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Sample records for adverse prognostic impact

  1. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  2. Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer

    PubMed Central

    Sang, Yulan; Bi, Xin; Liu, Yan; Zhang, Wei; Wang, Dongjie

    2017-01-01

    Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals. By using chi-square (χ2) test and Fisher’s exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan–Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients. PMID:28331344

  3. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia

    PubMed Central

    Qiu, Yi Hua; Zhang, Nianxiang; Singh, Neera; Faderl, Stefan; Ferrajoli, Alessandra; York, Heather; Qutub, Amina A.; Coombes, Kevin R.; Watson, Dennis K.

    2011-01-01

    Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P = .02). Compared with normal CD34+ cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P = .002) but not with age or cytogenetics. Mutated NPM1 (P = .0007) or FLT3-ITD (P < .02) had higher expression. FLI1 levels were negatively correlated with 10 of 195 proteins associated with proliferation and stromal interaction, and positively correlated (R > 0.3) with 19 others. The FLI1 level was not predictive of remission attainment, but patients with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs 51.1 weeks, respectively; P = .01) and overall survival (45.2 and 35.4 vs 59.4 weeks, respectively; P = .03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology. PMID:21917756

  4. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia.

    PubMed

    Kornblau, Steven M; Qiu, Yi Hua; Zhang, Nianxiang; Singh, Neera; Faderl, Stefan; Ferrajoli, Alessandra; York, Heather; Qutub, Amina A; Coombes, Kevin R; Watson, Dennis K

    2011-11-17

    Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P = .02). Compared with normal CD34(+) cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P = .002) but not with age or cytogenetics. Mutated NPM1 (P = .0007) or FLT3-ITD (P < .02) had higher expression. FLI1 levels were negatively correlated with 10 of 195 proteins associated with proliferation and stromal interaction, and positively correlated (R > 0.3) with 19 others. The FLI1 level was not predictive of remission attainment, but patients with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs 51.1 weeks, respectively; P = .01) and overall survival (45.2 and 35.4 vs 59.4 weeks, respectively; P = .03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology.

  5. Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia

    PubMed Central

    Roumier, Christophe; Peyrouze, Pauline; Gonzales, Fanny; Berthon, Céline; Quesnel, Bruno; Preudhomme, Claude; Behal, Hélène; Duhamel, Alain; Roche-Lestienne, Catherine; Cheok, Meyling

    2016-01-01

    CD81 is a cell surface protein which belongs to the tetraspanin family. While in multiple myeloma its expression on plasma cells is associated with worse prognosis, this has not yet been explored in acute myeloid leukemia (AML). We measured membrane expression of CD81 on AML cells at diagnosis, evaluated its association with AML characteristics and its influence on patient outcome after intensive chemotherapy in a cohort of 134 patients. CD81 was detected in 92/134 (69%) patients. Patients with AML expressing CD81 had elevated leukocyte count (P=0.02) and were more likely classified as intermediate or adverse-risk by cytogenetics (P<0.001). CD81 expression had a negative impact on survival (event-free survival, overall survival and relapse-free survival) in univariate (P<0.001) and in multivariate analyses (P=0.003, 0.002 and <0.001, respectively). CD81 has a negative impact on OS in patients with NPM1 mutation (P=0.01) and in patients ELN-favorable (P=0.002). In conclusion, this cell surface marker may be a new prognostic marker for diagnostic risk classification and a potential therapeutic target for drug development in AML. PMID:27566555

  6. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.

    PubMed

    O'Connor, Kate; Li-Chang, Hector H; Kalloger, Steven E; Peixoto, Renata D; Webber, Douglas L; Owen, David A; Driman, David K; Kirsch, Richard; Serra, Stefano; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-04-01

    Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

  7. Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Granito, Alessandro; Marinelli, Sara; Negrini, Giulia; Menetti, Saverio; Benevento, Francesca; Bolondi, Luigi

    2016-01-01

    Sorafenib is the standard treatment for patients with hepatocellular carcinoma (HCC) with advanced stage disease. Although its effectiveness has been demonstrated by randomized clinical trials and confirmed by field practice studies, reliable markers predicting therapeutic response have not yet been identified. Like other tyrosine kinase inhibitors, treatment with sorafenib is burdened by the development of adverse effects, the most frequent being cutaneous toxicity, diarrhoea, arterial hypertension and fatigue. In recent years, several studies have analysed the correlation between off-target effects and sorafenib efficacy in patients with HCC. In this review, an overview of the studies assessing the prognostic significance of sorafenib-related adverse events is provided. PMID:26929785

  8. Reducing Adverse Impact: One City's Efforts.

    ERIC Educational Resources Information Center

    Prewitt, Jeff

    Following a workshop on "Innovations in Employment Testing that Improve Validity and Reduce Adverse Impact," the City of Louisville (Kentucky) implemented a strategy to develop a comprehensive testing and recruiting program for police recruits. To improve candidate expectations and preparation, the following activities were undertaken:…

  9. Mitigation of adverse environmental and unavoidable impacts

    SciTech Connect

    1995-10-01

    This portion of the Energy Vision 2020 draft report is a broad scope discussion of the mitigation of adverse environmental and unavoidable impacts. TVA will mitigate site specific environmental impacts from the construction and operation of new power facilities through a combination of planning, pollution prevention, and environmental controls. However, one of the most important mitigative measures associated with Energy Vision 2020 is the multi-attribute tradeoff method used for the evaluation. This method allowed proposed strategies to be reformated in order to reduce potential impacts.

  10. Adverse weather impacts on arable cropping systems

    NASA Astrophysics Data System (ADS)

    Gobin, Anne

    2016-04-01

    Damages due to extreme or adverse weather strongly depend on crop type, crop stage, soil conditions and management. The impact is largest during the sensitive periods of the farming calendar, and requires a modelling approach to capture the interactions between the crop, its environment and the occurrence of the meteorological event. The hypothesis is that extreme and adverse weather events can be quantified and subsequently incorporated in current crop models. Since crop development is driven by thermal time and photoperiod, a regional crop model was used to examine the likely frequency, magnitude and impacts of frost, drought, heat stress and waterlogging in relation to the cropping season and crop sensitive stages. Risk profiles and associated return levels were obtained by fitting generalized extreme value distributions to block maxima for air humidity, water balance and temperature variables. The risk profiles were subsequently confronted with yields and yield losses for the major arable crops in Belgium, notably winter wheat, winter barley, winter oilseed rape, sugar beet, potato and maize at the field (farm records) to regional scale (statistics). The average daily vapour pressure deficit (VPD) and reference evapotranspiration (ET0) during the growing season is significantly lower (p < 0.001) and has a higher variability before 1988 than after 1988. Distribution patterns of VPD and ET0 have relevant impacts on crop yields. The response to rising temperatures depends on the crop's capability to condition its microenvironment. Crops short of water close their stomata, lose their evaporative cooling potential and ultimately become susceptible to heat stress. Effects of heat stress therefore have to be combined with moisture availability such as the precipitation deficit or the soil water balance. Risks of combined heat and moisture deficit stress appear during the summer. These risks are subsequently related to crop damage. The methodology of defining

  11. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  12. Childhood adversity impacts on brain subcortical structures relevant to depression.

    PubMed

    Frodl, Thomas; Janowitz, Deborah; Schmaal, Lianne; Tozzi, Leonardo; Dobrowolny, Henrik; Stein, Dan J; Veltman, Dick J; Wittfeld, Katharina; van Erp, Theo G M; Jahanshad, Neda; Block, Andrea; Hegenscheid, Katrin; Völzke, Henry; Lagopoulos, Jim; Hatton, Sean N; Hickie, Ian B; Frey, Eva Maria; Carballedo, Angela; Brooks, Samantha J; Vuletic, Daniella; Uhlmann, Anne; Veer, Ilya M; Walter, Henrik; Schnell, Knut; Grotegerd, Dominik; Arolt, Volker; Kugel, Harald; Schramm, Elisabeth; Konrad, Carsten; Zurowski, Bartosz; Baune, Bernhard T; van der Wee, Nic J A; van Tol, Marie-Jose; Penninx, Brenda W J H; Thompson, Paul M; Hibar, Derrek P; Dannlowski, Udo; Grabe, Hans J

    2017-03-01

    Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.

  13. Prognostic impact of metallothionein on oral squamous cell carcinoma.

    PubMed

    Cardoso, Sérgio V; Barbosa, Hugo M; Candellori, Ignez M; Loyola, Adriano M; Aguiar, Maria Cássia F

    2002-08-01

    Metallothionein (MT), a low-molecular-weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. MT overexpression in neoplasms of ectodermal origin is usually associated with a poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell carcinoma by immunohistochemistry to study its prognostic influence on oral cancer. Possible associations of MT immunoexpression were also investigated with respect to clinical stage (TNM), histological grading, and proliferation index (Ki-67) of the lesions. No significant statistical correlation was observed among these variables. The impact on overall survival was assessed by uni and multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling indexes (over 76%) predicted shorter survival in univariate statistical analysis. In multivariate analysis, MT labeling index and clinical stage were independent prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be related to a worse prognosis for patients.

  14. IDH mutations: genotype-phenotype correlation and prognostic impact.

    PubMed

    Wang, Xiao-Wei; Ciccarino, Pietro; Rossetto, Marta; Boisselier, Blandine; Marie, Yannick; Desestret, Virginie; Gleize, Vincent; Mokhtari, Karima; Sanson, Marc; Labussière, Marianne

    2014-01-01

    IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated--which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

  15. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    SciTech Connect

    Mestre, Francisco; Gutiérrez, Antonio; Rodriguez, Jose; Ramos, Rafael; Garcia, Juan Fernando; Martinez-Serra, Jordi; Casasus, Marta; Nicolau, Cristina; Bento, Leyre; Herraez, Ines; Lopez-Perezagua, Paloma; Daumal, Jaime; Besalduch, Joan

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  16. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  17. Incremental prognostic value of computed tomography in stroke: rationale and design of the IMPACTS study.

    PubMed

    Lee, Ji Won; Hur, Jin; Choi, Sang Il; Chun, Eun Ju; Kang, Joon-Won; Jin, Gong Yong; Kim, Eun Young; Yong, Hwan Seok; Kang, Eun-Ju; Han, Kyunghwa; Lee, Hoon-Suk; Choi, Byoung Wook

    2016-06-01

    This study was designed to determine the prognostic value of coronary computed tomography angiography (CCTA) in ischemic stroke patients and to identify any incremental risk stratification benefits of CCTA findings compared with coronary artery calcium scoring (CACS) and traditional Framingham risk scores (FRS) in ischemic stroke patients without chest pain. IMPACTS is a prospective, multicenter, observational cohort study in which at least seven centers in Korea will participate. All participants will be enrolled in this study after providing informed consent. Nine hundred total ischemic stroke patients without chest pain will be enrolled and will undergo CACS and CCTA. All participants will be followed-up for a minimum of 24 months to determine the endpoints. The primary endpoint will be occurrence of major adverse cardiovascular events (MACEs), defined as all-cause mortality, cardiovascular death, myocardial infarction, or cardiovascular events requiring hospitalization and revascularization either by percutaneous coronary intervention or by coronary artery bypass graft after 90 days of index testing during the follow-up period. Patient enrollment should be completed within 2.5 years. We plan to analyze and identify the CCTA predictors of MACEs. In addition, we will compare several models used to assess independent relationships between the variables and MACEs using a shared frailty model and therefore determine the incremental prognostic value of CCTA findings compared with either the CACS or FRS. The results of IMPACTS will provide valuable information for risk stratification with CCTA in ischemic stroke patients without chest pain.

  18. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  19. Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis

    PubMed Central

    Cho, Kyoung Im; Cho, Sang Hoon; Her, Ae-Young; Singh, Gillian Balbir; Shin, Eun-Seok

    2016-01-01

    Background Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS). We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) and major adverse cardiovascular events (MACE) in patients with severe calcific AS. Methods A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH) regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I) and undergoing aortic valve replacement (AVR). We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk) as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period. Results The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.04–1.09; p-value <0.001]. The goodness-of-fit and discriminability of the model including EuroSCORE-I and AVR (loglikelihood difference, 15.49; p-value <0.001; c-index difference, 0.035; p-value = 0.03) were significantly improved when NLR was incorporated into the model. The estimated Kaplan-Meier survival rates at 5 years for the NLR risk groups were 84.6% for the low risk group (NLR ≤ 2), 67.7% for the intermediate risk group (2 < NLR ≤ 9), and 42.6% for the high risk group (NLR > 9), respectively. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS. PMID:27548384

  20. PD-L1 expression and prognostic impact in glioblastoma

    PubMed Central

    Nduom, Edjah K.; Wei, Jun; Yaghi, Nasser K.; Huang, Neal; Kong, Ling-Yuan; Gabrusiewicz, Konrad; Ling, Xiaoyang; Zhou, Shouhao; Ivan, Cristina; Chen, Jie Qing; Burks, Jared K.; Fuller, Greg N.; Calin, George A.; Conrad, Charles A.; Creasy, Caitlin; Ritthipichai, Krit; Radvanyi, Laszlo; Heimberger, Amy B.

    2016-01-01

    Background Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. Methods Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. Results The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%–86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. Conclusions The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome. PMID:26323609

  1. Loss of RUNX3 expression is an independent adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Duncan, Virginia E; Ping, Zheng; Varambally, Sooryanarayana; Peker, Deniz

    2017-01-01

    Runt-related transcription factor-3 (RUNX3) is an apoptotic factor correlated with tumorigenesis and cancer progression. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. We investigated RUNX3 and EZH2 expression in diffuse large B-cell lymphoma (DLBCL). A chart review was conducted and tissue-microarray (TMA) was constructed using archived tissue from 83 DLBCL cases. RUNX3 and EZH2 protein expression was correlated with immunophenotypic subtypes and survival. Loss of RUNX3 was observed in 20 cases; EZH2 expression was observed in 59 cases. RUNX3-negative tumors had significantly lower overall and recurrence-free survival (log-rank test, p < 0.0001 for each). No correlation was found between RUNX3 and EZH2 staining (r = 0.14; p = 0.2). Results suggest a role for the RUNX3 gene in the pathogenesis of DLBCL. Loss of RUNX3 expression strongly correlated with adverse prognosis, independent of subtype. Further studies are warranted to elucidate the biology and prognostic utility of RUNX3 in DLBCL.

  2. Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma

    PubMed Central

    Shah, Monil; Mulcahy Levy, Jean M.; Griesinger, Andrea M.; Alimova, Irina; Harris, Peter S.; Birks, Diane K.; Donson, Andrew M.; Davidson, Nathan; Remke, Marc; Taylor, Michael D.; Handler, Michael H.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

    2016-01-01

    Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation. PMID:27449089

  3. Prognostic impact of stress testing in coronary artery disease

    SciTech Connect

    Severi, S.; Michelassi, C. )

    1991-05-01

    Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and {sup 201}Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.47 references.

  4. Prognostic Impact of Autophagy Biomarkers for Cutaneous Melanoma

    PubMed Central

    Tang, Diana Y. L.; Ellis, Robert A.; Lovat, Penny E.

    2016-01-01

    Prognosis and survival for malignant melanoma is highly dependent on early diagnosis and treatment. While the American Joint Committee on Cancer (AJCC) criterion provides a means of staging melanomas and guiding treatment approaches, it is unable to identify the risk of disease progression of early stage tumors or provide reliable stratification for novel adjuvant therapies. The demand for credible prognostic/companion biomarkers able to identify high-risk melanoma subgroups as well as guide more effective personalized/precision-based therapy is therefore of paramount importance. Autophagy, the principle lysosomal-mediated process for the degradation/recycling of cellular debris, is a hot topic in cancer medicine, and observations of its deregulation in melanoma have brought its potential as a prognostic biomarker to the forefront of current research. Key regulatory proteins, including Atg8/microtubule-associated light chain 3 (LC3) and BECN1 (Beclin 1), have been proposed as potential prognostic biomarkers. However, given the dynamic nature of autophagy, their expression in vitro does not translate to their use as a prognostic biomarker for melanoma in vivo. We have recently identified the expression levels of Sequestosome1/SQSTM1 (p62) and activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) as novel independent prognostic biomarkers for early stage melanomas. While increasing followed by subsequent decreasing levels of p62 expression reflects the paradoxical role of autophagy in melanoma, expression levels additionally define a novel prognostic biomarker for AJCC stage II tumors. Conversely, loss of AMBRA1 in the epidermis overlying primary melanomas defines a novel prognostic biomarker for AJCC stage I tumors. Collectively, the definition of AMBRA1 and p62 as prognostic biomarkers for early stage melanomas provides novel and accurate means through which to identify tumors at risk of disease progression, facilitating earlier patient therapeutic

  5. Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome

    PubMed Central

    Kim, Inho; Kim, Hyeoung-Joon; Shin, Dong-Yeop; Koh, Youngil; Yoon, Sung-Soo; Min, Yoo Hong; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Lee, Yun-Gyoo; Lee, Jeong-Ok; Bang, Soo-Mee; Mun, Yeung-Chul; Seong, Chu-Myoung; Park, Yong; Kim, Byung-Soo; Hong, Junshik; Park, Jinny; Lee, Jae Hoon; Kim, Sung-Yong; Lee, Hong Ghi

    2016-01-01

    Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment. PMID:27824923

  6. Prognostic Impact of del(17p) and del(22q) as Assessed by Interphase FISH in Sporadic Colorectal Carcinomas

    PubMed Central

    González-González, María; Muñoz-Bellvis, Luís; Mackintosh, Carlos; Fontanillo, Celia; Gutiérrez, M. Laura; Abad, M. Mar; Bengoechea, Oscar; Teodosio, Cristina; Fonseca, Emilio; Fuentes, Manuel; De Las Rivas, Javier

    2012-01-01

    Background Most sporadic colorectal cancer (sCRC) deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC. Methodology/Principal Findings We prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 1, 7, 8, 13, 14, 17, 18, 20, and 22 by iFISH in 58 sCRC patients: thirty-one non-metastatic (54%) vs. 27 metastatic (46%) disease. From a total of 18 probes, significant differences emerged only for the 17p11.2 and 22q11.2 chromosomal regions. Patients with liver metastatic sCRC showed an increased frequency of del(17p11.2) (10% vs. 67%;p<.001) and del(22q11.2) (0% vs. 22%;p = .02) versusnon-metastatic cases. Multivariate analysis of prognostic factors for overall survival (OS) showed that the only clinical and cytogenetic parameters that had an independent adverse impact on patient outcome were the presence of del(17p) with a 17p11.2 breakpoint and del(22q11.2). Based on these two cytogenetic variables, patients were classified into three groups: low- (no adverse features), intermediate- (one adverse feature) and high-risk (two adverse features)- with significantly different OS rates at 5-years (p<.001): 92%, 53% and 0%, respectively. Conclusions/Significance Our results unravel the potential implication of del(17p11.2) in sCRC patients with liver metastasis as this cytogenetic alteration appears to be intrinsically related to an increased metastatic potential and a poor outcome, providing additional prognostic information to that associated with other cytogenetic alterations such as del(22q11.2). Additional prospective studies in larger series of patients would be required to confirm the clinical utility of the new prognostic markers identified. PMID:22912721

  7. Adverse Pregnancy Outcomes: Opportunity for Analysis of Biospecimens and Co-development of Prognostics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pregnancy and Perinatology Branch seeks partners interested in collaborative research to: (i) evaluate data and samples taken from women for potential biomarkers indicative for adverse pregnancy outcomes and (ii) co-develop diagnostic kits useful as predictors of adverse pregnancy outcomes.

  8. SSAIS: A Program to Assess Adverse Impact in Multistage Selection Decisions

    ERIC Educational Resources Information Center

    De Corte, Wilfried

    2004-01-01

    The article describes a Windows program to estimate the expected value and sampling distribution function of the adverse impact ratio for general multistage selections. The results of the program can also be used to predict the risk that a future selection decision will result in an outcome that reflects the presence of adverse impact. The method…

  9. Negative affect predicts adults' ratings of the current, but not childhood, impact of adverse childhood events.

    PubMed

    LaNoue, Marianna; Graeber, David A; Helitzer, Deborah L; Fawcett, Jan

    2013-10-01

    Adverse childhood events (ACE's) have been empirically related to a wide range of negative health and mental health outcomes. However, not all individuals who experience ACE's follow a trajectory of poor outcomes, and not all individuals perceive the impact of ACE's as necessarily negative. The purpose of this study was to investigate positive and negative affect as predictors of adults' ratings of both the childhood and adult impact of their childhood adversity. Self-report data on ACE experiences, including number, severity, and 'impact' were collected from 158 community members recruited on the basis of having adverse childhood experiences. Results indicated that, regardless of event severity and number of different types of adverse events experienced, high levels of negative affect were the strongest predictor of whether the adult impact of the adverse childhood events was rated as negative. All individuals rated the childhood impact of events the same. Implications are discussed.

  10. Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

    PubMed Central

    Chang, I-Wei; Li, Chien-Feng; Lin, Victor Chia-Hsiang; He, Hong-Lin; Liang, Per-In; Wu, Wen-Jeng; Li, Ching-Chia; Huang, Chun-Nung

    2016-01-01

    Purpose: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene. Materials and Methods: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS). Results: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses. Conclusion: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs. PMID:27471570

  11. Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer

    PubMed Central

    Lee, Yong Joon; Kim, Woo Ram; Han, Jeonghee; Han, Yoon Dae; Cho, Min Soo; Hur, Hyuk; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Purpose Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (<5, 5–10, and >10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. Results No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (<5); only 15% had a high dPNI (>10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). Conclusion The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes. PMID:28119863

  12. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  13. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.

    PubMed

    Hatanpaa, Kimmo J; Hu, Tianshen; Vemireddy, Vamsidhara; Foong, Chan; Raisanen, Jack M; Oliver, Dwight; Hiemenz, Matthew C; Burns, Dennis K; White, Charles L; Whitworth, L Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A; Fink, Karen; Maher, Elizabeth A; Bachoo, Robert M

    2014-03-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).

  14. CD38+ CD58- is an independent adverse prognostic factor in paediatric Philadelphia chromosome negative B cell acute lymphoblastic leukaemia patients.

    PubMed

    Li, Xu-Mian; Zhang, Le-Ping; Wang, Ya-Zhe; Lu, Ai-Dong; Chang, Yan; Zhu, Hong-Hu; Qin, Ya-Zhen; Lai, Yue-Yun; Kong, Yuan; Huang, Xiao-Jun; Liu, Yan-Rong

    2016-04-01

    To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P<0.01; 32.5% vs 91.0%, P=0.01); CD38+ CD58- was an independent adverse prognostic predictor for relapse (hazard ratio [HR], 0.203; 95%CI, 0.063-0.656; P=0.01), 3-year EFS (HR, 0.091; 95%CI, 0.023-0.355; P<0.01) and OS (HR, 0.102; 95%CI, 0.026-0.3971; P<0.01) in this cohort, as determined by Cox multivariate analysis. We identified, for the first time, a higher risk population of paediatric Ph- B-ALL patients with CD38+ CD58- who had a higher relapse risk and a shorter survival. Our results may allow better risk stratification and individualized treatment.

