEEE Trans. Plasma Sci., v.33, p.723 (2005); Jarboe, Fusion Technology, v.36, p.85 (1999)]. Current and flux are driven sinusoidally with time in each injector, with the goal of generating and sustaining an axisymmetric spheromak in the main confinement region. Improvements in machine conditioning have enabled systematic study of HIT-SI discharges with significant toroidal current ITOR, including cases in which this current ITOR switches sign one or more times during the discharge. Statistical studies of all HIT-SI discharges to date demonstrate a minimum injected power to form significant ITOR, and that the maximum ITOR scales approximately linearly with the total injected power.

  5. 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.

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

    PubMed

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

    2013-11-22

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

  7. The finite layer method for modelling the sound transmission through double walls

    NASA Astrophysics Data System (ADS)

    Díaz-Cereceda, Cristina; Poblet-Puig, Jordi; Rodríguez-Ferran, Antonio

    2012-10-01

    The finite layer method (FLM) is presented as a discretisation technique for the computation of noise transmission through double walls. It combines a finite element method (FEM) discretisation in the direction perpendicular to the wall with trigonometric functions in the two in-plane directions. It is used for solving the Helmholtz equation at the cavity inside the double wall, while the wall leaves are modelled with the thin plate equation and solved with modal analysis. Other approaches to this problem are described here (and adapted where needed) in order to compare them with the FLM. They range from impedance models of the double wall behaviour to different numerical methods for solving the Helmholtz equation in the cavity. For the examples simulated in this work (impact noise and airborne sound transmission), the former are less accurate than the latter at low frequencies. The main advantage of FLM over the other discretisation techniques is the possibility of extending it to multilayered structures without changing the interpolation functions and with an affordable computational cost. This potential is illustrated with a calculation of the noise transmission through a multilayered structure: a double wall partially filled with absorbing material.

  8. 77 FR 23250 - HIT Standards Committee; Schedule for the Assessment of HIT Policy Committee Recommendations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-18

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

  9. New modified multi-level residue harmonic balance method for solving nonlinearly vibrating double-beam problem

    NASA Astrophysics Data System (ADS)

    Rahman, Md. Saifur; Lee, Yiu-Yin

    2017-10-01

    In this study, a new modified multi-level residue harmonic balance method is presented and adopted to investigate the forced nonlinear vibrations of axially loaded double beams. Although numerous nonlinear beam or linear double-beam problems have been tackled and solved, there have been few studies of this nonlinear double-beam problem. The geometric nonlinear formulations for a double-beam model are developed. The main advantage of the proposed method is that a set of decoupled nonlinear algebraic equations is generated at each solution level. This heavily reduces the computational effort compared with solving the coupled nonlinear algebraic equations generated in the classical harmonic balance method. The proposed method can generate the higher-level nonlinear solutions that are neglected by the previous modified harmonic balance method. The results from the proposed method agree reasonably well with those from the classical harmonic balance method. The effects of damping, axial force, and excitation magnitude on the nonlinear vibrational behaviour are examined.

  10. NIMROD simulations of HIT-SI plasmas

    NASA Astrophysics Data System (ADS)

    Akcay, Cihan; Jarboe, Thomas; Nelson, Brian; Kim, Charlson

    2011-10-01

    HIT-SI (Steady Inductive Helicity Injected Torus) is a current drive experiment that uses two semi-toroidal helicity injectors driven at 5-15 kHz to generate steady inductive helicity injection (SIHI). All the plasma-facing walls of the experiment are coated with an insulating material to guarantee an inductive discharge. NIMROD is a 3-D extended MHD code that can only model toroidally-uniform geometries. The helicity injectors of the experiment are simulated as flux and voltage boundary conditions with odd toroidal symmetry. A highly resistive, thin edge-layer approximates the insulating walls. The simulations are initial-value calculations that use a zero β resistive MHD (rMHD) model with uniform density. The Prandtl number (Pr = 10), and Lundquist number (S = 5 - 50) closely match the experimental values. rMHD calculations at S ~ 10 show no growth of an n = 0 mode and only a few kA of toroidal current whereas HIT-SI has demonstrated toroidal currents greater than 50 kA with a current amplification of 3. At higher S (>= 20) the simulations exhibit significant n = 0 magnetic energy growth and a current amplification exceeding unity: Itor/Iinj >= 1 . While HIT-SI has shown evidence for separatrix formation, rMHD calculations indicate an entirely stochastic magnetic structure during sustainment. Results will also presented for Hall MHD, anticipated to play a crucial role in the physics of SIHI.

  11. But Can You Hit?

    ERIC Educational Resources Information Center

    Johnson, R. E.

    2009-01-01

    The author shares a story told to him by a colleague more than thirty years ago. The dean of a midsized American university was explaining the path to tenure to a roomful of newly appointed assistant professors. "We know you boys can all "field"," he declared. "Now we want to see if you can hit." A lot has changed over the intervening decades. If…

  12. Object Rotation Effects on the Timing of a Hitting Action

    ERIC Educational Resources Information Center

    Scott, Mark A.; van der Kamp, John; Savelsbergh, Geert J. P.; Oudejans, Raoul R. D.; Davids, Keith

    2004-01-01

    In this article, the authors investigated how perturbing optical information affects the guidance of an unfolding hitting action. Using monocular and binocular vision, six participants were required to hit a rectangular foam object, released from two different heights, under four different approach conditions, two with object rotation (to perturb…

  13. Influence of Running on Pistol Shot Hit Patterns.

    PubMed

    Kerkhoff, Wim; Bolck, Annabel; Mattijssen, Erwin J A T

    2016-01-01

    In shooting scene reconstructions, risk assessment of the situation can be important for the legal system. Shooting accuracy and precision, and thus risk assessment, might be correlated with the shooter's physical movement and experience. The hit patterns of inexperienced and experienced shooters, while shooting stationary (10 shots) and in running motion (10 shots) with a semi-automatic pistol, were compared visually (with confidence ellipses) and statistically. The results show a significant difference in precision (circumference of the hit patterns) between stationary shots and shots fired in motion for both inexperienced and experienced shooters. The decrease in precision for all shooters was significantly larger in the y-direction than in the x-direction. The precision of the experienced shooters is overall better than that of the inexperienced shooters. No significant change in accuracy (shift in the hit pattern center) between stationary shots and shots fired in motion can be seen for all shooters. © 2015 American Academy of Forensic Sciences.

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

    PubMed

    Cook, Robyn; Foster, Joanne

    2009-01-01

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

  15. 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.

  16. 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.

  17. A novel attack method about double-random-phase-encoding-based image hiding method

    NASA Astrophysics Data System (ADS)

    Xu, Hongsheng; Xiao, Zhijun; Zhu, Xianchen

    2018-03-01

    By using optical image processing techniques, a novel text encryption and hiding method applied by double-random phase-encoding technique is proposed in the paper. The first step is that the secret message is transformed into a 2-dimension array. The higher bits of the elements in the array are used to fill with the bit stream of the secret text, while the lower bits are stored specific values. Then, the transformed array is encoded by double random phase encoding technique. Last, the encoded array is embedded on a public host image to obtain the image embedded with hidden text. The performance of the proposed technique is tested via analytical modeling and test data stream. Experimental results show that the secret text can be recovered either accurately or almost accurately, while maintaining the quality of the host image embedded with hidden data by properly selecting the method of transforming the secret text into an array and the superimposition coefficient.

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

    PubMed

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

    2016-07-01

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

  19. 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.

  20. 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

    HIT/SIHI/>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.

  1. 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.

  2. 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…

  3. Inverse scattering method and soliton double solution family for the general symplectic gravity model

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

    Gao Yajun

    A previously established Hauser-Ernst-type extended double-complex linear system is slightly modified and used to develop an inverse scattering method for the stationary axisymmetric general symplectic gravity model. The reduction procedures in this inverse scattering method are found to be fairly simple, which makes the inverse scattering method applied fine and effective. As an application, a concrete family of soliton double solutions for the considered theory is obtained.

  4. 77 FR 65691 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  5. 77 FR 2727 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  6. 77 FR 15760 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  7. 77 FR 73660 - HIT Policy Committee Advisory Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  8. 77 FR 57567 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  9. 77 FR 50690 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  10. 77 FR 28881 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  11. 76 FR 79684 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  12. 76 FR 70455 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  13. 77 FR 41788 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  14. 77 FR 27459 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: to provide recommendations to...

  15. 77 FR 37407 - HIT Policy Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Policy Committee Advisory Meeting; Notice of Meeting AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of... of Committee: HIT Policy Committee. General Function of the Committee: To provide recommendations to...

  16. Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine

    PubMed Central

    Sunada, Keijiro; Yamamoto, Hironori; Kita, Hiroto; Yano, Tomonori; Sato, Hiroyuki; Hayashi, Yoshikazu; Miyata, Tomohiko; Sekine, Yutaka; Kuno, Akiko; Iwamoto, Michiko; Ohnishi, Hirohide; Ido, Kenichi; Sugano, Kentaro

    2005-01-01

    AIM: To evaluate the clinical outcome of enteroscopy, using the double-balloon method, focusing on the involvement of neoplasms in strictures of the small intestine. METHODS: Enteroscopy, using the double-balloon method, was performed between December 1999 and December 2002 at Jichi Medical School Hospital, Japan and strictures of the small intestine were found in 17 out of 62 patients. These 17 consecutive patients were subjected to analysis. RESULTS: The double-balloon enteroscopy contributed to the diagnosis of small intestinal neoplasms found in 3 out of 17 patients by direct observation of the strictures as well as biopsy sampling. Surgical procedures were chosen for these three patients, while balloon dilation was chosen for the strictures in four patients diagnosed with inflammation without involvement of neoplasm. CONCLUSION: Double-balloon enteroscopy is a useful method for the diagnosis and treatment of strictures in the small bowel. PMID:15742422

  17. 42 CFR 495.340 - As-needed HIT PAPD update and as-needed HIT IAPD update requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.340 As... document or the HIT implementation advance planning document. (d) A change in implementation concept or a change to the scope of the project. (e) A change to the approved cost allocation methodology. ...

  18. 42 CFR 495.340 - As-needed HIT PAPD update and as-needed HIT IAPD update requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... HEALTH RECORD TECHNOLOGY INCENTIVE PROGRAM Requirements Specific to the Medicaid Program § 495.340 As... document or the HIT implementation advance planning document. (d) A change in implementation concept or a change to the scope of the project. (e) A change to the approved cost allocation methodology. ...

  19. Car Hits Boy on Bicycle

    ERIC Educational Resources Information Center

    Ruiz, Michael J.

    2005-01-01

    In this article we present the fascinating reconstruction of an accident where a car hit a boy riding his bicycle. The boy dramatically flew several metres through the air after the collision and was injured, but made a swift and complete recovery from the accident with no long-term after-effects. Students are challenged to determine the speed of…

  20. Fragment-based hit identification: thinking in 3D.

    PubMed

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

    2013-12-01

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

  1. 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.

  2. Improvements to the ion Doppler spectrometer diagnostic on the HIT-SI experiments.

    PubMed

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

    2018-03-01

    An ion Doppler spectrometer diagnostic system measuring impurity ion temperature and velocity on the HIT-SI and HIT-SI3 spheromak devices has been improved with higher spatiotemporal resolution and lower error than previously described devices. Hardware and software improvements to the established technique have resulted in a record of 6.9 μs temporal and ≤2.8 cm spatial resolution in the midplane of each device. These allow Ciii and Oii flow, displacement, and temperature profiles to be observed simultaneously. With 72 fused-silica fiber channels in two independent bundles, and an f/8.5 Czerny-Turner spectrometer coupled to a video camera, frame rates of up to ten times the imposed magnetic perturbation frequency of 14.5 kHz were achieved in HIT-SI, viewing the upper half of the midplane. In HIT-SI3, frame rates of up to eight times the perturbation frequency were achieved viewing both halves of the midplane. Biorthogonal decomposition is used as a novel filtering tool, reducing uncertainty in ion temperature from ≲13 to ≲5 eV (with an instrument temperature of 8-16 eV) and uncertainty in velocity from ≲2 to ≲1 km/s. Doppler shift and broadening are calculated via the Levenberg-Marquardt algorithm, after which the errors in velocity and temperature are uniquely specified. Axisymmetric temperature profiles on HIT-SI3 for Ciii peaked near the inboard current separatrix at ≈40 eV are observed. Axisymmetric plasma displacement profiles have been measured on HIT-SI3, peaking at ≈6 cm at the outboard separatrix. Both profiles agree with the upper half of the midplane observable by HIT-SI. With its complete midplane view, HIT-SI3 has unambiguously extracted axisymmetric, toroidal current dependent rotation of up to 3 km/s. Analysis of the temporal phase of the displacement uncovers a coherent structure, locked to the applied perturbation. Previously described diagnostic systems could not achieve such results.

  3. Improvements to the ion Doppler spectrometer diagnostic on the HIT-SI experiments

    NASA Astrophysics Data System (ADS)

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

    2018-03-01

    An ion Doppler spectrometer diagnostic system measuring impurity ion temperature and velocity on the HIT-SI and HIT-SI3 spheromak devices has been improved with higher spatiotemporal resolution and lower error than previously described devices. Hardware and software improvements to the established technique have resulted in a record of 6.9 μs temporal and ≤2.8 cm spatial resolution in the midplane of each device. These allow Ciii and Oii flow, displacement, and temperature profiles to be observed simultaneously. With 72 fused-silica fiber channels in two independent bundles, and an f/8.5 Czerny-Turner spectrometer coupled to a video camera, frame rates of up to ten times the imposed magnetic perturbation frequency of 14.5 kHz were achieved in HIT-SI, viewing the upper half of the midplane. In HIT-SI3, frame rates of up to eight times the perturbation frequency were achieved viewing both halves of the midplane. Biorthogonal decomposition is used as a novel filtering tool, reducing uncertainty in ion temperature from ≲13 to ≲5 eV (with an instrument temperature of 8-16 eV) and uncertainty in velocity from ≲2 to ≲1 km/s. Doppler shift and broadening are calculated via the Levenberg-Marquardt algorithm, after which the errors in velocity and temperature are uniquely specified. Axisymmetric temperature profiles on HIT-SI3 for Ciii peaked near the inboard current separatrix at ≈40 eV are observed. Axisymmetric plasma displacement profiles have been measured on HIT-SI3, peaking at ≈6 cm at the outboard separatrix. Both profiles agree with the upper half of the midplane observable by HIT-SI. With its complete midplane view, HIT-SI3 has unambiguously extracted axisymmetric, toroidal current dependent rotation of up to 3 km/s. Analysis of the temporal phase of the displacement uncovers a coherent structure, locked to the applied perturbation. Previously described diagnostic systems could not achieve such results.

  4. Improvements to the Ion Doppler Spectrometer Diagnostic on the HIT-SI Experiments

    DOE PAGES

    Hossack, Aaron; Chandra, Rian; Everson, Christopher; ...

    2018-03-09

    An Ion Doppler Spectrometer diagnostic system measuring impurity ion temperature and velocity on the HIT-SI and HIT-SI3 spheromak devices has been improved with higher spatiotemporal resolution and lower error than previously described devices. Hardware and software improvements to the established technique have resulted in a record 6.9 µs temporal and <=2.8 cm spatial resolution in the midplane of each device. These allow C III and O II flow, displacement, and temperature profiles to be simultaneously observed. With 72 fused-silica fiber channels in two independent bundles, and an f/8.5 Czerny-Turner spectrometer coupled to video camera, frame-rates of up to ten timesmore » the imposed magnetic perturbation frequency of 14.5 kHz were achieved in HIT-SI, viewing the upper 1/2 of the midplane. In HIT-SI3 frame-rates of up to eight times the perturbation frequency were achieved viewing both halves of the midplane. Biorthogonal Decomposition is used as a novel filtering tool, reducing uncertainty in ion temperature from <=13 to <=5 eV (with an instrument temperature of 8-16 eV), and uncertainty in velocity from <=2 to <=1 km/s. Doppler shift and broadening is calculated via the Levenberg-Marquart algorithm, after which errors in velocity and temperature are uniquely specified. Axisymmetric temperature profiles on HIT-SI3 for C III peaked near the inboard current separatrix at approximately 40 eV are observed. Axisymmetric plasma displacement profiles have been measured on HIT-SI3, peaking at approximately 6 cm at the outboard separatrix. Both profiles agree with the upper half of the midplane observable by HIT-SI. With its complete midplane view, HIT-SI3 has unambiguously extracted axisymmetric, toroidal current dependent rotation of up to 3 km/s. Analysis of the temporal phase of the displacement uncovers a coherent structure, locked to the applied perturbation. Previously described diagnostic systems could not achieve such results.« less

  5. Improvements to the Ion Doppler Spectrometer Diagnostic on the HIT-SI Experiments

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

    Hossack, Aaron; Chandra, Rian; Everson, Christopher

    An Ion Doppler Spectrometer diagnostic system measuring impurity ion temperature and velocity on the HIT-SI and HIT-SI3 spheromak devices has been improved with higher spatiotemporal resolution and lower error than previously described devices. Hardware and software improvements to the established technique have resulted in a record 6.9 µs temporal and <=2.8 cm spatial resolution in the midplane of each device. These allow C III and O II flow, displacement, and temperature profiles to be simultaneously observed. With 72 fused-silica fiber channels in two independent bundles, and an f/8.5 Czerny-Turner spectrometer coupled to video camera, frame-rates of up to ten timesmore » the imposed magnetic perturbation frequency of 14.5 kHz were achieved in HIT-SI, viewing the upper 1/2 of the midplane. In HIT-SI3 frame-rates of up to eight times the perturbation frequency were achieved viewing both halves of the midplane. Biorthogonal Decomposition is used as a novel filtering tool, reducing uncertainty in ion temperature from <=13 to <=5 eV (with an instrument temperature of 8-16 eV), and uncertainty in velocity from <=2 to <=1 km/s. Doppler shift and broadening is calculated via the Levenberg-Marquart algorithm, after which errors in velocity and temperature are uniquely specified. Axisymmetric temperature profiles on HIT-SI3 for C III peaked near the inboard current separatrix at approximately 40 eV are observed. Axisymmetric plasma displacement profiles have been measured on HIT-SI3, peaking at approximately 6 cm at the outboard separatrix. Both profiles agree with the upper half of the midplane observable by HIT-SI. With its complete midplane view, HIT-SI3 has unambiguously extracted axisymmetric, toroidal current dependent rotation of up to 3 km/s. Analysis of the temporal phase of the displacement uncovers a coherent structure, locked to the applied perturbation. Previously described diagnostic systems could not achieve such results.« less

  6. NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

    PubMed

    Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

    2017-01-01

    The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

    Høstgaard, Anna Marie; Bertelsen, Pernille

    2012-08-22

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

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2016-08-01

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

  10. 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

  11. 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.

  12. 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.

  13. Coupled double-distribution-function lattice Boltzmann method for the compressible Navier-Stokes equations.

    PubMed

    Li, Q; He, Y L; Wang, Y; Tao, W Q

    2007-11-01

    A coupled double-distribution-function lattice Boltzmann method is developed for the compressible Navier-Stokes equations. Different from existing thermal lattice Boltzmann methods, this method can recover the compressible Navier-Stokes equations with a flexible specific-heat ratio and Prandtl number. In the method, a density distribution function based on a multispeed lattice is used to recover the compressible continuity and momentum equations, while the compressible energy equation is recovered by an energy distribution function. The energy distribution function is then coupled to the density distribution function via the thermal equation of state. In order to obtain an adjustable specific-heat ratio, a constant related to the specific-heat ratio is introduced into the equilibrium energy distribution function. Two different coupled double-distribution-function lattice Boltzmann models are also proposed in the paper. Numerical simulations are performed for the Riemann problem, the double-Mach-reflection problem, and the Couette flow with a range of specific-heat ratios and Prandtl numbers. The numerical results are found to be in excellent agreement with analytical and/or other solutions.

  14. Progress on FIR interferometry and Thomson Scattering measurements on HIT-SI3

    NASA Astrophysics Data System (ADS)

    Everson, Christopher; Jarboe, Thomas; Morgan, Kyle

    2017-10-01

    Spatially resolved measurements of the electron temperature (Te) and density (ne) will be fundamental in assessing the degree to which HIT-SI3 demonstrates closed magnetic flux and energy confinement. Further, electron temperature measurements have not yet been made on an inductively-driven spheromak. Far infrared (FIR) interferometer and Thomson Scattering (TS) systems have been installed on the HIT-SI3 spheromak. The TS system currently implemented on HIT-SI3 was originally designed for other magnetic confinement experiments, and progress continues toward modifying and optimizing for HIT-SI3 plasmas. Initial results suggest that the electron temperature is of order 10 eV. Plans to modify the TS system to provide more sensitivity and accuracy at low temperatures are presented. The line-integrated ne is measured on one chord by the FIR interferometer, with densities near 5x1019 m-3. Four cylindrical volumes have been added to the HIT-SI3 apparatus to enhance passive pumping. It is hoped that this will allow for more control of the density during the 2 ms discharges. Density measurements from before and after the installation of the passive pumping volumes are presented for comparison.

  15. 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.

  16. Towards assessing corticospinal excitability bilaterally: Validation of a double-coil TMS method.

    PubMed

    Grandjean, Julien; Derosiere, Gerard; Vassiliadis, Pierre; Quemener, Louise; Wilde, Ysaline de; Duque, Julie

    2018-01-01

    For several decades, Transcranial magnetic stimulation (TMS) has been used to monitor corticospinal excitability (CSE) changes in various contexts. Habitually, single-coil TMS is applied over one primary motor cortex (M1), eliciting motor-evoked potentials (MEPs) in a contralateral limb muscle, usually a hand effector. However, in many situations, it would be useful to obtain MEPs in both hands simultaneously, to track CSE bilaterally. Such an approach requires stimulating both M1 concurrently while avoiding interference between the two descending stimuli. We examined MEPs obtained at rest using a double-coil TMS approach where the two M1 are stimulated with a 1ms inter-pulse interval (double-coil 1ms ). MEPs were acquired using double-coil 1ms (MEP double ) or single-coil (MEP single ) TMS, at five different intensities of stimulation (100, 115, 130, 145 or 160% of the resting motor threshold, rMT). Given the 1ms inter-pulse interval in double-coil 1ms trials, MEP double were either evoked by a 1st (MEP double-1 ) or a 2nd (MEP double-2 ) TMS pulse. All MEP TYPE (MEP TYPE =MEP single , MEP double-1 and MEP double-2 ) were equivalent, regardless of the hand within which they were elicited, the intensity of stimulation or the pulse order. This method allows one to observe state-related CSE changes for the two hands simultaneously on a trial-by-trial basis. These results infer the absence of any neural interactions between the two cortico-spinal volleys with double-coil 1ms TMS. Hence, this technique can be reliably used to assess CSE bilaterally, opening new research perspectives for scientists interested in physiological markers of activity in the motor output system. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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.

  18. 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...

  19. 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.