  15. Prognostic impact of monocyte count at presentation in mantle cell lymphoma.

    PubMed

    von Hohenstaufen, Kathrin Aprile; Conconi, Annarita; de Campos, Cassio Polpo; Franceschetti, Silvia; Bertoni, Francesco; Margiotta Casaluci, Gloria; Stathis, Anastasios; Ghielmini, Michele; Stussi, Georg; Cavalli, Franco; Gaidano, Gianluca; Zucca, Emanuele

    2013-08-01

    An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

  16. Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer

    PubMed Central

    Lu, Wei; Cao, Yang; Zhang, Yijian; Li, Sheng; Gao, Jian; Wang, Xu-An; Mu, Jiasheng; Hu, Yun-Ping; Jiang, Lin; Dong, Ping; Gong, Wei; Liu, Yingbin

    2016-01-01

    Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. PMID:27283076

  17. Tumor Epression of Major Vault Protein is an Adverse Prognostic Factor for Radiotherapy Outcome in Oropharyngeal Carcinoma

    SciTech Connect

    Silva, Priyamal; West, Catharine M.; Slevin, Nick F.R.C.R.; Valentine, Helen; Ryder, W. David J. Grad. I.S.; Hampson, Lynne; Bibi, Rufzan; Sloan, Philip; Thakker, Nalin; Homer, Jarrod; Hampson, Ian

    2007-09-01

    Purpose: Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport, with the major vault protein (MVP or lung resistance-related protein [LRP]) being the main component. The MVP gene is located on chromosome 16 close to the multidrug resistance-associated protein and protein kinase c-{beta} genes. The role of MVP in cancer drug resistance has been demonstrated in various cell lines as well as in ovarian carcinomas and acute myeloid leukemia, but nothing is known about its possible role in radiation resistance. Our aim was to examine this in head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Archived biopsy material was obtained for 78 patients with squamous cell carcinoma of the oropharynx who received primary radiotherapy with curative intent. Immunohistochemistry was used to detect MVP expression. Locoregional failure and cancer-specific survival were estimated using cumulative incidence and Cox multivariate analyses. Results: In a univariate and multivariate analysis, MVP expression was strongly associated with both locoregional failure and cancer-specific survival. After adjustment for disease site, stage, grade, anemia, smoking, alcohol, gender, and age, the estimated hazard ratio for high MVP (2/3) compared with low (0/1) was 4.98 (95% confidence interval, 2.17-11.42; p 0.0002) for locoregional failure and 4.28 (95% confidence interval, 1.85-9.95; p = 0.001) for cancer-specific mortality. Conclusion: These data are the first to show that MVP may be a useful prognostic marker associated with radiotherapy resistance in a subgroup of patients with HNSCC.

  18. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters.

    PubMed

    Catasus, Lluis; Gallardo, Alberto; Cuatrecasas, Miriam; Prat, Jaime

    2008-02-01

    Mutations of the oncogene PIK3CA occur frequently in endometrial carcinomas, but their prognostic significance is unclear. To determine the clinicopathological and molecular implications of these mutations, PIK3CA status was investigated in 109 endometrial (102 endometrioid and 7 mixed) carcinomas and the results were compared with clinicopathological parameters associated with prognosis. Tumors were also investigated for microsatellite instability and PTEN, beta-catenin gene (CTNNB1), K-RAS, and B-RAF mutations. We found 35 PIK3CA somatic missense mutations in 32 (29%) endometrial carcinomas. Eighteen mutations occurred in exon 20 (kinase domain), and 17 in exon 9 (helical domain). Almost all mutated tumors were pure endometrioid adenocarcinomas. All tumors with PIK3CA mutations exhibited myometrial invasion (P=0.032). Lymphovascular invasion was found more frequently in mutated (28%) than nonmutated carcinomas (18%). Histological grade varied significantly according to the location of the PIK3CA mutations whether in exon 9 or exon 20 (P=0.033). The frequency of exon 9 mutations was higher in grade 1 carcinomas (57%) than in grade 2 (29%) or grade 3 (14%) tumors. Conversely, mutations in exon 20 were more common in grade 3 (60%) than in grade 2 (20%) or grade 1 (20%) carcinomas. None of the tumors confined to the endometrium (stage IA) had PIK3CA mutations. Furthermore, whereas 64% of adenocarcinomas with exon 9 mutations had invaded < or =(1/2) of the myometrial thickness (stage IB), 73% of tumors with exon 20 mutations had either deeper myometrial invasion (stage IC) or cervical involvement (stage II) (P=0.045). PIK3CA mutations coexisted with microsatellite instability and mutations in PTEN, CTNNB1, K-RAS, and B-RAF genes. These results favor that PIK3CA mutations are associated with myometrial invasion and, moreover, that tumors harboring PIK3CA mutations in exon 20 are frequently high-grade, deeply invasive endometrial carcinomas that tend to exhibit

  19. The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

    PubMed Central

    Nahajevszky, Sarolta; Andrikovics, Hajnalka; Batai, Arpad; Adam, Emma; Bors, Andras; Csomor, Judit; Gopcsa, Laszlo; Koszarska, Magdalena; Kozma, Andras; Lovas, Nora; Lueff, Sandor; Matrai, Zoltan; Meggyesi, Nora; Sinko, Janos; Sipos, Andrea; Varkonyi, Andrea; Fekete, Sandor; Tordai, Attila; Masszi, Tamas

    2011-01-01

    Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus

  20. Prognostic value of depression, anxiety, and anger in hospitalized cardiovascular disease patients for predicting adverse cardiac outcomes.

    PubMed

    Nakamura, Shunichi; Kato, Koji; Yoshida, Asuka; Fukuma, Nagaharu; Okumura, Yasuyuki; Ito, Hiroto; Mizuno, Kyoichi

    2013-05-15

    Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease (CVD), the factors that have the greatest influence on prognosis have not yet been elucidated. The aim of this study was to evaluate the effects of depression, anxiety, and anger on the prognosis of patients with CVD. Four hundred fourteen consecutive patients hospitalized with CVD were prospectively enrolled. Depression was evaluated using the Patient Health Questionnaire, anxiety using the Generalized Anxiety Disorder Questionnaire, and anger using the Spielberger Trait Anger Scale. Cox proportional-hazards regression was used to examine the individual effects of depression, anxiety, and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up (median 14.2 months). Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors (hazard ratio 2.62, p = 0.02), whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment (hazard ratio 2.35, p = 0.10). Anger was associated with a low rate of cardiovascular hospitalization or death (hazard ratio 0.34, p <0.01). In conclusion, depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger. Anger may help prevent adverse outcomes. Routine screening for depression should therefore be performed in patients with CVD, and the potential effects of anger in clinical practice should be reconsidered.

  1. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukaemia definition.

    PubMed

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara M; Teixidó, Montserrat; Gimenez, Maria Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Blade, Joan; Fernández de Larrea, Carlos

    2017-03-02

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the present study, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analysed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukaemia were reviewed and patients were classified in four categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20% and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%) respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95%CI 2.6-9.3) independently of age, creatinine, Durie-Salmon and international stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86x109/L vs. 214x109/L, p<0.0001) and higher bone marrow plasma cells (median 53% vs. 36%, p=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has similar adverse prognostic impact as plasma cell leukemia.

  2. Impacts of Prognostic Phenology and Agriculture on the Seasonal Cycle of Carbon Fluxes

    NASA Astrophysics Data System (ADS)

    Haynes, K. D.; Baker, I. T.; Denning, A.; Stockli, R.; Lokupitiya, E. Y.

    2011-12-01

    Since terrestrial carbon fluxes cannot be measured directly on regional and global scales, land surface models are an important tool in improving estimates of carbon sources and sinks. One common limitation in biosphere models is requiring the use of remotely sensed data to represent vegetation phenology; however, prognostic phenology models are being developed to predict the phonological timing and leaf state of both natural vegetation and crops (Stockli et al., 2008; Lokupitiya et al., 2009; Stockli et al., 2011). Simulating phenology rather than relying on data products removes the uncertainty due to satellite retrievals, allows the short yet highly productive growing season of crops to be more accurately simulated, and enables predictive capabilities. The Simple Biosphere Model (SiB) has been modified to include prognostic phenology for twenty different plant functional types, including maize, soybean and wheat. Predicting the phenology will alter carbon fluxes regionally and globally on diurnal to seasonal timescales, and this study will discuss the impact of prognostic phenology on the resulting simulated net ecosystem exchange of carbon dioxide.

  3. The adverse prognostic hallmarks in identical twins with Langerhans cell histiocytosis: a clinical report and literature review.

    PubMed

    Chai, Damin; Tao, Yisheng; Bao, Zhengqi; Yang, Li; Feng, Zhenzhong; Ma, Li; Liang, Limei; Zhou, Xinwen

    2013-01-01

    Langerhans cell histiocytosis (LCH) is characterized by uncontrolled proliferation of Langerhans cells accompanying eosinophils. It often attacks children under 10 years of age. LCH in identical twins is very rare and its prognosis is different. Here we report identical-twin sisters with LCH. Computed tomography (CT) revealed osteolytic change in each twin's skull, and the elder exhibited poor eyesight. There were massive histiocyte-like cells surrounded by eosinophils in pathologic specimen of the abnormal lesions, which is typical pathologic finding in LCH. These pathologic cells were positive for S-100 and the cell surface protein CD1 antigen (CD1α), the known markers of LCH. After treating them with surgery, no symptoms were seen in the younger until now. While the older was found another soft mass (about 2.0 cm in diameter) in the left temporal area 18 months later. The same treatment was given to the older after admission, and she is healthy to date. To explore the relationship between hallmarks and the prognosis of identical-twin patients with LCH, we retrieved the 16 literatures (16 identical-twin pairs, 31 patients) listed in PubMed during the past 60 years. The data revealed all those patients who have disseminated to the bone marrow, spleen and liver with symptoms of fever and hepatosplenomegaly exhibited worse prognosis (9 out of the 31 patients). The other identical-twin subjects without infiltration of those organs recovered well. In conclusion, this study reveals the adverse hallmarks of prognosis in identical-twin patients with LCH by reviewing relevant literatures.

  4. The expressions of MIF and CXCR4 protein in tumor microenvironment are adverse prognostic factors in patients with esophageal squamous cell carcinoma

    PubMed Central

    2013-01-01

    Background Tumor-derived cytokines and their receptors usually take important roles in the disease progression and prognosis of cancer patients. In this survey, we aimed to detect the expression levels of MIF and CXCR4 in different cell populations of tumor microenvironments and their association with survivals of patients with esophageal squamous cell carcinoma (ESCC). Methods MIF and CXCR4 levels were measured by immunochemistry in tumor specimens from 136 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson’s chi-square test and Cox regression analysis. Results The expression of CXCR4 in tumor cells was positively associated with tumor status (P = 0.045) and clinical stage (P = 0.044); whereas the expression of CXCR4 in tumor-infiltrating lymphocytes (TILs) and the expression of MIF in tumor cells and in TILs were not associated with clinical parameters of ESCC patients. High MIF expression in tumor cells or in TILs or high CXCR4 expression in tumor cells was significantly related to poor survival of ESCC patients (P < 0.05). Multivariate analysis showed that the expression of MIF or CXCR4 in tumor cells and the expression of MIF in TILs were adverse independent factors for disease-free survival (DFS) and overall survival (OS) in the whole cohort of patients (P < 0.05). Furthermore, the expression of MIF and CXCR4 in tumor cells were independent factors for reduced DFS and OS in metastatic/recurrent ESCC patients (P < 0.05). Interestingly, the expressions of MIF and CXCR4 in tumor cells and in TILs were significantly positively correlated (P < 0.05), and the combined MIF and CXCR4 expression in tumor cells was an independent adverse predictive factor for DFS and OS (P < 0.05). Conclusion The expressions of MIF and CXCR4 proteins in tumor cells and TILs have different clinically predictive values in ESCC. PMID:23497377

  5. Impact of early life adversity on EMG stress reactivity of the trapezius muscle

    PubMed Central

    Luijcks, Rosan; Vossen, Catherine J.; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J.; Lousberg, Richel

    2016-01-01

    Abstract Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0–11 years) and adolescence (12–17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability. Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID:27684800

  6. Impact of childhood adversities on the short-term course of illness in psychotic spectrum disorders.

    PubMed

    Schalinski, Inga; Fischer, Yolanda; Rockstroh, Brigitte

    2015-08-30

    Accumulating evidence indicates an impact of childhood adversities on the severity and course of mental disorders, whereas this impact on psychotic disorders remains to be specified. Effects of childhood adversities on comorbidity, on symptom severity of the Positive and Negative Syndrome Scale and global functioning across four months (upon admission, 1 and 4 months after initial assessment), as well as the course of illness (measured by the remission rate, number of re-hospitalizations and dropout rate) were evaluated in 62 inpatients with psychotic spectrum disorders. Adverse experiences (of at least 1 type) were reported by 73% of patients. Patients with higher overall level of childhood adversities (n=33) exhibited more co-morbid disorders, especially alcohol/substance abuse and dependency, and higher dropout rates than patients with a lower levels of adverse experiences (n=29), together with higher levels of positive symptoms and symptoms of excitement and disorganization. Emotional and physical neglect were particularly related to symptom severity. Results suggest that psychological stress in childhood affects the symptom severity and, additionally, a more unfavorable course of disorder in patients diagnosed with psychoses. This impact calls for its consideration in diagnostic assessment and psychiatric care.

  7. Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer

    PubMed Central

    Zhou, Juan; Yang, Li-Chao; He, Zhen-Yu; Li, Fang-Yan; Wu, San-Gang; Sun, Jia-Yuan

    2015-01-01

    Purpose: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. Methods: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. Results: The median follow-up time was 57 months and the 5-year OS was 70.1%. The 5-year OS were 55.0%, 83.3%, 82.5%, and 70.0% in patients with A, B, AB, and O blood type, respectively (p = 0.003). Patients with blood type A had a poorer 5-year OS than patients with blood type non-A (55.0% vs. 75.0%, p = 0.001), especially in patients with age > 50 years (40.0% vs. 62.5%, p = 0.004). Univariate Cox analyses showed that blood type A was significantly associated with OS than those with non-A types (hazard ratio (HR) 2.210, 95% confidence interval (CI) 1.373-3.557, p = 0.001). Blood type A remained an independent prognostic factor for OS than those with non-A blood types in multivariate analyses (HR 2.235, 95% CI 1.360-3.674, p = 0.002). Conclusion: ABO blood group is associated with survival in patients with ovarian cancer, patients with blood type A had a significantly worse OS than patients with non-A blood types, especially in patients with age > 50 years. PMID:26316893

  8. On the impact of adverse pressure gradient on the supersonic turbulent boundary layer

    NASA Astrophysics Data System (ADS)

    Wang, Qian-Cheng; Wang, Zhen-Guo; Zhao, Yu-Xin

    2016-11-01

    By employing the particle image velocimetry, the mean and turbulent characteristics of a Mach 2.95 turbulent boundary layer are experimentally investigated without the impact of curvature. The physical mechanism with which the streamwise adverse pressure gradient affects the supersonic boundary layer is revealed. The data are compared to that of the concave boundary layer with similar streamwise distributions of wall static pressure to clarify the separate impacts of the adverse pressure gradient and the concave curvature. The logarithmic law is observed to be well preserved for both of the cases. The dip below the logarithmic law is not observed in present investigation. Theoretical analysis indicates that it could be the result of compromise between the opposite impacts of the compression wave and the increased turbulent intensity. Compared to the zero pressure gradient boundary layer, the principal strain rate and the turbulent intensities are increased by the adverse pressure gradient. The shear layer formed due the hairpin packets could be sharpened by the compression wave, which leads to higher principal strain rate and the associated turbulent level. Due to the additional impact of the centrifugal instability brought by the concave wall, even higher turbulent intensities than that of the adverse pressure gradient case are introduced. The existence of velocity modes within the zero pressure gradient boundary layer suggests that the large scale motions are statistically well organized. The generation of new velocity modes due to the adverse pressure gradient indicates that the turbulent structure is changed by the adverse pressure gradient, through which more turbulence production that cannot be effectively predicted by the Reynolds-stress transport equations could be brought.

  9. The Impact of Childhood Sexual Abuse and Other Forms of Childhood Adversity on Adulthood Parenting

    ERIC Educational Resources Information Center

    Barrett, Betty

    2009-01-01

    This study investigated the independent impact of child sexual abuse on five dimensions of adulthood parenting after controlling for other forms of childhood adversity in a predominantly African-American sample of mothers receiving public assistance (N = 483). An analysis of data previously collected as part of the Illinois Families Study Child…

  10. 25 CFR 170.109 - How do the Secretaries prevent discrimination or adverse impacts?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false How do the Secretaries prevent discrimination or adverse impacts? 170.109 Section 170.109 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND... Consultation, Collaboration, Coordination § 170.109 How do the Secretaries prevent discrimination or...

  11. 25 CFR 170.110 - How can State and local governments prevent discrimination or adverse impacts?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false How can State and local governments prevent discrimination or adverse impacts? 170.110 Section 170.110 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... Eligibility Consultation, Collaboration, Coordination § 170.110 How can State and local governments...

  12. The Risk of Adverse Impact in Selections Based on a Test with Known Effect Size

    ERIC Educational Resources Information Center

    De Corte, Wilfried; Lievens, Filip

    2005-01-01

    The authors derive the exact sampling distribution function of the adverse impact (AI) ratio for single-stage, top-down selections using tests with known effect sizes. Subsequently, it is shown how this distribution function can be used to determine the risk that a future selection decision on the basis of such tests will result in an outcome that…

  13. In Vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular Optical Coherence Tomography in Pulmonary Arterial Hypertension: A New Prognostic Marker of Adverse Clinical Follow-Up§

    PubMed Central

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Montero, María Angeles; Arredondo, Christian; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Bouteldja, Nadia; Hidalgo, Cristina; Roman, Antonio

    2013-01-01

    Background: The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. Methods: 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. Results: OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm2, % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (<22%). Events occurred in 6 (1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). Conclusions: In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome. PMID:23730366

  14. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

    PubMed Central

    Teixido, Cristina; Michels, Sebastian; Morales-Espinosa, Daniela; Viteri, Santiago; Hartmann, Wolfgang; Merkelbach-Bruse, Sabine; Fischer, Rieke; Schildhaus, Hans-Ulrich; Fassunke, Jana; Sebastian, Martin; Serke, Monika; Kaminsky, Britta; Randerath, Winfried; Gerigk, Ulrich; Ko, Yon-Dschun; Krüger, Stefan; Schnell, Roland; Rothe, Achim; Kropf-Sanchen, Cornelia; Heukamp, Lukas; Rosell, Rafael

    2015-01-01

    Background While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Patients and Methods 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. Conclusion ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC. PMID:25868855

  15. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome

    PubMed Central

    Klusmann, Jan-Henning; Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael; Jorch, Norbert; Langebrake, Claudia; Pekrun, Arnulf; Macakova-Reinhardt, Katarina

    2008-01-01

    Approximately 10% of the neonates with Down syndrome (DS) exhibit a unique transient leukemia (TL). Though TL resolves spontaneously in most patients, early death and development of myeloid leukemia (ML-DS) may occur. Prognostic factors as well as treatment indication are currently uncertain. To resolve that issue, we prospectively collected clinical, biologic, and treatment data of 146 patients with TL. The 5-year overall survival (OS) and event-free survival (EFS) were 85% plus or minus 3% and 63% plus or minus 4%, respectively. Multivariate analysis revealed a correlation between high white blood cell (WBC) count, ascites, preterm delivery, bleeding diatheses, failure of spontaneous remission, and the occurrence of early death. Treatment with cytarabine (0.5-1.5 mg/kg) was administered to 28 patients with high WBC count, thrombocytopenia, or liver dysfunction. The therapy had a beneficial effect on the outcome of those children with risk factors for early death (5-year EFS, 52% ± 12% vs 28% ± 11% [no treatment]; P = .02). Multivariate analysis demonstrated its favorable prognostic impact. A total of 29 (23%) patients with TL subsequently developed ML-DS. Patients with ML-DS with a history of TL had a significantly better 5-year EFS (91% ± 5%) than those without documented TL (70% ± 4%), primarily due to a lower relapse rate. A history of TL may therefore define a lower-risk ML-DS subgroup. This study was registered at www.clinicaltrials.gov as no. NCT 00111345. PMID:18182574

  16. Defining high, medium and low impact prognostic factors for developing multiple sclerosis.

    PubMed

    Tintore, Mar; Rovira, Àlex; Río, Jordi; Otero-Romero, Susana; Arrambide, Georgina; Tur, Carmen; Comabella, Manuel; Nos, Carlos; Arévalo, María Jesús; Negrotto, Laura; Galán, Ingrid; Vidal-Jordana, Angela; Castilló, Joaquin; Palavra, Filipe; Simon, Eva; Mitjana, Raquel; Auger, Cristina; Sastre-Garriga, Jaume; Montalban, Xavier

    2015-07-01

    [adjusted hazard ratio 0.6 (0.4-1.0)] in adjusted models. The presence of oligoclonal bands increased the risk of clinically definite multiple sclerosis [adjusted hazard ratio 1.3 (1.0-1.8)] and of disability [adjusted hazard ratio 2.0 (1.2-3.6)] independently of other factors. The presence of 10 or more brain lesions on magnetic resonance increased the risk of clinically definite multiple sclerosis [adjusted hazard ratio 11.3 (6.7-19.3)] and disability [adjusted hazard ratio 2.9 (1.4-6.0)]. Disease-modifying treatment before the second attack reduced the risk of McDonald multiple sclerosis [adjusted hazard ratio 0.6 (0.4-0.9)] and disability accumulation [adjusted hazard ratio 0.5 (0.3-0.9)]. We conclude that the demographic and topographic characteristics are low-impact prognostic factors, the presence of oligoclonal bands is a medium-impact prognostic factor, and the number of lesions on brain magnetic resonance is a high-impact prognostic factor.

  17. Shattering world assumptions: A prospective view of the impact of adverse events on world assumptions.

    PubMed

    Schuler, Eric R; Boals, Adriel

    2016-05-01

    Shattered Assumptions theory (Janoff-Bulman, 1992) posits that experiencing a traumatic event has the potential to diminish the degree of optimism in the assumptions of the world (assumptive world), which could lead to the development of posttraumatic stress disorder. Prior research assessed the assumptive world with a measure that was recently reported to have poor psychometric properties (Kaler et al., 2008). The current study had 3 aims: (a) to assess the psychometric properties of a recently developed measure of the assumptive world, (b) to retrospectively examine how prior adverse events affected the optimism of the assumptive world, and (c) to measure the impact of an intervening adverse event. An 8-week prospective design with a college sample (N = 882 at Time 1 and N = 511 at Time 2) was used to assess the study objectives. We split adverse events into those that were objectively or subjectively traumatic in nature. The new measure exhibited adequate psychometric properties. The report of a prior objective or subjective trauma at Time 1 was related to a less optimistic assumptive world. Furthermore, participants who experienced an intervening objectively traumatic event evidenced a decrease in optimistic views of the world compared with those who did not experience an intervening adverse event. We found support for Shattered Assumptions theory retrospectively and prospectively using a reliable measure of the assumptive world. We discuss future assessments of the measure of the assumptive world and clinical implications to help rebuild the assumptive world with current therapies. (PsycINFO Database Record

  18. Prognostic impact of the indexation of left ventricular mass in patients undergoing dialysis.

    PubMed

    Zoccali, C; Benedetto, F A; Mallamaci, F; Tripepi, G; Giacone, G; Cataliotti, A; Seminara, G; Stancanelli, B; Malatino, L S

    2001-12-01

    Left ventricular hypertrophy (LVH) is exceedingly frequent in patients undergoing dialysis. Cardiac mass is proportional to body size, but the influence of various indexing methods has not been studied in patients with end-stage renal disease. The issue is important because malnutrition and volume expansion would both tend to distort the estimate of LV mass (LVM) in these patients. In a cohort of 254 patients, the prognostic impact on all-cause mortality and cardiovascular outcomes of LVH values, calculated according to two established methods of indexing, either body surface area (BSA) or height(2.7), was assessed prospectively. When LVM was analyzed as a categorical variable, the height(2.7)-based method identified a larger number of patients with LVH than the corresponding BSA-based method. One hundred and thirty-seven fatal and nonfatal cardiovascular events occurred during the follow-up period. Overall, 90 patients died, 51 of cardiovascular causes. In separate Cox models, both the LVM/height(2.7) and the LVM/BSA index independently predicted total and cardiovascular mortality (P < 0.001). However, the height(2.7)-based method coherently produced a closer-fitting model (P < or = 0.02) than did the BSA-based method. The height(2.7) index was also important for the subcategorization of patients according to the presence of concentric or eccentric LVH because the prognostic value of such subcategorization was apparent only when the height(2.7)-based criterion was applied. In conclusion, LVM is a strong and independent predictor of survival and cardiovascular events in patients undergoing dialysis. The indexing of LVM by height(2.7) provides more powerful prediction of mortality and cardiovascular outcomes than the BSA-based method, and the use of this index appears to be appropriate in patients undergoing dialysis.

  19. Extracorporeal spread and its prognostic impact in stages I and II (FIGO) endometrial carcinoma.

    PubMed

    Sakuragi, N; Tanaka, T; Satoh, C; Nishiya, M; Ohkouchi, T; Tsumura, N; Takeda, N; Hirahatake, K; Sagawa, T; Ohkubo, H

    1991-09-01

    Prognostic risk factors were statistically analyzed from the histopathologic data obtained from 90 Japanese women with stages I and II endometrial carcinoma treated surgically, including systemic retroperitoneal lymph node dissection, between June 1979 and June 1989. In stage Ia endometrial carcinoma, pelvic and paraaortic nodes metastasis were seen in 13.8(4/29)% and 0.0(0/19)% of patients, respectively. In stage Ib, the incidence of pelvic and paraaortic node metastasis was 25.6(11/43)% and 9.7(3/31)%, respectively. In stage II, the incidence was 38.9(7/18)% and 13.3(2/15)%, respectively. Prognosis of patients even with deep myometrial invasion (greater than or equal to 2/3) or G3 tumor was fairly good (5-year survival rate: 87.5% and 85.7%, respectively) if the disease was histologically confined to the uterine corpus. Once the tumor spread outside the corpus uteri, the survival rate of patients was strongly affected by the grade of the tumor, moderate to marked lymph-vascular space invasion of tumor cells, or tumor invading middle or outer third of myometrium (P less than 0.05 for each factor). In summary, endometrial cancer frequently metastasize to pelvic and paraaortic lymph nodes even in the early stages, and lymph node metastasis and other extracorporeal spread of disease have a serious impact on patient survival. Prognosis of patients with extracorporeal spread of disease seems to be determined by the high grade of tumor and lymph-vascular space invasion. These results suggest that surgical exploration including paraaortic lymph node dissection to accurately evaluate the extent of the disease is essential to estimate the patient's prognostic risk and to individualize the treatment schedule.

  20. Clinical and Cost Impact Analysis of a Novel Prognostic Test for Early Detection of Preterm Birth

    PubMed Central

    Caughey, Aaron B.; Zupancic, John A. F.; Greenberg, James M.; Garfield, Susan S.; Thung, Stephen F.; Iams, Jay D.

    2016-01-01

    Objective The objective of this study was to evaluate the potential impact to the U.S. health care system by adopting a novel test that identifies women at risk for spontaneous preterm birth. Methods A decision-analytic model was developed to assess clinical and cost outcomes over a 1-year period. The use of a prognostic test to predict spontaneous preterm birth in a hypothetical population of women reflective of the U.S. population (predictive arm) was compared with the current baseline rate of spontaneous preterm birth and associated infant morbidity and mortality (baseline care arm). Results In a population of 3,528,593 births, our model predicts a 23.5% reduction in infant mortality (8,300 vs. 6,343 deaths) with use of the novel test. The rate of acute conditions at birth decreased from 11.2 to 8.1%; similarly, the rate of developmental disabilities decreased from 13.2 to 11.5%. The rate of spontaneous preterm birth decreased from 9.8 to 9.1%, a reduction of 23,430 preterm births. Direct medical costs savings was $511.7M (− 2.1%) in the first year of life. Discussion The use of a prognostic test for reducing spontaneous preterm birth is a dominant strategy that could reduce costs and improve outcomes. More research is needed once such a test is available to determine if these results are borne out upon real-world use. PMID:27917307

  1. The psychological impact of chronic environmental adversity: Responding to prolonged drought.

    PubMed

    Stain, Helen J; Kelly, Brian; Carr, Vaughan J; Lewin, Terry J; Fitzgerald, Michael; Fragar, Lyn

    2011-12-01

    The health effects of chronic environmental adversity have received insufficient attention, particularly those associated with the psychological impact of drought. Resilience or adaptive response to drought has received even less attention than vulnerability factors. This research examined factors associated with drought impact in rural and remote Australian communities. In 2008 postal surveys were completed by 302 adults (mean age 53 years; 57% female, 77% married) living in rural areas of prolonged drought exposure. Outcome measures were: (i) psychological distress (Kessler 10) and (ii) an index of concern or worry about drought. A range of predictor variables were assessed: adaptability (hopefulness, neuroticism), other adverse events, personal support and community connectedness, and sense of place, as a measure of connection to the local environment. Predictors of drought related worry differed from those associated with psychological distress levels. The former included socio-economic factors (living on a farm [Odds Ratio, OR 3.09], current employment [OR 3.64]), personal psychological characteristics (neuroticism [OR 1.29]), and greater connection with the environment (sense of place [OR 1.05]). On the other hand, psychological distress was associated chiefly with personal factors, such as higher neuroticism [OR 1.92], lower levels of hopefulness [OR 0.28], and lower perceived social support and community connectedness [OR 0.39]. Practical financial, employment and family factors were identified as important elements of drought impact, as to a lesser extent was sense of place, reflecting a confrontation with the consequences of chronic environmental degradation, while personal hopefulness may help mitigate the psychological impact of such adversity.

  2. Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

    PubMed

    Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien

    2016-02-03

    Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine.

  3. Mother-offspring dialogue in early pregnancy: impact of adverse environment on pregnancy maintenance and neurobiology.

    PubMed

    Douglas, Alison J

    2011-07-01

    The mother-offspring dialogue begins even before implantation and is essential to signal pregnancy, establish robust contact, and maintain embryo growth and development. Any circumstance that disrupts the dialogue risks pregnancy problems. A new look at how stress impacts on pregnancy involves its adverse effects on the key pregnancy hormones of progesterone and prolactin. These effects have far-reaching consequences on pregnancy maintenance, maternal anxiety and embryo programming. This review focuses on early pregnancy and how stress might compromise the multi-layer, two-way communication between mother and embryo.

  4. Assessing planetary and regional nitrogen boundaries related to food security and adverse environmental impacts

    NASA Astrophysics Data System (ADS)

    de Vries, Wim; Kros, Hans; Kroeze, Carolien; Seitzinger, Sybil

    2014-05-01

    In this presentation, we first discuss the concept of -, governance interest in- and criticism on planetary boundaries, specifically with respect to the nitrogen (N) cycle. We then systematically evaluate the criticism and argue that planetary N boundaries need to include both the benefits and adverse impacts of reactive N (Nr) and the spatial variability of Nr impacts, in terms of shortage and surplus, being main arguments for not deriving such boundaries. Next, we present an holistic approach for an updated planetary N boundary by considering the need to: (i) avoid adverse impacts of elevated Nr emissions to water, air and soils, and (ii) feed the world population in an adequate way. The derivation of a planetary N boundary, in terms of anthropogenic fixation of di-nitrogen (N2) by growing legumes and production of N fertilizer, is illustrated by (i) identification of multiple threat N indicators and setting critical limits for them, (ii) back calculating critical N losses from critical limits for N indicators, while accounting for the spatial variability of indicators and their exceedance and (iii) back calculating critical N fixation rates from critical N losses. The derivation of the needed planetary N fixation is assessed from the global population, the recommended dietary N consumption per capita and the N use efficiency in the complete chain from N fixation to N consumption. Results of example applications show that the previously suggested planetary N boundary of 25% of the current value is too low in view of needed N fixation and also unnecessary in view of most environmental impacts. We also illustrate the impacts of changes in the N use efficiency on planetary boundaries in terms of critical N fixation rates.

  5. Adverse reaction to irrigation with povidone-iodine after deep-impacted, lower third molar extraction.

    PubMed

    Sammartino, G; Tia, M; Tete, S; Perillo, L; Trosino, O

    2012-01-01

    Povidone-iodine is most commonly used worldwide because of its germicidal activity, relatively low irritancy or toxicity and low cost. Frequently, povidone-iodine is used as a topical antiseptic for treating and preventing wound infection. In rare cases skin irritation or iododerma-like eruption could represent possible adverse effects due to the oxidative effects of iodine and allergic hypersensitivity reaction. In this report we describe a case of a massive adverse reaction to the irrigation of surgical wound dehiscence with 10 percent povidone-iodine solution after deep-impacted, lower third molar extraction. This reaction was related to a central neurotrophic reflex involving three trigeminal branches and probably due to peripheral chemical insult of mandible nerve. This adverse reaction determined a severe edema and diffuse skin lesions, involving the whole left side of the face mimicking an iododerma-like eruption. These violent symptoms were solved after 60 days. Furthermore, we report a small permanent skin scar in the zygomatic area and transient alterations of facial sensitivity on the affected side which completely disappeared in 6 months.

  6. Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

    PubMed Central

    Kong, Pengfei; Wu, Ruiyan; Yang, Chenlu; Geng, Qirong; Liu, Jianjun; Chen, Shangxiang; Liu, Xuechao; Ye, Minting; He, Wenzhuo; Yang, Qiong; Xia, Liangping; Xu, Dazhi

    2016-01-01

    Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion. PMID:27381549

  7. Long-term prognostic impact of circulating tumour cells in gastric cancer patients

    PubMed Central

    Ito, Hiroaki; Sato, Jun; Tsujino, Yukio; Yamaguchi, Noriko; Kimura, Satoshi; Gohda, Keigo; Murakami, Katsuhiro; Onimaru, Manabu; Ohmori, Tohru; Ishikawa, Fumihiro; Inoue, Haruhiro

    2016-01-01

    AIM To analyse the long-term prognostic impact of circulating tumour cells (CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-mL peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-mL of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant (P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs (P = 0.034). CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer. PMID:28028372

  8. Annual Research Review: Positive adjustment to adversity -Trajectories of minimal-impact resilience and emergent resilience

    PubMed Central

    Bonanno, George A.; Diminich, Erica D.

    2012-01-01

    Background Research on resilience in the aftermath of potentially traumatic life events is still evolving. For decades researchers have documented resilience in children exposed to corrosive early environments, such as poverty or chronic maltreatment. Relatively more recently the study of resilience has migrated to the investigation of isolated and potentially traumatic life events (PTE) in adults. Methods In this article we first consider some of the key differences in the conceptualization of resilience following chronic adversity versus resilience following single-incident traumas, and then describe some of the misunderstandings that have developed about these constructs. To organize our discussion we introduce the terms emergent resilience and minimal-impact resilience to represent trajectories positive adjustment in these two domains, respectively. Results We focused in particular on minimal-impact resilience, and reviewed recent advances in statistical modeling of latent trajectories that have informed the most recent research on minimal-impact resilience in both children and adults and the variables that predict it, including demographic variables, exposure, past and current stressors, resources, personality, positive emotion, coping and appraisal, and flexibility in coping and emotion regulation. Conclusions The research on minimal impact resilience is nascent. Further research is warranted with implications for a multiple levels of analysis approach to elucidate the processes that may mitigate or modify the impact of a PTE at different developmental stages. PMID:23215790

  9. Cognitive predictors and age-based adverse impact among business executives.

    PubMed

    Klein, Rachael M; Dilchert, Stephan; Ones, Deniz S; Dages, Kelly D

    2015-09-01

    Age differences on measures of general mental ability and specific cognitive abilities were examined in 2 samples of job applicants to executive positions as well as a mix of executive/nonexecutive positions to determine which predictors might lead to age-based adverse impact in making selection and advancement decisions. Generalizability of the pattern of findings was also investigated in 2 samples from the general adult population. Age was negatively related to general mental ability, with older executives scoring lower than younger executives. For specific ability components, the direction and magnitude of age differences depended on the specific ability in question. Older executives scored higher on verbal ability, a measure most often associated with crystallized intelligence. This finding generalized across samples examined in this study. Also, consistent with findings that fluid abilities decline with age, older executives scored somewhat lower on figural reasoning than younger executives, and much lower on a letter series test of inductive reasoning. Other measures of inductive reasoning, such as Raven's Advanced Progressive Matrices, also showed similar age group mean differences across settings. Implications for employee selection and adverse impact on older job candidates are discussed.

  10. Defining "adverse environmental impact" and making paragraph 316(b) decisions: a fisheries management approach.

    PubMed

    Bailey, David E; Bulleit, Kristy A N

    2002-05-17

    The electric utility industry has developed an approach for decisionmaking that includes a definition of Adverse Environmental Impact (AEI) and an implementation process. The definition of AEI is based on lessons from fishery management science and analysis of the statutory term "adverse environmental impact" and is consistent with current natural resource management policy. The industry has proposed a definition focusing on "unacceptable risk to the population"s ability to sustain itself, to support reasonably anticipated commercial or recreational harvests, or to perform its normal ecological function." This definition focuses not on counting individual fish or eggs cropped by the various uses of a water body, but on preserving populations of aquatic organisms and their functions in the aquatic community. The definition recognizes that assessment of AEI should be site-specific and requires both a biological decision and a balancing of diverse societal values. The industry believes that the definition of AEI should be implemented in a process that will maximize the overall societal benefit of the paragraph 316(b) decision by considering the facility"s physical location, design, and operation, as well as the local biology. The approach considers effects on affected fish and shellfish populations and the benefits of any necessary best technology available (BTA) alternatives. This is accomplished through consideration of population impacts, which conversely allows consideration of the benefits of any necessary BTA modifications. This in turn allows selection of BTAs that will protect potentially affected populations in a cost-effective manner. The process also employs risk assessment with stakeholder participation, in accordance with EPA's Guidelines for Ecological Risk Assessment. The information and tools are now available to make informed decisions about site-specific impacts that will ensure protection of aquatic ecosystems and best serve the public interest.

  11. Frequence, Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors1234

    PubMed Central

    Kramer, K.; Wolf, S.; Mayer, B.; Schmidt, S.A.; Agaimy, A.; Henne-Bruns, D.; Knippschild, U.; Schwab, M.; Schmieder, M.

    2015-01-01

    Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted. PMID:25622906

  12. Impact of sample size on variation of adverse events and preventable adverse events: systematic review on epidemiology and contributing factors

    PubMed Central

    Schmitz, Astrid; Albers, Bernhard; Schrappe, Matthias

    2010-01-01

    Objectives To perform a systematic review of the frequency of (preventable) adverse events (AE/PAE) and to analyse contributing factors, such as sample size, settings, type of events, terminology, methods of collecting data and characteristics of study populations. Review methods Search of Medline and Embase from 1995 to 2007. Included were original papers with data on the frequency of AE or PAE, explicit definition of study population and information about methods of assessment. Results were included with percentages of patients having one or more AE/PAE. Extracted data enclosed contributing factors. Data were abstracted and analysed by two researchers independently. Results 156 studies in 152 publications met our inclusion criteria. 144/156 studies reported AE, 55 PAE (43 both). Sample sizes ranged from 60 to 8 493 876 patients (median: 1361 patients). The reported results for AE varied from 0.1% to 65.4%, and for PAE from 0.1% to 33.9%. Variation clearly decreased with increasing sample size. Estimates did not differ according to setting, type of event or terminology. In studies with fewer than 1000 patients, chart review prevailed, whereas surveys with more than 100 000 patients were based mainly on administrative data. No effect of patient characteristics was found. Conclusions The funnel-shaped distribution of AE and PAE rates with sample size is a probable consequence of variation and can be taken as an indirect indicator of study validity. A contributing factor may be the method of data assessment. Further research is needed to explain the results when analysing data by types of event or terminology. PMID:20679137

  13. The impact of adverse events on health care costs for older adults undergoing nonelective abdominal surgery

    PubMed Central

    Bailey, Jonathan G.; Davis, Philip J.B.; Levy, Adrian R.; Molinari, Michele; Johnson, Paul M.

    2016-01-01

    Background Postoperative complications have been identified as an important and potentially preventable cause of increased hospital costs. While older adults are at increased risk of experiencing complications and other adverse events, very little research has specifically examined how these events impact inpatient costs. We sought to examine the association between postoperative complications, hospital mortality and loss of independence and direct inpatient health care costs in patients 70 years or older who underwent nonelective abdominal surgery. Methods We prospectively enrolled consecutive patients 70 years or older who underwent nonelective abdominal surgery between July 1, 2011, and Sept. 30, 2012. Detailed patient-level data were collected regarding demographics, diagnosis, treatment and outcomes. Patient-level resource tracking was used to calculate direct hospital costs (2012 $CDN). We examined the association between complications, hospital mortality and loss of independence cost using multiple linear regression. Results During the study period 212 patients underwent surgery. Overall, 51.9% of patients experienced a nonfatal complication (32.5% minor and 19.4% major), 6.6% died in hospital and 22.6% experienced a loss of independence. On multivariate analysis nonfatal complications (p < 0.001), hospital mortality (p = 0.021) and loss of independence at discharge (p < 0.001) were independently associated with health care costs. These adverse events respectively accounted for 30%, 4% and 10% of the total costs of hospital care. Conclusion Adverse events were common after abdominal surgery in older adults and accounted for 44% of overall costs. This represents a substantial opportunity for better patient outcomes and cost savings with quality improvement strategies tailored to the needs of this high-risk surgical population. PMID:26999476

  14. The prognostic impact of the anatomical sites in the 'head and neck melanoma': scalp versus face and neck.

    PubMed

    de Giorgi, Vincenzo; Rossari, Susanna; Gori, Alessia; Grazzini, Marta; Savarese, Imma; Crocetti, Emanuele; Cervadoro, Elisa; Massi, Daniela

    2012-10-01

    Cutaneous melanoma is a malignant neoplasia with several demographic and histopathological prognostic factors. Many studies stress that the head and neck region has a worse prognosis compared with other localizations, but the reasons for this worse prognosis are unclear. Therefore, the aim of our study is to analyse the poor prognosis of head and neck melanoma (HNM) with respect to the other anatomical sites, considering the face and neck (F&N) and the scalp separately. We carried out a retrospective analysis of 757 melanoma patients. In particular, we studied the prognostic impact of different melanoma skin localizations (head and neck, trunk, upper extremities and lower extremities). Afterwards, we divided HNM into two subgroups, F&N and scalp, to evaluate their impact in the HNM prognosis. Data showed a significantly lower 5-year overall survival probability for HNM (78.9 versus 93.1% for other body sites; P=0.05). Moreover, on analysing the two anatomical areas considered among HNM, we observed a 5-year overall survival of 81.8% for F&N and 66.7% for scalp. HNM has different and worse prognostic features with respect to other sites, but this trend is not only because of scalp melanoma but is also determined by F&N melanoma, which we believe to be underestimated until now.

  15. Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

    PubMed Central

    Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

    2017-01-01

    Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

  16. Clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease.

    PubMed

    Park, Jin Kyoung; Lee, Chang Hun; Kim, In Hee; Kim, Seon Min; Jang, Ji Won; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae-Ghon

    2015-05-01

    Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na <135 mM/L, albumin <2.5 g/dL, C-reactive protein ≥20 mg/L, systemic inflammatory response syndrome (SIRS) positivity were independently associated with bacterial infection in patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P < 0.001) higher than those without infection (22.3% vs. 5.1% and 32.3% vs. 8.2%, respectively). Furthermore, bacterial infection (HR, 2.2; 95% CI, 1.049-4.579, P = 0.037), SIRS positivity (HR, 2.5; 95% CI, 1.240-4.861, P = 0.010), Maddrey's discriminant function score ≥32 (HR, 2.3; 95% CI, 1.036-5.222, P = 0.041), and hemoglobin <12 g/dL (HR, 2.4; 95% CI, 1.081-5.450, P = 0.032) were independent predictors of short-term mortality. In conclusion, bacterial infection and SIRS positivity predicted short-term prognosis in hospitalized patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.

  17. Prognostic Impact of Subclinical Microalbuminuria in Patients With Chronic Heart Failure.

    PubMed

    Miura, Masanobu; Sakata, Yasuhiko; Miyata, Satoshi; Nochioka, Kotaro; Takada, Tsuyoshi; Tadaki, Soichiro; Ushigome, Ryoichi; Yamauchi, Takeshi; Takahashi, Jun; Shimokawa, Hiroaki

    2014-10-30

    Background:Microalbuminuria, traditionally defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g, is a risk factor for mortality even in patients with preserved glomerular filtration rate (GFR). The prognostic impact of subclinical microalbuminuria, however, remains unknown in patients with chronic heart failure (CHF).Methods and Results:In the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 Study, we enrolled 2,039 consecutive symptomatic CHF patients (median age, 67.4 years; 68.9% male) after excluding those on hemodialysis. On classification and regression tree analysis, UACR=10.2 mg/g and 27.4 mg/g were identified as the first and second discriminating points to stratify the risk for composite of death, acute myocardial infarction, HF admission and stroke, therefore subclinical microalbuminuria was defined as UACR ≥10.2 and <27.4 mg/g. There were 506 composite endpoints (24.8%) during the median follow-up of 2.69 years. On Kaplan-Meier analysis and multivariate Cox modeling, subclinical microalbuminuria was significantly associated with increased composite endpoints with hazard ratios of 1.90 (P<0.001) and 2.29 (P<0.001) in patients with preserved (>60 ml·min(-1)·1.73 m(-2), n=1,129) or mildly reduced eGFR (30-59.9 ml·min(-1)·1.73 m(-2), n=789), respectively. In patients with severely reduced GFR (eGFR <30 ml·min(-1)·1.73 m(-2), n=121), >80% had microalbuminuria or macroalbuminuria, and only 9.1% were free from any composite endpoints.Conclusions:Subclinical microalbuminuria was associated with increased risk of cardiovascular events in CHF patients with mildly reduced or preserved renal function.