  20. B-Raf kinase inhibitors: hit enrichment through scaffold hopping.

    PubMed

    Gopalsamy, Ariamala; Shi, Mengxiao; Hu, Yongbo; Lee, Frederick; Feldberg, Larry; Frommer, Eileen; Kim, Steven; Collins, Karen; Wojciechowicz, Donald; Mallon, Robert

    2010-04-15

    In continuation of our efforts toward hit identification and optimization for a B-Raf kinase project, we have employed a scaffold hopping strategy. The original HTS hit scaffold pyrazolo[1,5-a]pyrimidine was replaced with different thienopyrimidine and thienopyridine scaffolds to append the optimal pharmacophore moieties in order to generate novel B-raf kinase inhibitors with desirable potency and properties. This strategy led to the identification of additional lead compound 11b which had good enzyme and cell potency, while maintaining selectivity over a number of kinases. Copyright 2010 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2002-01-01

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

  2. Use of HIT for adverse event reporting in nursing homes: barriers and facilitators.

    PubMed

    Wagner, Laura M; Castle, Nicholas G; Handler, Steven M

    2013-01-01

    Approximately 8 million adverse events occur annually in nursing homes (NHs). The focus of this research is to determine barriers and health information technology (HIT)-related facilitators to adverse event reporting among U.S. NHs. Surveys were returned by 399 nursing home administrators using a mailed survey approach. Respondents were asked to report on their adverse event reporting processes focusing on barriers and role of HIT facilitators. About 15% of NHs had computerized entry by the nurse on the unit and almost 18% used no computer technology to track, monitor, or maintain adverse event data. One-third of nursing directors conducted data analysis "by-hand." NHs without HIT were more likely to not be accredited (p = 0.04) and not part of a chain/corporation (p = 0.03). Two of the top three barriers focused on fears of reporting as a barrier. This study found numerous barriers and few HIT-related facilitators to assist with adverse event reporting. Improvements in facilitating adverse event reporting through the use of HIT approaches may be warranted. Copyright © 2013 Mosby, Inc. All rights reserved.

  3. MIDAS and HIT-6 French translation: reliability and correlation between tests.

    PubMed

    Magnoux, E; Freeman, M A; Zlotnik, G

    2008-01-01

    The aim was to evaluate the test-retest reliability of the French translation of the Migraine Disability Assessment (MIDAS) and Headache Impact Test (HIT)-6 questionnaires as applied to episodic and chronic headaches and to assess the correlation between these two questionnaires. The MIDAS and HIT-6 questionnaires, which assess the degree of migraine-related functional disability, are widely used in headache treatment clinics. The French translation has not been checked for test-retest reliability. MIDAS involves recall, over the previous 3 months, of the number of days with functional disability with regard to work and to home and social life. HIT-6 involves a more subjective and general assessment of headache-related disability over the previous 4 weeks. We expect that there may be greater impact recall bias for chronic headaches than for episodic headaches and considered it important to be able to determine if the reliability of these questionnaires is equally good for these two patient populations. Given that both questionnaires have the same objective, that of assessing headache impact, it was thought useful to determine if their results might show a correlation and if they could thus be used interchangeably. The study was approved by an external ethics committee. The subjects were patients who regularly visit the Clinique de la Migraine de Montréal, which specializes in the treatment of headaches. The MIDAS and HIT-6 questionnaires were completed by the patients during their regular visit. Twelve days later, the same questionnaires were mailed with a prepaid return envelope. Sixty-five patients were required in both the episodic and chronic headache groups, assuming an 80% questionnaire return rate. One hundred and eighty-five patients were enrolled, and 143 completed the study, 75 with episodic headaches and 68 with chronic headaches. The questionnaire return rate was 78.9%. On average, questionnaires were completed a second time 21 days after the first

  4. 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.

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

    PubMed

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

    2009-01-01

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

  6. Effective progression of nuclear magnetic resonance-detected fragment hits.

    PubMed

    Eaton, Hugh L; Wyss, Daniel F

    2011-01-01

    Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. COPD: A stepwise or a hit hard approach?

    PubMed

    Ferreira, A J; Reis, A; Marçal, N; Pinto, P; Bárbara, C

    2016-01-01

    Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

  8. 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.

  9. A method for generating double-ring-shaped vector beams

    NASA Astrophysics Data System (ADS)

    Huan, Chen; Xiao-Hui, Ling; Zhi-Hong, Chen; Qian-Guang, Li; Hao, Lv; Hua-Qing, Yu; Xu-Nong, Yi

    2016-07-01

    We propose a method for generating double-ring-shaped vector beams. A step phase introduced by a spatial light modulator (SLM) first makes the incident laser beam have a nodal cycle. This phase is dynamic in nature because it depends on the optical length. Then a Pancharatnam-Berry phase (PBP) optical element is used to manipulate the local polarization of the optical field by modulating the geometric phase. The experimental results show that this scheme can effectively create double-ring-shaped vector beams. It provides much greater flexibility to manipulate the phase and polarization by simultaneously modulating the dynamic and the geometric phases. Project supported by the National Natural Science Foundation of China (Grant No. 11547017), the Hubei Engineering University Research Foundation, China (Grant No. z2014001), and the Natural Science Foundation of Hubei Province, China (Grant No. 2014CFB578).

  10. Double Cross-Validation in Multiple Regression: A Method of Estimating the Stability of Results.

    ERIC Educational Resources Information Center

    Rowell, R. Kevin

    In multiple regression analysis, where resulting predictive equation effectiveness is subject to shrinkage, it is especially important to evaluate result replicability. Double cross-validation is an empirical method by which an estimate of invariance or stability can be obtained from research data. A procedure for double cross-validation is…

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

    PubMed

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

    2017-01-01

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

  12. The Missing Mantle Paradox, and the Statistical Argument for Repeated Hit and Run Collisions

    NASA Astrophysics Data System (ADS)

    Asphaug, E.; Reufer, A.

    2015-10-01

    Mercury's formation can be explained by a giant impact. However, a direct hit blasting off the mantle [1] leaves debris stranded in orbitabout the Sun,to be re-accumulated back onto Mercury. A hit and run collision [2] provides a cleaner solution, and in most cases,much lower levels of shock and potentially greater retention of volatiles. However, hit and run is usually followed by subsequent re-collision, and ultimate accretion; an embryo's survival after being a hit and run projectile is unlikely in any single instance. Most of the original planetary embryoshave been accreted by Earth and Venus; unaccreted planets are lucky. Here we show that the surviving terrestrial planet population is likely to have about as many hit and run survivors, as it is to have untouched survivors. That is, the differences between Mercury and Mars can be explained in a statistical manner as a consequence of accretionary attrition. We consider applications to asteroids, meteorites and exoplanets.

  13. 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.

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

    PubMed

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

    2016-08-08

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

  15. Mean centering of double divisor ratio spectra, a novel spectrophotometric method for analysis of ternary mixtures

    NASA Astrophysics Data System (ADS)

    Hassan, Said A.; Elzanfaly, Eman S.; Salem, Maissa Y.; El-Zeany, Badr A.

    2016-01-01

    A novel spectrophotometric method was developed for determination of ternary mixtures without previous separation, showing significant advantages over conventional methods. The new method is based on mean centering of double divisor ratio spectra. The mathematical explanation of the procedure is illustrated. The method was evaluated by determination of model ternary mixture and by the determination of Amlodipine (AML), Aliskiren (ALI) and Hydrochlorothiazide (HCT) in laboratory prepared mixtures and in a commercial pharmaceutical preparation. For proper presentation of the advantages and applicability of the new method, a comparative study was established between the new mean centering of double divisor ratio spectra (MCDD) and two similar methods used for analysis of ternary mixtures, namely mean centering (MC) and double divisor of ratio spectra-derivative spectrophotometry (DDRS-DS). The method was also compared with a reported one for analysis of the pharmaceutical preparation. The method was validated according to the ICH guidelines and accuracy, precision, repeatability and robustness were found to be within the acceptable limits.

  16. 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.

  17. 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

  18. Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

    PubMed

    Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

    2014-04-01

    Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

  19. Heparin-induced thrombocytopenia (HIT) in pediatric cardiac surgery: an emerging cause of morbidity and mortality.

    PubMed

    Alsoufi, Bahaaldin; Boshkov, Lynn K; Kirby, Aileen; Ibsen, Laura; Dower, Nancy; Shen, Irving; Ungerleider, Ross

    2004-01-01

    Unfractionated heparin (UFH) is immunogenic, and heparin-dependent antibodies can be demonstrated 5 to 10 days postoperatively in 25% to 50% of adult postcardiac surgery patients. In a minority of these cases (1% to 3% if UFH is continued longer than 1 week) these antibodies strongly activate platelets, causing thrombocytopenia and massive thrombin generation (HIT syndrome). HIT is an intensely procoagulant disorder, and in adult cardiac surgery patients carries both significant thrombotic morbidity (38% to 81%) and mortality (28%). Despite the ubiquitous use of UFH in pediatric intensive care units, and the repeated and sustained exposures to UFH in neonates and young children with congenital heart disease, HIT has been infrequently recognized and reported in this patient population. However, emerging experience at our institution and elsewhere suggests that HIT is significantly under-recognized in pediatric congenital heart disease patients, and may in fact have an incidence and associated thrombotic morbidity and mortality in this patient group comparable to that seen in adult cardiac surgery patients. This article will review HIT in pediatric patients with congenital heart disease and emphasize the special challenges posed in clinical recognition, laboratory diagnosis, and treatment of HIT in this patient group. We will also outline our experience with the off-label use of the direct thrombin inhibitor, argatroban, in pediatric patients with HIT.

  20. Novel method for hit-position reconstruction using voltage signals in plastic scintillators and its application to Positron Emission Tomography

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    Currently inorganic scintillator detectors are used in all commercial Time of Flight Positron Emission Tomograph (TOF-PET) devices. The J-PET collaboration investigates a possibility of construction of a PET scanner from plastic scintillators which would allow for single bed imaging of the whole human body. This paper describes a novel method of hit-position reconstruction based on sampled signals and an example of an application of the method for a single module with a 30 cm long plastic strip, read out on both ends by Hamamatsu R4998 photomultipliers. The sampling scheme to generate a vector with samples of a PET event waveform with respect to four user-defined amplitudes is introduced. The experimental setup provides irradiation of a chosen position in the plastic scintillator strip with an annihilation gamma quanta of energy 511 keV. The statistical test for a multivariate normal (MVN) distribution of measured vectors at a given position is developed, and it is shown that signals sampled at four thresholds in a voltage domain are approximately normally distributed variables. With the presented method of a vector analysis made out of waveform samples acquired with four thresholds, we obtain a spatial resolution of about 1 cm and a timing resolution of about 80 ps (σ).

  1. 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.

  2. 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.

  3. Evaluation of double photon coincidence Compton imaging method with GEANT4 simulation

    NASA Astrophysics Data System (ADS)

    Yoshihara, Yuri; Shimazoe, Kenji; Mizumachi, Yuki; Takahashi, Hiroyuki

    2017-11-01

    Compton imaging has been used for various applications including astronomical observations, radioactive waste management, and biomedical imaging. The positions of radioisotopes are determined in the intersections of multiple cone traces through a large number of events, which reduces signal to noise ratio (SNR) of the images. We have developed an advanced Compton imaging method to localize radioisotopes with high SNR by using information of the interactions of Compton scattering caused by two gamma rays at the same time, as the double photon coincidence Compton imaging method. The targeted radioisotopes of this imaging method are specific nuclides that emit several gamma rays at the same time such as 60Co, 134Cs, and 111In, etc. Since their locations are determined in the intersections of two Compton cones, the most of cone traces would disappear in the three-dimensional space, which enhances the SNR and angular resolution. In this paper, the comparison of the double photon coincidence Compton imaging method and the single photon Compton imaging method was conducted by using GEANT4 Monte Carlo simulation.

  4. 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.

  5. HIT-SI Injector Voltage Measurements Using Injector Langmuir Probes

    NASA Astrophysics Data System (ADS)

    Aboul Hosn, Rabih; Smith, Roger; Jarboe, Thomas

    2006-10-01

    A pair of Langmuir probe arrays have been designed and built to measure floating potentials of the plasma at the injector mouth of the HIT-SI device. The Helicity Injected Torus using Steady Inductive Helicity Injection (HIT-SI) [1,2] is a ``bow tie'' spheromak using an electrodeless formation and sustainment concept. HIT-SI is powered by two inductive helicity injectors operated in quadrature to maintain a constant helicity injection rate. The electric probes consist of an array of four floating potential Langmuir probes measuring the voltage distribution in each injector from the shell to midpoint of the injector mouth. The probe measurements combine to determine the part of the injector loop voltage driving the n = 0 spheromak equilibrium region. Preliminary data suggest the spheromak voltage is the loop voltage minus the nearly constant injector voltage of 150-180 volts. These probe data will be used to calculate the helicity decay time of the spheromak. [1] T. R. Jarboe. Steady inductive helicity injection and its application to a high-beta spheromak. Fusion Technology, 36(1):85--91, July 1999. [2] P.E.Sieck et al., ``Demonstration of Steady Inductive Helicity Injection'', Nuc. Fusion, in press (2006).

  6. Quantum algorithms for Gibbs sampling and hitting-time estimation

    DOE PAGES

    Chowdhury, Anirban Narayan; Somma, Rolando D.

    2017-02-01

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

  7. Service life of fence posts treated by double-diffusion methods

    Treesearch

    Donald C. Markstrom; Lee R. Gjovik

    1999-01-01

    Service-life tests indicate that Engelmann spruce, lodgepole pine, and Rocky Mountain Douglas-fir fence posts treated by double-diffusion methods performed excellently after field exposure of 30 years with no failures. The test site was located in the semiarid Central Plains near Nunn, Colorado. Although Engelmann spruce posts generally defy treatment by other treating...

  8. Systematic Convergence in Applying Variational Method to Double-Well Potential

    ERIC Educational Resources Information Center

    Mei, Wai-Ning

    2016-01-01

    In this work, we demonstrate the application of the variational method by computing the ground- and first-excited state energies of a double-well potential. We start with the proper choice of the trial wave functions using optimized parameters, and notice that accurate expectation values in excellent agreement with the numerical results can be…

  9. Visual Illusions and the Control of Ball Placement in Goal-Directed Hitting

    ERIC Educational Resources Information Center

    Caljouw, Simone R.; Van der Kamp, John; Savelsbergh, Geert J. P.

    2010-01-01

    When hitting, kicking, or throwing balls at targets, online control in the target area is impossible. We assumed this lack of late corrections in the target area would induce an effect of a single-winged Muller-Lyer illusion on ball placement. After extensive practice in hitting balls to different landing locations, participants (N = 9) had to hit…

  10. Staff Responses When Parents Hit Children in a Hospital Setting.

    PubMed

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

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

  11. 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.

  12. HIT implementation in critical access hospitals: extent of implementation and business strategies supporting IT use.

    PubMed

    Bahensky, James A; Ward, Marcia M; Nyarko, Kwame; Li, Pengxiang

    2011-08-01

    Small rural hospitals face considerable financial and personnel resource shortages which hinder their efforts to implement complex health information technology (HIT) systems. A survey on the use of HIT was completed by 85% of Iowa's 82 Critical Access Hospitals (CAH). Analyses indicate that low IT staffing in CAHs is a barrier to implementing HIT solutions. CAHs with fewer staff tend to employ alternative business strategies. There is a clear relationship between having IT staff at a CAH and the types of technologies used. Many CAHs report having difficulty expanding upon HIT functionalities due to the challenges of finding IT staff with healthcare expertise. Most CAHs are in the transition point of planning for or beginning implementation of complex clinical information systems. Strategies for addressing these challenges will need to evolve as the HIT investments by rural hospitals race to keep pace with the goals for the nation.

  13. Simulation optimizing of n-type HIT solar cells with AFORS-HET

    NASA Astrophysics Data System (ADS)

    Yao, Yao; Xiao, Shaoqing; Zhang, Xiumei; Gu, Xiaofeng

    2017-07-01

    This paper presents a study of heterojunction with intrinsic thin layer (HIT) solar cells based on n-type silicon substrates by a simulation software AFORS-HET. We have studied the influence of thickness, band gap of intrinsic layer and defect densities of every interface. Details in mechanisms are elaborated as well. The results show that the optimized efficiency reaches more than 23% which may give proper suggestions to practical preparation for HIT solar cells industry.

  14. 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.

  15. Acute hormonal responses before and after 2 weeks of HIT in well trained junior triathletes.

    PubMed

    Zinner, C; Wahl, P; Achtzehn, S; Reed, J L; Mester, J

    2014-04-01

    The aim was to compare the acute hormonal response to a single HIT session at the beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8±1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples were collected before and after the first and last HIT session. Significant increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first session +435.1%; last session +314.6%) concentrations were observed after both training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3 were not different between the first and last HIT sessions (P=1.00). Although no acute changes in testosterone were detected after the training sessions, testosterone concentrations were significantly higher at all time points (62.6-80.1%) during the last compared to first training session (P≤0.001). Findings from the present study reveal that 16 sessions of HIT led to significant increases in baseline concentrations of serum testosterone. This might indicate a heightened anabolic state even in junior triathletes. Based on the hormonal data, we conclude that at the end of this 2 week microcycle no familiarization effect was evident and that the training stimulus produced by HIT was still great enough to "stress" the athletes and induce positive training adaptations. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Hit rates and radiation doses to nuclei of bone lining cells from alpha-particle-emitting radionuclides

    NASA Technical Reports Server (NTRS)

    Polig, E.; Jee, W. S.; Kruglikov, I. L.

    1992-01-01

    Factors relating the local concentration of a bone-seeking alpha-particle emitter to the mean hit rate have been determined for nuclei of bone lining cells using a Monte Carlo procedure. Cell nuclei were approximated by oblate spheroids with dimensions and location taken from a previous histomorphometric study. The Monte Carlo simulation is applicable for planar and diffuse labels at plane or cylindrical bone surfaces. Additionally, the mean nuclear dose per hit, the dose mean per hit, the mean track segment length and its second moment, the percentage of stoppers, and the frequency distribution of the dose have been determined. Some basic features of the hit statistics for bone lining cells have been outlined, and the consequences of existing standards of radiation protection with regard to the hit frequency to cell nuclei are discussed.

  17. Detection of HIT antibody dependent platelet aggregation using novel surface imprinting approach.

    PubMed

    Hussain, Munawar; Northoff, Hinnak; Gehring, Frank K

    2016-01-15

    We present a fast, robust and straightforward spin force assisted surface imprinting approach for activated platelets and demonstrate that Heparin induced thrombocytopenia (HIT) platelet aggregation can be measured by this approach. A critical and challenging step in functional assays for HIT is platelet separation from the healthy donor's platelet-rich plasma (PRP). Our approach using surface imprinted polymer (MIP) for measurements on a quartz crystal microbalance with dissipation (QCM-D) enables monitoring of platelet aggregation directly in PRP thus eliminating the challenge of platelet separation. This is the first report of platelet imprinting. We also provide proof of principle that QCM-D technology can be applied for functional measurements of HIT antibodies. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. USER FRUSTRATION IN HIT INTERFACES: EXPLORING PAST HCI RESEARCH FOR A BETTER UNDERSTANDING OF CLINICIANS’ EXPERIENCES

    PubMed Central

    Opoku-Boateng, Gloria A.

    2015-01-01

    User frustration research has been one way of looking into clinicians’ experience with health information technology use and interaction. In order to understand how clinician frustration with Health Information Technology (HIT) use occurs, there is the need to explore Human-Computer Interaction (HCI) literature that addresses both frustration and HIT use. In the past three decades, HCI frustration research has increased and expanded. Researchers have done a lot of work to understand emotions, end-user frustration and affect. This paper uses a historical literature review approach to review the origins of emotion and frustration research and explore the research question; Does HCI research on frustration provide insights on clinicians’ frustration with HIT interfaces? From the literature review HCI research on emotion and frustration provides additional insights that can indeed help explain user frustration in HIT. Different approaches and HCI perspectives also help frame HIT user frustration research as well as inform HIT system design. The paper concludes with a suggested directions on how future design and research may take. PMID:26958238

  19. USER FRUSTRATION IN HIT INTERFACES: EXPLORING PAST HCI RESEARCH FOR A BETTER UNDERSTANDING OF CLINICIANS' EXPERIENCES.

    PubMed

    Opoku-Boateng, Gloria A

    2015-01-01

    User frustration research has been one way of looking into clinicians' experience with health information technology use and interaction. In order to understand how clinician frustration with Health Information Technology (HIT) use occurs, there is the need to explore Human-Computer Interaction (HCI) literature that addresses both frustration and HIT use. In the past three decades, HCI frustration research has increased and expanded. Researchers have done a lot of work to understand emotions, end-user frustration and affect. This paper uses a historical literature review approach to review the origins of emotion and frustration research and explore the research question; Does HCI research on frustration provide insights on clinicians' frustration with HIT interfaces? From the literature review HCI research on emotion and frustration provides additional insights that can indeed help explain user frustration in HIT. Different approaches and HCI perspectives also help frame HIT user frustration research as well as inform HIT system design. The paper concludes with a suggested directions on how future design and research may take.

  20. A double expansion method for the frequency response of finite-length beams with periodic parameters

    NASA Astrophysics Data System (ADS)

    Ying, Z. G.; Ni, Y. Q.

    2017-03-01

    A double expansion method for the frequency response of finite-length beams with periodic distribution parameters is proposed. The vibration response of the beam with spatial periodic parameters under harmonic excitations is studied. The frequency response of the periodic beam is the function of parametric period and then can be expressed by the series with the product of periodic and non-periodic functions. The procedure of the double expansion method includes the following two main steps: first, the frequency response function and periodic parameters are expanded by using identical periodic functions based on the extension of the Floquet-Bloch theorem, and the period-parametric differential equation for the frequency response is converted into a series of linear differential equations with constant coefficients; second, the solutions to the linear differential equations are expanded by using modal functions which satisfy the boundary conditions, and the linear differential equations are converted into algebraic equations according to the Galerkin method. The expansion coefficients are obtained by solving the algebraic equations and then the frequency response function is finally determined. The proposed double expansion method can uncouple the effects of the periodic expansion and modal expansion so that the expansion terms are determined respectively. The modal number considered in the second expansion can be reduced remarkably in comparison with the direct expansion method. The proposed double expansion method can be extended and applied to the other structures with periodic distribution parameters for dynamics analysis. Numerical results on the frequency response of the finite-length periodic beam with various parametric wave numbers and wave amplitude ratios are given to illustrate the effective application of the proposed method and the new frequency response characteristics, including the parameter-excited modal resonance, doubling-peak frequency response

  1. 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.

  2. 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.

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

    PubMed

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

    2016-01-01

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

  4. 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.