  18. Prognostic impact of body mass index stratified by smoking status in patients with esophageal squamous cell carcinoma

    PubMed Central

    Sun, Peng; Zhang, Fei; Chen, Cui; Ren, Chao; Bi, Xi-Wen; Yang, Hang; An, Xin; Wang, Feng-Hua; Jiang, Wen-Qi

    2016-01-01

    Background As smoking affects the body mass index (BMI) and causes the risk of esophageal squamous cell carcinoma (ESCC), the prognostic impact of BMI in ESCC could be stratified by smoking status. We investigated the true prognostic effect of BMI and its potential modification by smoking status in ESCC. Methods We retrospectively analyzed 459 patients who underwent curative treatment at a single institution between January 2007 and December 2010. BMI was calculated using the measured height and weight before surgery. Chi-square test was used to evaluate the relationships between smoking status and other clinicopathological variables. The Cox proportional hazard models were used for univariate and multivariate analyses of variables related to overall survival. Results BMI <18.5 kg/m2 was a significantly independent predictor of poor survival in the overall population and never smokers after adjusting for covariates, but not in ever smokers. Among never smokers, underweight patients (BMI <18.5 kg/m2) had a 2.218 times greater risk of mortality than non-underweight (BMI ≥18.5 kg/m2) patients (P=0.015). Among ever smokers, BMI <18 kg/m2 increased the risk of mortality to 1.656 (P=0.019), compared to those having BMI ≥18 kg/m2. Conclusion Our study is likely the first to show that the prognostic effect of BMI was substantial in ESCC, even after stratifying by smoking status. Furthermore, the risk of death due to low BMI would be significantly increased in never smokers. We believe that the prognostic impact of BMI is modified but not eliminated by the smoking status in ESCC. PMID:27799787

  19. Caregiver traumatization adversely impacts young children's mental representations on the MacArthur Story Stem Battery.

    PubMed

    Schechter, Daniel S; Zygmunt, Annette; Coates, Susan W; Davies, Mark; Trabka, Kimberly; McCaw, Jaime; Kolodji, Ann; Robinson, Joann

    2007-09-01

    The aim of our study was to investigate the impact of maternal exposure to family violence, maltreatment, and related posttraumatic stress disorder (PTSD) on young children's mental representations of self and caregivers. Participant mothers (n=24) and children (n=25) were recruited from a referred sample when they were 4-7 years old. Maternal report and child story stem narratives were used. Mother's experience of domestic violence and severity of violence-related PTSD symptoms robustly predicted more dysregulated aggression, attentional bias to danger and distress, as well as more avoidance of and withdrawal from conflicts presented in the children's story stems. Less narrative coherence was also noted. Traumatized mothers experience and symptoms prior to their child's turning 4 years old adversely affected their child's mental representations from 4-7 years.

  20. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered plants on non-target organisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs...

  1. Do Verbal Interactions with Infants during Electronic Media Exposure Mitigate Adverse Impacts on Their Language Development as Toddlers?

    ERIC Educational Resources Information Center

    Mendelsohn, Alan L.; Brockmeyer, Carolyn A.; Dreyer, Benard P.; Fierman, Arthur H.; Berkule-Silberman, Samantha B.; Tomopoulos, Suzy

    2010-01-01

    The goal of this study was to determine whether verbal interactions between mothers and their 6-month-old infants during media exposure ("media verbal interactions") might have direct positive impacts, or mitigate any potential adverse impacts of media exposure, on language development at 14 months. For 253 low-income mother-infant dyads…

  2. Prognostic impact of alkaline phosphatase measured at time of presentation in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction

    PubMed Central

    Kim, Tae-Hoon; Moon, Jeonggeun; Park, Hyun Woo; Jang, Ho-Jun; Park, Sang-Don; Kwon, Sung Woo; Suh, Jon

    2017-01-01

    Background Serum alkaline phosphatase (ALP) has been shown to be a prognostic factor in several subgroups of patients due to its promotion of vascular calcification. However, the prognostic impact of serum ALP level in ST-segment elevation myocardial infarction (STEMI) patients with a relatively low calcification burden has not been determined. We aimed to investigate the association of ALP level measured at time of presentation on clinical outcomes in patients with STEMI requiring primary percutaneous coronary intervention (PCI). Methods A total of 1178 patients with STEMI undergoing primary PCI between 2007 and 2014 were retrospectively enrolled from the INTERSTELLAR registry and classified into tertiles by ALP level (<64, 65–82, or >83 IU/L). The primary study outcome was a major adverse cardiac or cerebrovascular event (MACCE), defined as the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and ischemia-driven revascularization. Results Median follow-up duration was 25 months (interquartile range, 10–39 months). The incidence of MACCE significantly increased as ALP level increased, that is, for the <64, 65–82, and >83 IU/L tertiles incidences were 8.7%, 11.7%, and 15.7%, respectively; p for trend = 0.003). After adjustment for potential confounders, the adjusted hazard ratios for MACCE in the middle and highest tertiles were 1.69 (95% CI 1.01–2.81) and 2.46 (95% CI 1.48–4.09), respectively, as compared with the lowest ALP tertile. Conclusions Elevated ALP level at presentation, but within the higher limit of normal, was found to be independently associated with higher risk of MACCE after primary PCI in patients with STEMI. PMID:28182682

  3. 25 CFR 170.110 - How can State and local governments prevent discrimination or adverse impacts?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and adverse effects on tribes and Native American populations. (b) Examples of adverse effects include... excessive access to culturally or religiously sensitive areas; (3) Negatively affecting natural resources, trust resources, tribal businesses, religious, and cultural sites; (4) Harming indigenous plants...

  4. The prognostic impact of sex on surgically resected non-small cell lung cancer depends on clinicopathologic characteristics.

    PubMed

    Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Oberaigner, Wilhelm; Schmid, Thomas; Hilbe, Wolfgang; Fiegl, Michael

    2011-04-01

    The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non-small cell lung cancers (NSCLCs) using a standardized tissue microarray platform. Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less. Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.

  5. Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma.

    PubMed

    Li, Ling; Xu-Monette, Zijun Y; Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C; Sun, Ruifang; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Møller, Michael B; Wang, Jinfen; Parsons, Ben M; Winter, Jane N; Piris, Miguel A; Pham, Lan V; Medeiros, L Jeffrey; Young, Ken H

    2015-09-15

    Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2- activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications.

  6. Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients.

    PubMed

    Choi, Seyoun; Lee, Keun-Wook; Bang, Soo-Mee; Kim, Sujung; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Park, Young Soo; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Jae-Sung; Oh, Doyeun; Lee, Jong Seok

    2011-12-01

    This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.

  7. Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma.

    PubMed

    Unger, Ulrike; Denkert, Carsten; Braicu, Ioana; Sehouli, Jalid; Dietel, Manfred; Loibl, Sibylle; Darb-Esfahani, Silvia

    2017-02-01

    HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26-0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.

  8. The Impact of Various Platelet Indices as Prognostic Markers of Septic Shock

    PubMed Central

    Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li

    2014-01-01

    Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886

  9. Incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with neuromuscular scoliosis

    PubMed Central

    Jia, Rui; Li, Na; Xu, Bi-Yun; Zhang, Wei; Gu, Xiao-ping; Ma, Zheng-Liang

    2017-01-01

    Abstract Factors influencing massive blood loss for neuromuscular scoliosis (NMS) patients. Despite advances in surgical and anesthetic techniques, scoliosis surgery is still associated with intraoperative massive blood loss, which can result in postoperative mortality and morbidity. The aim of this study was to assess the incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with NMS. A retrospective review of adolescents who underwent posterior spinal instrumentation and fusion for NMS was performed. Perioperative variables and data were recorded. Massive blood loss was defined as an estimated blood loss that exceeds 30% of total blood volume. We obtained data for 114 patients, of whom 63 (55%) had intraoperative massive blood loss. Compared with those without, patients with massive blood loss were more likely to be older, have lower body mass indexes (BMIs), larger Cobb angles, more fused levels, more osteotomy procedures, and prolonged duration of operation. Logistic regression analysis identified the number of fused levels to be more than 12 (P = 0.003, odds ratio = 6.614, 95% confidence interval [CI]: 1.891–23.131), BMI lower than 16.8 kg/m2 (P = 0.025, odds ratio = 3.293, 95% CI: 1.159–9.357), age greater than 15 years (P = 0.014, odds ratio = 3.505, 95% CI: 1.259–9.761), and duration of operation longer than 4.4 hours (P = 0.016, odds ratio = 3.746, 95% CI: 1.428–9.822) as influencing factors. Patients with massive blood loss are associated with more intraoperative colloids infusion and blood transfusions (red blood cell and fresh frozen plasma), as well as postoperative drainage volume. In adolescents with NMS who underwent posterior spinal instrumentation and fusion operations, intraoperative massive blood loss is common. The number of fused levels, BMI, age, and duration of operation are factors influencing intraoperative massive blood loss. PMID:28296737

  10. Assessment of nitrogen ceilings for Dutch agricultural soils to avoid adverse environmental impacts.

    PubMed

    de Vries, W; Kros, H; Oenema, O; Erisman, J W

    2001-11-09

    In the Netherlands, high traffic density and intensive animal husbandry have led to high emissions of reactive nitrogen (N) into the environment. This leads to a series of environmental impacts, including: (1) nitrate (NO3) contamination of drinking water, (2) eutrophication of freshwater lakes, (3) acidification and biodiversity impacts on terrestrial ecosystems, (4) ozone and particle formation affecting human health, and (5) global climate change induced by emissions of N2O. Measures to control reactive N emissions were, up to now, directed towards those different environmental themes. Here we summarize the results of a study to analyse the agricultural N problem in the Netherlands in an integrated way, which means that all relevant aspects are taken into account simultaneously. A simple N balance model was developed, representing all crucial processes in the N chain, to calculate acceptable N inputs to the farm (so-called N ceiling) and to the soil surface (application in the field) by feed concentrates, organic manure, fertiliser, deposition, and N fixation. The N ceilings were calculated on the basis of critical limits for NO 3 concentrations in groundwater, N concentrations in surface water, and ammonia (NH3) emission targets related to the protection of biodiversity of natural areas. Results show that in most parts of the Netherlands, except the western and the northern part, the N ceilings are limited by NH 3 emissions, which are derived from critical N loads for nature areas, rather than limits for both ground- and surface water. On the national scale, the N ceiling ranges between 372 and 858 kton year(-1) depending on the choice of critical limits. The current N import is 848 kton year(-1). A decrease of nearly 60% is needed to reach the ceilings that are necessary to protect the environment against all adverse impacts of N pollution from agriculture.

  11. Clinical characteristics and prognostic impact of atrial fibrillation in patients with chronic heart failure

    PubMed Central

    Gigli, Lorenzo; Ameri, Pietro; Secco, Gianmarco; De Blasi, Gabriele; Miceli, Roberta; Lorenzoni, Alessandra; Torre, Francesco; Chiarella, Francesco; Brunelli, Claudio; Canepa, Marco

    2016-01-01

    AIM To assess the prevalence, clinical characteristics and independent prognostic impact of atrial fibrillation (AF) in chronic heart failure (CHF) patients, and the potential protective effect of disease-modifying medications, particularly beta-blockers (BB). METHODS We retrospectively reviewed the charts of patients referred to our center since January 2004, and collected all clinical information available at their first visit. We assessed mortality to the end of June 2015. We compared patients with and without AF, and assessed the association between AF and all-cause mortality by multivariate Cox regression and Kaplan-Meyer analysis, particularly accounting for ongoing treatment with BB. RESULTS A total of 903 patients were evaluated (mean age 68 ± 12 years, 73% male). Prevalence of AF was 19%, ranging from 10% to 28% in patients ≤ 60 and ≥ 77 years, respectively. Besides the older age, patients with AF had more symptoms (New York Heart Association II-III 60% vs 44%), lower prevalence of dyslipidemia (23% vs 37%), coronary artery disease (28% vs 52%) and left bundle branch block (9% vs 16%). On the contrary, they more frequently presented with an idiopathic etiology (50% vs 24%), a history of valve surgery (13% vs 4%) and received overall more devices implantation (31% vs 21%). The use of disease-modifying medications (i.e., BB and ACE inhibitors/angiotensin receptor blockers) was lower in patients with AF (72% vs 80% and 71% vs 79%, respectively), who on the contrary were more frequently treated with symptomatic and antiarrhythmic drugs including diuretics (87% vs 69%) and digoxin (51% vs 11%). At a mean follow-up of about 5 years, all-cause mortality was significantly higher in patients with AF as compared to those in sinus rhythm (SR) (45% vs 34%, P value < 0.05 for all previous comparisons). However, in a multivariate analysis including the main significant predictors of all-cause mortality, the univariate relationship between AF and death (HR = 1

  12. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study.

    PubMed

    Trotta, Antonella; Murray, Robin M; David, Anthony S; Kolliakou, Anna; O'Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L

    2016-03-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services.

  13. Impact of Isotope Dilution Mass Spectrometry (IDMS) Standardization on Carboplatin Dose and Adverse Events

    PubMed Central

    Lawson, Justin; Switchenko, Jeffrey M.; McKibbin, Trevor; Harvey, R. Donald

    2017-01-01

    BACKGROUND When using area under the concentration-time curve-based strategies for dosing carboplatin, accurate estimation of glomerular filtration rate is required for determining dose. Commonly, the Cockcroft–Gault equation is used, which is dependent on measurement of serum creatinine (SCr). Because analysis of SCr changed to an isotope dilution mass spectrometry (IDMS) standard, we sought to determine the impact of this assay change on carboplatin dosing and related toxicity. METHODS This was a single-center, retrospective chart review of adults treated with carboplatin between April 2008 and April 2010 divided into cohorts that initiated carboplatin before or after IDMS standardization. End points included grade 3 thrombocytopenia, decrease in platelet count, and hospitalization and were evaluated in cohorts based on concomitant chemotherapy. RESULTS The chart review identified 158 patients, with 63 patients in the pre-IDMS group and 95 patients in the post-IDMS group. Average SCr (pre 1.01 mg/dl vs post 0.86 mg/dl, p<0.001) and average carboplatin dose (pre 580 mg vs post 703 mg, p<0.001) were significantly different between the groups. The frequency of grade 3 thrombocytopenia was not statistically significant across three partner chemotherapy cohorts before and after IDMS implementation. CONCLUSION IDMS standardization led to an overall decrease in SCr with subsequent increase in carboplatin doses. However, no increase in recorded adverse events was observed, suggesting that the clinical relevance in toxicity from higher doses was minimal. PMID:27130286

  14. Adverse Impact of Sleep Restriction and Circadian Misalignment on Autonomic Function in Healthy Young Adults.

    PubMed

    Grimaldi, Daniela; Carter, Jason R; Van Cauter, Eve; Leproult, Rachel

    2016-07-01

    Insufficient sleep and circadian rhythm disturbances have been each associated with adverse cardiovascular outcomes in epidemiological studies, but experimental evidence for a causal link is scarce. The present study compares the impact of circadian misalignment (CM) to circadian alignment (CA) on human autonomic function using a nonrandomized parallel group design to achieve the same total sleep time in both conditions. After baseline assessments (3 days with 10-hour bedtimes), 26 healthy young adults were assigned to sleep restriction (SR; eight 5-hour bedtimes) with either fixed nocturnal bedtimes (CA; n=13) or bedtimes delayed by 8.5 hours on 4 of the 8 days (CM; n=13). Daytime ambulatory blood pressure and heart rate (HR; CA, n=11; CM, n=10) and 24-hour urinary norepinephrine levels (CA, n=13; CM, n=13) were assessed at baseline and the end of SR. Nocturnal HR and HR variability were analyzed during sleep at baseline and during the fourth and seventh nights of SR (CA, n=8; CM, n=12). SR resulted in a significant increase in daytime HR in both groups, without changes in blood pressure. SR increased 24-hour urinary norepinephrine in the CM group (30±4 versus 21±2 μg), but not in the circadian alignment group (group×condition, P=0.005). In contrast to the lack of detectable impact of CM on daytime autonomic function, SR with CM elicited greater increases in nocturnal HR, as well as greater reductions in vagal indices of HR variability, than SR without CM (group×condition, P<0.05). In conclusion, SR and CM both result in impaired autonomic function that could lead, under chronic conditions, to enhanced cardiovascular risk.

  15. Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast Conserving Surgery

    PubMed Central

    Gosset, Marie; Hamy, Anne-Sophie; Mallon, Peter; Delomenie, Myriam; Mouttet, Delphine; Pierga, Jean-Yves; Lae, Marick; Fourquet, Alain; Rouzier, Roman; Reyal, Fabien; Feron, Jean-Guillaume

    2016-01-01

    Background The poor prognosis of patients who experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A short time between primary cancer and IBTR is a prognostic factor but no clinically relevant threshold was determined. Classification of IBTR may help tailor treatment strategies. Purpose We determined a specific time frame, which differentiates IBTR into early and late recurrence, and identified prognostic factors for patients with IBTR at time of the recurrence. Methods We analyzed 2209 patients with IBTR after BCS. We applied the optimal cut-points method for survival data to determine the cut-off times to IBTR. A subgroup analysis was performed by hormone receptor (HR) status. Survival analyses were performed using a Cox proportional hazard model to determine clinical features associated with distant-disease-free survival (DDFS) after IBTR. We therefor built decision trees. Results On the 828 metastatic events observed, the majority occurred within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR negative group. We found different prognostic times to IBTR: 49 months in the HR positive group, 33 in the HR negative group. After multivariate analysis, time to IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95% [0.54–0.79] and 0.42 [0.30–0.57] respectively). The other following variables were significantly correlated with the DDFS: the initial number of positive lymph nodes for both groups, the initial tumor size and grade for HR positive tumors. Conclusion A short interval time to IBTR is the strongest factor of poor prognosis and reflects occult distant disease. It would appear that prognosis after IBTR depends more on clinical and histological parameters than on surgical treatment. A prospective trial in a low-risk group of patients to validate the safety of salvage BCS instead of mastectomy in IBTR is needed. PMID:27494111

  16. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy.

    PubMed

    Santacruz, Rodrigo; Villamor, Neus; Aymerich, Marta; Martínez-Trillos, Alejandra; López, Cristina; Navarro, Alba; Rozman, María; Beà, Sílvia; Royo, Cristina; Cazorla, Maite; Colomer, Dolors; Giné, Eva; Pinyol, Magda; Puente, Xose S; López-Otín, Carlos; Campo, Elías; López-Guillermo, Armando; Delgado, Julio

    2014-05-01

    A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV, TP53, NOTCH1 and SF3B1 mutations. The median follow-up was 73 months (range, 2-202) from disease evaluation. The median treatment-free survival durations for patients achieving a complete response without or with minimal residual disease, a partial response and no response were 76, 40, 11 and 11 months, respectively (P<0.001). Multivariate analysis revealed that three variables had a significant impact on treatment-free survival: minimal residual disease (P<0.001), IGHV status (P<0.001) and β2-microglobulin levels (P=0.012). With regards to overall survival, factors predictive of an unfavorable outcome were minimal residual disease positivity (P=0.014), together with advanced age (P<0.001), unmutated IGHV status (P=0.001), TP53 mutations (P<0.001) and elevated levels of β2-microglobulin (P=0.003). In conclusion, for patients requiring front-line therapy, achievement of minimal residual disease negativity is associated with significantly prolonged treatment-free and overall survival irrespective of other prognostic markers or treatment administered.

  17. Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

    PubMed Central

    Usha, Lydia; Tabesh, Bita; Morrison, Larry E; Rao, Ruta D; Jacobson, Kris; Zhu, April; Basu, Sanjib; Coon, John S

    2008-01-01

    Background Amplification of the ERBB2 (Her-2/neu) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for topoisomerase II alpha (TOP2A), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy. Methods and patients Archival tissue samples from 63 breast cancer patients with ERBB2 amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near ERBB2. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available. Results Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted TOP2A had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. TOP2A deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between TOP2A deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06). Conclusion TOP2A deletion is associated with poor prognosis in ERBB2-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study. PMID:18702822

  18. Upregulation of Trefoil Factor 3 (TFF3) After Rectal Cancer Chemoradiotherapy Is an Adverse Prognostic Factor and a Potential Therapeutic Target

    SciTech Connect

    Casado, Enrique; Moreno Garcia, Victor; Sanchez, Jose Javier; Gomez del Pulgar, Maria Teresa; Feliu, Jaime; Maurel, Joan; Castelo, Beatriz; Moreno Rubio, Juan; Lopez, Rocio A.B.; Garcia-Cabezas, Miguel Angel; Burgos, Emilio; and others

    2012-12-01

    Purpose: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. Methods: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. Results: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. Conclusion: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.

  19. Reduced expression of argininosuccinate synthetase 1 has a negative prognostic impact in patients with pancreatic ductal adenocarcinoma

    PubMed Central

    Liu, Qingqing; Stewart, John; Wang, Hua; Rashid, Asif; Zhao, Jun; Katz, Matthew H.; Lee, Jeffrey E.; Fleming, Jason B.; Maitra, Anirban; Wolff, Robert A.; Varadhachary, Gauri R.; Krishnan, Sunil; Wang, Huamin

    2017-01-01

    Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme for arginine biosynthesis, is expressed in many types of human malignancies. Recent studies showed that ASS1 may have tumor suppressor function and that ASS1 deficiency is associated with clinical aggressiveness in nasopharyngeal carcinoma, myxofibrosarcomas and bladder cancer. The goal of this study was to evaluate the prognostic impact of ASS1 expression in patients with pancreatic ductal adenocarcinoma (PDAC). Our study included two independent cohorts: untreated cohort, which was comprised of 135 patients with PDAC who underwent pancreatoduodenectomy (PD) without pre-operative neoadjuvant therapy, and treated cohort, which was comprised of 122 patients with PDAC who have completed neoadjuvant therapy and PD. The expression level of ASS1 was evaluated by immunohistochemistry and the results were correlated with clinicopathologic parameters and survival using SPSS statistics. Our study showed that 12% of PDAC in untreated cohort and 15% of PDAC in treated cohort has low expression of ASS1 (ASS1-low). ASS1-low was associated with higher recurrence (p = 0.045), shorter disease-free survival (DFS, 4.8 ± 1.6 months vs 15.3 ± 2.2 months, p = 0.001) and shorter overall survival (OS, 14.6 ± 6.4 months vs 26.5 ± 3.5 months, p = 0.005) in untreated cohort and shorter OS in treated cohort compared to ASS1-high tumors. In multivariate analysis, ASS1-low (HR: 0.45, 95% CI: 0.26–0.79, p = 0.005) was an independent prognostic factor for DFS in untreated cohort and an independent prognostic factor for OS (HR: 0.56, 95% CI: 0.32–0.97, p = 0.04) in treated cohort. Our results provide supporting evidence for future clinical trial using arginine deprivation agents either alone or in combination with conventional chemotherapy in treating pancreatic cancer. PMID:28187218

  20. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

    PubMed

    Tabouret, Emeline; Nguyen, Anh Tuan; Dehais, Caroline; Carpentier, Catherine; Ducray, François; Idbaih, Ahmed; Mokhtari, Karima; Jouvet, Anne; Uro-Coste, Emmanuelle; Colin, Carole; Chinot, Olivier; Loiseau, Hugues; Moyal, Elisabeth; Maurage, Claude-Alain; Polivka, Marc; Lechapt-Zalcman, Emmanuèle; Desenclos, Christine; Meyronet, David; Delattre, Jean-Yves; Figarella-Branger, Dominique

    2016-10-01

    The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1-84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH (mut)) (11.0 %), anaplastic astrocytoma IDH wild type (IDH (wt)) (5.3 %), glioblastoma IDH (mut) (17.1 %), and glioblastoma IDH (wt) (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p < 0.001). We did not find prognosis differences between grades III and IV for IDH (mut) 1p/19q intact and IDH (wt) gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma IDH (wt), cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (p = 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas.

  1. Do Verbal Interactions with Infants During Electronic Media Exposure Mitigate Adverse Impacts on their Language Development as Toddlers?

    PubMed Central

    Mendelsohn, Alan L.; Brockmeyer, Carolyn A.; Dreyer, Benard P.; Fierman, Arthur H.; Berkule-Silberman, Samantha B.; Tomopoulos, Suzy

    2011-01-01

    The goal of this study was to determine whether verbal interactions between mothers and their 6-month-old infants during media exposure (‘media verbal interactions’) might have direct positive impacts, or mitigate any potential adverse impacts of media exposure, on language development at 14 months. For 253 low-income mother–infant dyads participating in a longitudinal study, media exposure and media verbal interactions were assessed using 24-hour recall diaries. Additionally, general level of cognitive stimulation in the home [StimQ] was assessed at 6 months and language development [Preschool Language Scale-4] was assessed at 14 months. Results suggest that media verbal interactions play a role in the language development of infants from low-income, immigrant families. Evidence showed that media verbal interactions moderated adverse impacts of media exposure found on 14-month language development, with adverse associations found only in the absence the these interactions. Findings also suggest that media verbal interactions may have some direct positive impacts on language development, in that media verbal interactions during the co-viewing of media with educational content (but not other content) were predictive of 14-month language independently of overall level of cognitive stimulation in the home. PMID:21593996

  2. Do Verbal Interactions with Infants During Electronic Media Exposure Mitigate Adverse Impacts on their Language Development as Toddlers?

    PubMed

    Mendelsohn, Alan L; Brockmeyer, Carolyn A; Dreyer, Benard P; Fierman, Arthur H; Berkule-Silberman, Samantha B; Tomopoulos, Suzy

    2010-11-01

    The goal of this study was to determine whether verbal interactions between mothers and their 6-month-old infants during media exposure ('media verbal interactions') might have direct positive impacts, or mitigate any potential adverse impacts of media exposure, on language development at 14 months. For 253 low-income mother-infant dyads participating in a longitudinal study, media exposure and media verbal interactions were assessed using 24-hour recall diaries. Additionally, general level of cognitive stimulation in the home [StimQ] was assessed at 6 months and language development [Preschool Language Scale-4] was assessed at 14 months. Results suggest that media verbal interactions play a role in the language development of infants from low-income, immigrant families. Evidence showed that media verbal interactions moderated adverse impacts of media exposure found on 14-month language development, with adverse associations found only in the absence the these interactions. Findings also suggest that media verbal interactions may have some direct positive impacts on language development, in that media verbal interactions during the co-viewing of media with educational content (but not other content) were predictive of 14-month language independently of overall level of cognitive stimulation in the home.

  3. Impact of Adverse Childhood Experiences on Psychotic-Like Symptoms and Stress Reactivity in Daily Life in Nonclinical Young Adults

    PubMed Central

    Ballespí, Sergi; Mitjavila, Mercè; Myin-Germeys, Inez; Kwapil, Thomas R.; Barrantes-Vidal, Neus

    2016-01-01

    Background There is increasing interest in elucidating the association of different childhood adversities with psychosis-spectrum symptoms as well as the mechanistic processes involved. This study used experience sampling methodology to examine (i) associations of a range of childhood adversities with psychosis symptom domains in daily life; (ii) whether associations of abuse and neglect with symptoms are consistent across self-report and interview methods of trauma assessment; and (iii) the role of different adversities in moderating affective, psychotic-like, and paranoid reactivity to situational and social stressors. Method A total of 206 nonclinical young adults were administered self-report and interview measures to assess childhood abuse, neglect, bullying, losses, and general traumatic events. Participants received personal digital assistants that signaled them randomly eight times daily for one week to complete questionnaires about current experiences, including symptoms, affect, and stress. Results Self-reported and interview-based abuse and neglect were associated with psychotic-like and paranoid symptoms, whereas only self-reported neglect was associated with negative-like symptoms. Bullying was associated with psychotic-like symptoms. Losses and general traumatic events were not directly associated with any of the symptom domains. All the childhood adversities were associated with stress reactivity in daily life. Interpersonal adversities (abuse, neglect, bullying, and losses) moderated psychotic-like and/or paranoid reactivity to situational and social stressors, whereas general traumatic events moderated psychotic-like reactivity to situational stress. Also, different interpersonal adversities exacerbated psychotic-like and/or paranoid symptoms in response to distinct social stressors. Discussion The present study provides a unique examination of how childhood adversities impact the expression of spectrum symptoms in the real world and lends support

  4. Sex-specific impact of early-life adversity on chronic pain: a large population-based study in Japan

    PubMed Central

    Yamada, Keiko; Matsudaira, Ko; Tanaka, Eizaburo; Oka, Hiroyuki; Katsuhira, Junji; Iso, Hiroyasu

    2017-01-01

    Background Responses to early-life adversity may differ by sex. We investigated the sex-specific impact of early-life adversity on chronic pain, chronic multisite pain, and somatizing tendency with chronic pain. Methods We examined 4229 respondents aged 20–79 years who participated in the Pain Associated Cross-Sectional Epidemiological Survey in Japan. Outcomes were: 1) chronic pain prevalence, 2) multisite pain (≥3 sites) prevalence, and 3) multiple somatic symptoms (≥3 symptoms) among respondents with chronic pain related to the presence or absence of early-life adversity. Multivariable-adjusted odds ratios (ORs) were calculated with 95% confidence intervals using a logistic regression model including age, smoking status, exercise routine, sleep time, body mass index, household expenditure, and the full distribution of scores on the Mental Health Inventory-5. We further adjusted for pain intensity when we analyzed the data for respondents with chronic pain. Results The prevalence of chronic pain was higher among respondents reporting the presence of early-life adversity compared with those reporting its absence, with multivariable ORs of 1.62 (1.22–2.15, p<0.01) in men and 1.47 (1.13–1.90, p<0.01) in women. Among women with chronic pain, early-life adversity was associated with multisite pain and multiple somatic symptoms; multivariable ORs were 1.78 (1.22–2.60, p<0.01) for multisite pain and 1.89 (1.27–2.83, p<0.01) for ≥3 somatic symptoms. No associations were observed between early-life adversity and chronic multisite pain or multiple somatic symptoms among men with chronic pain. Conclusion Early-life adversity may be linked to a higher prevalence of chronic pain among both sexes and to multisite pain and somatizing tendency among women with chronic pain. PMID:28243147

  5. Iron Deficiency Anemia Coexists with Cancer Related Anemia and Adversely Impacts Quality of Life

    PubMed Central

    Kanuri, Giridhar; Sawhney, Ritica; Varghese, Jeeva; Britto, Madonna; Shet, Arun

    2016-01-01

    Cancer related anemia (CRA) adversely affects patient Quality of Life (QoL) and overall survival. We prospectively studied the prevalence, etiology and the impact of anemia on QoL in 218 Indian cancer patients attending a tertiary referral hospital. The study used the sTfR/log Ferritin index to detect iron deficiency anemia and assessed patient QoL using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) tool, standardized for language. Mean patient age was 51±13 years and 60% were female. The prevalence of cancer related anemia in this setting was 64% (n = 139). As expected, plasma ferritin did not differ significantly between anemic (n = 121) and non-anemic cancer patients (n = 73). In contrast, plasma sTfR levels were significantly higher in anemic cancer patients compared to non-anemic cancer patients (31 nmol/L vs. 24 nmol/L, p = 0.002). Among anemic cancer patients, using the sTfR/log Ferritin index, we found that 60% (n = 83) had iron deficiency anemia (IDA). Interestingly, plasma sTfR levels were significantly higher in cancer patients with CRA+IDA (n = 83) compared with patients having CRA (n = 38) alone (39 nmol/L vs. 20 nmol/L, p<0.001). There was a significant linear correlation between Hb and QoL (Spearman ρ = 0.21; p = 0.001) and multivariate regression analysis revealed that every gram rise in Hb was accompanied by a 3.1 unit increase in the QoL score (95% CI = 0.19–5.33; p = 0.003). The high prevalence of anemia in cancer patients, a major portion of which is due to iron deficiency anemia, the availability of sensitive and specific biomarkers of iron status to detect IDA superimposed on anemia of inflammation, suggests an urgent need to diagnose and treat such patients. Despite the potential negative consequences of increasing metabolically available plasma iron in cancer, our clinical data suggest that detecting and treating IDA in anemic cancer patients will have important consequences to their QoL and overall survival. Clinical

  6. Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas

    PubMed Central

    Aaberg-Jessen, Charlotte; Hermansen, Simon K.; Kristensen, Bjarne W.

    2017-01-01

    Astrocytomas are the most frequent primary brain tumors in adults, and despite aggressive treatment patients often experience recurrence. Survival decreases with increasing tumor grade, and especially patients with grade IV glioblastoma have poor prognosis due to the aggressive character of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2 expression in tumor cells and blood vessels. Measurements of MMP-2 intensity increased with tumor grade, and MMP-2 expression was found to be significantly higher in glioblastomas compared to normal brain tissue (p<0.001), diffuse astrocytomas (p<0.001) and anaplastic astrocytomas (p<0.05). MMP-2 expression was associated with shorter overall survival in patients with grade II-IV astrocytic tumors (HR 1.60; 95% CI 1.03–2.48; p = 0.036). In glioblastoma, high MMP-2 was associated with poorer prognosis in patients who survived longer than 8.5 months independent of age and gender (HR 2.27; 95% CI 1.07–4.81; p = 0.033). We found a positive correlation between MMP-2 and tissue inhibitor of metalloproteinases-1 (TIMP-1), and combined MMP-2 and TIMP-1 had stronger prognostic value than MMP-2 alone also when adjusting for age and gender (HR 2.78; 95% CI 1.30–5.92; p = 0.008). These findings were validated in bioinformatics databases. In conclusion, this study indicates that MMP-2 is associated with aggressiveness in astrocytomas and may hold an unfavorable prognostic value in

  7. Prognostic factors in cancer.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

  8. Prognostic Impact of the Geriatric Nutritional Risk Index on Long-Term Outcomes in Patients Who Underwent Percutaneous Coronary Intervention.

    PubMed

    Wada, Hideki; Dohi, Tomotaka; Miyauchi, Katsumi; Doi, Shinichiro; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Ogita, Manabu; Kasai, Takatoshi; Hassan, Ahmed; Okazaki, Shinya; Isoda, Kikuo; Suwa, Satoru; Daida, Hiroyuki

    2017-03-16

    Malnutrition has been identified as an important predictor of poor clinical outcomes in patients with heart failure. The aim of this study is to examine the prognostic impact of nutritional status in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). The impact of nutrition, assessed using the geriatric nutritional risk index (GNRI) calculated by serum albumin and body mass index, was evaluated in 2,853 patients with CAD who underwent their first PCI between 2000 and 2011. Patients were assigned to tertiles based on their GNRI levels. The incidences of all-cause death and cardiac death were assessed. The median GNRI values were 101 (interquartile range 95 to 106). Lower GNRI levels were associated with older age and higher prevalence of acute coronary syndrome and chronic kidney disease. During the median follow-up period of 7.4 years, Kaplan-Meier curves showed ongoing divergence in rates of mortality among tertiles (GNRI <98: 35.1%; 98 to 104: 20.6%; ≥104: 12.1%; log-rank p <0.0001). Stratification analysis by age also showed that the lowest GNRI tertile was associated with mortality in both patients <65 years and those ≥65 years. After adjusting for established cardiovascular risk factors, lower GNRI was an independent predictor of all-cause death (hazard ratio 1.55 per 10 decrease, 95% confidence interval 1.30 to 1.84, p <0.0001) and cardiac death (hazard ratio 1.44, 95% confidence interval 1.08 to 1.90, p = 0.01). In conclusion, nutritional status was associated with long-term clinical outcomes in CAD patients after PCI. Evaluation of GNRI carries important prognostic information and may guide the therapeutic approach to such patients.

  9. Adverse events in the intensive care unit: impact on mortality and length of stay in a prospective study.

    PubMed

    Roque, Keroulay Estebanez; Tonini, Teresa; Melo, Enirtes Caetano Prates

    2016-10-20

    This study sought to evaluate the occurrence of adverse events and their impacts on length of stay and mortality in an intensive care unit (ICU). This is a prospective study carried out in a teaching hospital in Rio de Janeiro, Brazil. The cohort included 355 patients over 18 years of age admitted to the ICU between August 1, 2011 and July 31, 2012. The process we used to identify adverse events was adapted from the method proposed by the Institute for Healthcare Improvement. We used a logistical regression to analyze the association between adverse event occurrence and death, adjusted by case severity. We confirmed 324 adverse events in 115 patients admitted over the year we followed. The incidence rate was 9.3 adverse events per 100 patients-day and adverse event occurrence impacted on an increase in length of stay (19 days) and in mortality (OR = 2.047; 95%CI: 1.172-3.570). This study highlights the serious problem of adverse events in intensive care and the risk factors associated with adverse event incidence. Resumo: Este estudo teve como objetivo avaliar a ocorrência de eventos adversos e o impacto deles sobre o tempo de permanência e a mortalidade na unidade de terapia intensiva (UTI). Trata-se de um estudo prospectivo desenvolvido em um hospital de ensino do Rio de Janeiro, Brasil. A coorte foi formada por 355 pacientes maiores de 18 anos, admitidos na UTI, no período de 1º de agosto de 2011 a 31 de julho de 2012. O processo de identificação de eventos adversos baseou-se em uma adaptação do método proposto pelo Institute for Healthcare Improvement. A regressão logística foi utilizada para analisar a associação entre a ocorrência de evento adverso e o óbito, ajustado pela gravidade do paciente. Confirmados 324 eventos adversos em 115 pacientes internados ao longo de um ano de seguimento. A taxa de incidência foi de 9,3 eventos adversos por 100 pacientes-dia, e a ocorrência de evento adverso impactou no aumento do tempo de internação (19

  10. Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications.

    PubMed

    Del Principe, Maria Ilaria; Buccisano, Francesco; Maurillo, Luca; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; Consalvo, Maria Irno; Sarlo, Chiara; Conti, Consuelo; De Santis, Giovanna; De Bellis, Eleonora; Di Veroli, Ambra; Palomba, Patrizia; Attrotto, Cristina; Zizzari, Annagiulia; Paterno, Giovangiacinto; Voso, Maria Teresa; Del Poeta, Giovanni; Lo-Coco, Francesco; Arcese, William; Amadori, Sergio; Venditti, Adriano

    2016-01-01

    Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients' risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help to identify patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry(MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management.

  11. Prognostic impact of MYH9 expression on patients with acute myeloid leukemia

    PubMed Central

    Hu, Chao; Ma, Qiuling; Li, Xia; Yin, Xiufeng; Huang, Jiansong; Zhang, Ting; Ma, Zhixin; Zhou, Yile; Li, Chenying; Chen, Feifei; Chen, Jian; Wang, Yungui; Pan, Hanzhang; Wang, Dongmei; Jin, Jie

    2017-01-01

    MYH9 expression has previously been demonstrated as an independent predictor of clinical outcome in solid tumors. However, the prognostic relevance of MYH9 expression in acute myeloid leukemia is still unclear. Here, we found high MYH9 expressers were seen more frequently in females and more frequently in M4 morphology. We also found high MYH9 expressers had lower percentage of bone marrow blasts. In addition, overexpression of MYH9 was associated with an inferior overall survival. Notably, distinct microRNA signatures were seen in high MYH9 expressers. These results were also validated in an independent cohort of AML patients using the published data. In conclusion, gene of MYH9 expression might serve as a reliable predictor for overall survival in AML patients. PMID:27437869

  12. The prognostic impact of age in different molecular subtypes of breast cancer.

    PubMed

    Liedtke, Cornelia; Rody, Achim; Gluz, Oleg; Baumann, Kristin; Beyer, Daniel; Kohls, Eva-Beatrice; Lausen, Kerstin; Hanker, Lars; Holtrich, Uwe; Becker, Sven; Karn, Thomas

    2015-08-01

    Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.

  13. Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

    PubMed Central

    2014-01-01

    Background New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. Methods MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. Results Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. Conclusions Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility. PMID:25015560

  14. Impact of adverse weather on sensors for vehicle collision avoidance systems

    NASA Astrophysics Data System (ADS)

    Everson, Jeffrey H.; Kopala, Edward W.; Lazofson, Laurence E.; Choe, Howard C.; Pomerleau, Dean A.

    1995-12-01

    This paper treats the use of in-vehicle imaging sensors to achieve lateral control to avoid single vehicle roadway departure crashes. Since the sensor is expected to function under a variety of weather conditions, it is important to determine the overall performance envelope of the combined sensor/image processing algorithm. Initial roadway imagery was acquired under favorable ambient conditions and subsequently transformed to specified levels of adverse weather by means of software originally developed for military sensor applications. The transformed imagery was utilized to determine the relationship between adverse weather, measured in visibility ranges, versus the ability of the sensor/image processing algorithm to maintain lateral vehicle stability.

  15. The Noise from Wind Turbines: Potential Adverse Impacts on Children's Well-Being

    ERIC Educational Resources Information Center

    Bronzaft, Arline L.

    2011-01-01

    Research linking loud sounds to hearing loss in youngsters is now widespread, resulting in the issuance of warnings to protect children's hearing. However, studies attesting to the adverse effects of intrusive sounds and noise on children's overall mental and physical health and well-being have not received similar attention. This, despite the…

  16. The Impact of Adverse Childhood Experiences on an Urban Pediatric Population

    ERIC Educational Resources Information Center

    Burke, Nadine J.; Hellman, Julia L.; Scott, Brandon G.; Weems, Carl F.; Carrion, Victor G.

    2011-01-01

    Objective: The goal of this study was to investigate the adverse childhood experiences (ACEs) in youth in a low-income, urban community. Study design: Data from a retrospective chart review of 701 subjects from the Bayview Child Health Center in San Francisco are presented. Medical chart documentation of ACEs as defined in previous studies were…

  17. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

    PubMed Central

    Min, James K.; Labounty, Troy M.; Gomez, Millie J.; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor; Chinnaiyan, Kavitha M.; Chow, Benjamin; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jorg; Kaufmann, Philipp; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y.; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J.; Villines, Todd C.; Berman, Daniel S.

    2015-01-01

    Background Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Methods From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification. Results Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of

  18. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

    PubMed

    Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

    2016-12-01

    Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD.

  19. A holistic look at minimizing adverse environmental impact under Section 316(b) of the Clean Water Act.

    PubMed

    Veil, John A; Puder, Markus G; Littleton, Debra J; Johnson, Nancy

    2002-04-18

    Section 316(b) of the Clean Water Act (CWA) requires that "the location, design, construction, and capacity of cooling water intake structures reflect the best technology available for minimizing adverse environmental impact." As the U.S. Environmental Protection Agency (EPA) develops new regulations to implement Section 316(b), much of the debate has centered on adverse impingement and entrainment impacts of cooling-water intake structures. Depending on the specific location and intake layout, once-through cooling systems withdrawing many millions of gallons of water per day can, to a varying degree, harm fish and other aquatic organisms in the water bodies from which the cooling water is withdrawn. Therefore, opponents of once-through cooling systems have encouraged the EPA to require wet or dry cooling tower systems as the best technology available (BTA), without considering site-specific conditions. However, within the context of the broader scope of the CWA mandate, this focus seems too narrow. Therefore, this article examines the phrase "minimizing adverse environmental impact" in a holistic light. Emphasis is placed on the analysis of the terms "environmental" and "minimizing." Congress chose "environmental" in lieu of other more narrowly focused terms like "impingement and entrainment," "water quality," or "aquatic life." In this light, BTA for cooling-water intake structures must minimize the entire suite of environmental impacts, as opposed to just those associated with impingement and entrainment. Wet and dry cooling tower systems work well to minimize entrainment and impingement, but they introduce other equally important impacts because they impose an energy penalty on the power output of the generating unit. The energy penalty results from a reduction in plant operating efficiency and an increase in internal power consumption. As a consequence of the energy penalty, power companies must generate additional electricity to achieve the same net output

  20. Mir-21–Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact

    PubMed Central

    Sathyan, Pratheesh; Zinn, Pascal O.; Marisetty, Anantha L.; Liu, Bin; Kamal, Mohamed Mostafa; Singh, Sanjay K.; Bady, Pierre; Lu, Li; Wani, Khalida M.; Veo, Bethany L.; Gumin, Joy; Kassem, Dina Hamada; Robinson, Frederick; Weng, Connie; Baladandayuthapani, Veerabhadran; Suki, Dima; Colman, Howard; Bhat, Krishna P.; Sulman, Erik P.; Aldape, Ken; Colen, Rivka R.; Verhaak, Roel G.W.; Lu, Zhimin; Fuller, Gregory N.; Huang, Suyun; Lang, Frederick F.; Sawaya, Raymond; Hegi, Monika

    2015-01-01

    Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21–Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not

  1. Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures

    PubMed Central

    Barger, Laura K; Ayas, Najib T; Cade, Brian E; Cronin, John W; Rosner, Bernard; Speizer, Frank E; Czeisler, Charles A

    2006-01-01

    Background A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States. Methods and Findings We conducted a Web-based survey, across the United States, in which 2,737 residents in their first postgraduate year (interns) completed 17,003 monthly reports. The association between the number of extended-duration shifts worked in the month and the reporting of significant medical errors, preventable adverse events, and attentional failures was assessed using a case-crossover analysis in which each intern acted as his/her own control. Compared to months in which no extended-duration shifts were worked, during months in which between one and four extended-duration shifts and five or more extended-duration shifts were worked, the odds ratios of reporting at least one fatigue-related significant medical error were 3.5 (95% confidence interval [CI], 3.3–3.7) and 7.5 (95% CI, 7.2–7.8), respectively. The respective odds ratios for fatigue-related preventable adverse events, 8.7 (95% CI, 3.4–22) and 7.0 (95% CI, 4.3–11), were also increased. Interns working five or more extended-duration shifts per month reported more attentional failures during lectures, rounds, and clinical activities, including surgery and reported 300% more fatigue-related preventable adverse events resulting in a fatality. Conclusions In our survey, extended-duration work shifts were associated with an

  2. p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

    PubMed Central

    Silva, S.D.; Nonogaki, S.; Soares, F.A.; Kowalski, L.P.