  5. On the accuracy of the Head Impact Telemetry (HIT) System used in football helmets.

    PubMed

    Jadischke, Ron; Viano, David C; Dau, Nathan; King, Albert I; McCarthy, Joe

    2013-09-03

    On-field measurement of head impacts has relied on the Head Impact Telemetry (HIT) System, which uses helmet mounted accelerometers to determine linear and angular head accelerations. HIT is used in youth and collegiate football to assess the frequency and severity of helmet impacts. This paper evaluates the accuracy of HIT for individual head impacts. Most HIT validations used a medium helmet on a Hybrid III head. However, the appropriate helmet is large based on the Hybrid III head circumference (58 cm) and manufacturer's fitting instructions. An instrumented skull cap was used to measure the pressure between the head of football players (n=63) and their helmet. The average pressure with a large helmet on the Hybrid III was comparable to the average pressure from helmets used by players. A medium helmet on the Hybrid III produced average pressures greater than the 99th percentile volunteer pressure level. Linear impactor tests were conducted using a large and medium helmet on the Hybrid III. Testing was conducted by two independent laboratories. HIT data were compared to data from the Hybrid III equipped with a 3-2-2-2 accelerometer array. The absolute and root mean square error (RMSE) for HIT were computed for each impact (n=90). Fifty-five percent (n=49) had an absolute error greater than 15% while the RMSE was 59.1% for peak linear acceleration. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2015-05-01

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

  7. Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging.

    PubMed

    Khurana, Aman; Chapelin, Fanny; Xu, Hongyan; Acevedo, Joseph R; Molinolo, Alfred; Nguyen, Quyen; Ahrens, Eric T

    2018-04-01

    To evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine-19 ( 19 F) MRI technology. Tumor cell lines single-hit/SCC4 or double-hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages. Longitudinal spin density-weighted 19 F MRI data enabled quantification of the macrophage burden in tumor and surrounding tissue. The average number of 19 F atoms within the tumors was twice as high in the Cal27 group compared with SCC4 (3.9 × 10 19 and 2.0 × 10 19 19 F/tumor, respectively; P = 0.0034) two days after contrast injection, signifying increased tumor-associated macrophages in double-hit tumors. The difference was still significant 10 days after injection. Histology stains correlated with in vivo results, exhibiting numerous perfluorocarbon-labeled macrophages in double-hit tumors and to a lesser extent in single-hit tumors. This study helps to establish 19 F MRI as a method for quantifying immune cells in the tumor microenvironment, allowing distinction between double and single-hit head and neck tumors. This technique would be extremely valuable in the clinic for pretreatment planning, prognostics, and post-treatment surveillance. Magn Reson Med 79:1972-1980, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  8. 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…

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

    PubMed

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

    2016-04-01

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

  10. 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

  11. Stochastic dynamics and the predictability of big hits in online videos.

    PubMed

    Miotto, José M; Kantz, Holger; Altmann, Eduardo G

    2017-03-01

    The competition for the attention of users is a central element of the Internet. Crucial issues are the origin and predictability of big hits, the few items that capture a big portion of the total attention. We address these issues analyzing 10^{6} time series of videos' views from YouTube. We find that the average gain of views is linearly proportional to the number of views a video already has, in agreement with usual rich-get-richer mechanisms and Gibrat's law, but this fails to explain the prevalence of big hits. The reason is that the fluctuations around the average views are themselves heavy tailed. Based on these empirical observations, we propose a stochastic differential equation with Lévy noise as a model of the dynamics of videos. We show how this model is substantially better in estimating the probability of an ordinary item becoming a big hit, which is considerably underestimated in the traditional proportional-growth models.

  12. Stochastic dynamics and the predictability of big hits in online videos

    NASA Astrophysics Data System (ADS)

    Miotto, José M.; Kantz, Holger; Altmann, Eduardo G.

    2017-03-01

    The competition for the attention of users is a central element of the Internet. Crucial issues are the origin and predictability of big hits, the few items that capture a big portion of the total attention. We address these issues analyzing 106 time series of videos' views from YouTube. We find that the average gain of views is linearly proportional to the number of views a video already has, in agreement with usual rich-get-richer mechanisms and Gibrat's law, but this fails to explain the prevalence of big hits. The reason is that the fluctuations around the average views are themselves heavy tailed. Based on these empirical observations, we propose a stochastic differential equation with Lévy noise as a model of the dynamics of videos. We show how this model is substantially better in estimating the probability of an ordinary item becoming a big hit, which is considerably underestimated in the traditional proportional-growth models.

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

    PubMed

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

    2017-11-01

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

  14. Structure-based analysis of catalysis and substrate definition in the HIT protein family.

    PubMed

    Lima, C D; Klein, M G; Hendrickson, W A

    1997-10-10

    The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of apo, substrate analog, pentacovalent transition-state analog, and product states of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.

  15. 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

  16. New Methods for Improved Double Circular-Arc Helical Gears

    NASA Technical Reports Server (NTRS)

    Litvin, Faydor L.; Lu, Jian

    1997-01-01

    The authors have extended the application of double circular-arc helical gears for internal gear drives. The geometry of the pinion and gear tooth surfaces has been determined. The influence of errors of alignment on the transmission errors and the shift of the bearing contact have been investigated. Application of a predesigned parabolic function for the reduction of transmission errors was proposed. Methods of grinding of the pinion-gear tooth surfaces by a disk-shaped tool and a grinding worm were proposed.

  17. A new hybrid double divisor ratio spectra method for the analysis of ternary mixtures

    NASA Astrophysics Data System (ADS)

    Youssef, Rasha M.; Maher, Hadir M.

    2008-10-01

    A new spectrophotometric method was developed for the simultaneous determination of ternary mixtures, without prior separation steps. This method is based on convolution of the double divisor ratio spectra, obtained by dividing the absorption spectrum of the ternary mixture by a standard spectrum of two of the three compounds in the mixture, using combined trigonometric Fourier functions. The magnitude of the Fourier function coefficients, at either maximum or minimum points, is related to the concentration of each drug in the mixture. The mathematical explanation of the procedure is illustrated. The method was applied for the assay of a model mixture consisting of isoniazid (ISN), rifampicin (RIF) and pyrazinamide (PYZ) in synthetic mixtures, commercial tablets and human urine samples. The developed method was compared with the double divisor ratio spectra derivative method (DDRD) and derivative ratio spectra-zero-crossing method (DRSZ). Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are included in the text.

  18. 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

  19. Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaled radon progenies.

    PubMed

    Balásházy, Imre; Farkas, Arpád; Madas, Balázs Gergely; Hofmann, Werner

    2009-06-01

    Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive bronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors at bronchial airway bifurcations, expressed as the ratio of local to average deposition densities, were determined to characterise the inhomogeneity of deposition and to elucidate their effect on resulting hit probabilities. The results obtained suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high, even at low average doses. Assuming a uniform distribution of activity there are practically no multiple hits and the hit probability as a function of dose exhibits a linear shape in the low dose range. The results are quite the opposite in the case of hot spots revealed by realistic deposition calculations, where practically all cells receive multiple hits and the hit probability as a function of dose is non-linear in the average dose range of 10-100 mGy.

  20. Monitoring Hitting Load in Tennis Using Inertial Sensors and Machine Learning.

    PubMed

    Whiteside, David; Cant, Olivia; Connolly, Molly; Reid, Machar

    2017-10-01

    Quantifying external workload is fundamental to training prescription in sport. In tennis, global positioning data are imprecise and fail to capture hitting loads. The current gold standard (manual notation) is time intensive and often not possible given players' heavy travel schedules. To develop an automated stroke-classification system to help quantify hitting load in tennis. Nineteen athletes wore an inertial measurement unit (IMU) on their wrist during 66 video-recorded training sessions. Video footage was manually notated such that known shot type (serve, rally forehand, slice forehand, forehand volley, rally backhand, slice backhand, backhand volley, smash, or false positive) was associated with the corresponding IMU data for 28,582 shots. Six types of machine-learning models were then constructed to classify true shot type from the IMU signals. Across 10-fold cross-validation, a cubic-kernel support vector machine classified binned shots (overhead, forehand, or backhand) with an accuracy of 97.4%. A second cubic-kernel support vector machine achieved 93.2% accuracy when classifying all 9 shot types. With a view to monitoring external load, the combination of miniature inertial sensors and machine learning offers a practical and automated method of quantifying shot counts and discriminating shot types in elite tennis players.

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

    NASA Astrophysics Data System (ADS)

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

    2007-11-01

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

  2. Estimated Radiation on Mars, Hits per Cell Nucleus

    NASA Technical Reports Server (NTRS)

    2002-01-01

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

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

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

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

  3. A joint sparse representation-based method for double-trial evoked potentials estimation.

    PubMed

    Yu, Nannan; Liu, Haikuan; Wang, Xiaoyan; Lu, Hanbing

    2013-12-01

    In this paper, we present a novel approach to solving an evoked potentials estimating problem. Generally, the evoked potentials in two consecutive trials obtained by repeated identical stimuli of the nerves are extremely similar. In order to trace evoked potentials, we propose a joint sparse representation-based double-trial evoked potentials estimation method, taking full advantage of this similarity. The estimation process is performed in three stages: first, according to the similarity of evoked potentials and the randomness of a spontaneous electroencephalogram, the two consecutive observations of evoked potentials are considered as superpositions of the common component and the unique components; second, making use of their characteristics, the two sparse dictionaries are constructed; and finally, we apply the joint sparse representation method in order to extract the common component of double-trial observations, instead of the evoked potential in each trial. A series of experiments carried out on simulated and human test responses confirmed the superior performance of our method. © 2013 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Violent aggression predicted by multiple pre-adult environmental hits.

    PubMed

    Mitjans, Marina; Seidel, Jan; Begemann, Martin; Bockhop, Fabian; Moya-Higueras, Jorge; Bansal, Vikas; Wesolowski, Janina; Seelbach, Anna; Ibáñez, Manuel Ignacio; Kovacevic, Fatka; Duvar, Oguzhan; Fañanás, Lourdes; Wolf, Hannah-Ulrike; Ortet, Generós; Zwanzger, Peter; Klein, Verena; Lange, Ina; Tänzer, Andreas; Dudeck, Manuela; Penke, Lars; van Elst, Ludger Tebartz; Bittner, Robert A; Schmidmeier, Richard; Freese, Roland; Müller-Isberner, Rüdiger; Wiltfang, Jens; Bliesener, Thomas; Bonn, Stefan; Poustka, Luise; Müller, Jürgen L; Arias, Bárbara; Ehrenreich, Hannelore

    2018-05-24

    Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.

  5. Digital double random amplitude image encryption method based on the symmetry property of the parametric discrete Fourier transform

    NASA Astrophysics Data System (ADS)

    Bekkouche, Toufik; Bouguezel, Saad

    2018-03-01

    We propose a real-to-real image encryption method. It is a double random amplitude encryption method based on the parametric discrete Fourier transform coupled with chaotic maps to perform the scrambling. The main idea behind this method is the introduction of a complex-to-real conversion by exploiting the inherent symmetry property of the transform in the case of real-valued sequences. This conversion allows the encrypted image to be real-valued instead of being a complex-valued image as in all existing double random phase encryption methods. The advantage is to store or transmit only one image instead of two images (real and imaginary parts). Computer simulation results and comparisons with the existing double random amplitude encryption methods are provided for peak signal-to-noise ratio, correlation coefficient, histogram analysis, and key sensitivity.

  6. 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.

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

    PubMed

    Nilsen, Vegard; Wyller, John

    2016-01-01

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

  8. STING versus HIT technique of endoscopic treatment for vesicoureteral reflux: A systematic review and meta-analysis.

    PubMed

    Yap, Te-Lu; Chen, Yong; Nah, Shireen A; Ong, Caroline Choo Phaik; Jacobsen, Anette; Low, Yee

    2016-12-01

    Our study aimed to compare the efficacy of two endoscopic techniques used for the correction of vesicoureteral reflux (VUR): subureteral transurethral injection (STING) and hydrodistension implantation technique (HIT). A systematic review was conducted using MEDLINE, Google scholar, and Cochrane databases from 1984 to 2015. Meta-analysis of the selected studies was performed to compare the extent of reflux resolution following both techniques. Six observational studies met the inclusion criteria for content. These comprised 632 ureters treated by STING and 895 ureters treated by HIT procedure. All included studies utilized dextranomer/hyaluronic acid (Deflux) as the bulking agent. The overall resolution of VUR was significantly higher in HIT (82.5%) compared to STING (71.4%) [pooled odds ratio (OR)=0.54; 95% confidence interval (CI) 0.42-0.69; P<0.0001; I 2 =8%]. A subgroup analysis showed that HIT had better outcomes than STING for both lower grade (I-III) [OR=0.43; 95% CI 0.23-0.82; P=0.01; I 2 =0%] and high-grade VUR (IV-V) [OR=0.43; 95% CI 0.20-0.91; P=0.03; I 2 =0%]. However, there was no statistical difference in the requirement of additional injections between STING and HIT groups. HIT is superior to STING technique for resolution of VUR after Deflux injection. However, more randomized trials with longer follow-up are necessary to demonstrate the benefit of HIT compared to STING procedure. Retrospective comparative studies - level III. Copyright © 2016. Published by Elsevier Inc.

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

    PubMed

    Gray, Rob

    2013-08-01

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

  10. 75 FR 6398 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Adoption/Certification Workgroup Meeting; Notice of Meeting AGENCY: Office... of Committee: HIT Policy Committee's Adoption/Certification Workgroup. General Function of the...

  11. 42 CFR 495.342 - Annual HIT IAPD requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (CONTINUED) STANDARDS AND CERTIFICATION STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY INCENTIVE... delays in meeting target dates in the approved HIT technology PAPD/IAPD and approved changes to it. (c) A... products. (d) A project activity schedule for the remainder of the project. (e) A project expenditure...

  12. 42 CFR 495.342 - Annual HIT IAPD requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) STANDARDS AND CERTIFICATION STANDARDS FOR THE ELECTRONIC HEALTH RECORD TECHNOLOGY INCENTIVE... delays in meeting target dates in the approved HIT technology PAPD/IAPD and approved changes to it. (c) A... products. (d) A project activity schedule for the remainder of the project. (e) A project expenditure...

  13. 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.

  14. On the Relationship between Molecular Hit Rates in High-Throughput Screening and Molecular Descriptors.

    PubMed

    Hansson, Mari; Pemberton, John; Engkvist, Ola; Feierberg, Isabella; Brive, Lars; Jarvis, Philip; Zander-Balderud, Linda; Chen, Hongming

    2014-06-01

    High-throughput screening (HTS) is widely used in the pharmaceutical industry to identify novel chemical starting points for drug discovery projects. The current study focuses on the relationship between molecular hit rate in recent in-house HTS and four common molecular descriptors: lipophilicity (ClogP), size (heavy atom count, HEV), fraction of sp(3)-hybridized carbons (Fsp3), and fraction of molecular framework (f(MF)). The molecular hit rate is defined as the fraction of times the molecule has been assigned as active in the HTS campaigns where it has been screened. Beta-binomial statistical models were built to model the molecular hit rate as a function of these descriptors. The advantage of the beta-binomial statistical models is that the correlation between the descriptors is taken into account. Higher degree polynomial terms of the descriptors were also added into the beta-binomial statistic model to improve the model quality. The relative influence of different molecular descriptors on molecular hit rate has been estimated, taking into account that the descriptors are correlated to each other through applying beta-binomial statistical modeling. The results show that ClogP has the largest influence on the molecular hit rate, followed by Fsp3 and HEV. f(MF) has only a minor influence besides its correlation with the other molecular descriptors. © 2013 Society for Laboratory Automation and Screening.

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

    PubMed

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

    2016-08-01

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

  16. Orbit determination performances using single- and double-differenced methods: SAC-C and KOMPSAT-2

    NASA Astrophysics Data System (ADS)

    Hwang, Yoola; Lee, Byoung-Sun; Kim, Haedong; Kim, Jaehoon

    2011-01-01

    In this paper, Global Positioning System-based (GPS) Orbit Determination (OD) for the KOrea-Multi-Purpose-SATellite (KOMPSAT)-2 using single- and double-differenced methods is studied. The requirement of KOMPSAT-2 orbit accuracy is to allow 1 m positioning error to generate 1-m panchromatic images. KOMPSAT-2 OD is computed using real on-board GPS data. However, the local time of the KOMPSAT-2 GPS receiver is not synchronized with the zero fractional seconds of the GPS time internally, and it continuously drifts according to the pseudorange epochs. In order to resolve this problem, an OD based on single-differenced GPS data from the KOMPSAT-2 uses the tagged time of the GPS receiver, and the accuracy of the OD result is assessed using the overlapping orbit solution between two adjacent days. The clock error of the GPS satellites in the KOMPSAT-2 single-differenced method is corrected using International GNSS Service (IGS) clock information at 5-min intervals. KOMPSAT-2 OD using both double- and single-differenced methods satisfies the requirement of 1-m accuracy in overlapping three dimensional orbit solutions. The results of the SAC-C OD compared with JPL’s POE (Precise Orbit Ephemeris) are also illustrated to demonstrate the implementation of the single- and double-differenced methods using a satellite that has independent orbit information available for validation.

  17. Subgroup conflicts? Try the psychodramatic "double triad method".

    PubMed

    Verhofstadt-Denève, Leni M F

    2012-04-01

    The present article suggests the application of a psychodramatic action method for tackling subgroup conflicts in which the direct dialogue between representatives of two opposing subgroups is prepared step by step through an indirect dialogue strategy within two triads, a strategy known as the Double Triad Method (DTM). In order to achieve integration in the group as a whole, it is important that all the members of both subgroups participate actively during the entire process. The first part of the article briefly explores the theoretical background, with a special emphasis on the Phenomenological-Dialectical Personality Model (Phe-Di PModel). In the second part, the DTM procedure is systematically described through its five action stages, each accompanied with 1) a spatial representation of the consecutive actions, 2) some illustrative statements for each stage, and 3) a theoretical interpretation of the dialectically involved personality dimensions in both protagonists. The article concludes with a discussion and suggestions for more extensive applications of the DTM method, including the question of its relationships to Agazarian's functional subgrouping, psychodrama, and sociodrama.

  18. 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

  19. Double-label immunofluorescence method for simultaneous detection of adenovirus and herpes simplex virus from the eye.

    PubMed

    Walpita, P; Darougar, S

    1989-07-01

    The development and application of a double-label immunofluorescence method which has the potential to screen for single or dual infections from any site, in single shell vial cultures, is described. In this study, a total of 1,141 ocular specimens were inoculated in shell vials, centrifuged at 15,000 X g for 1 h, incubated at 37 degrees C for 48 h, and fixed in methanol at room temperature for 15 min. The virus inclusions were detected by staining with a double-label indirect immunofluorescence procedure using mixtures of appropriate first antibodies, followed by fluorescein- and rhodamine-conjugated second antibodies. Each specimen was also inoculated in parallel by the conventional virus isolation method. The sensitivity and specificity of the double-label shell vial procedure were comparable to those with the conventional method, and the former test took only 48 h to complete. The test offers a rapid and simple single-vial procedure which allows for individual or simultaneous detection of multiple pathogens. It results in savings in time and cost over the conventional virus isolation method and other shell vial procedures.

  20. UN study reports Asian economic crisis has hit women's health.

    PubMed

    Ciment, J

    1999-02-13

    A UN Population Fund report, "Southeast Asian Populations in Crisis," revealed that the economic crisis in Southeastern Asia has had a disproportionately adverse effect on the health of women and girls. This has occurred because the industries employing women have been hardest hit and because governments have reduced spending on health care and female education. Thailand, for example, has reduced its AIDS budget by 25% even as increasing numbers of women are pushed into the sex trade by economic necessity. Reproductive health services for adolescents have been hit just as shrinking family budgets are forcing adolescents to drop out of school. The report's authors are calling for a more detailed look at the situation.

  1. 75 FR 33811 - Office of the National Coordinator for Health Information Technology; HIT Policy Committee's...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology; HIT Policy Committee's Privacy & Security Tiger Team Meeting; Notice of Meeting AGENCY: Office of... of Committee: HIT Policy Committee's Privacy & Security Tiger Team. General Function of the Committee...

  2. Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol.

    PubMed

    von Bueren, André O; Friedrich, Carsten; von Hoff, Katja; Kwiecien, Robert; Müller, Klaus; Pietsch, Torsten; Warmuth-Metz, Monika; Hau, Peter; Benesch, Martin; Kuehl, Joachim; Kortmann, Rolf D; Rutkowski, Stefan

    2015-11-01

    Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited. Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy. Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10). Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease. Copyright © 2015 Elsevier Ltd. All rights

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

    PubMed

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

    2018-05-10

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  6. 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.

  7. Key management of the double random-phase-encoding method using public-key encryption

    NASA Astrophysics Data System (ADS)

    Saini, Nirmala; Sinha, Aloka

    2010-03-01

    Public-key encryption has been used to encode the key of the encryption process. In the proposed technique, an input image has been encrypted by using the double random-phase-encoding method using extended fractional Fourier transform. The key of the encryption process have been encoded by using the Rivest-Shamir-Adelman (RSA) public-key encryption algorithm. The encoded key has then been transmitted to the receiver side along with the encrypted image. In the decryption process, first the encoded key has been decrypted using the secret key and then the encrypted image has been decrypted by using the retrieved key parameters. The proposed technique has advantage over double random-phase-encoding method because the problem associated with the transmission of the key has been eliminated by using public-key encryption. Computer simulation has been carried out to validate the proposed technique.

  8. Double sided circuit board and a method for its manufacture

    DOEpatents

    Lindenmeyer, Carl W.

    1989-01-01

    Conductance between the sides of a large double sided printed circuit board is provided using a method which eliminates the need for chemical immersion or photographic exposure of the entire large board. A plurality of through-holes are drilled or punched in a substratum according to the desired pattern, conductive laminae are made to adhere to both sides of the substratum covering the holes and the laminae are pressed together and permanently joined within the holes, providing conductive paths.

  9. Double sided circuit board and a method for its manufacture

    DOEpatents

    Lindenmeyer, Carl W.

    1989-07-04

    Conductance between the sides of a large double sided printed circuit board is provided using a method which eliminates the need for chemical immersion or photographic exposure of the entire large board. A plurality of through-holes are drilled or punched in a substratum according to the desired pattern, conductive laminae are made to adhere to both sides of the substratum covering the holes and the laminae are pressed together and permanently joined within the holes, providing conductive paths.

  10. Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

    PubMed Central

    Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

    2009-01-01

    High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

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

    PubMed Central

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

    2012-01-01

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

  12. "Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".

    PubMed

    Doidy, Joan; Li, Ying; Neymotin, Benjamin; Edwards, Molly B; Varala, Kranthi; Gresham, David; Coruzzi, Gloria M

    2016-02-03

    Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the

  13. Role of Health Information Technology (HIT) in disability determinations: when medical records become medical evidence.

    PubMed

    Tulu, Bengisu; Daniels, Susan; Feldman, Sue; Horan, Thomas A

    2008-11-06

    This exploratory study investigated the impact of incomplete medical evidence on the SSA disability determination process and the role of HIT as a solution. We collected qualitative data from nineteen expert-interviews. Findings indicate that HIT can lead to innovative solutions that can significantly improve the determination process.