    2012-01-01

    CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis. PMID:22948376

  3. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

    SciTech Connect

    Twu, C.-W.; Wang, W.-Y.; Liang, W.-M.; Jan, J.-S.; Jiang, R.-S.; Chao, Jeffrey; Jin, Y.-T.; Lin, J.-C. . E-mail: jclin@vghtc.gov.tw

    2007-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

  4. Incidence and Prognostic Impact of DNMT3A Mutations in Korean Normal Karyotype Acute Myeloid Leukemia Patients

    PubMed Central

    Park, Sang Hyuk; Choi, Jae-Cheol; Kim, Shine Young; Yi, Jongyoun; Oh, Seung Hwan; Kim, In-Suk; Kim, Hyung-Hoi; Chang, Chulhun Ludgerus; Lee, Eun Yup; Song, Moo-Kon; Shin, Ho-Jin; Chung, Joo Seop

    2015-01-01

    Background. DNA methyltransferase 3A (DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact of DNMT3A mutations in Korean NK AML patients. Methods. Total 67 NK AML patients diagnosed during the recent 10 years were enrolled. DNMT3A mutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based on in silico analysis results. Clinical features and prognosis were compared with respect to DNMT3A mutation status. Results. Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs. DNMT3A NSVs, DMs, and R882 mutation were identified in 14.9%–17.9%, 10.3%–10.4%, and 7.5% of patients, respectively. DNMT3A mutations were frequently detected in FLT3 ITD mutated patients (P = 0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly. Conclusions. Incidences of DNMT3A NSVs, DMs, and R882 mutation are 14.9%–17.9%, 10.3%–10.4%, and 7.5%, respectively, in Korean NK AML patients. DNMT3A mutations are associated with FLT3 ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients. PMID:25650308

  5. Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications

    PubMed Central

    Del Principe, Maria Ilaria; Buccisano, Francesco; Maurillo, Luca; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; Consalvo, Maria Irno; Sarlo, Chiara; Conti, Consuelo; De Santis, Giovanna; De Bellis, Eleonora; Di Veroli, Ambra; Palomba, Patrizia; Attrotto, Cristina; Zizzari, Annagiulia; Paterno, Giovangiacinto; Voso, Maria Teresa; Del Poeta, Giovanni; Lo-Coco, Francesco; Arcese, William; Amadori, Sergio; Venditti, Adriano

    2016-01-01

    Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients’ risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help to identify patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry(MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management. PMID:27872732

  6. A Holistic Look at Minimizing Adverse Environmental Impact Under Section 316(b) of the Clean Water Act

    DOE PAGES

    Veil, John A.; Puder, Markus G.; Littleton, Debra J.; ...

    2002-01-01

    Section 316(b) of the Clean Water Act (CWA) requires that “the location, design, construction, and capacity of cooling water intake structures reflect the best technology available for minimizing adverse environmental impact.” As the U.S. Environmental Protection Agency (EPA) develops new regulations to implement Section 316(b), much of the debate has centered on adverse impingement and entrainment impacts of cooling-water intake structures. Depending on the specific location and intake layout, once-through cooling systems withdrawing many millions of gallons of water per day can, to a varying degree, harm fish and other aquatic organisms in the water bodies from which the coolingmore » water is withdrawn. Therefore, opponents of once-through cooling systems have encouraged the EPA to require wet or dry cooling tower systems as the best technology available (BTA), without considering site-specific conditions. However, within the context of the broader scope of the CWA mandate, this focus seems too narrow. Therefore, this article examines the phrase “minimizing adverse environmental impact” in a holistic light. Emphasis is placed on the analysis of the terms “environmental” and “minimizing.” Congress chose “environmental” in lieu of other more narrowly focused terms like “impingement and entrainment,” “water quality,” or “aquatic life.” In this light, BTA for cooling-water intake structures must minimize the entire suite of environmental impacts, as opposed to just those associated with impingement and entrainment. Wet and dry cooling tower systems work well to minimize entrainment and impingement, but they introduce other equally important impacts because they impose an energy penalty on the power output of the generating unit. The energy penalty results from a reduction in plant operating efficiency and an increase in internal power consumption. As a consequence of the energy penalty, power companies must generate additional

  7. The impact of outpatient chemotherapy-related adverse events on the quality of life of breast cancer patients.

    PubMed

    Tachi, Tomoya; Teramachi, Hitomi; Tanaka, Kazuhide; Asano, Shoko; Osawa, Tomohiro; Kawashima, Azusa; Yasuda, Masahiro; Mizui, Takashi; Nakada, Takumi; Noguchi, Yoshihiro; Tsuchiya, Teruo; Goto, Chitoshi

    2015-01-01

    The objective of our study was to clarify the impact of adverse events associated with the initial course of outpatient chemotherapy on the quality of life of breast cancer patients. We conducted a survey to assess the quality of life in 48 breast cancer patients before and after receiving their first course of outpatient chemotherapy at Gifu Municipal Hospital. Patients completed the European Quality of Life 5 Dimensions and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs before and after 1 course of outpatient chemotherapy. European Quality of Life 5 Dimensions utility value and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score decreased significantly after chemotherapy (p<0.001 and p = 0.018, respectively). The mean scores for the activity, physical condition, and psychological condition subscales of the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs decreased significantly after chemotherapy (p = 0.003, p<0.001, and p = 0.032, respectively), whereas the social relationships score increased significantly (p<0.001). Furthermore, in the evaluation of quality of life according to individual adverse events, the decrease in quality of life after chemotherapy in terms of the European Quality of Life 5 Dimensions utility value and the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score was greater in anorexic patients than in non-anorexic patients (p = 0.009 and p<0.001, respectively). This suggests that anorexia greatly reduces quality of life. Our findings reveal that anticancer drug-related adverse events, particularly anorexia, reduce overall quality of life following the first course of outpatient chemotherapy in current breast cancer patients. These findings are extremely useful and important in understanding the impact of anticancer drug-related adverse events on quality of life.

  8. Renal Outcomes in Patients with AL Amyloidosis: Prognostic Factors, Renal response and the Impact of Therapy.

    PubMed

    Kastritis, Efstathios; Gavriatopoulou, Maria; Roussou, Maria; Migkou, Magdalini; Fotiou, Despina; Ziogas, Dimitrios C; Kanellias, Nikos; Eleutherakis-Papaiakovou, Evangelos; Panagiotidis, Ioannis; Giannouli, Stavroula; Psimenou, Erasmia; Marinaki, Smaragdi; Apostolou, Theofanis; Gakiopoulou, Hariklia; Tasidou, Anna; Papassotiriou, Ioannis; Terpos, Evangelos; Dimopoulos, Meletios A

    2017-03-28

    A staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m(2) ) and proteinuria (≥5gr/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction. We identified the ratio of 24h proteinuria to eGFR as a sensitive marker of renal risk which also accounts for changes in both proteinuria and eGFR: 24h proteinuria/eGFR ratio <30 (in mg/ml/min/1.73 m(2) ) was associated with a 2-year progression to dialysis rate of 0% compared to 9% for a ratio of 31-99 and 35% for a ratio ≥100 (p<0.001). In landmark analysis, patients who achieved a reduction of this ratio by at least 25% or ≤100 (if initially >100) at 3 months had a 2-year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (p=0.001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib-based therapy was more effective than lenalidomide-based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival. This article is protected by copyright. All rights reserved.

  9. Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteraemia.

    PubMed

    Robert, R; Deraignac, A; Le Moal, G; Ragot, S; Grollier, G

    2008-08-01

    Bacteraemia due to anaerobic bacteria occurs infrequently, making the systematic use of an anaerobic blood sample bottle in patients with sepsis controversial. We retrospectively reviewed the clinical and microbiological data from all cases of anaerobic bacteraemia in a teaching hospital over 2 years and determined the prognostic factors and antibiotic management. With the goal of evaluating the morbidity and mortality of bacteraemia due to anaerobic bacteria, a case-control study was also performed. One hundred eighty-four blood cultures from 125 patients grew at least one anaerobic bacterium, representing 0.5% of all and 7.0% of the positive blood cultures. One hundred seventeen patients were studied. In 24 cases, anaerobic blood cultures were associated with concomitant aerobic bacteria isolation. The most frequently isolated anaerobic species were Bacteroides sp. (n = 62), Clostridium sp. (n = 25), and Fusobacterium sp. (n = 12). The most frequent site of origin was the digestive tract (n = 61). In 51 cases, patients did not receive adequate empirical antianaerobic therapy. The mortality rate was 27%. Age [odds ratio (OR) 1.059; 95% confidence interval (CI) 1.021-1.100], cancer history (OR 3.21, 95% CI 1.126-9.156), and ineffective definitive antibiotherapy (OR 19.292, 95% CI 5.330-69.832) were independently associated with increased hospital mortality. The 72 patients that could be matched with patients without anaerobic bacteria according to their primary diagnosis had a longer hospitalisation and a trend toward increased mortality (P = 0.08). Anaerobic bacteraemia contributed significantly to the morbidity of the patients, and adequate empirical antibiotherapy may play an important role in the clinical outcomes.

  10. Identification and prioritization of relationships between environmental stressor and adverse human health impacts

    EPA Science Inventory

    AbstractBackground: There are over 80,000 chemicals in commerce with little data available describing their impacts on human health. Biomonitoring surveys, such as the NHANES, offer one route to identifying possible relationships between environmental chemicals and health impacts...

  11. Adverse Impact of Racial Isolation on Student Performance: A Study in North Carolina

    ERIC Educational Resources Information Center

    Sharma, Andy; Joyner, Ann Moss; Osment, Ashley

    2014-01-01

    This study examines the impact of racial isolation on high school student performance in North Carolina, a state in the southeast United States. Our research goal is to investigate if increased isolation negatively impacts Black students' academic performance. Employing the North Carolina State Department of Public Instruction (NCDPI) dataset, we…

  12. Relationship Between Adverse Childhood Experiences and Homelessness and the Impact of Axis I and II Disorders

    PubMed Central

    Roos, Leslie E.; Mota, Natalie; Afifi, Tracie O.; Katz, Laurence Y.; Distasio, Jino

    2013-01-01

    Objectives. We investigated the links between homelessness associated with serious mental and physical healthy disparities and adverse childhood experiences (ACEs) in nationally representative data, with Axis I and II disorders as potential mediators. Methods. We examined data from the National Epidemiologic Survey of Alcohol and Related Conditions in 2001–2002 and 2004–2005, and included 34 653 participants representative of the noninstitutionalized US population who were 20 years old or older. We studied the variables related to 4 classes of Axis I disorders, all 10 Axis II personality disorders, a wide range of ACEs, and a lifetime history of homelessness. Results. Analyses revealed high prevalences of each ACE in individuals experiencing lifetime homelessness (17%–60%). A mediation model with Axis I and II disorders determined that childhood adversities were significantly related to homelessness through direct effects (adjusted odd ratios = 2.04, 4.24) and indirect effects, indicating partial mediation. Population attributable fractions were also reported. Conclusions. Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways. PMID:24148049

  13. Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

    PubMed

    Chen, Marcus Y; Rochitte, Carlos E; Arbab-Zadeh, Armin; Dewey, Marc; George, Richard T; Miller, Julie M; Niinuma, Hiroyuki; Yoshioka, Kunihiro; Kitagawa, Kakuya; Sakuma, Hajime; Laham, Roger; Vavere, Andrea L; Cerci, Rodrigo J; Mehra, Vishal C; Nomura, Cesar; Kofoed, Klaus F; Jinzaki, Masahiro; Kuribayashi, Sachio; Scholte, Arthur J; Laule, Michael; Tan, Swee Yaw; Hoe, John; Paul, Narinder; Rybicki, Frank J; Brinker, Jeffrey A; Arai, Andrew E; Matheson, Matthew B; Cox, Christopher; Clouse, Melvin E; Di Carli, Marcelo F; Lima, João A C

    2017-03-14

    Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not

  14. Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma

    PubMed Central

    Peng, Hai-Hua; Huang, Wen-Jin; Cai, Long-Mei; Zhou, Tong-Chong

    2017-01-01

    Background Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. Methods Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical–pathological parameters was examined. Univariate and multivariate survival analyses were performed. Findings The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. Conclusion The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant

  15. Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Ujiie, Hideki; Buitrago, Daniel H.; Woo, Kaitlin M.; Sima, Camelia S.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Introduction We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma. Methods We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999 to 2009) that were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, IL-7R, and IL-12Rβ2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. Results Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10+ neutrophils were associated with worse prognoses in the training cohort (P = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10+ neutrophil and low CD20+ lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; P < 0.001); this was confirmed in the validation cohort (P = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (HR = 1.61, P = 0.006) and validation cohort (HR = 1.75; P = 0.043). Conclusions High CD10+/low CD20+ immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma. PMID:26291010

  16. IMPACT OF ABDOMINAL OBESITY ON INCIDENCE OF ADVERSE METABOLIC EFFECTS ASSOCIATED WITH ANTIHYPERTENSIVE MEDICATIONS

    PubMed Central

    Cooper-DeHoff, Rhonda M.; Wen, Sheron; Beitelshees, Amber L.; Zineh, Issam; Gums, John G.; Turner, Stephen T.; Gong, Yan; Hall, Karen; Parekh, Vishal; Chapman, Arlene B.; Boerwinkle, Eric; Johnson, Julie A.

    2009-01-01

    We assessed adverse metabolic effects (AMEs) of atenolol and hydrochlorothiazide (HCTZ) among hypertensive patients with and without abdominal obesity using data from a randomized, open-label study of hypertensive patients without evidence of cardiovascular disease or diabetes. Intervention included randomization to HCTZ 25mg or atenolol 100mg monotherapy followed by their combination. Fasting glucose, insulin, triglycerides, HDL cholesterol and uric acid were measured at baseline and after mono-and combination therapy. Outcomes included new occurrence of and predictors for new cases of glucose ≥ 100mg/dl (impaired fasting glucose [IFG]), triglyceride ≥ 150 mg/dl, HDL ≤ 40mg/dl for men or ≤ 50mg/dl for women, or new onset diabetes according to presence or absence of abdominal obesity. Abdominal obesity was present in 167/395 (58%). Regardless of strategy, in those with abdominal obesity, 20% had IFG at baseline compared with 40% at end of study (p<0.0001). Proportion with triglycerides ≥ 150 mg/dl increased from 33% at baseline to 46% at end of study (p<0.01). New onset diabetes occurred in 13 (6%) with and in 4 (2%) without abdominal obesity. Baseline levels of glucose, triglyceride and HDL predicted adverse outcomes and predictors for new onset diabetes after monotherapy in those with abdominal obesity included HCTZ strategy (OR 47, 95% CI 2.55-862), female sex (OR 31.3, 95% CI 2.10-500) and uric acid (OR 3.2, 95% CI 2.35-7.50). Development of AME, including new onset diabetes associated with short term exposure to HCTZ and atenolol was more common in those with abdominal obesity. PMID:19917874

  17. Interactions of early adversity with stress-related gene polymorphisms impact regional brain structure in females

    PubMed Central

    Gupta, Arpana; Labus, Jennifer; Kilpatrick, Lisa A.; Bonyadi, Mariam; Ashe-McNalley, Cody; Heendeniya, Nuwanthi; Bradesi, Sylvie; Chang, Lin; Mayer, Emeran A.

    2015-01-01

    Early adverse life events (EALs) have been associated with regional thinning of the subgenual cingulate cortex (sgACC), a brain region implicated in the development of disorders of mood and affect, and often comorbid functional pain disorders, such as irritable bowel syndrome (IBS). Regional neuroinflammation related to chronic stress system activation has been suggested as a possible mechanism underlying these neuroplastic changes. However, the interaction of genetic and environmental factors in these changes is poorly understood. The current study aimed to evaluate the interactions of EALs and candidate gene polymorphisms in influencing thickness of the sgACC. 210 female subjects (137 healthy controls; 73 IBS) were genotyped for stress and inflammation-related gene polymorphisms. Genetic variation with EALs, and diagnosis on sgACC thickness was examined, while controlling for race, age, and total brain volume. Compared to HCs, IBS had significantly reduced sgACC thickness (p = 0.03). Regardless of disease group (IBS vs. HC), thinning of the left sgACC was associated with a significant gene-gene environment interaction between the IL-1β genotype, the NR3C1 haplotype, and a history of EALs (p = 0.05). Reduced sgACC thickness in women with the minor IL-1β allele, was associated with EAL total scores regardless of NR3C1 haplotype status (p = 0.02). In subjects homozygous for the major IL-1β allele, reduced sgACC with increasing levels of EALs was seen only with the less common NR3C1 haplotype (p = 0.02). These findings support an interaction between polymorphisms related to stress and inflammation and early adverse life events in modulating a key region of the emotion arousal circuit. PMID:25630611

  18. Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior

    PubMed Central

    Levoe, S. Nikki; Flannery, Brenna M.; Brignolo, Laurie; Imai, Denise M.; Koehne, Amanda; Austin, Adam T.; Bruun, Donald A.; Tancredi, Daniel J.; Lein, Pamela J.

    2015-01-01

    Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory. PMID:25705100

  19. Population Trends of Central European Montane Birds Provide Evidence for Adverse Impacts of Climate Change on High-Altitude Species.

    PubMed

    Flousek, Jiří; Telenský, Tomáš; Hanzelka, Jan; Reif, Jiří

    2015-01-01

    Climate change is among the most important global threats to biodiversity and mountain areas are supposed to be under especially high pressure. Although recent modelling studies suggest considerable future range contractions of montane species accompanied with increased extinction risk, data allowing to test actual population consequences of the observed climate changes and identifying traits associated to their adverse impacts are very scarce. To fill this knowledge gap, we estimated long-term population trends of montane birds from 1984 to 2011 in a central European mountain range, the Giant Mountains (Krkonoše), where significant warming occurred over this period. We then related the population trends to several species' traits related to the climate change effects. We found that the species breeding in various habitats at higher altitudes had more negative trends than species breeding at lower altitudes. We also found that the species moved upwards as a response to warming climate, and these altitudinal range shifts were associated with more positive population trends at lower altitudes than at higher altitudes. Moreover, long-distance migrants declined more than residents or species migrating for shorter distances. Taken together, these results indicate that the climate change, besides other possible environmental changes, already influences populations of montane birds with particularly adverse impacts on high-altitude species such as water pipit (Anthus spinoletta). It is evident that the alpine species, predicted to undergo serious climatically induced range contractions due to warming climate in the future, already started moving along this trajectory.

  20. Population Trends of Central European Montane Birds Provide Evidence for Adverse Impacts of Climate Change on High-Altitude Species

    PubMed Central

    Flousek, Jiří; Telenský, Tomáš; Hanzelka, Jan; Reif, Jiří

    2015-01-01

    Climate change is among the most important global threats to biodiversity and mountain areas are supposed to be under especially high pressure. Although recent modelling studies suggest considerable future range contractions of montane species accompanied with increased extinction risk, data allowing to test actual population consequences of the observed climate changes and identifying traits associated to their adverse impacts are very scarce. To fill this knowledge gap, we estimated long-term population trends of montane birds from 1984 to 2011 in a central European mountain range, the Giant Mountains (Krkonoše), where significant warming occurred over this period. We then related the population trends to several species' traits related to the climate change effects. We found that the species breeding in various habitats at higher altitudes had more negative trends than species breeding at lower altitudes. We also found that the species moved upwards as a response to warming climate, and these altitudinal range shifts were associated with more positive population trends at lower altitudes than at higher altitudes. Moreover, long-distance migrants declined more than residents or species migrating for shorter distances. Taken together, these results indicate that the climate change, besides other possible environmental changes, already influences populations of montane birds with particularly adverse impacts on high-altitude species such as water pipit (Anthus spinoletta). It is evident that the alpine species, predicted to undergo serious climatically induced range contractions due to warming climate in the future, already started moving along this trajectory. PMID:26426901

  1. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  2. Adverse Impact on Educational Opportunity in Cases Challenging State School Financing Schemes.

    ERIC Educational Resources Information Center

    Brannan, Patricia A.; Minorini, Paul A.

    1991-01-01

    A number of state supreme courts have decided cases involving challenges to state public school financing. Summarizes the reactions of courts to plaintiffs' proof concerning the negative impact of inadequate funding on the educational opportunities provided to students in poor school districts. (43 references) (MLF)

  3. An Auxiliary Method To Reduce Potential Adverse Impacts Of Projected Land Developments: Subwatershed Prioritization

    EPA Science Inventory

    An index based method is developed that ranks the subwatersheds of a watershed based on their relative impacts on watershed response to anticipated land developments, and then applied to an urbanizing watershed in Eastern Pennsylvania. Simulations with a semi-distributed hydrolo...

  4. Building associations between markers of environmental stressors and adverse human health impacts using frequent itemset mining

    EPA Science Inventory

    Building associations between markers of exposure and effect using frequent itemset mining The human-health impact of environmental contaminant exposures is unclear. While some exposure-effect relationships are well studied, health effects are unknown for the vast majority of the...

  5. Two Degrees of Separation: Abrupt Climate Change and the Adverse Impact to US National Security

    DTIC Science & Technology

    2009-04-01

    trend of increasing GHG emissions is marginally impacting or irrelevant altogether. “Other factors, including sun spots, solar winds, variations ...climate variations over a wide range of time scales, making it a natural sensor of climate variability and providing a visible expression of climate...many observed changes in phenology and distribution have been associated with rising water temperatures, as well as changes in salinity, oxygen levels

  6. Adverse Psychosexual Impact Related to the Treatment of Genital Warts and Cervical Intraepithelial Neoplasia

    PubMed Central

    Campaner, Adriana Bittencourt; Vespa Junior, Nelson; Giraldo, Paulo César; Leal Passos, Mauro Romero

    2013-01-01

    Objective. To compare the psychosexual impact related to the treatment of genital warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients presenting with HPV-induced genital lesions, belonging to one of two patient groups, were included in the study: 29 individuals with genital warts (GWs) and 46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of each woman were examined for extraction of data on the type of HPV-induced infection and treatment administered. Subjects were interviewed to collect sociodemographic data as well as personal, gynecologic, obstetric, and sexual history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F) questionnaire was applied to assess sexual function. After application of the questionnaire, patients answered specific questions produced by the researchers, aimed at assessing the impact of the disease and its treatment on their sexual lives. Results. It is noteworthy that patients with CIN 2/3 had statistically similar classification of sexual quotient to patients with GWs (P = 0.115). However, patients with GWs more frequently gave positive answers to the specific questions compared to patients with CIN 2/3. Conclusion. Based on these findings, it is clear that GWs have a greater impact on sexual behavior compared to CIN 2/3. PMID:26316956

  7. Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation

    PubMed Central

    Briggs, Andrew; Wild, Diane; Lees, Michael; Reaney, Matthew; Dursun, Serdar; Parry, David; Mukherjee, Jayanti

    2008-01-01

    Objective To examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons. Methods Health state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores. Results Patients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups. Conclusion Events associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire. PMID:19040721

  8. Ozone exposure and systemic biomarkers: Evaluation of evidence for adverse cardiovascular health impacts.

    PubMed

    Goodman, Julie E; Prueitt, Robyn L; Sax, Sonja N; Pizzurro, Daniella M; Lynch, Heather N; Zu, Ke; Venditti, Ferdinand J

    2015-05-01

    The US Environmental Protection Agency (EPA) recently concluded that there is likely to be a causal relationship between short-term (< 30 days) ozone exposure and cardiovascular (CV) effects; however, biological mechanisms to link transient effects with chronic cardiovascular disease (CVD) have not been established. Some studies assessed changes in circulating levels of biomarkers associated with inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and glucose metabolism after ozone exposure to elucidate a biological mechanism. We conducted a weight-of-evidence (WoE) analysis to determine if there is evidence supporting an association between changes in these biomarkers and short-term ozone exposure that would indicate a biological mechanism for CVD below the ozone National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb). Epidemiology findings were mixed for all biomarker categories, with only a few studies reporting statistically significant changes and with no consistency in the direction of the reported effects. Controlled human exposure studies of 2 to 5 hours conducted at ozone concentrations above 75 ppb reported small elevations in biomarkers for inflammation and oxidative stress that were of uncertain clinical relevance. Experimental animal studies reported more consistent results among certain biomarkers, although these were also conducted at ozone exposures well above 75 ppb and provided limited information on ozone exposure-response relationships. Overall, the current WoE does not provide a convincing case for a causal relationship between short-term ozone exposure below the NAAQS and adverse changes in levels of biomarkers within and across categories, but, because of study limitations, they cannot not provide definitive evidence of a lack of causation.