  14. A FORTRAN Program for Computing Refractive Index Using the Double Variation Method.

    ERIC Educational Resources Information Center

    Blanchard, Frank N.

    1984-01-01

    Describes a computer program which calculates a best estimate of refractive index and dispersion from a large number of observations using the double variation method of measuring refractive index along with Sellmeier constants of the immersion oils. Program listing with examples will be provided on written request to the author. (Author/JM)

  15. 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.

  16. Double sided circuit board and a method for its manufacture

    DOEpatents

    Lindenmeyer, C.W.

    1988-04-14

    Conductance between the sides of a large double sided printed circuit board is provided using a method which eliminates the need for chemical immersion or photographic exposure of the entire large board. A plurality of through-holes are drilled or punched in a substratum according to the desired pattern, conductive laminae are made to adhere to both sides of the substratum covering the holes and the laminae are pressed together and permanently joined within the holes, providing conductive paths. 4 figs.

  17. Development of a Double Glass Mounting Method Using Formaldehyde Alcohol Azocarmine Lactophenol (FAAL) and its Evaluation for Permanent Mounting of Small Nematodes

    PubMed Central

    ZAHABIUN, Farzaneh; SADJJADI, Seyed Mahmoud; ESFANDIARI, Farideh

    2015-01-01

    Background: Permanent slide preparation of nematodes especially small ones is time consuming, difficult and they become scarious margins. Regarding this problem, a modified double glass mounting method was developed and compared with classic method. Methods: A total of 209 nematode samples from human and animal origin were fixed and stained with Formaldehyde Alcohol Azocarmine Lactophenol (FAAL) followed by double glass mounting and classic dehydration method using Canada balsam as their mounting media. The slides were evaluated in different dates and times, more than four years. Different photos were made with different magnification during the evaluation time. Results: The double glass mounting method was stable during this time and comparable with classic method. There were no changes in morphologic structures of nematodes using double glass mounting method with well-defined and clear differentiation between different organs of nematodes in this method. Conclusion: Using this method is cost effective and fast for mounting of small nematodes comparing to classic method. PMID:26811729

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

    PubMed

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

    2012-06-01

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

  19. Development of a Double Glass Mounting Method Using Formaldehyde Alcohol Azocarmine Lactophenol (FAAL) and its Evaluation for Permanent Mounting of Small Nematodes.

    PubMed

    Zahabiun, Farzaneh; Sadjjadi, Seyed Mahmoud; Esfandiari, Farideh

    2015-01-01

    Permanent slide preparation of nematodes especially small ones is time consuming, difficult and they become scarious margins. Regarding this problem, a modified double glass mounting method was developed and compared with classic method. A total of 209 nematode samples from human and animal origin were fixed and stained with Formaldehyde Alcohol Azocarmine Lactophenol (FAAL) followed by double glass mounting and classic dehydration method using Canada balsam as their mounting media. The slides were evaluated in different dates and times, more than four years. Different photos were made with different magnification during the evaluation time. The double glass mounting method was stable during this time and comparable with classic method. There were no changes in morphologic structures of nematodes using double glass mounting method with well-defined and clear differentiation between different organs of nematodes in this method. Using this method is cost effective and fast for mounting of small nematodes comparing to classic method.

  20. #MaybeHeDoesntHitYou: Social Media Underscore the Realities of Intimate Partner Violence.

    PubMed

    McCauley, Heather L; Bonomi, Amy E; Maas, Megan K; Bogen, Katherine W; O'Malley, Teagen L

    2018-03-22

    Public intimate partner violence (IPV) discourse emphasizes physical violence. In May 2016, the Twitter hashtag #MaybeHeDoesntHitYou generated a public conversation about abuse beyond physical IPV. Because of the often-disconnect between IPV research and what survivors struggle to name as abuse in their daily lives, we sought to understand how IPV discourse was unfolding as a result of the #MaybeHeDoesntHitYou hashtag. NCapture was used to collect publically available Twitter data containing the hashtag "#MaybeHeDoesntHitYou" from May 10, 2016 to May 17, 2016. Using the Duluth Power and Control Wheel (a range of tactics used by abusers to control and harm their partners) and the Women's Experience with Battering (WEB) framework (emotional and behavioral responses to being abused), we analyzed 1,229 original content tweets using qualitative content analysis. All dimensions of the Power and Control Wheel and five of six dimensions of the WEB framework were expressed via #MaybeHeDoesntHitYou; users did not express yearning for intimacy with their abusive partners. Users described one form of IPV not currently represented within the Power and Control Wheel-reproductive coercion (e.g., "#MaybeHeDoesntHitYou but he refuses to use condoms and forces you not to use contraception so you try to do it behind his back"). Two additional themes emerged; users challenged the gender pronoun of the hashtag, highlighting that abuse may happen with partners of all genders, and users provided social support for others (e.g., "#MaybeHeDoesntHitYou is real. Bruises and scars aren't the only measure of abuse! If this is you, help is there…"). Results from our study underscore the potential for social media platforms to be powerful agents for engaging public dialogue about the realities of IPV, as well as a space for seeking and providing social support about this critical women's health issue.

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

    NASA Astrophysics Data System (ADS)

    Ghate, Aditya; Ghaisas, Niranjan; Lele, Sanjiva

    2017-11-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  6. DEPDC5 takes a second hit in familial focal epilepsy.

    PubMed

    Anderson, Matthew P

    2018-04-30

    Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

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

    PubMed

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

    2014-12-01

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

  8. Analysis of impact noise induced by hitting of titanium head golf driver.

    PubMed

    Kim, Young Ho; Kim, Young Chul; Lee, Jun Hee; An, Yong-Hwi; Park, Kyung Tae; Kang, Kyung Min; Kang, Yeon June

    2014-11-01

    The hitting of titanium head golf driver against golf ball creates a short duration, high frequency impact noise. We analyzed the spectra of these impact noises and evaluated the auditory hazards from exposure to the noises. Noises made by 10 titanium head golf drivers with five maximum hits were collected, and the spectra of the pure impact sounds were studied using a noise analysis program. The noise was measured at 1.7 m (position A) and 3.4 m (position B) from the hitting point in front of the hitter and at 3.4 m (position C) behind the hitting point. Average time duration was measured and auditory risk units (ARUs) at position A were calculated using the Auditory Hazard Assessment Algorithm for Humans. The average peak levels at position A were 119.9 dBA at the sound pressure level (SPL) peak and 100.0 dBA at the overall octave level. The average peak levels (SPL and overall octave level) at position B were 111.6 and 96.5 dBA, respectively, and at position C were 111.5 and 96.7 dBA, respectively. The average time duration and ARUs measured at position A were 120.6 ms and 194.9 units, respectively. Although impact noises made by titanium head golf drivers showed relatively low ARUs, individuals enjoying golf frequently may be susceptible to hearing loss due to the repeated exposure of this intense impact noise with short duration and high frequency. Unprotected exposure to impact noises should be limited to prevent cochleovestibular disorders.

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

    PubMed

    Bollas, Audrey; Shahriyari, Leili

    2017-01-01

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

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

    PubMed Central

    Bollas, Audrey

    2017-01-01

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

  11. Promiscuous 2-aminothiazoles (PrATs): a frequent hitting scaffold.

    PubMed

    Devine, Shane M; Mulcair, Mark D; Debono, Cael O; Leung, Eleanor W W; Nissink, J Willem M; Lim, San Sui; Chandrashekaran, Indu R; Vazirani, Mansha; Mohanty, Biswaranjan; Simpson, Jamie S; Baell, Jonathan B; Scammells, Peter J; Norton, Raymond S; Scanlon, Martin J

    2015-02-12

    We have identified a class of molecules, known as 2-aminothiazoles (2-ATs), as frequent-hitting fragments in biophysical binding assays. This was exemplified by 4-phenylthiazol-2-amine being identified as a hit in 14/14 screens against a diverse range of protein targets, suggesting that this scaffold is a poor starting point for fragment-based drug discovery. This prompted us to analyze this scaffold in the context of an academic fragment library used for fragment-based drug discovery (FBDD) and two larger compound libraries used for high-throughput screening (HTS). This analysis revealed that such "promiscuous 2-aminothiazoles" (PrATs) behaved as frequent hitters under both FBDD and HTS settings, although the problem was more pronounced in the fragment-based studies. As 2-ATs are present in known drugs, they cannot necessarily be deemed undesirable, but the combination of their promiscuity and difficulties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds for fragment libraries.

  12. Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

    PubMed

    Evangelista, Wilfredo; Weir, Rebecca L; Ellingson, Sally R; Harris, Jason B; Kapoor, Karan; Smith, Jeremy C; Baudry, Jerome

    2016-10-15

    This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach

    PubMed Central

    Zhu, Qianqian; Shepherd, Lori; Lunetta, Kathryn L.; Yao, Song; Liu, Qian; Hu, Qiang; Haddad, Stephen A.; Sucheston-Campbell, Lara; Bensen, Jeannette T.; Bandera, Elisa V.; Rosenberg, Lynn; Liu, Song; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

    2016-01-01

    Leveraging population-distinct linkage equilibrium (LD) patterns, trans-ethnic follow-up of variants discovered from genome-wide association studies (GWAS) has proved to be useful in facilitating the identification of bona fide causal variants. We previously developed the preferential LD approach, a novel method that successfully identified causal variants driving the GWAS signals within European-descent populations even when the causal variants were only weakly linked with the GWAS-discovered variants. To evaluate the performance of our approach in a trans-ethnic setting, we applied it to follow up breast cancer GWAS hits identified mostly from populations of European ancestry in African Americans (AA). We evaluated 74 breast cancer GWAS variants in 8,315 AA women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Only 27% of them were associated with breast cancer risk at significance level α=0.05, suggesting race-specificity of the identified breast cancer risk loci. We followed up on those replicated GWAS hits in the AMBER consortium utilizing the preferential LD approach, to search for causal variants or better breast cancer markers from the 1000 Genomes variant catalog. Our approach identified stronger breast cancer markers for 80% of the GWAS hits with at least nominal breast cancer association, and in 81% of these cases, the marker identified was among the top 10 of all 1000 Genomes variants in the corresponding locus. The results support trans-ethnic application of the preferential LD approach in search for candidate causal variants, and may have implications for future genetic research of breast cancer in AA women. PMID:27825120

  14. On hitting children: a review of corporal punishment in the United States.

    PubMed

    Knox, Michele

    2010-01-01

    Research has clearly demonstrated associations between corporal punishment of children and maladaptive behavior patterns such as aggression and delinquency. Hitting children is an act of violence and a clear violation of children's human rights. In this article, the position of the United States on corporal punishment of children is discussed. Professional and international progress on ending corporal punishment is explained, and the relationship between corporal punishment and child abuse is discussed. An appeal is made for prevention efforts such as parent education and removal of social sanctions for hitting children that may hold significant promise for preventing child maltreatment.

  15. 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

  16. Quantitative assessment of hit detection and confirmation in single and duplicate high-throughput screenings.

    PubMed

    Wu, Zhijin; Liu, Dongmei; Sui, Yunxia

    2008-02-01

    The process of identifying active targets (hits) in high-throughput screening (HTS) usually involves 2 steps: first, removing or adjusting for systematic variation in the measurement process so that extreme values represent strong biological activity instead of systematic biases such as plate effect or edge effect and, second, choosing a meaningful cutoff on the calculated statistic to declare positive compounds. Both false-positive and false-negative errors are inevitable in this process. Common control or estimation of error rates is often based on an assumption of normal distribution of the noise. The error rates in hit detection, especially false-negative rates, are hard to verify because in most assays, only compounds selected in primary screening are followed up in confirmation experiments. In this article, the authors take advantage of a quantitative HTS experiment in which all compounds are tested 42 times over a wide range of 14 concentrations so true positives can be found through a dose-response curve. Using the activity status defined by dose curve, the authors analyzed the effect of various data-processing procedures on the sensitivity and specificity of hit detection, the control of error rate, and hit confirmation. A new summary score is proposed and demonstrated to perform well in hit detection and useful in confirmation rate estimation. In general, adjusting for positional effects is beneficial, but a robust test can prevent overadjustment. Error rates estimated based on normal assumption do not agree with actual error rates, for the tails of noise distribution deviate from normal distribution. However, false discovery rate based on empirically estimated null distribution is very close to observed false discovery proportion.

  17. Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening hit.

    PubMed

    Liu, Jiuyang; Zhang, Shuya; Liu, Mingqing; Liu, Yaqian; Nshogoza, Gilbert; Gao, Jia; Ma, Rongsheng; Yang, Yang; Wu, Jihui; Zhang, Jiahai; Li, Fudong; Ruan, Ke

    2018-04-12

    As a reader of di-methylated arginine on various proteins, such as histone, RNA polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3 implication in cancer cell proliferation and invasion, warheads to block the di-methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor domain through NMR fragment-based screening. These hits were further cross-validated by using competitive fluorescence polarization and isothermal titration calorimetry experiments. The crystal structure of the TDRD3 Tudor domain in complex with hit 1 reveals a distinct binding mode from the nature substrate. Hit 1 protrudes into the aromatic cage of the TDRD3 Tudor domain, where the aromatic residues are tilted to accommodate a sandwich-like π-π interaction. The side chain of the conserved residue N596 swings away 3.1 Å to form a direct hydrogen bond with hit 1. Moreover, this compound shows a decreased affinity against the single Tudor domain of survival motor neuron protein, but no detectable binding to neither the tandem Tudor domain of TP53-binding protein 1 nor the extended Tudor domain of staphylococcal nuclease domain-containing protein 1. Our work depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for the subsequent structure-guided discovery of selective inhibitors targeting Tudor domains. Structural data are available in the PDB under the accession number 5YJ8. © 2018 Federation of European Biochemical Societies.

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

    PubMed Central

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

    2014-01-01

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

  19. The Effect of Three Methods of Supporting the Double Bass on Muscle Tension.

    ERIC Educational Resources Information Center

    Dennis, Allan

    1984-01-01

    Using different methods of holding the double bass, college students performed Beethoven's Symphony No. 9. Audio recordings of performance were rated. Muscle tension readings from the left arm, right arm, upper back, and lower back were taken, using electromyography. Results suggest nonsignificant differences in both performance quality and muscle…

  20. Microdosimetry and Katz's track structure theory. I. One-hit detectors

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

    Zaider, M.

    1990-10-01

    A microdosimetric treatment of the response of one-hit detectors to radiation is formulated and compared with the model proposed by R. Katz, S. C. Sharma, and M. Homayoonfar within the framework of their track-structure theory. It is shown that radial dose distributions (on which the track structure theory is based) are generally poor substitutes for the exact microdosimetric distributions except when (a) the target is much larger than the radial extent of the track or (b) the effective specific energy in the target (alpha z) is negligibly small. Since neither one of these conditions is generally satisfied, it is suggestedmore » that a meaningful search for one-hit detectors be based on a microdosimetric description of the stochastics of energy deposition. An analysis of the phi x-174 bacteriophage inactivation data is presented.« less

  1. Design of the Helicity Injected Torus with Steady Inductive Helicity Injection (HIT-SI)

    NASA Astrophysics Data System (ADS)

    Sieck, P. E.; Gu, P.; Hamp, W. T.; Izzo, V. A.; McCollam, K. J.; Jarboe, T. R.; Nelson, B. A.; Redd, A. J.; Rogers, J. A.; Shumlak, U.

    2000-10-01

    Steady Inductive Helicity Injection (SIHI) is an inductive current drive 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), p. 85, 1999. SIHI directly produces a rotating magnetic field structure, and the current profile is nearly time independent in the frame of the rotating field. The Helicity Injected Torus with SIHI (HIT-SI) is a ``bow tie'' spheromak designed to implement SIHI so that the current profile in the rotating frame is optimized. SIHI is accomplished using two inductive helicity injectors that operate 90^o out of phase with each other. Each helicity injector is a 180^o segment of a ZT-P size (a ≈ 8cm, R ≈ 32cm) RFP. The presence of a spheromak equilibrium will be readily apparent on several diagnostics, including the surface magnetic probes. The design of HIT-SI is presented, including the manufacturing techniques and metallurgical processes being used in the construction of the one-meter diameter close-fitting flux conserver. Several small prototype tests have been performed to prove the vacuum seal and electrical insulation capabilities of the design, and a finite element stress analysis of the flux conserver will be presented.

  2. Profile of Instrumentation Laboratory's HemosIL® AcuStar HIT-Ab(PF4-H) assay for diagnosis of heparin-induced thrombocytopenia.

    PubMed

    Nagler, Michael; Cuker, Adam

    2017-05-01

    Immunoassays play an essential role in the diagnosis of heparin-induced thrombocytopenia (HIT). The objective of this article is to review HemosIL® AcuStar HIT-Ab(PF4-H) (Instrumentation Laboratory, Bedford, MA, USA), a new chemiluminescent immunoassay for HIT. Areas covered: The authors searched the published literature for evaluation studies of HemosIL® AcuStar HIT-Ab(PF4-H) and sought information from the manufacturer. In this paper, the authors discuss the analytical principle and technical aspects of the assay; describe its diagnostic performance in validation studies; report on its reproducibility, cost-effectiveness, and regulatory status; and discuss the implications of the assay on clinical practice and means of integrating it in diagnostic pathways. HemosIL® AcuStar HIT-Ab(PF4-H) is compared with other rapid assays and widely used enzyme-linked immunoassays for the diagnosis of HIT. Expert commentary: HemosIL® AcuStar HIT-Ab(PF4-H) is automatable, can be performed 24 h per day, offers a rapid turnaround time, and appears to have favorable diagnostic accuracy, particularly at thresholds above that listed in the label. These advantages could lead to improved patient outcomes through rapid provision of results at the point of care, enhancing the accuracy of initial diagnosis.

  3. Regularization of the double period method for experimental data processing

    NASA Astrophysics Data System (ADS)

    Belov, A. A.; Kalitkin, N. N.

    2017-11-01

    In physical and technical applications, an important task is to process experimental curves measured with large errors. Such problems are solved by applying regularization methods, in which success depends on the mathematician's intuition. We propose an approximation based on the double period method developed for smooth nonperiodic functions. Tikhonov's stabilizer with a squared second derivative is used for regularization. As a result, the spurious oscillations are suppressed and the shape of an experimental curve is accurately represented. This approach offers a universal strategy for solving a broad class of problems. The method is illustrated by approximating cross sections of nuclear reactions important for controlled thermonuclear fusion. Tables recommended as reference data are obtained. These results are used to calculate the reaction rates, which are approximated in a way convenient for gasdynamic codes. These approximations are superior to previously known formulas in the covered temperature range and accuracy.

  4. The Chelyabinsk Meteorite Hits an Anomalous Zone in the Urals

    NASA Astrophysics Data System (ADS)

    Kochemasov, G. G.

    2013-09-01

    The Chelyabinsk meteorite is "strange" because it hits an area in the Urals where anomalous events are observed: shining skies, light balls, UFOs, electrphonic bolids. The area tectonically occurs at the intersection of two fold belts: Urals and Timan.

  5. 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.

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

    PubMed

    Murray, Elizabeth; May, Carl; Mair, Frances

    2010-10-18

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed

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

    2013-04-01

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

  9. Linear energy transfer in water phantom within SHIELD-HIT transport code

    NASA Astrophysics Data System (ADS)

    Ergun, A.; Sobolevsky, N.; Botvina, A. S.; Buyukcizmeci, N.; Latysheva, L.; Ogul, R.

    2017-02-01

    The effect of irradiation in tissue is important in hadron therapy for the dose measurement and treatment planning. This biological effect is defined by an equivalent dose H which depends on the Linear Energy Transfer (LET). Usually, H can be expressed in terms of the absorbed dose D and the quality factor K of the radiation under consideration. In literature, various types of transport codes have been used for modeling and simulation of the interaction of the beams of protons and heavier ions with tissue-equivalent materials. In this presentation we used SHIELD-HIT code to simulate decomposition of the absorbed dose by LET in water for 16O beams. A more detailed description of capabilities of the SHIELD-HIT code can be found in the literature.

  10. Organizations disseminating health messages: the roles of organizational identification and HITs.

    PubMed

    Stephens, Keri K; Goins, Elizabeth S; Dailey, Stephanie L

    2014-01-01

    Research into the dissemination of health information now includes more focus on how various organizations (e.g., beauty shops, schools, workplaces, and churches) and health information technologies (HITs) reach and affect audiences. One relational feature of organizations is identification--the feeling of belongingness. Our study explores how it influences audiences, especially in combination with HITs such as e-mail, websites, and social media. We use social identity theory to predict how organizational identification and social media might function in health communication. Using a 3 × 2 experimental design, we find that people's identification with a message source mediates the effect of social media on outcomes. These findings improve our understanding of when organizations might be most helpful for disseminating health information.

  11. Healthcare Information Technology (HIT) in an Anti-Access (A2) and Area Denial (AD) Environment

    DTIC Science & Technology

    2014-03-01

    OFFICE OF THE COMMAND SURGEON, AIR COMBAT COMMAND FELLOWSHIP PAPER HEALTHCARE INFORMATION TECHNOLOGY (HIT) IN AN ANTI-ACCESS (A2) AND AREA...expeditionary responses. A light and lean medical response that utilizes emerging technology , specifically HIT, enhances the AFMS’ readiness posture and...expeditionary medical capability. The new USAF reality in an A2/AD environment is impeded access, very little if any technological dominance

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

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

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

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

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

    PubMed

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

    2012-09-01

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

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

    DOE PAGES

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

    2017-01-31

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

  15. A Double-difference Earthquake location algorithm: Method and application to the Northern Hayward Fault, California

    USGS Publications Warehouse

    Waldhauser, F.; Ellsworth, W.L.

    2000-01-01

    We have developed an efficient method to determine high-resolution hypocenter locations over large distances. The location method incorporates ordinary absolute travel-time measurements and/or cross-correlation P-and S-wave differential travel-time measurements. Residuals between observed and theoretical travel-time differences (or double-differences) are minimized for pairs of earthquakes at each station while linking together all observed event-station pairs. A least-squares solution is found by iteratively adjusting the vector difference between hypocentral pairs. The double-difference algorithm minimizes errors due to unmodeled velocity structure without the use of station corrections. Because catalog and cross-correlation data are combined into one system of equations, interevent distances within multiplets are determined to the accuracy of the cross-correlation data, while the relative locations between multiplets and uncorrelated events are simultaneously determined to the accuracy of the absolute travel-time data. Statistical resampling methods are used to estimate data accuracy and location errors. Uncertainties in double-difference locations are improved by more than an order of magnitude compared to catalog locations. The algorithm is tested, and its performance is demonstrated on two clusters of earthquakes located on the northern Hayward fault, California. There it colapses the diffuse catalog locations into sharp images of seismicity and reveals horizontal lineations of hypocenter that define the narrow regions on the fault where stress is released by brittle failure.

  16. Transfer, loss and physical processing of water in hit-and-run collisions of planetary embryos

    NASA Astrophysics Data System (ADS)

    Burger, C.; Maindl, T. I.; Schäfer, C. M.

    2018-01-01

    Collisions between large, similar-sized bodies are believed to shape the final characteristics and composition of terrestrial planets. Their inventories of volatiles such as water are either delivered or at least significantly modified by such events. Besides the transition from accretion to erosion with increasing impact velocity, similar-sized collisions can also result in hit-and-run outcomes for sufficiently oblique impact angles and large enough projectile-to-target mass ratios. We study volatile transfer and loss focusing on hit-and-run encounters by means of smooth particle hydrodynamics simulations, including all main parameters: impact velocity, impact angle, mass ratio and also the total colliding mass. We find a broad range of overall water losses, up to 75% in the most energetic hit-and-run events, and confirm the much more severe consequences for the smaller body also for stripping of volatile layers. Transfer of water between projectile and target inventories is found to be mostly rather inefficient, and final water contents are dominated by pre-collision inventories reduced by impact losses, for similar pre-collision water mass fractions. Comparison with our numerical results shows that current collision outcome models are not accurate enough to reliably predict these composition changes in hit-and-run events. To also account for non-mechanical losses, we estimate the amount of collisionally vaporized water over a broad range of masses and find that these contributions are particularly important in collisions of ˜ Mars-sized bodies, with sufficiently high impact energies, but still relatively low gravity. Our results clearly indicate that the cumulative effect of several (hit-and-run) collisions can efficiently strip protoplanets of their volatile layers, especially the smaller body, as it might be common, e.g., for Earth-mass planets in systems with Super-Earths. An accurate model for stripping of volatiles that can be included in future planet

  17. [An ADAA model and its analysis method for agronomic traits based on the double-cross mating design].

    PubMed

    Xu, Z C; Zhu, J

    2000-01-01

    According to the double-cross mating design and using principles of Cockerham's general genetic model, a genetic model with additive, dominance and epistatic effects (ADAA model) was proposed for the analysis of agronomic traits. Components of genetic effects were derived for different generations. Monte Carlo simulation was conducted for analyzing the ADAA model and its reduced AD model by using different generations. It was indicated that genetic variance components could be estimated without bias by MINQUE(1) method and genetic effects could be predicted effectively by AUP method; at least three generations (including parent, F1 of single cross and F1 of double-cross) were necessary for analyzing the ADAA model and only two generations (including parent and F1 of double-cross) were enough for the reduced AD model. When epistatic effects were taken into account, a new approach for predicting the heterosis of agronomic traits of double-crosses was given on the basis of unbiased prediction of genotypic merits of parents and their crosses. In addition, genotype x environment interaction effects and interaction heterosis due to G x E interaction were discussed briefly.

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

    PubMed

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

    2018-05-09

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

  19. 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.

  20. Cosmic Ray Hits in the Central Nervous System at Solar Maximum

    NASA Technical Reports Server (NTRS)

    Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Kim, M.-H. Y.

    1997-01-01

    It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of some interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus (100 mm2 area) are that the probability of any given cell nucleus being hit decreases from 10 percent at solar minimum to 6 percent at solar maximum for particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. We conclude that this modest decrease in hit frequency (less than a factor of two) is not a compelling reason to avoid solar minimum for a manned mission to Mars.

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

    PubMed

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

    2018-03-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-12-07

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

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

    PubMed

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

    2018-12-01

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

  5. Compact Torus Injection Experiments on the H.I.T. teststand and the JFT-2M tokamak

    NASA Astrophysics Data System (ADS)

    Fukumoto, Naoyuki; Fujiwara, Makoto; Kuramoto, Keiji; Ageishi, Masaya; Nagata, Masayoshi; Uyama, Tadao; Ogawa, Hiroaki; Kasai, Satoshi; Hasegawa, Kouichi; Shibata, Takatoshi

    1997-11-01

    A spheromak-type compact torus (CT) acceleration and injection experiment has been carried out using the Himeji Institute of Technology Compact Torus Injector (HIT-CTI). We investigate the possibility of refueling, density control, current drive, and edge electric field control of tokamak plasmas by means of CT injection. The HIT-CTI produces a CT with a speed of 200 km/s and a density of 1× 10^21m-3. We have constructed new electrodes and power supplies, and will install the HIT-CTI on the JFT-2M tokamak at JAERI in Autumn 1997. The outer electrode serves as a common ground for both the formation bank (144μF, 20kV) and the acceleration bank (92.4μF, 40kV). If the external toroidal field of the tokamak is applied across the CT acceleration region, the CT kinetic energy might decrease during penetration into the field lines joining the inner and outer electrode. This could result in the CT not being able to reach the core of the tokamak plasma. Determining the optimum position of the inner electrode is one of the near term goals of this research. We will present magnetic probe, He-Ne interferometer and fast framing camera data from experiments at H.I.T., where a CT was accelerated into a transverse field. We will also present initial results from the operation of the HIT-CTI on the JFT-2M tokamak.

  6. Combined measurement system for double shield tunnel boring machine guidance based on optical and visual methods.

    PubMed

    Lin, Jiarui; Gao, Kai; Gao, Yang; Wang, Zheng

    2017-10-01

    In order to detect the position of the cutting shield at the head of a double shield tunnel boring machine (TBM) during the excavation, this paper develops a combined measurement system which is mainly composed of several optical feature points, a monocular vision sensor, a laser target sensor, and a total station. The different elements of the combined system are mounted on the TBM in suitable sequence, and the position of the cutting shield in the reference total station frame is determined by coordinate transformations. Subsequently, the structure of the feature points and matching technique for them are expounded, the position measurement method based on monocular vision is presented, and the calibration methods for the unknown relationships among different parts of the system are proposed. Finally, a set of experimental platforms to simulate the double shield TBM is established, and accuracy verification experiments are conducted. Experimental results show that the mean deviation of the system is 6.8 mm, which satisfies the requirements of double shield TBM guidance.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2013-01-01

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

  9. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    PubMed

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is

  10. Advance in multi-hit detection and quantization in atom probe tomography.

    PubMed

    Da Costa, G; Wang, H; Duguay, S; Bostel, A; Blavette, D; Deconihout, B

    2012-12-01

    The preferential retention of high evaporation field chemical species at the sample surface in atom-probe tomography (e.g., boron in silicon or in metallic alloys) leads to correlated field evaporation and pronounced pile-up effects on the detector. The latter severely affects the reliability of concentration measurements of current 3D atom probes leading to an under-estimation of the concentrations of the high-field species. The multi-hit capabilities of the position-sensitive time-resolved detector is shown to play a key role. An innovative method based on Fourier space signal processing of signals supplied by an advance delay-line position-sensitive detector is shown to drastically improve the time resolving power of the detector and consequently its capability to detect multiple events. Results show that up to 30 ions on the same evaporation pulse can be detected and properly positioned. The major impact of this new method on the quantization of chemical composition in materials, particularly in highly-doped Si(B) samples is highlighted.

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

    PubMed

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

    2017-05-01

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

  12. Upscaling of Hydraulic Conductivity using the Double Constraint Method

    NASA Astrophysics Data System (ADS)

    El-Rawy, Mustafa; Zijl, Wouter; Batelaan, Okke

    2013-04-01

    The mathematics and modeling of flow through porous media is playing an increasingly important role for the groundwater supply, subsurface contaminant remediation and petroleum reservoir engineering. In hydrogeology hydraulic conductivity data are often collected at a scale that is smaller than the grid block dimensions of a groundwater model (e.g. MODFLOW). For instance, hydraulic conductivities determined from the field using slug and packer tests are measured in the order of centimeters to meters, whereas numerical groundwater models require conductivities representative of tens to hundreds of meters of grid cell length. Therefore, there is a need for upscaling to decrease the number of grid blocks in a groundwater flow model. Moreover, models with relatively few grid blocks are simpler to apply, especially when the model has to run many times, as is the case when it is used to assimilate time-dependent data. Since the 1960s different methods have been used to transform a detailed description of the spatial variability of hydraulic conductivity to a coarser description. In this work we will investigate a relatively simple, but instructive approach: the Double Constraint Method (DCM) to identify the coarse-scale conductivities to decrease the number of grid blocks. Its main advantages are robustness and easy implementation, enabling to base computations on any standard flow code with some post processing added. The inversion step of the double constraint method is based on a first forward run with all known fluxes on the boundary and in the wells, followed by a second forward run based on the heads measured on the phreatic surface (i.e. measured in shallow observation wells) and in deeper observation wells. Upscaling, in turn is inverse modeling (DCM) to determine conductivities in coarse-scale grid blocks from conductivities in fine-scale grid blocks. In such a way that the head and flux boundary conditions applied to the fine-scale model are also honored at the

  13. Prediction of Potential Hit Song and Musical Genre Using Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Monterola, Christopher; Abundo, Cheryl; Tugaff, Jeric; Venturina, Lorcel Ericka

    Accurately quantifying the goodness of music based on the seemingly subjective taste of the public is a multi-million industry. Recording companies can make sound decisions on which songs or artists to prioritize if accurate forecasting is achieved. We extract 56 single-valued musical features (e.g. pitch and tempo) from 380 Original Pilipino Music (OPM) songs (190 are hit songs) released from 2004 to 2006. Based on an effect size criterion which measures a variable's discriminating power, the 20 highest ranked features are fed to a classifier tasked to predict hit songs. We show that regardless of musical genre, a trained feed-forward neural network (NN) can predict potential hit songs with an average accuracy of ΦNN = 81%. The accuracy is about +20% higher than those of standard classifiers such as linear discriminant analysis (LDA, ΦLDA = 61%) and classification and regression trees (CART, ΦCART = 57%). Both LDA and CART are above the proportional chance criterion (PCC, ΦPCC = 50%) but are slightly below the suggested acceptable classifier requirement of 1.25*ΦPCC = 63%. Utilizing a similar procedure, we demonstrate that different genres (ballad, alternative rock or rock) of OPM songs can be automatically classified with near perfect accuracy using LDA or NN but only around 77% using CART.

  14. Functional and Structural Insights of the Zinc-Finger HIT protein family members Involved in Box C/D snoRNP Biogenesis.

    PubMed

    Bragantini, Benoit; Tiotiu, Decebal; Rothé, Benjamin; Saliou, Jean-Michel; Marty, Hélène; Cianférani, Sarah; Charpentier, Bruno; Quinternet, Marc; Manival, Xavier

    2016-06-05

    Zf–HIT family members share the zf–HIT domain (ZHD), which is characterized by a fold in “treble-clef” through interleaved CCCC and CCHC ZnF motifs that both bind a zinc atom. Six proteins containing ZHD are present in human and three in yeast proteome, all belonging to multimodular RNA/protein complexes involved in gene regulation, chromatin remodeling, and snoRNP assembly. An interesting characteristic of the cellular complexes that ensure these functions is the presence of the RuvBL1/2/Rvb1/2 ATPases closely linked with zf–HIT proteins. Human ZNHIT6/BCD1 and its counterpart in yeast Bcd1p were previously characterized as assembly factors of the box C/D snoRNPs. Our data reveal that the ZHD of Bcd1p is necessary but not sufficient for yeast growth and that the motif has no direct RNA-binding capacity but helps Bcd1p maintain the box C/D snoRNAs level in steady state. However, we demonstrated that Bcd1p interacts nonspecifically with RNAs depending on their length. Interestingly, the ZHD of Bcd1p is functionally interchangeable with that of Hit1p, another box C/D snoRNP assembly factor belonging to the zf–HIT family. This prompted us to use NMR to solve the 3D structures of ZHD from yeast Bcd1p and Hit1p to highlight the structural similarity in the zf–HIT family. We identified structural features associated with the requirement of Hit1p and Bcd1p ZHD for cell growth and box C/D snoRNA stability under heat stress. Altogether, our data suggest an important role of ZHD could be to maintain functional folding to the rest of the protein, especially under heat stress conditions.

  15. Cosmic Ray Hits in the Central Nervous System at Solar Maximum

    NASA Technical Reports Server (NTRS)

    Curtis, S. B.; Vazquez, M. E.; Wilson, J. W.; Atwell, W.; Kin, M.-H. Y.

    2000-01-01

    It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus are that the probability of any particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. The extra shielding provided in the equipment room makes little difference in these numbers. We conclude that this decrease in hit frequency (less than a factor of two) does not provide a compelling reason to avoid solar minimum for a manned mission to Mars. This conclusion could be revised, however, if a very small number of hits is found to cause critical malfunction within the brain.

  16. Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method.

    PubMed

    Kawakubo, Kazumichi; Kawakami, Hiroshi; Toyokawa, Yoshihide; Otani, Koichi; Kuwatani, Masaki; Abe, Yoko; Kawahata, Shuhei; Kubo, Kimitoshi; Kubota, Yoshimasa; Sakamoto, Naoya

    2015-01-01

    Endoscopic double self-expandable metallic stent (SEMS) placement by the partial stent-in-stent (PSIS) method has been reported to be useful for the management of unresectable hilar malignant biliary obstruction. However, it is technically challenging, and the optimal SEMS for the procedure remains unknown. The aim of this study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable malignant hilar biliary obstruction (MHBO). Between December 2009 and May 2013, 50 consecutive patients with MHBO underwent endoscopic double SEMS placement by the PSIS method. We retrospectively evaluated the rate of successful double SEMS placement and identified the risk factors for technical failure. The technical success rate for double SEMS placement was 82.0% (95% confidence interval [CI]: 69.2-90.2). On univariate analysis, the rate of technical failure was high in patients with metastatic disease and unilateral placement. Multivariate analysis revealed that metastatic disease was a significant risk factor for technical failure (odds ratio: 9.63, 95% CI: 1.11-105.5). The subgroup analysis after double guidewire insertion showed that the rate of technical success was higher in the laser-cut type SEMS with a large mesh and thick delivery system than in the braided type SEMS with a small mesh and thick delivery system. Metastatic disease was a significant risk factor for technical failure of double SEMS placement for unresectable MHBO. The laser-cut type SEMS with a large mesh and thin delivery system might be preferable for the PSIS procedure. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  17. Validation of concussion risk curves for collegiate football players derived from HITS data.

    PubMed

    Funk, James R; Rowson, Steven; Daniel, Ray W; Duma, Stefan M

    2012-01-01

    For several years, Virginia Tech and other schools have measured the frequency and severity of head impacts sustained by collegiate American football players in real time using the Head Impact Telemetry (HIT) System of helmet-mounted accelerometers. In this study, data from 37,128 head impacts collected at Virginia Tech during games from 2006 to 2010 were analyzed. Peak head acceleration exceeded 100 g in 516 impacts, and the Head Injury Criterion (HIC) exceeded 200 in 468 impacts. Four instrumented players in the dataset sustained a concussion. These data were used to develop risk curves for concussion as a function of peak head acceleration and HIC. The validity of this biomechanical approach was assessed using epidemiological data on concussion incidence from other sources. Two specific aspects of concussion incidence were addressed: the variation by player position, and the frequency of repeat concussions. The HIT System data indicated that linemen sustained the highest overall number of head impacts, while skill positions sustained a higher number of more severe head impacts (peak acceleration > 100 g or HIC > 200). When weighted using injury risk curves, the HIT System data predicted a higher incidence of concussion in skill positions compared to linemen at rates that were in strong agreement with the epidemiological literature (Pearson's r = 0.72-0.87). The predicted rates of repeat concussions (21-39% over one season and 33-50% over five seasons) were somewhat higher than the ranges reported in the epidemiological literature. These analyses demonstrate that simple biomechanical parameters that can be measured by the HIT System possess a high level of power for predicting concussion.

  18. Overview of HIT-SI3 experiment: Simulations, Diagnostics, and Summary of Current Results

    NASA Astrophysics Data System (ADS)

    Penna, James; Jarboe, Thomas; Nelson, Brian; Hossack, Aaron; Sutherland, Derek; Morgan, Kyle; Hansen, Chris; Benedett, Thomas; Everson, Chris; Victor, Brian

    2016-10-01

    The Helicity Injected Torus - Steady Inductive 3(HIT-SI3)experiment forms and maintains spheromaks via Steady Inductive Helicity Injection (SIHI). Three injector units allow for continuous injection of helicity into a copper flux conserver in order to sustain a spheromak. Firing of the injectors with a phase difference allows finite rotation of the plasma to provide a stabilizing effect. Simulations in the MHD code NIMROD and the fluid-model code PSI-TET provide validation and a basis for interpretation of the observed experimental data. Thompson Scattering (TS) and Far Infrared (FIR) Interferometer systems allow temperature and line-averaged density measurements to be taken. An Ion Doppler Spectroscopy (IDS) system allows measurement of the plasma rotation and velocity. HIT-SI3 data has been used for validation of IDCD predictions, in particular the projected impedance of helicity injectors according to the theory. The experimental impedances have been calculated here for the first time for different HIT-SI3 regimes. Such experimental evidence will contribute to the design of future experiments employing IDCD as a current-drive mechanism. Work supported by the D.O.E., Office of Science, Office of Fusion Science.

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

    PubMed

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

    2017-09-01

    Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 10 9 /L. Prior to diagnostic consideration of spontaneous HIT syndrome, the patient briefly received unfractionated heparin (UFH) and one dose of enoxaparin. The patient's serum tested strongly positive for anti-PF4/heparin antibodies by two different PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin release assay (SRA). Failure of fondaparinux anticoagulation (persisting HIT-associated disseminated intravascular coagulation) prompted switching to argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 × 10 9 /L, on POD21), and 9 days after starting argatroban symptomatic right leg deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, her course was uneventful, although platelet count recovery was prolonged, reaching 99 × 10 9 /L by POD45 and 199 × 10 9 /L by POD79. The patient's serum elicited strong serotonin release in the absence of heparin (seen even with 1/32 serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 and 0.3 IU/mL) and fondaparinux (0.1-1.2 μg/mL, i.e., in vitro fondaparinux "cross-reactivity"). Ultimately, platelet count recovery was

  20. A time-resolved Langmuir double-probe method for the investigation of pulsed magnetron discharges

    NASA Astrophysics Data System (ADS)

    Welzel, Th.; Dunger, Th.; Kupfer, H.; Richter, F.

    2004-12-01

    Langmuir probes are important means for the characterization of plasma discharges. For measurements in plasmas used for the deposition of thin films, the Langmuir double probe is especially suited. With the increasing popularity of pulsed deposition discharges, there is also an increasing need for time-resolved characterization methods. For Langmuir probes, several single-probe approaches to time-resolved measurements are reported but very few for the double probe. We present a time-resolved Langmuir double-probe technique, which is applied to a pulsed magnetron discharge at several 100 kHz used for MgO deposition. The investigations show that a proper treatment of the current measurement is necessary to obtain reliable results. In doing so, a characteristic time dependence of the charge-carrier density during the "pulse on" time containing maximum values of almost 2•1011cm-3 was found. This characteristic time dependence varies with the pulse frequency and the duty cycle. A similar time dependence of the electron temperature is only observed when the probe is placed near the magnesium target.

  1. New preparation method of {beta}{double_prime}-alumina and application for AMTEC

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

    Nishi, Toshiro; Tsuru, Yasuhiko; Yamamoto, Hirokazu

    1995-12-31

    The Alkali Metal Thermo-Electric Converter(AMTEC) is an energy conversion system that converts heat to electrical energy with high efficiency. The {beta}{double_prime}-alumina solid electrolyte (BASE) is the most important component in the AMTEC system. In this paper, the relationship among the conduction property, the microstructure and the amount of chemical component for BASE is studied. As an analysis of the chemical reaction for each component, the authors established a new BASE preparation method rather than using the conventional method. They also report the AMTFC cell performance using this electrolyte tube on which Mo or TiC electrode is filmed by the screenmore » printing method. Then, an electrochemical analysis and a heat cycle test of AMTEC cell are studied.« less

  2. An automated single ion hit at JAERI heavy ion microbeam to observe individual radiation damage

    NASA Astrophysics Data System (ADS)

    Kamiya, Tomihiro; Sakai, Takuro; Naitoh, Yutaka; Hamano, Tsuyoshi; Hirao, Toshio

    1999-10-01

    Microbeam scanning and a single ion hit technique have been combined to establish an automated beam positioning and single ion hit system at the JAERI Takasaki heavy ion microbeam system. Single ion irradiation on preset points of a sample in various patterns can be performed automatically in a short period. The reliability of the system was demonstrated using CR-39 nuclear track detectors. Single ion hit patterns were achieved with a positioning accuracy of 2 μm or less. In measurement of single event transient current using this system, the reduction of the pulse height by accumulation of radiation damages was observed by single ion injection to the same local areas. This technique showed a possibility to get some quantitative information about the lateral displacement of an individual radiation effect in silicon PIN photodiodes. This paper will give details of the irradiation system and present results from several experiments.

  3. Comparison of validity and reliability of the Migraine disability assessment (MIDAS) versus headache impact test (HIT) in an Iranian population.

    PubMed

    Ghorbani, Abbas; Chitsaz, Ahmad

    2011-01-01

    Migraine is one of the most common headaches that affect 11% or more adult population. Recently, researchers have designed two questionnaires, namely Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS), with the aim of improving migraine care. These two tests provide a standard measurement about migraine's effects on people's life style that divide patients into 4 groups (grades) based on headaches intensity. The aim of this study was to compare the validity and reliability of these two tests. This study was designed as a multicenter, descriptive study to compare validity and reliability of Persian version of MIDAS and HIT questionnaires in 240 males and females with a migraine diagnosis according to criteria for headache and facial pain of the International Headache Society (IHS). The patients were enrolled in the study from 3 neurology clinics in Isfahan, Iran, between July 2004 and January 2005 and were evaluated at baseline (visit 1) and 4 weeks later (visit 2). According to our study, there was a high correlation between two tests (r = 0.94). This decreased their MIDAS grade in comparison to their grade HIT questionnaire. These findings demonstrated that Persian version of HIT have the same validity and reliability as MIDAS. Replying to HIT questionnaire was easier than MIDAS for Iranian patients. Physicians can reliably use the Persian translation of both MIDAS and HIT questionnaires to define the severity of illness and its treatment strategy as a self-administered report by migraine patients. However, we recommend HIT for its simplicity in headache clinics.

  4. 75 FR 29762 - HIT Policy Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the National Coordinator for Health Information Technology HIT Policy Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of meetings. This notice announces...

  5. 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

  6. Earthquake hypocenter relocation using double difference method in East Java and surrounding areas

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

    C, Aprilia Puspita; Meteorological, Climatological, and Geophysical Agency; Nugraha, Andri Dian, E-mail: nugraha@gf.itb.ac.id

    Determination of precise hypocenter location is very important in order to provide information about subsurface fault plane and for seismic hazard analysis. In this study, we have relocated hypocenter earthquakes in Eastern part of Java and surrounding areas from local earthquake data catalog compiled by Meteorological, Climatological, and Geophysical Agency of Indonesia (MCGA) in time period 2009-2012 by using the double-difference method. The results show that after relocation processes, there are significantly changes in position and orientation of earthquake hypocenter which is correlated with the geological setting in this region. We observed indication of double seismic zone at depths ofmore » 70-120 km within the subducting slab in south of eastern part of Java region. Our results will provide useful information for advance seismological studies and seismic hazard analysis in this study.« less

  7. Sonic Simulation of Near Projectile Hits

    NASA Technical Reports Server (NTRS)

    Statman, J. I.; Rodemich, E. R.