  9. Severe burn and disuse in the rat independently adversely impact body composition and adipokines

    PubMed Central

    2013-01-01

    Introduction Severe trauma is accompanied by a period of hypermetabolism and disuse. In this study, a rat model was used to determine the effects of burn and disuse independently and in combination on body composition, food intake and adipokines. Methods Male rats were assigned to four groups 1) sham ambulatory (SA), 2) sham hindlimb unloaded (SH), 3) 40% total body surface area full thickness scald burn ambulatory (BA) and 4) burn and hindlimb unloaded (BH). Animals designated to the SH and BH groups were placed in a tail traction system and their hindlimbs unloaded. Animals were followed for 14 days. Plasma, urine, fecal and tissue samples were analyzed. Results SA had a progressive increase in body mass (BM), SH and BA no change and BH a reduction. Compared to SA, BM was reduced by 10% in both SH and BA and by 17% when combined in BH. Compared to SA, all groups had reductions in lean and fat body mass with BH being greater. The decrease in lean mass was associated with the rate of urinary corticosterone excretion. The loss in fat mass was associated with decreases in plasma leptin and adiponectin and an increase in ghrelin. Following the acute response to injury, BH had a greater food intake per 100 g BM. Food intake was associated with the levels of leptin, adiponectin and ghrelin. Conclusions The effects of the combination of burn and disuse in this animal model were additive, therefore in assessing metabolic changes with severe trauma both injury and disuse should be considered. Furthermore, the observed changes in adipokines, corticosterone and ghrelin provide insights for interventions to attenuate the hypermetabolic state following injury, possibly reducing catabolism and muscle loss and subsequent adverse effects on recovery and function. PMID:24099533

  10. Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

    PubMed Central

    Azim, Hatem A.; Kroman, Niels; Paesmans, Marianne; Gelber, Shari; Rotmensz, Nicole; Ameye, Lieveke; De Mattos-Arruda, Leticia; Pistilli, Barbara; Pinto, Alvaro; Jensen, Maj-Britt; Cordoba, Octavi; de Azambuja, Evandro; Goldhirsch, Aron; Piccart, Martine J.; Peccatori, Fedro A.

    2013-01-01

    Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence. PMID:23169515

  11. Impact of Adverse Childhood Experiences on Intimate Partner Violence Perpetration among Sri Lankan Men.

    PubMed

    Fonseka, Ruvani W; Minnis, Alexandra M; Gomez, Anu Manchikanti

    2015-01-01

    In Sri Lanka, over one in three women experience intimate partner violence (IPV) victimization in their lifetime, making it a serious public health concern. Adverse childhood experiences (ACEs) such as child abuse and neglect, witnessing domestic violence, parental separation, and bullying are also widespread. Studies in Western settings have shown positive associations between ACEs and IPV perpetration in adulthood, but few have examined this relationship in a non-Western context. In the present study, we examined the association of ACEs with IPV perpetration among Sri Lankan men surveyed for the UN Multi-Country Study on Men and Violence in Asia and the Pacific. We found statistically significant positive associations between the number of ACE categories (ACE score) and emotional, financial, physical, and sexual IPV perpetration among Sri Lankan men. We analyzed the contributions of each ACE category and found that childhood abuse was strongly associated with perpetration of IPV in adulthood, with sexual abuse associated with the greatest increase in odds of perpetration (Adjusted odds ratio 2.36; 95% confidence interval: 1.69, 3.30). Witnessing abuse of one's mother was associated with the greatest increase in the odds of perpetrating physical IPV (AOR 1.82; 95% CI: 1.29, 2.58), while lack of a male parental figure was not associated with physical IPV perpetration (AOR 0.76; 95% CI: 0.53, 1.09). These findings support a social learning theory of IPV perpetration, in which children who are exposed to violence learn to perpetrate IPV in adulthood. They also suggest that in Sri Lanka, being raised in a female-headed household does not increase the risk of IPV perpetration in adulthood compared to being raised in a household with a male parental figure. The relationship between being raised in a female-headed household (the number of which increased dramatically during Sri Lanka's recent civil war) and perpetration of IPV warrants further study. Interventions that

  12. Impact of Adverse Childhood Experiences on Intimate Partner Violence Perpetration among Sri Lankan Men

    PubMed Central

    Fonseka, Ruvani W.; Minnis, Alexandra M.; Gomez, Anu Manchikanti

    2015-01-01

    In Sri Lanka, over one in three women experience intimate partner violence (IPV) victimization in their lifetime, making it a serious public health concern. Adverse childhood experiences (ACEs) such as child abuse and neglect, witnessing domestic violence, parental separation, and bullying are also widespread. Studies in Western settings have shown positive associations between ACEs and IPV perpetration in adulthood, but few have examined this relationship in a non-Western context. In the present study, we examined the association of ACEs with IPV perpetration among Sri Lankan men surveyed for the UN Multi-Country Study on Men and Violence in Asia and the Pacific. We found statistically significant positive associations between the number of ACE categories (ACE score) and emotional, financial, physical, and sexual IPV perpetration among Sri Lankan men. We analyzed the contributions of each ACE category and found that childhood abuse was strongly associated with perpetration of IPV in adulthood, with sexual abuse associated with the greatest increase in odds of perpetration (Adjusted odds ratio 2.36; 95% confidence interval: 1.69, 3.30). Witnessing abuse of one’s mother was associated with the greatest increase in the odds of perpetrating physical IPV (AOR 1.82; 95% CI: 1.29, 2.58), while lack of a male parental figure was not associated with physical IPV perpetration (AOR 0.76; 95% CI: 0.53, 1.09). These findings support a social learning theory of IPV perpetration, in which children who are exposed to violence learn to perpetrate IPV in adulthood. They also suggest that in Sri Lanka, being raised in a female-headed household does not increase the risk of IPV perpetration in adulthood compared to being raised in a household with a male parental figure. The relationship between being raised in a female-headed household (the number of which increased dramatically during Sri Lanka’s recent civil war) and perpetration of IPV warrants further study. Interventions

  13. Bioremediation of adverse impact of cadmium toxicity on Cassia italica Mill by arbuscular mycorrhizal fungi

    PubMed Central

    Hashem, Abeer; Abd_Allah, E.F.; Alqarawi, A.A.; Egamberdieva, Dilfuza

    2015-01-01

    Cassia italica Mill is an important medicinal plant within the family Fabaceae. Pot experiment was conducted to evaluate cadmium stress induced changes in physiological and biochemical attributes in C. italica with and without arbuscular mycorrhizal fungi (AMF). Cadmium stressed plant showed reduced chlorophyll pigment and protein content while AMF inoculation enhanced the chlorophyll and protein content considerably. AMF also ameliorated the cadmium stress induced reduction in total chlorophyll and protein contents by 19.30% and 38.29%, respectively. Cadmium stress enhanced lipid peroxidation while AMF inoculation reduced lipid peroxidation considerably. Increase in proline and phenol content was observed due to cadmium stress and AMF inoculation caused a further increase in proline and phenol content ensuring better growth under stressed conditions. AMF alone also enhanced proline and phenol content. Activity of antioxidant enzymes enhanced under cadmium treatment and AMF inoculation further enhanced their activity thereby strengthening the antioxidant system. Enhanced activities of antioxidants and increased accumulation of osmolytes help plants to avoid damaging impact of oxidative damage. The research has shown that AMF inoculation mitigated the negative impact of stress by reducing the lipid peroxidation and enhancing the antioxidant activity. The present study strongly supports employing AMF as the biological mean for enhancing the cadmium stress tolerance of C. italica. PMID:26858537

  14. [Prognostic Impact of Radiation Therapy and Molecular Classification of Infant Atypical Teratoid/Rhabdoid Tumors].

    PubMed

    Otani, Yoshihiro; Ichikawa, Tomotsugu; Kurozumi, Kazuhiko; Yasuhara, Takao; Washio, Kana; Shimada, Akira; Katayama, Norihisa; Katsui, Kuniaki; Yanai, Hiroyuki; Date, Isao

    2017-02-01

    Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9.3 months and all patients were female. All patients underwent surgical resection. Of the four patients, two received combined irradiation and chemotherapy. Specifically, one patient received conformal craniospinal radiation therapy and the other received craniospinal irradiation with proton beams. Immunohistochemical analyses of tumor specimens revealed that the two patients were positive for ASCL1, a regulator of Notch signaling. Patients who received radiation therapy and exhibited ASCL1-positive tumors had a better prognosis. We conclude that radiation therapy may prolong survival in AT/RT patients who are less than 3 years of age. However, further study is required to evaluate long-term functional outcomes.

  15. The prognostic impact of bone marrow micrometastases in women with breast cancer.

    PubMed

    Braun, Stephan; Auer, Doris; Marth, Christian

    2009-07-01

    Metastasis is the overwhelming cause of mortality in patients with breast cancer and our understanding of its cellular and molecular determinants is limited. Among cellular determinants, disseminated (DTC) tumor cells undoubtedly are key players in the metastatic cascade. In the past, several models have been constructed to explain the presence of individual tumor cells in secondary organs and their influence on the subsequent course of the disease. According to most recent transcriptome and genome analyses, DTCs are viewed as rare and much earlier indicators of metastasis than generally assumed from the typical course of breast cancer. Despite the observation that the numerous genetic alterations in such cells are rarely identical or even similar, characterization of the long interval between dissemination and clinically manifested metastases, the resistance to chemotherapy and significant effect on disease progression despite the low abundance in secondary organs, support the idea that some of these cells might be progenitor cells with self-renewing properties that give rise to most of the tumor mass that is dealt with clinically. Here, we review evidence from translational research and data from observational studies on DTCs to elucidate their potential impact for both future clinical trial design and, in the long run, decision-making in our daily patient management.

  16. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

    PubMed Central

    Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.

    2012-01-01

    Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

  17. AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for early cancer detection.

    PubMed

    Garczyk, Stefan; von Stillfried, Saskia; Antonopoulos, Wiebke; Hartmann, Arndt; Schrauder, Michael G; Fasching, Peter A; Anzeneder, Tobias; Tannapfel, Andrea; Ergönenc, Yavuz; Knüchel, Ruth; Rose, Michael; Dahl, Edgar

    2015-01-01

    Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.

  18. Using patient safety indicators to estimate the impact of potential adverse events on outcomes.

    PubMed

    Rivard, Peter E; Luther, Stephen L; Christiansen, Cindy L; Shibei Zhao; Loveland, Susan; Elixhauser, Anne; Romano, Patrick S; Rosen, Amy K

    2008-02-01

    The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching- were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems.

  19. Prognostic impact of second primary tumors in head and neck cancer.

    PubMed

    Patrucco, Marta S; Aramendi, Marina V

    2016-07-01

    The incidence of Second Primary Tumors in the upper aerodigestive tract varies from 5 to 30 %. Most of them are located either in the same anatomical region or in the lungs, and are related to a poor overall survival. Our objective is to assess the incidence of Second Primary Tumors, factors related to its outcome, frequent associations, and impact on overall survival. 27 patients with Second Primary Tumors were reviewed out of 307 with head and neck cancer, between 2002 and 2011. Patients had a minimum follow-up period of 3 years, or until their death after the last treatment. Sex: 85.2 % were male; male:female ratio of 23:4. The mean age of appearance for the primary tumor was 66.8 years. Only 1 patient had a synchronous Second Primary Tumor, while 26 had metachronous Second Primary Tumors. Second neoplasms were grouped into synchronous and metachronous for statistical analysis. The following parameters were considered: age at diagnosis of the first tumor, gender, smoking and persistence of the habit, primary tumor's location in the larynx, association between two squamous cell carcinomas (index and second primary tumor), and radiotherapy for the primary tumor. The incidence of Second Primary Tumors was 8.79 %. Overall survival of metachronous tumors was 95 months (7.9 years). The primary tumor's location that prevailed when developing a Second Primary Tumor was the larynx. Regarding the histology, the most common association was head and neck squamous cell carcinoma with head and neck squamous cell carcinoma (9 patients). The Second Primary Tumor was the cause of death in 51.9 % of the patients and its most frequent location was the lungs. 19 patients underwent radiotherapy. Second Primary Tumors are common in the head and neck. The authors would like to enforce the importance of an extended follow-up, since second neoplasms worsen considerably the patient's prognosis. Patients who keep on smoking after treatment decrease even more their overall survival.

  20. Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions.

    PubMed

    Stamoulis, Catherine; Vanderwert, Ross E; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2015-12-01

    Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1-3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross

  1. Impact of lymph node ratio as a valuable prognostic factor in gallbladder carcinoma, focusing on stage IIIB gallbladder carcinoma

    PubMed Central

    Choi, Byung-Gwan; Kim, Choong-Young; Cho, Seung-Hyun; Kim, Hee-Joon; Koh, Yang-Seok; Kim, Jung-Chul; Cho, Chol-Kyoon; Kim, Hyun-Jong

    2013-01-01

    Purpose It is increasingly being recognized that the lymph node ratio (LNR) is an important prognostic factor for gallbladder carcinoma patients. The present study evaluated predictors of tumor recurrence and survival in a large, mono-institutional cohort of patients who underwent surgical resection for gallbladder carcinoma, focusing specifically on the prognostic value of lymph node (LN) status and of LNR in stage IIIB patients. Methods Between 2004 and 2011, 123 patients who underwent R0 radical resection for gallbladder carcinoma at the Chonnam National University Hwasun Hospital were reviewed retrospectively. Patients were staged according to the American Joint Committee on Cancer 7th edition, and prognostic factors affecting disease free survival, such as age, sex, comorbidity, body mass index, presence of preoperative symptoms, perioperative blood transfusion, postoperative complications, LN dissection, tumor size, differentiation, lymph-vascular invasion, perineural invasion, T stage, presence of LN involvement, N stage, numbers of positive LNs, LNR and implementation of adjuvant chemotherapy, were statistically analyzed. Results LN status was an important prognostic factor in patients undergoing curative resection for gallbladder carcinoma. The total number of LNs examined was implicated with prognosis, especially in N0 patients. LNR was a powerful predictor of disease free survival even after controlling for competing risk factors, in curative resected gallbladder cancer patients, and especially in stage IIIB patients. Conclusion LNR is confirmed as an independent prognostic factor in curative resected gallbladder cancer patients, especially in stage IIIB gallbladder carcinoma. PMID:23487246

  2. The long-term impact of early adversities on psychiatric disorders: focus on neuronal plasticity.

    PubMed

    Luoni, Alessia; Richetto, Juliet; Racagni, Giorgio; Molteni, Raffaella

    2015-01-01

    The impact of early physical and social environments on life-long pathological phenotypes is well known and there is now compelling evidence that stressful experiences during gestation or early in life can lead to enhanced susceptibility to mental illness. Here, we discuss the data from preclinical studies aimed at investigating the molecular consequences of the exposure to stressful events during prenatal or early postnatal life that might contribute to later psychopathology. Particularly, we will discuss the existence of age windows of vulnerability to environmental conditions during brain maturation using as examples several studies performed with different animal models. Specifically, major deviations from normative neurobehavioural trajectories have been reported in animal models obtained following exposure to severe stress (maternal separation) ea rly in infancy or with rodent models of difficult and/or stressful pregnancies, including obstetric complications (e.g. prenatal restrain stress) and gestational exposure to infection (e.g prenatal immune challenge). These models have been associated with profound long-lasting deficits in the offspring's emotional and social behaviour, and with molecular changes associated with neuroplasticity.

  3. Adverse Impact of Electromagnetic Radiation on Urban Environment and Natural Resources using Optical Sensors

    NASA Astrophysics Data System (ADS)

    Kumar, Pawan; Katiyar, Swati; Rani, Meenu

    2016-07-01

    We are living in the age of a rapidly growing population and changing environmental conditions with an advance technical capacity.This has resulted in wide spread land cover change. One of the main causes for increasing urban heat is that more than half of the world's population lives in a rapidly growing urbanized environment. Satellite data can be highly useful to map change in land cover and other environmental phenomena with the passage of time. Among several human-induced environmental and urban thermal problems are reported to be negatively affecting urban residents in many ways. The built-up structures in urbanized areas considerably alter land cover thereby affecting thermal energy flow which leads to development of elevated surface and air temperature. The phenomenon Urban Heat Island implies 'island' of high temperature in cities, surrounded by relatively lower temperature in rural areas. The UHI for the temporal period is estimated using geospatial techniques which are then utilized for the impact assessment on climate of the surrounding regions and how it reduce the sustainability of the natural resources like air, vegetation. The present paper describes the methodology and resolution dynamic urban heat island change on climate using the geospatial approach. NDVI were generated using day time LANDSAT ETM+ image of 1990, 2000 and 2013. Temperature of various land use and land cover categories was estimated. Keywords: NDVI, Surface temperature, Dynamic changes.

  4. Adverse impact of feed channel spacers on the performance of pressure retarded osmosis.

    PubMed

    Kim, Yu Chang; Elimelech, Menachem

    2012-04-17

    This article analyzes the influence of feed channel spacers on the performance of pressure retarded osmosis (PRO). Unlike forward osmosis (FO), an important feature of PRO is the application of hydraulic pressure on the high salinity (draw solution) side to retard the permeating flow for energy conversion. We report the first observation of membrane deformation under the action of the high hydraulic pressure on the feed channel spacer and the resulting impact on membrane performance. Because of this observation, reverse osmosis and FO tests that are commonly used for measuring membrane transport properties (water and salt permeability coefficients, A and B, respectively) and the structural parameter (S) can no longer be considered appropriate for use in PRO analysis. To accurately predict the water flux as a function of applied hydraulic pressure difference and the resulting power density in PRO, we introduced a new experimental protocol that accounts for membrane deformation in a spacer-filled channel to determine the membrane properties (A, B, and S). PRO performance model predictions based on these determined A, B, and S values closely matched experimental data over a range of draw solution concentrations (0.5 to 2 M NaCl). We also showed that at high pressures feed spacers block the permeation of water through the membrane area in contact with the spacer, a phenomenon that we term the shadow effect, thereby reducing overall water flux. The implications of the results for power generation by PRO are evaluated and discussed.

  5. Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma.

    PubMed

    Hao, S; Chen, S; Yang, X; Wan, C

    2017-01-01

    Introduction To evaluate the impact of intermittent portal clamping (IPC) on long-term postoperative outcomes in patients with hepatocellular carcinoma (HCC). Methods Clinical records of 355 patients underwent curative liver resection for HCC in January 2007 to December 2010 were retrospectively reviewed. According to how portal clamping was performed, patients were grouped as: IPC, n=113; other portal clamping (OPC), n=190; and no portal clamping (NPC), n=52. Results Median recurrence-free survival (RFS) was statistically significantly shorter in the IPC (39.4 months) than OPC (47.3 months, p=0.010) and NPC groups (51.4 months, p=0.008). Median overall survival (OS) was also significantly shorter with IPC (46.3 months), versus 52.9 months with OPC (p=0.022) and 56.2 months with NPC (p=0.015). Kaplan-Meier survival analysis revealed that 5-year cumulative RFS was much lower in the IPC (42.5%) than OPC (50.9%, p=0.014) and NPC groups (49.6%, p=0.013). Five-year cumulative OS was also much lower in the IPC (44.9%) than OPC (58.0%, p=0.020) and NPC groups (57.7%, p=0.025). On univariate analysis, tumour grade, size and number, TNM stage, blood transfusion, vascular invasion and IPC were significantly inversely correlated with RFS and OS. On multivariate analysis, tumour size and number, blood transfusion, vascular invasion and IPC remained significant. Conclusions Our study suggests that IPC is an independent risk factor for poor long-term postoperative outcomes in patients with HCC.

  6. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

    PubMed Central

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsaker, Bard; Pawinski, Adam

    2017-01-01

    Background The aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment. Methods This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months). Results The median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3. Conclusions Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model. PMID:28179964

  7. Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma--a matched pair analysis from the German Hodgkin Study Group (GHSG).

    PubMed

    Hartmann, Sylvia; Eichenauer, Dennis A; Plütschow, Annette; Mottok, Anja; Bob, Roshanak; Koch, Karoline; Bernd, Heinz-Wolfram; Cogliatti, Sergio; Hummel, Michael; Feller, Alfred C; Ott, German; Möller, Peter; Rosenwald, Andreas; Stein, Harald; Hansmann, Martin-Leo; Engert, Andreas; Klapper, Wolfram

    2014-10-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity. We performed a matched-pair analysis to evaluate the prognostic impact of several histopathological features in this distinct Hodgkin lymphoma subtype. Lymph node samples of NLPHL patients were tested for CD15, IgD, phosphorylated STAT6, ICOS and Epstein-Barr virus status of the malignant lymphocyte-predominant cells as well as epithelioid cell clusters and activated T cells in the microenvironment. None of these features was associated with a particular clinical outcome. However, patients presenting with epithelioid cell clusters showed a non-significant trend towards a lower relapse rate, justifying further evaluation of this marker.

  8. Acute renal failure requiring renal replacement therapy in the intensive care unit: impact on prognostic assessment for shared decision making.

    PubMed

    Johnson, Robert F; Gustin, Jillian

    2011-07-01

    A 69-year-old female was receiving renal replacement therapy (RRT) for acute renal failure (ARF) in an intensive care unit (ICU). Consultation was requested from the palliative medicine service to facilitate a shared decision-making process regarding goals of care. Clinician responsibility in shared decision making includes the formulation and expression of a prognostic assessment providing the necessary perspective for a spokesperson to match patient values with treatment options. For this patient, ARF requiring RRT in the ICU was used as a focal point for preparing a prognostic assessment. A prognostic assessment should include the outcomes of most importance to a discussion of goals of care: mortality risk and survivor functional status, in this case including renal recovery. A systematic review of the literature was conducted to document published data regarding these outcomes for adult patients receiving RRT for ARF in the ICU. Forty-one studies met the inclusion criteria. The combined mean values for short-term mortality, long-term mortality, renal-function recovery of short-term survivors, and renal-function recovery of long-term survivors were 51.7%, 68.6%, 82.0%, and 88.4%, respectively. This case example illustrates a process for formulating and expressing a prognostic assessment for an ICU patient requiring RRT for ARF. Data from the literature review provide baseline information that requires adjustment to reflect specific patient circumstances. The nature of the acute primary process, comorbidities, and severity of illness are key modifiers. Finally, the prognostic assessment is expressed during a family meeting using recommended principles of communication.

  9. Impact of Gender on the Prognostic Value of Coronary Artery Calcium in Symptomatic Patients With Normal Single-Photon Emission Computed Tomography Myocardial Perfusion.