    1988-01-01

    Measured frequencies identify projectiles and indicate miss distances. Developmental battlefield-simulation system for training soldiers uses sounds emitted by incoming projectiles to identify projectiles and indicate miss distances. Depending on projectile type and closeness of each hit, system generates "kill" or "near-kill" indication. Artillery shell simulated by lightweight plastic projectile launched by compressed air. Flow of air through groove in nose of projectile generates acoustic tone. Each participant carries audio receiver measure and process tone signal. System performs fast Fourier transforms of received tone to obtain dominant frequency during each succeeding interval of approximately 40 ms (an interval determined from practical signal-processing requirements). With modifications, system concept applicable to collision-warning or collision-avoidance systems.

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

    PubMed

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

    2017-06-01

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

  9. 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.

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

    PubMed

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

    2014-09-01

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

  11. Nano sized La2Co2O6 double perovskite synthesized by sol gel method

    NASA Astrophysics Data System (ADS)

    Solanki, Neha; Lodhi, Pavitra Devi; Choudhary, K. K.; Kaurav, Netram

    2018-05-01

    We report here the synthesis of double perovskite La2Co2O6 (LCO) compound by a sol gel route method. The double perovskite structure of LCO system was confirmed via X-ray diffraction (XRD) analysis. Further, the lattice parameter, unit cell volume and bond length were refined by means of rietveld analysis using the full proof software. Debye Scherer formula was used to determine the particle size. The compound crystallized in triclinic structure with space group P-1 in ambient condition. We also obtained Raman modes from XRD spectra of poly-crystalline LCO sample. These results were interpreted for the observation of phonon excitations in this compound.

  12. The accelerator facility of the Heidelberg Ion-Beam Therapy Centre (HIT)

    NASA Astrophysics Data System (ADS)

    Peters, Andreas

    The following sections are included: * Introduction * Beam parameters * General layout of the HIT facility * The accelerator chain in detail * Operational aspects of a particle therapy facility * 24/7 accelerator operation at 335 days per year * Safety and regulatory aspects * Status and perspectives * References

  13. 77 FR 66617 - HIT Policy and Standards Committees; Workgroup Application Database

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... Database AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice of New ONC HIT FACA Workgroup Application Database. The Office of the National Coordinator (ONC) has launched a new Health Information Technology Federal Advisory Committee Workgroup Application Database...

  14. 77 FR 16035 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... with the implementation of the Federal Health IT Strategic Plan, and in accordance with policies..., Office of Policy and Planning, Office of the National Coordinator for Health Information Technology. [FR... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of...

  15. 76 FR 46297 - HIT Standards Committee's Workgroup Meetings; Notice of Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-02

    ... with the implementation of the Federal Health IT Strategic Plan, and in accordance with policies... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee's Workgroup Meetings; Notice of Meetings AGENCY: Office of the National Coordinator for Health Information Technology, HHS. ACTION: Notice...

  16. 77 FR 22787 - HIT Standards Committee Advisory Meeting; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-17

    ... with the implementation of the Federal Health IT Strategic Plan, and in accordance with policies... Adviser, Office of Policy and Planning, Office of the National Coordinator for Health Information... DEPARTMENT OF HEALTH AND HUMAN SERVICES HIT Standards Committee Advisory Meeting; Notice of...

  17. Tracking, aiming, and hitting the UAV with ordinary assault rifle

    NASA Astrophysics Data System (ADS)

    Racek, František; Baláž, Teodor; Krejčí, Jaroslav; Procházka, Stanislav; Macko, Martin

    2017-10-01

    The usage small-unmanned aerial vehicles (UAVs) is significantly increasing nowadays. They are being used as a carrier of military spy and reconnaissance devices (taking photos, live video streaming and so on), or as a carrier of potentially dangerous cargo (intended for destruction and killing). Both ways of utilizing the UAV cause the necessity to disable it. From the military point of view, to disable the UAV means to bring it down by a weapon of an ordinary soldier that is the assault rifle. This task can be challenging for the soldier because he needs visually detect and identify the target, track the target visually and aim on the target. The final success of the soldier's mission depends not only on the said visual tasks, but also on the properties of the weapon and ammunition. The paper deals with possible methods of prediction of probability of hitting the UAV targets.

  18. Fast-forwarding hit to lead: aurora and epidermal growth factor receptor kinase inhibitor lead identification.

    PubMed

    Coumar, Mohane Selvaraj; Chu, Chang-Ying; Lin, Cheng-Wei; Shiao, Hui-Yi; Ho, Yun-Lung; Reddy, Randheer; Lin, Wen-Hsing; Chen, Chun-Hwa; Peng, Yi-Hui; Leou, Jiun-Shyang; Lien, Tzu-Wen; Huang, Chin-Ting; Fang, Ming-Yu; Wu, Szu-Huei; Wu, Jian-Sung; Chittimalla, Santhosh Kumar; Song, Jen-Shin; Hsu, John T-A; Wu, Su-Ying; Liao, Chun-Chen; Chao, Yu-Sheng; Hsieh, Hsing-Pang

    2010-07-08

    A focused library of furanopyrimidine (350 compounds) was rapidly synthesized in parallel reactors and in situ screened for Aurora and epidermal growth factor receptor (EGFR) kinase activity, leading to the identification of some interesting hits. On the basis of structural biology observations, the hit 1a was modified to better fit the back pocket, producing the potent Aurora inhibitor 3 with submicromolar antiproliferative activity in HCT-116 colon cancer cell line. On the basis of docking studies with EGFR hit 1s, introduction of acrylamide Michael acceptor group led to 8, which inhibited both the wild and mutant EGFR kinase and also showed antiproliferative activity in HCC827 lung cancer cell line. Furthermore, the X-ray cocrystal study of 3 and 8 in complex with Aurora and EGFR, respectively, confirmed their hypothesized binding modes. Library construction, in situ screening, and structure-based drug design (SBDD) strategy described here could be applied for the lead identification of other kinases.

  19. 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.

  20. Madoff Debacle Hits Colleges and Raises Questions about Trustee Conflicts

    ERIC Educational Resources Information Center

    Fain, Paul

    2009-01-01

    Several colleges and universities lost millions in the alleged $50-billion Ponzi scheme run by the Wall Street trader Bernard L. Madoff. The losses include institutions' endowment holdings in hedge funds that were invested with Madoff as well as hits taken by supporting foundations and donors. Several foundations that have been active in higher…

  1. 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.

  2. Uniscale multi-view registration using double dog-leg method

    NASA Astrophysics Data System (ADS)

    Chen, Chao-I.; Sargent, Dusty; Tsai, Chang-Ming; Wang, Yuan-Fang; Koppel, Dan

    2009-02-01

    3D computer models of body anatomy can have many uses in medical research and clinical practices. This paper describes a robust method that uses videos of body anatomy to construct multiple, partial 3D structures and then fuse them to form a larger, more complete computer model using the structure-from-motion framework. We employ the Double Dog-Leg (DDL) method, a trust-region based nonlinear optimization method, to jointly optimize the camera motion parameters (rotation and translation) and determine a global scale that all partial 3D structures should agree upon. These optimized motion parameters are used for constructing local structures, and the global scale is essential for multi-view registration after all these partial structures are built. In order to provide a good initial guess of the camera movement parameters and outlier free 2D point correspondences for DDL, we also propose a two-stage scheme where multi-RANSAC with a normalized eight-point algorithm is first performed and then a few iterations of an over-determined five-point algorithm is used to polish the results. Our experimental results using colonoscopy video show that the proposed scheme always produces more accurate outputs than the standard RANSAC scheme. Furthermore, since we have obtained many reliable point correspondences, time-consuming and error-prone registration methods like the iterative closest points (ICP) based algorithms can be replaced by a simple rigid-body transformation solver when merging partial structures into a larger model.

  3. Hit-to-lead optimization of pyrrolo[1,2-a]quinoxalines as novel cannabinoid type 1 receptor antagonists.

    PubMed

    Szabó, György; Kiss, Róbert; Páyer-Lengyel, Dóra; Vukics, Krisztina; Szikra, Judit; Baki, Andrea; Molnár, László; Fischer, János; Keseru, György M

    2009-07-01

    Hit-to-lead optimization of a novel series of N-alkyl-N-[2-oxo-2-(4-aryl-4H-pyrrolo[1,2-a]quinoxaline-5-yl)-ethyl]-carboxylic acid amides, derived from a high throughput screening (HTS) hit, are described. Subsequent optimization led to identification of in vitro potent cannabinoid 1 receptor (CB1R) antagonists representing a new class of compounds in this area.

  4. Hamiltonian Markov Chain Monte Carlo Methods for the CUORE Neutrinoless Double Beta Decay Sensitivity

    NASA Astrophysics Data System (ADS)

    Graham, Eleanor; Cuore Collaboration

    2017-09-01

    The CUORE experiment is a large-scale bolometric detector seeking to observe the never-before-seen process of neutrinoless double beta decay. Predictions for CUORE's sensitivity to neutrinoless double beta decay allow for an understanding of the half-life ranges that the detector can probe, and also to evaluate the relative importance of different detector parameters. Currently, CUORE uses a Bayesian analysis based in BAT, which uses Metropolis-Hastings Markov Chain Monte Carlo, for its sensitivity studies. My work evaluates the viability and potential improvements of switching the Bayesian analysis to Hamiltonian Monte Carlo, realized through the program Stan and its Morpho interface. I demonstrate that the BAT study can be successfully recreated in Stan, and perform a detailed comparison between the results and computation times of the two methods.

  5. Protective effects of Lagerstroemia speciosa on 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in HIT-T15 pancreatic β cells.

    PubMed

    Song, Jia-Le; Zhao, Xin; Wang, Qiang; Zhang, Ting

    2013-05-01

    Reactive oxygen species (ROS)-induced pancreatic β cell death affects insulin secretion and is important in the pathogenesis of diabetes. Lagerstroemia speciosa, a traditional folk medicine, has been used for t he prevention and treatment of diabetes. However, whether Lagerstroemia speciosa has a cytoprotective effect on pancreatic β cells remains to be elucidated. The present study aimed to investigate the cytoprotective effects of hot water extracts from Lagerstroemia speciosa leaves (LWE) on 3-morpholinosydnonimine (SIN-1)-induced oxidative damage in Syrian hamster pancreatic insulinoma HIT-T15 cells. The HIT-T15 cells were first treated with SIN-1 (50 µM) for 24 h and then co-incubated with LWE for 48 h. SIN-1 significantly decreased HIT-T15 cell viability (P<0.05); however, LWE did not exert a significant cytotoxic effect and increased the viability of HIT-T15 cells in a dose‑dependent manner. To further investigate the protective effects of LWE on SIN-1‑induced oxidative stress in HIT-T15 cells, the cellular levels of ROS, lipid peroxidation and endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px), were determined. LWE decreased the intracellular levels of ROS and lipid peroxidation, and increased the activities of antioxidant enzymes. These results suggest that LWE has a cytoprotective effect against SIN-1‑induced oxidative stress in HIT-T15 cells through the inhibition of lipid peroxidation, a decrease in ROS levels and an increase in antioxidant enzyme activity. In addition, LWE increased insulin secretion in SIN-1-treated HIT-T15 cells. Our results suggested that LWE were effective in the treatment of diabetes. Further studies are required to study the anti-diabetic molecular mechanism in a cell model.

  6. A note on the velocity derivative flatness factor in decaying HIT

    NASA Astrophysics Data System (ADS)

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

    2017-05-01

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

  7. A noniterative asymmetric triple excitation correction for the density-fitted coupled-cluster singles and doubles method: Preliminary applications

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

    Bozkaya, Uğur, E-mail: ugrbzky@gmail.com

    2016-04-14

    An efficient implementation of the asymmetric triples correction for the coupled-cluster singles and doubles [ΛCCSD(T)] method [S. A. Kucharski and R. J. Bartlett, J. Chem. Phys. 108, 5243 (1998); T. D. Crawford and J. F. Stanton, Int. J. Quantum Chem. 70, 601 (1998)] with the density-fitting [DF-ΛCCSD(T)] approach is presented. The computational time for the DF-ΛCCSD(T) method is compared with that of ΛCCSD(T). Our results demonstrate that the DF-ΛCCSD(T) method provide substantially lower computational costs than ΛCCSD(T). Further application results show that the ΛCCSD(T) and DF-ΛCCSD(T) methods are very beneficial for the study of single bond breaking problems as wellmore » as noncovalent interactions and transition states. We conclude that ΛCCSD(T) and DF-ΛCCSD(T) are very promising for the study of challenging chemical systems, where the coupled-cluster singles and doubles with perturbative triples method fails.« less

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

    PubMed

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

    2014-02-01

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

  9. Capture orbits around asteroids by hitting zero-velocity curves

    NASA Astrophysics Data System (ADS)

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

    2017-12-01

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

  10. MHD Simulation of the HIT-SI Experiment

    NASA Astrophysics Data System (ADS)

    Marklin, George

    2003-10-01

    The Helicity Injected Torus (HIT) experiment at the University of Washington has been reconfigured into a high beta spheromak with steady state AC current drive [1]. Helicity is injected by two half torus Reversed Field Pinches (RFP's) connected to the ends of the cylindrically symmetric flux conserver, rotated by 90 degrees from each other. The RFP's are driven with sinusoidally varying voltage and flux. Each side has its voltage and flux in phase, but is 90 degrees out of phase from the other side. The helicity injection rate, which is proportional to the voltage times the flux, goes like sin(wt)^2 on one side and cos(wt)^2 on the other, making the total injection rate constant in time. The complex multiply connected 3-dimensional geometry of this device make it difficult to simulate with existing codes that typically use a structured mesh. This poster will describe a new 3D MHD simulation code and a new 3D Taylor state code which both use an unstructured finite element mesh. The mesh is generated from a CAD-like description of an arbitrary arrangement of 3D geometrical objects. Taylor states in the HIT-SI geometry will be shown for different combinations of fluxes in the two injectors. MHD simulation results will be shown starting from a Taylor state with uniform density and temperature and continuing through several cycles of time dependent helicity injection. Field line tracing plots will show the quality of the flux surfaces at various stages in the injection cycle. [1] T. R. Jarboe, Fusion Technology, vol. 36, p. 85, 1999

  11. "Hits" emerge through self-organized coordination in collective response of free agents

    NASA Astrophysics Data System (ADS)

    Chakrabarti, Anindya S.; Sinha, Sitabhra

    2016-10-01

    Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".

  12. "Hits" emerge through self-organized coordination in collective response of free agents.

    PubMed

    Chakrabarti, Anindya S; Sinha, Sitabhra

    2016-10-01

    Individuals in free societies frequently exhibit striking coordination when making independent decisions en masse. Examples include the regular appearance of hit products or memes with substantially higher popularity compared to their otherwise equivalent competitors or extreme polarization in public opinion. Such segregation of events manifests as bimodality in the distribution of collective choices. Here we quantify how apparently independent choices made by individuals result in a significantly polarized but stable distribution of success in the context of the box-office performance of movies and show that it is an emergent feature of a system of noninteracting agents who respond to sequentially arriving signals. The aggregate response exhibits extreme variability amplifying much smaller differences in individual cost of adoption. Due to self-organization of the competitive landscape, most events elicit only a muted response but a few stimulate widespread adoption, emerging as "hits".

  13. From benchmarking HITS-CLIP peak detection programs to a new method for identification of miRNA-binding sites from Ago2-CLIP data

    PubMed Central

    Bottini, Silvia; Hamouda-Tekaya, Nedra; Tanasa, Bogdan; Zaragosi, Laure-Emmanuelle; Grandjean, Valerie; Repetto, Emanuela

    2017-01-01

    Abstract Experimental evidence indicates that about 60% of miRNA-binding activity does not follow the canonical rule about the seed matching between miRNA and target mRNAs, but rather a non-canonical miRNA targeting activity outside the seed or with a seed-like motifs. Here, we propose a new unbiased method to identify canonical and non-canonical miRNA-binding sites from peaks identified by Ago2 Cross-Linked ImmunoPrecipitation associated to high-throughput sequencing (CLIP-seq). Since the quality of peaks is of pivotal importance for the final output of the proposed method, we provide a comprehensive benchmarking of four peak detection programs, namely CIMS, PIPE-CLIP, Piranha and Pyicoclip, on four publicly available Ago2-HITS-CLIP datasets and one unpublished in-house Ago2-dataset in stem cells. We measured the sensitivity, the specificity and the position accuracy toward miRNA binding sites identification, and the agreement with TargetScan. Secondly, we developed a new pipeline, called miRBShunter, to identify canonical and non-canonical miRNA-binding sites based on de novo motif identification from Ago2 peaks and prediction of miRNA::RNA heteroduplexes. miRBShunter was tested and experimentally validated on the in-house Ago2-dataset and on an Ago2-PAR-CLIP dataset in human stem cells. Overall, we provide guidelines to choose a suitable peak detection program and a new method for miRNA-target identification. PMID:28108660

  14. Optimizing the Launch of a Projectile to Hit a Target

    ERIC Educational Resources Information Center

    Mungan, Carl E.

    2017-01-01

    Some teenagers are exploring the outer perimeter of a castle. They notice a spy hole in its wall, across the moat a horizontal distance "x" and vertically up the wall a distance "y." They decide to throw pebbles at the hole. One girl wants to use physics to throw with the minimum speed necessary to hit the hole. What is the…

  15. Double peak-induced distance error in short-time-Fourier-transform-Brillouin optical time domain reflectometers event detection and the recovery method.

    PubMed

    Yu, Yifei; Luo, Linqing; Li, Bo; Guo, Linfeng; Yan, Jize; Soga, Kenichi

    2015-10-01

    The measured distance error caused by double peaks in the BOTDRs (Brillouin optical time domain reflectometers) system is a kind of Brillouin scattering spectrum (BSS) deformation, discussed and simulated for the first time in the paper, to the best of the authors' knowledge. Double peak, as a kind of Brillouin spectrum deformation, is important in the enhancement of spatial resolution, measurement accuracy, and crack detection. Due to the variances of the peak powers of the BSS along the fiber, the measured starting point of a step-shape frequency transition region is shifted and results in distance errors. Zero-padded short-time-Fourier-transform (STFT) can restore the transition-induced double peaks in the asymmetric and deformed BSS, thus offering more accurate and quicker measurements than the conventional Lorentz-fitting method. The recovering method based on the double-peak detection and corresponding BSS deformation can be applied to calculate the real starting point, which can improve the distance accuracy of the STFT-based BOTDR system.

  16. Study on a Multi-Frequency Homotopy Analysis Method for Period-Doubling Solutions of Nonlinear Systems

    NASA Astrophysics Data System (ADS)

    Fu, H. X.; Qian, Y. H.

    In this paper, a modification of homotopy analysis method (HAM) is applied to study the two-degree-of-freedom coupled Duffing system. Firstly, the process of calculating the two-degree-of-freedom coupled Duffing system is presented. Secondly, the single periodic solutions and double periodic solutions are obtained by solving the constructed nonlinear algebraic equations. Finally, comparing the periodic solutions obtained by the multi-frequency homotopy analysis method (MFHAM) and the fourth-order Runge-Kutta method, it is found that the approximate solution agrees well with the numerical solution.

  17. ISS Double-Gimbaled CMG Subsystem Simulation Using the Agile Development Method

    NASA Technical Reports Server (NTRS)

    Inampudi, Ravi

    2016-01-01

    This paper presents an evolutionary approach in simulating a cluster of 4 Control Moment Gyros (CMG) on the International Space Station (ISS) using a common sense approach (the agile development method) for concurrent mathematical modeling and simulation of the CMG subsystem. This simulation is part of Training systems for the 21st Century simulator which will provide training for crew members, instructors, and flight controllers. The basic idea of how the CMGs on the space station are used for its non-propulsive attitude control is briefly explained to set up the context for simulating a CMG subsystem. Next different reference frames and the detailed equations of motion (EOM) for multiple double-gimbal variable-speed control moment gyroscopes (DGVs) are presented. Fixing some of the terms in the EOM becomes the special case EOM for ISS's double-gimbaled fixed speed CMGs. CMG simulation development using the agile development method is presented in which customer's requirements and solutions evolve through iterative analysis, design, coding, unit testing and acceptance testing. At the end of the iteration a set of features implemented in that iteration are demonstrated to the flight controllers thus creating a short feedback loop and helping in creating adaptive development cycles. The unified modeling language (UML) tool is used in illustrating the user stories, class designs and sequence diagrams. This incremental development approach of mathematical modeling and simulating the CMG subsystem involved the development team and the customer early on, thus improving the quality of the working CMG system in each iteration and helping the team to accurately predict the cost, schedule and delivery of the software.

  18. Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit

    NASA Technical Reports Server (NTRS)

    Yasuda, H.; Komiyama, T.; Fujitaka, K.; Badhwar, G. D. (Principal Investigator)

    2002-01-01

    The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  19. Generation of astaxanthin mutants in Xanthophyllomyces dendrorhous using a double recombination method based on hygromycin resistance.

    PubMed

    Niklitschek, Mauricio; Baeza, Marcelo; Fernández-Lobato, María; Cifuentes, Víctor

    2012-01-01

    Generally two selection markers are required to obtain homozygous mutations in a diploid background, one for each gene copy that is interrupted. In this chapter is described a method that allows the double gene deletions of the two copies of a gene from a diploid organism, a wild-type strain of the Xanthophyllomyces dendrorhous yeast, using hygromycin B resistance as the only selection marker. To accomplish this, in a first step, a heterozygous hygromycin B-resistant strain is obtained by a single process of transformation (carrying the inserted hph gene). Following, the heterozygous mutant is grown in media with increasing concentrations of the antibiotic. In this way, the strains that became homozygous (by mitotic recombination) for the antibiotic marker would able to growth at higher concentration of the antibiotic than the heterozygous. The method can be potentially applied for obtaining double mutants of other diploid organisms.

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

    PubMed

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

    2016-12-01

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

  1. EASY-HIT: HIV full-replication technology for broad discovery of multiple classes of HIV inhibitors.

    PubMed

    Kremb, Stephan; Helfer, Markus; Heller, Werner; Hoffmann, Dieter; Wolff, Horst; Kleinschmidt, Andrea; Cepok, Sabine; Hemmer, Bernhard; Durner, Jörg; Brack-Werner, Ruth

    2010-12-01

    HIV replication assays are important tools for HIV drug discovery efforts. Here, we present a full HIV replication system (EASY-HIT) for the identification and analysis of HIV inhibitors. This technology is based on adherently growing HIV-susceptible cells, with a stable fluorescent reporter gene activated by HIV Tat and Rev. A fluorescence-based assay was designed that measures HIV infection by two parameters relating to the early and the late phases of HIV replication, respectively. Validation of the assay with a panel of nine reference inhibitors yielded effective inhibitory concentrations consistent with published data and allowed discrimination between inhibitors of early and late phases of HIV replication. Finer resolution of the effects of reference drugs on different steps of HIV replication was achieved in secondary time-of-addition assays. The EASY-HIT assay yielded high Z' scores (>0.9) and signal stabilities, confirming its robustness. Screening of the LOPAC(1280) library identified 10 compounds (0.8%), of which eight were known to inhibit HIV, validating the suitability of this assay for screening applications. Studies evaluating anti-HIV activities of natural products with the EASY-HIT technology led to the identification of three novel inhibitory compounds that apparently act at different steps of HIV-1 replication. Furthermore, we demonstrate successful evaluation of plant extracts for HIV-inhibitory activities, suggesting application of this technology for the surveillance of biological extracts with anti-HIV activities. We conclude that the EASY-HIT technology is a versatile tool for the discovery and characterization of HIV inhibitors.

  2. Hurricane Iris Hits Belize

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Hurricane Iris hit the small Central American country of Belize around midnight on October 8, 2001. At the time, Iris was the strongest Atlantic hurricane of the season, with sustained winds up to 225 kilometers per hour (140 mph). The hurricane caused severe damage-destroying homes, flooding streets, and leveling trees-in coastal towns south of Belize City. In addition, a boat of American recreational scuba divers docked along the coast was capsized by the storm, leaving 20 of the 28 passengers missing. Within hours the winds had subsided to only 56 kph (35 mph), a modest tropical depression, but Mexico, Guatemala, El Salvador, and Honduras were still expecting heavy rains. The above image is a combination of visible and thermal infrared data (for clouds) acquired by a NOAA Geostationary Operational Environmental Satellite (GOES-8) on October 8, 2001, at 2:45 p.m., and the Moderate-resolution Imaging Spectroradiometer (MODIS) (for the color of the ground). The three-dimensional view is from the south-southeast (north is towards the upper left). Belize is off the image to the left. Image courtesy Marit Jentoft-Nilsen, NASA GSFC Visualization Analysis Lab

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

    PubMed Central

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

    2016-01-01

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

  4. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

    PubMed Central

    Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens

    2016-01-01

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’. PMID:27160596

  5. The hit problem for symmetric polynomials over the Steenrod algebra

    NASA Astrophysics Data System (ADS)

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

    2002-09-01

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

  6. Simulation of electric double-layer capacitors: evaluation of constant potential method

    NASA Astrophysics Data System (ADS)

    Wang, Zhenxing; Laird, Brian; Yang, Yang; Olmsted, David; Asta, Mark

    2014-03-01

    Atomistic simulations can play an important role in understanding electric double-layer capacitors (EDLCs) at a molecular level. In such simulations, typically the electrode surface is modeled using fixed surface charges, which ignores the charge fluctuation induced by local fluctuations in the electrolyte solution. In this work we evaluate an explicit treatment of charges, namely constant potential method (CPM)[1], in which the electrode charges are dynamically updated to maintain constant electrode potential. We employ a model system with a graphite electrode and a LiClO4/acetonitrile electrolyte, examined as a function of electrode potential differences. Using various molecular and macroscopic properties as metrics, we compare CPM simulations on this system to results using fixed surface charges. Specifically, results for predicted capacity, electric potential gradient and solvent density profile are identical between the two methods; However, ion density profiles and solvation structure yield significantly different results.

  7. A logistic model of the effects of roadway, environmental, vehicle, crash and driver characteristics on hit-and-run crashes.

    PubMed

    Tay, Richard; Rifaat, Shakil Mohammad; Chin, Hoong Chor

    2008-07-01

    Leaving the scene of a crash without reporting it is an offence in most countries and many studies have been devoted to improving ways to identify hit-and-run vehicles and the drivers involved. However, relatively few studies have been conducted on identifying factors that contribute to the decision to run after the crash. This study identifies the factors that are associated with the likelihood of hit-and-run crashes including driver characteristics, vehicle types, crash characteristics, roadway features and environmental characteristics. Using a logistic regression model to delineate hit-and-run crashes from nonhit-and-run crashes, this study found that drivers were more likely to run when crashes occurred at night, on a bridge and flyover, bend, straight road and near shop houses; involved two vehicles, two-wheel vehicles and vehicles from neighboring countries; and when the driver was a male, minority, and aged between 45 and 69. On the other hand, collisions involving right turn and U-turn maneuvers, and occurring on undivided roads were less likely to be hit-and-run crashes.

  8. Hit-Validation Methodologies for Ligands Isolated from DNA-Encoded Chemical Libraries.

    PubMed

    Zimmermann, Gunther; Li, Yizhou; Rieder, Ulrike; Mattarella, Martin; Neri, Dario; Scheuermann, Jörg

    2017-05-04

    DNA-encoded chemical libraries (DECLs) are large collections of compounds linked to DNA fragments, serving as amplifiable barcodes, which can be screened on target proteins of interest. In typical DECL selections, preferential binders are identified by high-throughput DNA sequencing, by comparing their frequency before and after the affinity capture step. Hits identified in this procedure need to be confirmed, by resynthesis and by performing affinity measurements. In this article we present new methods based on hybridization of oligonucleotide conjugates with fluorescently labeled complementary oligonucleotides; these facilitate the determination of affinity constants and kinetic dissociation constants. The experimental procedures were demonstrated with acetazolamide, a binder to carbonic anhydrase IX with a dissociation constant in the nanomolar range. The detection of binding events was compatible not only with fluorescence polarization methodologies, but also with Alphascreen technology and with microscale thermophoresis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. A Double-Coil TMS Method to Assess Corticospinal Excitability Changes at a Near-Simultaneous Time in the Two Hands during Movement Preparation

    PubMed Central

    Wilhelm, Emmanuelle; Quoilin, Caroline; Petitjean, Charlotte; Duque, Julie

    2016-01-01

    Background: Many previous transcranial magnetic stimulation (TMS) studies have investigated corticospinal excitability changes occurring when choosing which hand to use for an action, one of the most frequent decision people make in daily life. So far, these studies have applied single-pulse TMS eliciting motor-evoked potential (MEP) in one hand when this hand is either selected or non-selected. Using such method, hand choices were shown to entail the operation of two inhibitory mechanisms, suppressing MEPs in the targeted hand either when it is non-selected (competition resolution, CR) or selected (impulse control, IC). However, an important limitation of this “Single-Coil” method is that MEPs are elicited in selected and non-selected conditions during separate trials and thus those two settings may not be completely comparable. Moreover, a more important problem is that MEPs are computed in relation to the movement of different hands. The goal of the present study was to test a “Double-Coil” method to evaluate IC and CR preceding the same hand responses by applying Double-Coil TMS over the two primary motor cortices (M1) at a near-simultaneous time (1 ms inter-pulse interval). Methods: MEPs were obtained in the left (MEPLEFT) and right (MEPRIGHT) hands while subjects chose between left and right hand key-presses in blocks using a Single-Coil or a Double-Coil method; in the latter blocks, TMS was either applied over left M1 first (TMSLRM1 group, n = 12) or right M1 first (TMSRLM1 group, n = 12). Results: MEPLEFT were suppressed preceding both left (IC) and right (CR) hand responses whereas MEPRIGHT were only suppressed preceding left (CR) but not right (IC) hand responses. This result was observed regardless of whether Single-Coil or Double-Coil TMS was applied in the two subject groups. However, in the TMSLRM1 group, the MEP suppression was attenuated in Double-Coil compared to Single-Coil blocks for both IC and CR, when probed with MEPLEFT (elicited by

  10. Contribution of Visual Information about Ball Trajectory to Baseball Hitting Accuracy.

    PubMed

    Higuchi, Takatoshi; Nagami, Tomoyuki; Nakata, Hiroki; Watanabe, Masakazu; Isaka, Tadao; Kanosue, Kazuyuki

    2016-01-01

    The contribution of visual information about a pitched ball to the accuracy of baseball-bat contact may vary depending on the part of trajectory seen. The purpose of the present study was to examine the relationship between hitting accuracy and the segment of the trajectory of the flying ball that can be seen by the batter. Ten college baseball field players participated in the study. The systematic error and standardized variability of ball-bat contact on the bat coordinate system and pitcher-to-catcher direction when hitting a ball launched from a pitching machine were measured with or without visual occlusion and analyzed using analysis of variance. The visual occlusion timing included occlusion from 150 milliseconds (ms) after the ball release (R+150), occlusion from 150 ms before the expected arrival of the launched ball at the home plate (A-150), and a condition with no occlusion (NO). Twelve trials in each condition were performed using two ball speeds (31.9 m·s-1 and 40.3 m·s-1). Visual occlusion did not affect the mean location of ball-bat contact in the bat's long axis, short axis, and pitcher-to-catcher directions. Although the magnitude of standardized variability was significantly smaller in the bat's short axis direction than in the bat's long axis and pitcher-to-catcher directions (p < 0.001), additional visible time from the R+150 condition to the A-150 and NO conditions resulted in a further decrease in standardized variability only in the bat's short axis direction (p < 0.05). The results suggested that there is directional specificity in the magnitude of standardized variability with different visible time. The present study also confirmed the limitation to visual information is the later part of the ball trajectory for improving hitting accuracy, which is likely due to visuo-motor delay.

  11. As the Economic Crisis Hits Home, Colleges Seek Help from Congress

    ERIC Educational Resources Information Center

    Field, Kelly

    2008-01-01

    Congress is crafting a second economic-stimulus bill, and the nation's colleges, hit by the deepening fiscal crisis, want a share of the money. Over the last few weeks, colleges and their lobbyists have bombarded members of Congress with letters and phone calls seeking money for research, student aid, and infrastructure. However, Congress is…

  12. Double checking: a second look

    PubMed Central

    Chreim, Samia; Forster, Alan

    2015-01-01

    Abstract Rationale, aims and objectives Double checking is a standard practice in many areas of health care, notwithstanding the lack of evidence supporting its efficacy. We ask in this study: ‘How do front line practitioners conceptualize double checking? What are the weaknesses of double checking? What alternate views of double checking could render it a more robust process?’ Method This is part of a larger qualitative study based on 85 semi‐structured interviews of health care practitioners in general internal medicine and obstetrics and neonatology; thematic analysis of the transcribed interviews was undertaken. Inductive and deductive themes are reported. Results Weaknesses in the double checking process include inconsistent conceptualization of double checking, double (or more) checking as a costly and time‐consuming procedure, double checking trusted as an accepted and stand‐alone process, and double checking as preventing reporting of near misses. Alternate views of double checking that would render it a more robust process include recognizing that double checking requires training and a dedicated environment, Introducing automated double checking, and expanding double checking beyond error detection. These results are linked with the concepts of collective efficiency thoroughness trade off (ETTO), an in‐family approach, and resilience. Conclusion(s) Double checking deserves more questioning, as there are limitations to the process. Practitioners could view double checking through alternate lenses, and thus help strengthen this ubiquitous practice that is rarely challenged. PMID:26568537

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

    PubMed

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

    2017-12-01

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

  14. Hit efficiency study of CMS prototype forward pixel detectors

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

    Kim, Dongwook; /Johns Hopkins U.

    2006-01-01

    In this paper the author describes the measurement of the hit efficiency of a prototype pixel device for the CMS forward pixel detector. These pixel detectors were FM type sensors with PSI46V1 chip readout. The data were taken with the 120 GeV proton beam at Fermilab during the period of December 2004 to February 2005. The detectors proved to be highly efficient (99.27 {+-} 0.02%). The inefficiency was primarily located near the corners of the individual pixels.

  15. Development of double-pair double difference location algorithm and its application to the regular earthquakes and non-volcanic tremors

    NASA Astrophysics Data System (ADS)

    Guo, H.; Zhang, H.

    2016-12-01

    Relocating high-precision earthquakes is a central task for monitoring earthquakes and studying the structure of earth's interior. The most popular location method is the event-pair double-difference (DD) relative location method, which uses the catalog and/or more accurate waveform cross-correlation (WCC) differential times from event pairs with small inter-event separations to the common stations to reduce the effect of the velocity uncertainties outside the source region. Similarly, Zhang et al. [2010] developed a station-pair DD location method which uses the differential times from common events to pairs of stations to reduce the effect of the velocity uncertainties near the source region, to relocate the non-volcanic tremors (NVT) beneath the San Andreas Fault (SAF). To utilize advantages of both DD location methods, we have proposed and developed a new double-pair DD location method to use the differential times from pairs of events to pairs of stations. The new method can remove the event origin time and station correction terms from the inversion system and cancel out the effects of the velocity uncertainties near and outside the source region simultaneously. We tested and applied the new method on the northern California regular earthquakes to validate its performance. In comparison, among three DD location methods, the new double-pair DD method can determine more accurate relative locations and the station-pair DD method can better improve the absolute locations. Thus, we further proposed a new location strategy combining station-pair and double-pair differential times to determine accurate absolute and relative locations at the same time. For NVTs, it is difficult to pick the first arrivals and derive the WCC event-pair differential times, thus the general practice is to measure station-pair envelope WCC differential times. However, station-pair tremor locations are scattered due to the low-precision relative locations. The ability that double-pair data

  16. From benchmarking HITS-CLIP peak detection programs to a new method for identification of miRNA-binding sites from Ago2-CLIP data.

    PubMed

    Bottini, Silvia; Hamouda-Tekaya, Nedra; Tanasa, Bogdan; Zaragosi, Laure-Emmanuelle; Grandjean, Valerie; Repetto, Emanuela; Trabucchi, Michele

    2017-05-19

    Experimental evidence indicates that about 60% of miRNA-binding activity does not follow the canonical rule about the seed matching between miRNA and target mRNAs, but rather a non-canonical miRNA targeting activity outside the seed or with a seed-like motifs. Here, we propose a new unbiased method to identify canonical and non-canonical miRNA-binding sites from peaks identified by Ago2 Cross-Linked ImmunoPrecipitation associated to high-throughput sequencing (CLIP-seq). Since the quality of peaks is of pivotal importance for the final output of the proposed method, we provide a comprehensive benchmarking of four peak detection programs, namely CIMS, PIPE-CLIP, Piranha and Pyicoclip, on four publicly available Ago2-HITS-CLIP datasets and one unpublished in-house Ago2-dataset in stem cells. We measured the sensitivity, the specificity and the position accuracy toward miRNA binding sites identification, and the agreement with TargetScan. Secondly, we developed a new pipeline, called miRBShunter, to identify canonical and non-canonical miRNA-binding sites based on de novo motif identification from Ago2 peaks and prediction of miRNA::RNA heteroduplexes. miRBShunter was tested and experimentally validated on the in-house Ago2-dataset and on an Ago2-PAR-CLIP dataset in human stem cells. Overall, we provide guidelines to choose a suitable peak detection program and a new method for miRNA-target identification. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Demand spillovers of smash-hit papers: evidence from the 'Male Organ Incident'.

    PubMed

    Kässi, Otto; Westling, Tatu

    2013-12-01

    This study explores the short-run spillover effects of popular research papers. We consider the publicity of 'Male Organ and Economic Growth: Does Size Matter?' as an exogenous shock to economics discussion paper demand, a natural experiment of a sort. In particular, we analyze how the very substantial visibility influenced the downloads of Helsinki Center of Economic Research discussion papers. Difference in differences and regression discontinuity analysis are conducted to elicit the spillover patterns. This study finds that the spillover effect to average economics paper demand is positive and statistically significant. It seems that hit papers increase the exposure of previously less downloaded papers. We find that part of the spillover effect could be attributable to Internet search engines' influence on browsing behavior. Conforming to expected patterns, papers residing on the same web page as the hit paper evidence very significant increases in downloads which also supports the spillover thesis. A11, C21. 97K80.

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

    PubMed

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

    2010-01-01

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

  19. Mechanical characteristics and comparisons of cerclage wires: introduction of the double-wrap and loop/twist tying methods.

    PubMed

    Roe, S C

    1997-01-01

    Evaluate the mechanical properties of twist, loop, double loop, double-wrap and loop/twist cerclage. The initial tension generated by 18 cerclage of each type was determined using a materials testing machine after tying around a testing jig. Six wires from each type were distracted and the initial stiffness and yield load were determined. Yield behavior was further investigated in six wires of each type by determining the load required to reduce cerclage tension below 30 Newton (N) following and incremental (50 N) stepwise load and unload regimen. The amount of collapse of the simulated bone fragments that resulted in the reduction of initial tension to 30 N was measured for the final six wires of each group. Data were analyzed by analysis of variance and a multiple comparison test. Twist type cerclage generated less tension than loop-type cerclage. The yield load of these two types was similar. Double-loop and double-wrap cerclage generated superior tension and resisted a greater load before loosening. Loop/twist cerclage had an intermediate initial tension but had the greatest resistance to loading. In the collapse test, the greater the initial tension, the more collapse could occur before the wire was loose. For all types of cerclage wire fixation, a reduction of diameter of the testing jig of more than 1% caused loosening. Double-loop and double-wrap cerclage provide greater compression of fragments and resist loads associated with weight-bearing better than the twist and loop methods. Loop/twist cerclage may have advantages because of their superior resistance to loading. All cerclage will loosen if fracture fragments collapse.

  20. QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

    PubMed

    Nilsen, Vegard; Wyller, John

    2016-01-01

    Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. © 2016 Society for Risk Analysis.

  1. Optimisation of a double-centrifugation method for preparation of canine platelet-rich plasma.

    PubMed

    Shin, Hyeok-Soo; Woo, Heung-Myong; Kang, Byung-Jae

    2017-06-26

    Platelet-rich plasma (PRP) has been expected for regenerative medicine because of its growth factors. However, there is considerable variability in the recovery and yield of platelets and the concentration of growth factors in PRP preparations. The aim of this study was to identify optimal relative centrifugal force and spin time for the preparation of PRP from canine blood using a double-centrifugation tube method. Whole blood samples were collected in citrate blood collection tubes from 12 healthy beagles. For the first centrifugation step, 10 different run conditions were compared to determine which condition produced optimal recovery of platelets. Once the optimal condition was identified, platelet-containing plasma prepared using that condition was subjected to a second centrifugation to pellet platelets. For the second centrifugation, 12 different run conditions were compared to identify the centrifugal force and spin time to produce maximal pellet recovery and concentration increase. Growth factor levels were estimated by using ELISA to measure platelet-derived growth factor-BB (PDGF-BB) concentrations in optimised CaCl 2 -activated platelet fractions. The highest platelet recovery rate and yield were obtained by first centrifuging whole blood at 1000 g for 5 min and then centrifuging the recovered platelet-enriched plasma at 1500 g for 15 min. This protocol recovered 80% of platelets from whole blood and increased platelet concentration six-fold and produced the highest concentration of PDGF-BB in activated fractions. We have described an optimised double-centrifugation tube method for the preparation of PRP from canine blood. This optimised method does not require particularly expensive equipment or high technical ability and can readily be carried out in a veterinary clinical setting.

  2. Applying the new HIT results to tokamak and solar plasmas

    NASA Astrophysics Data System (ADS)

    Jarboe, Thomas; Sutherland, Derek; Hossack, Aaron; Nelson, Brian; Morgan, Kyle; Chris, Hansen; Benedett, Thomas; Everson, Chris; Penna, James

    2016-10-01

    Understanding sustainment of stable equilibria with helicity injection in HIT-SI has led to a simple picture of several tokamak features. Perturbations cause a viscous-like force on the current that flattens the λ profile, which sustains and stabilizes the equilibrium. An explanation of the mechanism is based on two properties of stable, ideal, two-fluid, magnetized plasma. First, the electron fluid is frozen to magnetic fields and, therefore, current flow is also magnetic field flow. Second, for a stable equilibrium the structure perpendicular to the flux surface resists deformation. Thus toroidal current is from electrons frozen in nested, rotating resilient flux surfaces. Only symmetric flux surfaces allow free differential current flow. Perturbations cause interference of the flux surfaces. Thus, perturbations cause forces that oppose differential electron rotation and forced differential flow produces a symmetrizing force against perturbations and instability. This mechanism can explain the level of field error that spoils tokamak performance and the rate of poloidal flux loss in argon-induced disruptions in DIII-D. This new understanding has led to an explanation of the source of the solar magnetic fields and the power source for the chromosphere, solar wind and corona. Please place in spheromak and FRC section with other HIT posters.

  3. Efficient elimination of nonstoichiometric enzyme inhibitors from HTS hit lists.

    PubMed

    Habig, Michael; Blechschmidt, Anke; Dressler, Sigmar; Hess, Barbara; Patel, Viral; Billich, Andreas; Ostermeier, Christian; Beer, David; Klumpp, Martin

    2009-07-01

    High-throughput screening often identifies not only specific, stoichiometrically binding inhibitors but also undesired compounds that unspecifically interfere with the targeted activity by nonstoichiometrically binding, unfolding, and/or inactivating proteins. In this study, the effect of such unwanted inhibitors on several different enzyme targets was assessed based on screening results for over a million compounds. In particular, the shift in potency on variation of enzyme concentration was used as a means to identify nonstoichiometric inhibitors among the screening hits. These potency shifts depended on both compound structure and target enzyme. The approach was confirmed by statistical analysis of thousands of dose-response curves, which showed that the potency of competitive and therefore clearly stoichiometric inhibitors was not affected by increasing enzyme concentration. Light-scattering measurements of thermal protein unfolding further verified that compounds that stabilize protein structure by stoichiometric binding show the same potency irrespective of enzyme concentration. In summary, measuring inhibitor IC(50) values at different enzyme concentrations is a simple, cost-effective, and reliable method to identify and eliminate compounds that inhibit a specific target enzyme via nonstoichiometric mechanisms.

  4. 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.

  5. Optimizing the Launch of a Projectile to Hit a Target

    NASA Astrophysics Data System (ADS)

    Mungan, Carl E.

    2017-12-01

    Some teenagers are exploring the outer perimeter of a castle. They notice a spy hole in its wall, across the moat a horizontal distance x and vertically up the wall a distance y. They decide to throw pebbles at the hole. One girl wants to use physics to throw with the minimum speed necessary to hit the hole. What is the required launch speed v and launch angle θ above the horizontal?

  6. The immune imbalance in the second hit of pancreatitis is independent of IL-17A.

    PubMed

    Thomson, John-Edwin; Brand, Martin; Fonteh, Pascaline

    2018-04-01

    Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP. Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations. There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days. An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  7. 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

  8. Standardizing the double-observer survey method for estimating mountain ungulate prey of the endangered snow leopard.

    PubMed

    Suryawanshi, Kulbhushansingh R; Bhatnagar, Yash Veer; Mishra, Charudutt

    2012-07-01

    Mountain ungulates around the world have been threatened by illegal hunting, habitat modification, increased livestock grazing, disease and development. Mountain ungulates play an important functional role in grasslands as primary consumers and as prey for wild carnivores, and monitoring of their populations is important for conservation purposes. However, most of the several currently available methods of estimating wild ungulate abundance are either difficult to implement or too expensive for mountainous terrain. A rigorous method of sampling ungulate abundance in mountainous areas that can allow for some measure of sampling error is therefore much needed. To this end, we used a combination of field data and computer simulations to test the critical assumptions associated with double-observer technique based on capture-recapture theory. The technique was modified and adapted to estimate the populations of bharal (Pseudois nayaur) and ibex (Capra sibirica) at five different sites. Conducting the two double-observer surveys simultaneously led to underestimation of the population by 15%. We therefore recommend separating the surveys in space or time. The overall detection probability for the two observers was 0.74 and 0.79. Our surveys estimated mountain ungulate populations (± 95% confidence interval) of 735 (± 44), 580 (± 46), 509 (± 53), 184 (± 40) and 30 (± 14) individuals at the five sites, respectively. A detection probability of 0.75 was found to be sufficient to detect a change of 20% in populations of >420 individuals. Based on these results, we believe that this method is sufficiently precise for scientific and conservation purposes and therefore recommend the use of the double-observer approach (with the two surveys separated in time or space) for the estimation and monitoring of mountain ungulate populations.

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

    PubMed

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

    2015-11-01

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

  10. A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat.

    PubMed

    Lim, Ann Li; Taylor, David Alan; Malone, Daniel Thomas

    2012-09-01

    This study combined two neurodevelopmental manipulations, neonatal MK-801 treatment and isolation rearing, to produce a 'two-hit' model and determine whether two hits induce a more robust behavioural phenotype of an animal model of aspects of schizophrenia compared with individual manipulations alone. The effect of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK-801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10 and were assigned to group or isolation rearing at weaning (PND 21). From PND 77, they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were subjected to three prepulse inhibition (PPI) tests, a locomotor activity assessment and a novel object recognition task. MK-801-treated rats reared in isolation displayed robust PPI disruptions which were consistently manifested in all three tests. PPI deficits were also detected in saline-treated rats reared in isolation but not in all tests. Only the two-hit rats demonstrated hyperlocomotion and impaired object recognition memory. Clozapine restored PPI anomalies in the two-hit rats. The two-hit model showed greater psychotic-like effects than either neonatal MK-801 or isolation rearing alone. The preliminary predictive validity shown with clozapine suggests this model may be useful for predicting the efficacy of putative antipsychotics.

  11. Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

    PubMed

    Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

    2013-01-01

    The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

  12. Two-fluid (plasma-neutral) Extended-MHD simulations of spheromak configurations in the HIT-SI experiment with PSI-Tet

    NASA Astrophysics Data System (ADS)

    Sutherland, D. A.; Hansen, C. J.; Jarboe, T. R.

    2017-10-01

    A self-consistent, two-fluid (plasma-neutral) dynamic neutral model has been implemented into the 3-D, Extended-MHD code PSI-Tet. A monatomic, hydrogenic neutral fluid reacts with a plasma fluid through elastic scattering collisions and three inelastic collision reactions: electron-impact ionization, radiative recombination, and resonant charge-exchange. Density, momentum, and energy are evolved for both the plasma and neutral species. The implemented plasma-neutral model in PSI-Tet is being used to simulate decaying spheromak configurations in the HIT-SI experimental geometry, which is being compare to two-photon absorption laser induced fluorescence measurements (TALIF) made on the HIT-SI3 experiment. TALIF is used to measure the absolute density and temperature of monatomic deuterium atoms. Neutral densities on the order of 1015 m-3 and neutral temperatures between 0.6-1.7 eV were measured towards the end of decay of spheromak configurations with initial toroidal currents between 10-12 kA. Validation results between TALIF measurements and PSI-Tet simulations with the implemented dynamic neutral model will be presented. Additionally, preliminary dynamic neutral simulations of the HIT-SI/HIT-SI3 spheromak plasmas sustained with inductive helicity injection will be presented. Lastly, potential benefits of an expansion of the two-fluid model into a multi-fluid model that includes multiple neutral species and tracking of charge states will be discussed.

  13. A simple and widely applicable hit validation strategy for protein-protein interaction inhibitors based on a quantitative ligand displacement assay.

    PubMed

    Sameshima, Tomoya; Miyahisa, Ikuo; Homma, Misaki; Aikawa, Katsuji; Hixon, Mark S; Matsui, Junji

    2014-12-15

    Identification of inhibitors for protein-protein interactions (PPIs) from high-throughput screening (HTS) is challenging due to the weak affinity of primary hits. We present a hit validation strategy of PPI inhibitors using quantitative ligand displacement assay. From an HTS for Bcl-xL/Mcl-1 inhibitors, we obtained a hit candidate, I1, which potentially forms a reactive Michael acceptor, I2, inhibiting Bcl-xL/Mcl-1 through covalent modification. We confirmed rapid reversible and competitive binding of I1 with a probe peptide, suggesting non-covalent binding. The advantages of our approach over biophysical assays include; simplicity, higher throughput, low protein consumption and universal application to PPIs including insoluble membrane proteins. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-03-04

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

  15. Contribution of Visual Information about Ball Trajectory to Baseball Hitting Accuracy

    PubMed Central

    Higuchi, Takatoshi; Nagami, Tomoyuki; Nakata, Hiroki; Watanabe, Masakazu; Isaka, Tadao; Kanosue, Kazuyuki

    2016-01-01

    The contribution of visual information about a pitched ball to the accuracy of baseball-bat contact may vary depending on the part of trajectory seen. The purpose of the present study was to examine the relationship between hitting accuracy and the segment of the trajectory of the flying ball that can be seen by the batter. Ten college baseball field players participated in the study. The systematic error and standardized variability of ball-bat contact on the bat coordinate system and pitcher-to-catcher direction when hitting a ball launched from a pitching machine were measured with or without visual occlusion and analyzed using analysis of variance. The visual occlusion timing included occlusion from 150 milliseconds (ms) after the ball release (R+150), occlusion from 150 ms before the expected arrival of the launched ball at the home plate (A-150), and a condition with no occlusion (NO). Twelve trials in each condition were performed using two ball speeds (31.9 m·s-1 and 40.3 m·s-1). Visual occlusion did not affect the mean location of ball-bat contact in the bat’s long axis, short axis, and pitcher-to-catcher directions. Although the magnitude of standardized variability was significantly smaller in the bat’s short axis direction than in the bat’s long axis and pitcher-to-catcher directions (p < 0.001), additional visible time from the R+150 condition to the A-150 and NO conditions resulted in a further decrease in standardized variability only in the bat’s short axis direction (p < 0.05). The results suggested that there is directional specificity in the magnitude of standardized variability with different visible time. The present study also confirmed the limitation to visual information is the later part of the ball trajectory for improving hitting accuracy, which is likely due to visuo-motor delay. PMID:26848742

  16. 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.

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

    PubMed

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

    2017-10-26

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

  18. Double stranded nucleic acid biochips

    DOEpatents

    Chernov, Boris; Golova, Julia

    2006-05-23

    This invention describes a new method of constructing double-stranded DNA (dsDNA) microarrays based on the use of pre-synthesized or natural DNA duplexes without a stem-loop structure. The complementary oligonucleotide chains are bonded together by a novel connector that includes a linker for immobilization on a matrix. A non-enzymatic method for synthesizing double-stranded nucleic acids with this novel connector enables the construction of inexpensive and robust dsDNA/dsRNA microarrays. DNA-DNA and DNA-protein interactions are investigated using the microarrays.

  19. Hit Generation in TB Drug Discovery: From Genome to Granuloma

    PubMed Central

    2018-01-01

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

  20. Double hard scattering without double counting

    NASA Astrophysics Data System (ADS)

    Diehl, Markus; Gaunt, Jonathan R.; Schönwald, Kay

    2017-06-01

    Double parton scattering in proton-proton collisions includes kinematic regions in which two partons inside a proton originate from the perturbative splitting of a single parton. This leads to a double counting problem between single and double hard scattering. We present a solution to this problem, which allows for the definition of double parton distributions as operator matrix elements in a proton, and which can be used at higher orders in perturbation theory. We show how the evaluation of double hard scattering in this framework can provide a rough estimate for the size of the higher-order contributions to single hard scattering that are affected by double counting. In a numeric study, we identify situations in which these higher-order contributions must be explicitly calculated and included if one wants to attain an accuracy at which double hard scattering becomes relevant, and other situations where such contributions may be neglected.

  1. 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.

  2. 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

  3. Variational method based on Retinex with double-norm hybrid constraints for uneven illumination correction

    NASA Astrophysics Data System (ADS)

    Li, Shuo; Wang, Hui; Wang, Liyong; Yu, Xiangzhou; Yang, Le

    2018-01-01

    The uneven illumination phenomenon reduces the quality of remote sensing image and causes interference in the subsequent processing and applications. A variational method based on Retinex with double-norm hybrid constraints for uneven illumination correction is proposed. The L1 norm and the L2 norm are adopted to constrain the textures and details of reflectance image and the smoothness of the illumination image, respectively. The problem of separating the illumination image from the reflectance image is transformed into the optimal solution of the variational model. In order to accelerate the solution, the split Bregman method is used to decompose the variational model into three subproblems, which are calculated by alternate iteration. Two groups of experiments are implemented on two synthetic images and three real remote sensing images. Compared with the variational Retinex method with single-norm constraint and the Mask method, the proposed method performs better in both visual evaluation and quantitative measurements. The proposed method can effectively eliminate the uneven illumination while maintaining the textures and details of the remote sensing image. Moreover, the proposed method using split Bregman method is more than 10 times faster than the method with the steepest descent method.

  4. Could the novel ‘double-hole’ technique be an alternative for the inflow occlusion method?

    PubMed Central

    Bozok, Sahin; Gokhan, Ilhan; Izmir,, Kazdal; Berkan, Ozpak; Ismail, Yurekli; Mert, Kestelli; Serdar, Bayrak

    2016-01-01

    Summary Background Inflow occlusion on beating heart and cardiopulmonary bypass techniques have been proposed for the removal of foreign material, such as stents, catheters and mass lesions, from cardiac chambers. However, both techniques are not devoid of disadvantages and complications. In this article, we define an alternative, novel ‘double-hole’ technique, which is based on opening the right atrium without cardiopulmonary bypass . Methods Bovine hearts were obtained from a local supermarket. Two purse-string sutures were placed in the right atrium using 2-0 braided, non-absorbable polyester suture material, one close to the auricle, and the other close to the interatrial septum. The guidewire of a haemodialysis catheter was inserted through the superior vena cava into the right atrium and passed all the way through the right ventricle. Results We suggest that the double-hole technique may be useful, especially in revision cases with adhesions. Further research should be performed to document the efficacy and safety of this method. Conclusion We are aware that further extensive research is necessary to investigate the utility of this novel technique in contemporary cardiovascular surgery. We believe the doublehole technique has the potential to become a safe, practical and effective measure in the future. PMID:27078129

  5. Macrocyclic BACE inhibitors: Optimization of a micromolar hit to nanomolar leads.

    PubMed

    Huang, Yifang; Strobel, Eric D; Ho, Chih Y; Reynolds, Charles H; Conway, Kelly A; Piesvaux, Jennifer A; Brenneman, Douglas E; Yohrling, George J; Moore Arnold, H; Rosenthal, Daniel; Alexander, Richard S; Tounge, Brett A; Mercken, Marc; Vandermeeren, Marc; Parker, Michael H; Reitz, Allen B; Baxter, Ellen W

    2010-05-15

    We have identified macrocyclic inhibitors of the aspartic protease BACE, implicated in the etiology of Alzheimer's disease. An X-ray structure of screening hit 1 in the BACE active site revealed a hairpin conformation suggesting that constrained macrocyclic derivatives may also bind there. Several of the analogs we prepared were >100x more potent than 1, such as 7 (5 nM K(i)). Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Research on liquid impact forming technology of double-layered tubes

    NASA Astrophysics Data System (ADS)

    Sun, Changying; Liu, Jianwei; Yao, Xinqi; Huang, Beixing; Li, Yuhan

    2018-03-01

    A double-layered tube is widely used and developed in various fields because of its perfect comprehensive performance and design. With the advent of the era of a double-layered tube, the requirements for double layered tube forming quality, manufacturing cost and forming efficiency are getting higher, so forming methods of a double-layered tube are emerged in an endless stream, the forming methods of a double-layered tube have a great potential in the future. The liquid impact forming technology is a combination of stamping technology and hydroforming technology. Forming a double-layered tube has huge advantages in production cost, quality and efficiency.

  7. Simulation of plasma double-layer structures

    NASA Technical Reports Server (NTRS)

    Borovsky, J. E.; Joyce, G.

    1982-01-01

    Electrostatic plasma double layers are numerically simulated by means of a magnetized 2 1/2 dimensional particle in cell method. The investigation of planar double layers indicates that these one dimensional potential structures are susceptible to periodic disruption by instabilities in the low potential plasmas. Only a slight increase in the double layer thickness with an increase in its obliqueness to the magnetic field is observed. Weak magnetization results in the double layer electric field alignment of accelerated particles and strong magnetization results in their magnetic field alignment. The numerical simulations of spatially periodic two dimensional double layers also exhibit cyclical instability. A morphological invariance in two dimensional double layers with respect to the degree of magnetization implies that the potential structures scale with Debye lengths rather than with gyroradii. Electron beam excited electrostatic electron cyclotron waves and (ion beam driven) solitary waves are present in the plasmas adjacent to the double layers.

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

    PubMed

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

    2016-10-01

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

  9. 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.

  10. Computing Determinants by Double-Crossing

    ERIC Educational Resources Information Center

    Leggett, Deanna; Perry, John; Torrence, Eve

    2011-01-01

    Dodgson's method of computing determinants is attractive, but fails if an interior entry of an intermediate matrix is zero. This paper reviews Dodgson's method and introduces a generalization, the double-crossing method, that provides a workaround for many interesting cases.

  11. Rich-Poor Income Gap Hits 40-Year High As Poverty Rate Stalls.

    ERIC Educational Resources Information Center

    Center on Budget and Policy Priorities, Washington, DC.

    On September 26, 1990, the Census Bureau released its 1989 figures on poverty and income which showed that no significant progress was made in reducing poverty in 1989, and that gaps between rich and poor and between the wealthy and the middle class hit their widest points in more than 40 years. Although 1989 marked the seventh year of economic…

  12. Double reading.

    PubMed

    Kopans, D B

    2000-07-01

    Clearly, the cost of double reading varies with the approach used. The Massachusetts General Hospital method can only lead to an increase in recalls and the costs that these engender (anxiety for the women recalled, trauma from any biopsies obtained, and the actual monetary costs of additional imaging and interventions). It is of interest that one potential cost, the concern that women recalled may be reluctant to participate again in screening, does not seem to be the case. Women who are recalled appear to be more likely to participate in future screening. Double interpretation where there must be a consensus between the interpreting radiologists, and if this cannot be reached a third arbiter, is the most labor intensive, but can reduce the number of recalls in a double reading system. Computer systems have been developed to act as a second reader. The films must be digitized and then fed through the reader, but studies suggest that the computer can identify cancers that may be overlooked by a human reader. The challenge is to do this without too many false-positive calls. If the radiologist finds the false-positives are too numerous and distracting, then the system is not used. As digital mammographic systems proliferate, and computer algorithms become more sophisticated, the second human reader will likely be replaced by a computer-aided detection system and double reading will become the norm.

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

    DTIC Science & Technology

    2010-09-01

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

  14. Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi.

    PubMed

    Keenan, Martine; Alexander, Paul W; Chaplin, Jason H; Abbott, Michael J; Diao, Hugo; Wang, Zhisen; Best, Wayne M; Perez, Catherine J; Cornwall, Scott M J; Keatley, Sarah K; Thompson, R C Andrew; Charman, Susan A; White, Karen L; Ryan, Eileen; Chen, Gong; Ioset, Jean-Robert; von Geldern, Thomas W; Chatelain, Eric

    2013-10-01

    Inhibitors of Trypanosoma cruzi with novel mechanisms of action are urgently required to diversify the current clinical and preclinical pipelines. Increasing the number and diversity of hits available for assessment at the beginning of the discovery process will help to achieve this aim. We report the evaluation of multiple hits generated from a high-throughput screen to identify inhibitors of T. cruzi and from these studies the discovery of two novel series currently in lead optimization. Lead compounds from these series potently and selectively inhibit growth of T. cruzi in vitro and the most advanced compound is orally active in a subchronic mouse model of T. cruzi infection. High-throughput screening of novel compound collections has an important role to play in diversifying the trypanosomatid drug discovery portfolio. A new T. cruzi inhibitor series with good drug-like properties and promising in vivo efficacy has been identified through this process.

  15. "I Feel like I'm Being Hit from All Directions": Enduring the Bombardment as a Mature-Age Learner Returning to Formal Learning

    ERIC Educational Resources Information Center

    Willans, Julie; Seary, Karen

    2011-01-01

    The mature-age learner's re-engagement with a formal learning environment may be somewhat akin to the novice Paintball player who, unless well positioned and attuned to the rules of the combative game, is bombarded and worn down by constant "hits". For the mature-age learner, such "hits" may come in the form of tensions…

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

    PubMed Central

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

    2015-01-01

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

  17. 'That's OK. He's a guy': a mixed-methods study of gender double-standards for alcohol use.

    PubMed

    de Visser, Richard O; McDonnell, Elizabeth J

    2012-01-01

    Although drinking and drunkenness have traditionally been considered masculine behaviours, young women's alcohol consumption has increased in recent years. This mixed methods study was conducted to examine the extent to which young people endorse gender double-standards for alcohol use--i.e., less acceptance of drinking and drunkenness in women than men--and how these influence men's and women's alcohol consumption. A sample of 731 English university students completed an online survey of gender role attitudes, beliefs about the gendered nature of alcohol use and recent alcohol consumption. Sixteen participants were then purposively selected for individual interviews: eight women and men with the most egalitarian gender role beliefs, and eight women and men with the least egalitarian beliefs. The two sets of data revealed that although there were few sex differences in actual levels of drinking or drunkenness, gender double-standards for alcohol use persist: beer drinking, binge drinking and public drunkenness tended to be perceived as masculine, and even the most egalitarian respondents were more judgemental of women's drinking. Participants modified their drinking style so as to maintain a desired gender identity. Although gender double-standards could be a focus of interventions to encourage moderate drinking, such approaches could reinforce gender inequalities.

  18. Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia.

    PubMed

    Richards, Edward J; Zhang, Gu; Li, Zhu-Peng; Permuth-Wey, Jennifer; Challa, Sridevi; Li, Yajuan; Kong, William; Dan, Su; Bui, Marilyn M; Coppola, Domenico; Mao, Wei-Min; Sellers, Thomas A; Cheng, Jin Q

    2015-03-13

    Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes. Epithelial-to-mesenchymal transition (EMT) is a developmental process hijacked by tumor cells to depart from the primary tumor site, invade surrounding tissue, and establish distant metastases. Transforming growth factor β (TGFβ) signaling has been shown to be a major inducer of EMT and to facilitate breast cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here we report a genome-wide lncRNA profile in mouse mammary epithelial NMuMG cells upon TGFβ induction of EMT. Among 10,802 lncRNAs profiled, over 600 were up-regulated and down-regulated during the EMT, respectively. Furthermore, we identify that lncRNA-HIT (HOXA transcript induced by TGFβ) mediates TGFβ function, i.e. depletion of lncRNA-HIT inhibits TGFβ-induced migration, invasion, and EMT in NMuMG. LncRNA-HIT is also significantly elevated in the highly metastatic 4T1 cells. Knockdown of lncRNA-HIT in 4T1 results in decrease of cell migration, invasion, tumor growth, and metastasis. E-cadherin was identified as a major target of lncRNA-HIT. Moreover, lncRNA-HIT is conserved in humans and elevated expression associates with more invasive human primary breast carcinoma. Collectively, these data suggest that a subset of lncRNAs such as lncRNA-HIT play a significant role in regulation of EMT and breast cancer invasion and metastasis, and could be potential therapeutic targets in breast cancers. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Hurricane Matthew Hits Haiti

    NASA Image and Video Library

    2017-12-08

    Read more from: go.nasa.gov/2duxEeZ On October 4, 2016, Hurricane Matthew made landfall on southwestern Haiti as a category-4 storm—the strongest storm to hit the Caribbean nation in more than 50 years. Just hours after landfall, the Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA’s Terra satellite acquired this natural-color image. At the time, Matthew had top sustained winds of about 230 kilometers (145 miles) per hour. Earlier on October 4, temperature data collected by MODIS on NASA’s Aqua satellite revealed that the cloud tops around Matthew were very cold (at least -57° Celsius, or -70° Fahrenheit). Cold cloud tops are known to produce heavy rainfall. The National Hurricane Center called for 380 to 500 millimeters (15 to 20 inches) of rain in Southern Haiti and in the southwestern Dominican Republic. The northward movement of the storm should bring the center of Matthew over eastern Cuba late on October 4. Dangerous conditions can extend far beyond a storm’s center. According to National Hurricane Center forecasters, Matthew is “likely to produce devastating impacts from storm surge, extreme winds, heavy rains, flash floods, and/or mudslides in portions of the watch and warning areas in Haiti, Cuba, and the Bahamas.” NASA Earth Observatory image by Joshua Stevens, using MODIS data from the Land Atmosphere Near real-time Capability for EOS (LANCE). Caption by Kathryn Hansen.

  20. TJC: HCOs need to be on alert for HIT problems related to sociotechnical factors, take steps to improve safety culture, process, and leadership.

    PubMed

    2015-06-01

    Noting that too many errors related to health information technology (HIT) are resulting in adverse consequences, The Joint Commission (TJC) has issued a Sentinel Event Alert, urging health care providers to take steps to improve their safety culture, approach to process improvement, and leadership in this area. In this latest alert, the accrediting agency is taking particular aim at risks posed by sociotechnical factors--or the ways in which HIT is implemented and used. Experts say that many of these risks are, in fact, exemplified at a higher level in the emergency setting, where providers are under constant pressure to see more patients and move them though the system faster. In an analysis of 3,375 sentinel events that resulted in permanent patient harm or death between January 1, 2010, and June 20, 2013, The Joint Commission (TJC) found that 120 events included HIT-related contributing factors. Many of the problems cited by TJC relate to orders or medicines being prescribed for the wrong patients. These can result from toggling errors or pop-up screens where providers are asked to click on the appropriate patient or medicine, and they mistakenly click on the wrong selection. In the ED, experts recommend the creation of a multidisciplinary performance improvement group to continuously monitor the ED information system (EDIS), recognize problems, and work with the vendor to resolve them. Also important is a quick and easy way for providers to report HIT-related problems. Experts add that emergency providers need to be fully engaged in the process of selecting HIT that they will be using, and that health care organizations should arrange for usability assessments before purchasing HIT.