    PubMed

    Engbers, Elsemiek M; Timmer, Jorik R; Ottervanger, Jan Paul; Mouden, Mohamed; Knollema, Siert; Jager, Pieter L

    2016-12-01

    The coronary artery calcium (CAC) score provides independent prognostic value on top of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). We sought to determine whether the prognostic value of the CAC score in patients with normal SPECT MPI is gender specific. We studied 3,705 consecutive symptomatic patients without a history of coronary artery disease with normal SPECT MPI. All patients underwent concomitant CAC scoring, which was categorized as CAC score 0, 1 to 99, 100 to 399, 400 to 999, or ≥1,000. Major adverse cardiac events were defined as revascularization, nonfatal myocardial infarction, or all-cause mortality. The median CAC score was 9 in women (interquartile range 0 to 113) and 47 in men (interquartile range 1 to 307, p <0.001). The annual event rate was lower in women than in men (1.6% and 2.7%, respectively, p <0.001). When stratified by CAC score, annual event rates were similar (for women and men, respectively: CAC score 0, 0.6% and 0.5%, p = 0.95; CAC score 1 to 99, 0.9% and 1.2%, p = 0.45; CAC score 100 to 399, 2.7% and 3.8%, p = 0.23; CAC score 400 to 999, 3.8% and 5.3%, p = 0.34; CAC score ≥1,000, 8.4% and 8.7%, p = 0.99). The CAC score was an independent predictor of major adverse cardiac events in both genders (CAC score ≥1,000: hazard ratio for women 8.5, 95% confidence interval 4.0 to 18.1; hazard ratio for men 14.8, 95% confidence interval 5.3 to 41.1). In conclusion, risk for events is similar for both genders when stratified by CAC score, wherein a high CAC score carries a high risk for events despite normal SPECT MPI. Our findings do not reveal a gender-specific prognostic value of the CAC score.

  10. Littoral Refractivity Prognostic Advancement

    DTIC Science & Technology

    2009-09-30

    situational awareness of the 3D radio-frequency (RF) propagation environment and a quantitative diagnostic and prognostic capability for assessing sub- and...Rev. 8-98) Prescribed by ANSI Std Z39-18 2 with the benchmark showing the quantitative improvement with each stage of model development...grid point. Modified the NSWCDD littoral clutter model ( LCM ) to accept COAMPS® derived refractivity fields. Analyzed the impact on ducting of

  11. Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: Impact of tumor volume

    SciTech Connect

    Basaki, Kiyoshi . E-mail: basaki-rad@umin.ac.jp; Abe, Yoshinao; Aoki, Masahiko; Kondo, Hidehiro; Hatayama, Yoshiomi; Nakaji, Shigeyuki

    2006-02-01

    Purpose: To investigate the impact of tumor volume on overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). Methods and Materials: Between May 1997 and February 2003, 71 patients with Stage III NSCLC were treated with radiation therapy of 60 Gy or more. The total target dose was between 60 and 77 Gy (average, 66.3 Gy). Chemotherapy was used in 45 cases. The primary tumor and nodal volume were identified in pretreatment computed tomography scans. Univariate and multivariate analyses were used to evaluate the impact of tumor volume on survival after RT. Results: The overall 2-year survival rate was 23%, with a median survival time of 14 months. The median survival times were 10 months and 19 months with large primary tumor volume more than median volume and smaller primary tumor volume, respectively. At a univariate analysis, the total tumor volume (TTV) (p < 0.0003) and the primary tumor volume (p < 0.00008) were significant and the nodal volume was not. At multivariate analyses, both the TTV and the primary tumor volume were significant prognostic factors. Conclusion: The primary tumor volume as well as TTV is a significant prognostic factor on survival in patients with Stage III NSCLC treated with RT and should be recorded in clinical results when the survivals are compared among clinical studies.

  12. Negative prognostic impact of low absolute CD4(+) T cell counts in peripheral blood in mantle cell lymphoma.

    PubMed

    Zhang, Xin-Yu; Xu, Ji; Zhu, Hua-Yuan; Wang, Yan; Wang, Li; Fan, Lei; Wu, Yu-Jie; Li, Jian-Yong; Xu, Wei

    2016-10-01

    Tumor microenvironment and host immunity are closely related to outcome in patients with mantle cell lymphoma (MCL). However, few researchers have focused on the prognostic value of peripheral blood lymphocyte subsets counts. The purpose of this study was to investigate the prognostic value of lymphocyte subsets and absolute monocyte counts. Sixty-eight patients were analyzed retrospectively. Absolute CD4(+) T cell counts (ACD4C), CD8(+) T cell counts, nature killer cell counts, and CD4/CD8 ratios were assessed by peripheral blood flow cytometry and correlated with clinical parameters and long-term outcomes. The median follow-up for all patients was 21 months and the median survival time was 44 months. The overall survival (OS) rate at 1, 3, and 5 years was 80%, 51%, and 41%, respectively. In our cohort, high absolute monocyte count, and low ACD4C and CD4/CD8 ratio were associated with unfavorable OS (P = 0.029, P = 0.027, and P = 0.045, respectively) by univariate analysis. Multivariate analysis indicated that low ACD4C was a significant predictor of unfavorable OS (P = 0.004) independent of the simplified MCL International Prognostic Index (P = 0.048) in patients treated with or without rituximab (P = 0.011). Low CD4(+) T cell counts proved to be a significant predictor of unfavorable OS in patients with MCL.

  13. Proposed methods and endpoints for defining and assessing adverse environmental impact (AEI) on fish communities/populations in Tennessee River reservoirs.

    PubMed

    Hickman, Gary D; Brown, Mary L

    2002-06-07

    Two multimetric indices have been developed to help address fish community (reservoir fish assemblage index [RFAI]) and individual population quality (sport fishing index [SFI]) in Tennessee River reservoirs. The RFAI, with characteristics similar to the index of biotic integrity (IBI) used in stream fish community determinations, was developed to monitor the existing condition of resident fish communities. The index, which incorporates standardized electrofishing of littoral areas and experimental gill netting for limnetic bottom-dwelling species, has been used to determine residential fish community response to various anthropogenic impacts in southeastern reservoirs. The SFI is a multimetric index designed to address the quality of the fishery for individual resident sport fish species in a particular lake or reservoir[4]. The SFI incorporates measures of fish population aspects and angler catch and pressure estimates. This paper proposes 70% of the maximum RFAI score and 10% above the average SFI score for individual species as "screening" endpoints for balanced indigenous populations (BIP) or adverse environmental impact (AEI). Endpoints for these indices indicate: (1) communities/populations are obviously balanced indigenous populations (BIP) indicating no adverse environmental impact (AEI), or are "screened out"; (2) communities/populations are considered to be potentially impacted; and (3) where the resident fish community/population should be considered adversely impacted. Suggestions are also made concerning how examination of individual metric scores can help determine the source or cause of the impact.

  14. BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.

    PubMed

    Buchmann, Arlette F; Hellweg, Rainer; Rietschel, Marcella; Treutlein, Jens; Witt, Stephanie H; Zimmermann, Ulrich S; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred; Deuschle, Michael

    2013-08-01

    Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype.

  15. Business oriented EU human cell and tissue product legislation will adversely impact Member States' health care systems.

    PubMed

    Pirnay, Jean-Paul; Vanderkelen, Alain; De Vos, Daniel; Draye, Jean-Pierre; Rose, Thomas; Ceulemans, Carl; Ectors, Nadine; Huys, Isabelle; Jennes, Serge; Verbeken, Gilbert

    2013-12-01

    The transplantation of conventional human cell and tissue grafts, such as heart valve replacements and skin for severely burnt patients, has saved many lives over the last decades. The late eighties saw the emergence of tissue engineering with the focus on the development of biological substitutes that restore or improve tissue function. In the nineties, at the height of the tissue engineering hype, industry incited policymakers to create a European regulatory environment, which would facilitate the emergence of a strong single market for tissue engineered products and their starting materials (human cells and tissues). In this paper we analyze the elaboration process of this new European Union (EU) human cell and tissue product regulatory regime-i.e. the EU Cell and Tissue Directives (EUCTDs) and the Advanced Therapy Medicinal Product (ATMP) Regulation and evaluate its impact on Member States' health care systems. We demonstrate that the successful lobbying on key areas of regulatory and policy processes by industry, in congruence with Europe's risk aversion and urge to promote growth and jobs, led to excessively business oriented legislation. Expensive industry oriented requirements were introduced and contentious social and ethical issues were excluded. We found indications that this new EU safety and health legislation will adversely impact Member States' health care systems; since 30 December 2012 (the end of the ATMP transitional period) there is a clear threat to the sustainability of some lifesaving and established ATMPs that were provided by public health institutions and small and medium-sized enterprises under the frame of the EUCTDs. In the light of the current economic crisis it is not clear how social security systems will cope with the inflation of costs associated with this new regulatory regime and how priorities will be set with regard to reimbursement decisions. We argue that the ATMP Regulation should urgently be revised to focus on delivering

  16. Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor.

    PubMed

    Ohara, Masahiro; Akimoto, Etsushi; Noma, Midori; Matsuura, Kazuo; Doi, Mihoko; Kagawa, Naoki; Itamoto, Toshiyuki

    2015-11-01

    Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m(2) (high, H) or <25 kg/m(2) (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR- and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR- tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2- breast cancer in patients treated with adjuvant aromatase inhibitors.

  17. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    PubMed

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  18. Age-Related Prognostic Impact of Different Types of DNMT3A Mutations in Adults With Primary Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Marcucci, Guido; Metzeler, Klaus H.; Schwind, Sebastian; Becker, Heiko; Maharry, Kati; Mrózek, Krzysztof; Radmacher, Michael D.; Kohlschmidt, Jessica; Nicolet, Deedra; Whitman, Susan P.; Wu, Yue-Zhong; Powell, Bayard L.; Carter, Thomas H.; Kolitz, Jonathan E.; Wetzler, Meir; Carroll, Andrew J.; Baer, Maria R.; Moore, Joseph O.; Caligiuri, Michael A.; Larson, Richard A.; Bloomfield, Clara D.

    2012-01-01

    Purpose To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays. Results Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non–R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A–wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non–R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P = .002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status. Conclusion DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non–R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to

  19. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    PubMed

    Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

    2014-01-01

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

  20. Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years.

    PubMed

    Boecker, Regina; Holz, Nathalie E; Buchmann, Arlette F; Blomeyer, Dorothea; Plichta, Michael M; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2014-01-01

    Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.

  1. A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma.

    PubMed

    Mai, Elias K; Hielscher, Thomas; Kloth, Jost K; Merz, Maximilian; Shah, Sofia; Raab, Marc S; Hillengass, Michaela; Wagner, Barbara; Jauch, Anna; Hose, Dirk; Weber, Marc-André; Delorme, Stefan; Goldschmidt, Hartmut; Hillengass, Jens

    2015-06-01

    Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated. Compared to salt and pepper/minimal diffuse infiltration, moderate/severe diffuse infiltration had a negative prognostic impact on both progression-free survival (P<0.001) and overall survival (P=0.003). More than 25 focal lesions on whole-body magnetic resonance imaging or more than seven on axial magnetic resonance imaging were associated with an adverse prognosis (progression-free survival: P=0.001/0.003 and overall survival: P=0.04/0.02). A magnetic resonance imaging-based prognostic scoring system, combining grouped diffuse and focal infiltration patterns, was formulated and is applicable to whole-body as well as axial magnetic resonance imaging. The score identified high-risk patients with median progression-free and overall survival of 23.4 and 55.9 months, respectively (whole-body-based). Multivariate analyses demonstrated that the magnetic resonance imaging-based prognostic score stage III (high-risk) and adverse cytogenetics are independent prognostic factors for both progression-free and overall survival (whole-body-based, progression-free survival: hazard ratio=3.65, P<0.001; overall survival: hazard ratio=5.19, P=0.005). In conclusion, we suggest a magnetic resonance imaging-based prognostic scoring system which is a robust, easy to assess and interpret parameter summarizing significant magnetic resonance imaging findings in transplant

  2. Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

    SciTech Connect

    Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko

    2014-07-01

    Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

  3. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    SciTech Connect

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  4. Tourism impacts of Three Mile Island and other adverse events: Implications for Lincoln County and other rural counties bisected by radioactive wastes intended for Yucca Mountain

    SciTech Connect

    Himmelberger, J.J.; Ogneva-Himmelberger, Y.A.; Baughman, M.

    1995-11-01

    Whether the proposed Yucca Mountain nuclear waste repository system will adversely impact tourism in southern Nevada is an open question of particular importance to visitor-oriented rural counties bisected by planned waste transportation corridors (highway or rail). As part of one such county`s repository impact assessment program, tourism implications of Three Mile Island (TMI) and other major hazard events have been revisited to inform ongoing county-wide socioeconomic assessments and contingency planning efforts. This paper summarizes key research implications of such research as applied to Lincoln County, Nevada. Implications for other rural counties are discussed in light of the research findings. 29 refs., 3 figs., 1 tab.

  5. Tourism impacts of Three Mile Island and other adverse events: Implications for Lincoln County and other rural counties bisected by radioactive wastes intended for Yucca Mountain

    NASA Astrophysics Data System (ADS)

    Himmelberger, Jeffery J.; Baughman, Mike; Ogneva-Himmelberger, Yelena A.

    1995-11-01

    Whether the proposed Yucca Mountain nuclear waste repository system will adversely impact tourism in southern Nevada is an open question of particular importance to visitor-oriented rural counties bisected by planned waste transportatin corridors (highway or rail). As part of one such county's repository impact assessment program, tourism implications of Three Mile Island (TMI) and other major hazard events have beem revisited to inform ongoing county-wide socioeconomic assessments and contingency planning efforts. This paper summarizes key research implications of such research as applied to Lincoln County, Nevada. Implications for other rural counties are discussed in light of the research findings.

  6. Impact of age, sex and route of administration on adverse events after opioid treatment in the emergency department: A retrospective study

    PubMed Central

    Daoust, Raoul; Paquet, Jean; Lavigne, Gilles; Piette, Éric; Chauny, Jean-Marc

    2015-01-01

    BACKGROUND: The efficacy of opioids for acute pain relief in the emergency department (ED) is well recognized, but treatment with opioids is associated with adverse events ranging from minor discomforts to life-threatening events. OBJECTIVE: To assess the impact of age, sex and route of administration on the incidence of adverse events due to opioid administration in the ED. METHODS: Real-time archived data were analyzed retrospectively in a tertiary care urban hospital. All consecutive patients (≥16 years of age) who were assigned to an ED bed and received an opioid between March 2008 and December 2012 were included. Adverse events were defined as: nausea/vomiting (minor); systolic blood pressure (SBP) <90 mmHg, oxygen saturation (Sat) <92% and respiration rate <10 breaths/min (major) within 2 h of the first opioid doses. RESULTS: In the study period, 31,742 patients were treated with opioids. The mean (± SD) age was 55.8±20.5 years, and 53% were female. The overall incidence of adverse events was 12.0% (95% CI 11.6% to 12.4%): 5.9% (95% CI 5.6% to 6.2%) experienced nausea/vomiting, 2.4% (95% CI 2.2% to 2.6%) SBP <90 mmHg, 4.7% (95% CI 4.5% to 4.9%) Sat that dropped to <92% and 0.09% respiration rate <10 breaths/min. After controlling for confounding factors, these adverse events were associated with: female sex (more nausea/vomiting, more SBP <90 mmHg, less Sat <92%); age ≥65 years (less nausea/vomiting, more SBP <90 mmHg, more Sat <92%); and route of administration (intravenous > subcutaneous > oral). CONCLUSIONS: The incidence of adverse events associated with opioid administration in the ED is generally low and is associated with age, sex and route of administration. PMID:25664538

  7. Bio-pathologic characteristics related to chromosome 11 aneusomy and cyclin D1 gene status in surgically resected stage I and II breast cancer: Identification of an adverse prognostic profile.

    PubMed

    Mottolese, Marcella; Orlandi, Giulia; Sperduti, Isabella; Merola, Roberta; Buglioni, Simonetta; Di Benedetto, Anna; Pinnarò, Paola; Perracchio, Letizia; Venturo, Irene; Cognetti, Francesco; Cianciulli, AnnaMaria

    2007-02-01

    We aimed at developing a more detailed understanding of cyclin D1 in early stage human breast cancer and defining the biologic profiles with different prognostic value correlating cyclin D1 gene amplification and chromosome 11 aneusomy with bio-pathologic variables of known clinical importance. Cyclin D1 gene amplification and chromosome 11 aneusomy were investigated using fluorescence in situ hybridization whereas cyclin D1, PgR, HER-2, Bcl2, p53, and Ki-67 expressions were analyzed by immunohistochemistry in 121 stage I or II breast cancer patients uniformly treated with cyclophosphamide/metotrexate/5-fluorouracil-based chemotherapy. Cyclin D1 was amplified in 6.6% and overexpressed in 32.2% of cases. Amplification was not associated with any selected bio-pathologic variables, whereas the chromosome 11 aneusomy level significantly increased in tumors with higher histologic grade (P < 0.01), higher tumor size (P < 0.003), p53 nuclear accumulation (P < 0.04), and ERalpha negativity (P < 0.049). Multiple correspondence analysis showed 4 different biologic tumor profiles. The first, characterized by high Ki-67 score, p53+, cyclin D1+, HER-2+, aneusomy level > 30%, ratio (cyclin D1 gene/CEP11) > 2, was associated with tumor relapse defining the most unfavorable biologic profile. Kaplan-Meier's method showed significantly shorter disease-free survival in patients with at least 3 variables positive out of the 6 detected by multiple correspondence analysis. In multivariate analysis, the identified biologic profile emerged as the only significant prognostic indicator. Our findings are of particular clinical interest for early stage breast cancer patients, because the assessment of biologic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.

  8. Prevalence and Predictors of Adverse Events in Older Surgical Patients: Impact of the Present on Admission Indicator

    ERIC Educational Resources Information Center

    Kim, Hongsoo; Capezuti, Elizabeth; Kovner, Christine; Zhao, Zhonglin; Boockvar, Kenneth

    2010-01-01

    Purpose of the Study: To examine the effects of the present on admission (POA) indicator on the prevalence of and factors associated with postsurgical adverse events in older patients. Design and Methods: This is a secondary data analysis of 82,898 surgical patients aged 65 years or older in 252 acute care hospitals in California in 2004. Four…

  9. The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients.

    PubMed

    König, Lisa; Kasimir-Bauer, Sabine; Hoffmann, Oliver; Bittner, Ann-Kathrin; Wagner, Bettina; Manvailer, Luis Felipe Santos; Schramm, Sabine; Bankfalvi, Agnes; Giebel, Bernd; Kimmig, Rainer; Horn, Peter A; Rebmann, Vera

    2016-09-01

    The non-classical human leukocyte antigen G (HLA-G) molecule and its soluble forms exert multiple immune suppressive regulatory functions in malignancy and in stem cells contributing to immune escape mechanisms. HLA-G can be secreted as free soluble HLA-G molecules or via extracellular vesicles (EVs). Here we evaluated these soluble HLA-G forms as prognostic marker for prediction of the clinical outcome of neoadjuvant chemotherapy (NACT) treated breast cancer (BC) patients. Plasma samples of BC patients procured before (n=142) and after (n=154) NACT were quantified for total soluble HLA-G (sHLA-Gtot) and HLA-G levels in ExoQuick™ derived EV fractions (sHLA-GEV) by ELISA. The corresponding increments were specified as free sHLA-G (sHLA-Gfree). Total and free sHLA-G were significantly increased in NACT treated BC patients compared to healthy controls (n=16). High sHLA-Gfree levels were exclusively associated to estrogen receptor expression before NACT. Importantly, high sHLA-GEV levels before NACT were related to disease progression and the detection of stem cell-like circulating tumor cells, but high sHLA-Gfree levels indicated an improved clinical outcome. Thus, this study demonstrates for the first time that the different sHLA-G subcomponents represent dissimilar qualitative prognostic impacts on the clinical outcome of NACT treated BC patients, whereas the total sHLA-G levels without separating into subcomponents are not related to clinical outcome.

  10. Lipoprotein Lipase as a Prognostic Marker in Chronic Lymphocytic Leukemia.

    PubMed

    Mátrai, Zoltán; Andrikovics, Hajnalka; Szilvási, Anikó; Bors, András; Kozma, András; Ádám, Emma; Halm, Gabriella; Karászi, Éva; Tordai, Attila; Masszi, Tamás

    2017-01-01

    The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism. We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0.0001) and time to first treatment intervals (36 vs 144 months, p < 0.002) were documented. LPL values correlated with male gender, higher stages, more treatment requirement, CD38 positivity and unmutated IgVH genes. Among cases with 13q deletion, LPL positivity identified a subcohort with poor outcome (median survival 108 months vs NR, p < 0.0001). In multivariate analysis, cytogenetic aberrations and LPL had significant impact on survival. Our results confirm that LPL is a strong predictor of outcome in CLL, able to improve prognostic accuracy in good risk cytogenetic subgroups. The relationship between its prognostic and functional role in CLL needs to be explored further.

  11. Ventricular Dysfunction in Patients with Acute Coronary Syndrome Undergoing Coronary Surgical Revascularization: Prognostic Impact on Long-Term Outcomes

    PubMed Central

    Popovic, Batric; Agrinier, Nelly; Voilliot, Damien; Elfarra, Mazen; Villemot, Jean Pierre; Maureira, Pablo

    2016-01-01

    Background Patients with non-ST elevation acute coronary syndrome complicated by left ventricular dysfunction (LVEF) are a poor prognosis group. The aim of our study was to assess the short and long term LEVF prognostic value in a cohort of NSTE-ACS patients undergoing surgical revascularization. Methods We performed elective and isolated CABG on a cohort of 206 consecutive patients with LVEF≤0.40 complicating acute coronary syndrome. The case cohort was compared with a cohort of controls (LVEF>0.40) randomly selected (2:1) among patients who underwent the procedure during this period. Results The Kaplan-Meier 5-year estimated survival rates for patients in the low and normal LVEF groups were 70.8% (95% confidence interval CI: 64.2–77.4) and 81.7% (95%CI: 77.8–85.6), respectively. A low LVEF was associated with both a higher all-cause (HR [95%CI] = 1.84[1.18–2.86]) and a higher cardiovascular mortality (HR = 2.07 [1.27–3.38]) during the first 12 months of follow-up. After adjustment for potential confounders, a low LVEF remained associated with a higher cardiovascular mortality only (1.87[1.03–3.38]) during the first 12 months of follow-up. After 12 months of follow-up, a low LVEF was no more associated with all-cause, nor cardiovascular mortality. Conclusion Patients with low LVEF might require more intensive care than patients with normal LVEF during the year after the surgical procedure, but once the first postoperative year over, the initial low LVEF was no more associated with long term mortality. PMID:28005944

  12. The Prognostic Importance of Impaired Systolic Function in Heart Failure with Preserved Ejection Fraction and the Impact of Spironolactone

    PubMed Central

    Shah, Amil M.; Claggett, Brian; Sweitzer, Nancy K.; Shah, Sanjiv J.; Anand, Inder S.; Liu, Li; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

    2015-01-01

    Background Impairment in left ventricular (LV) systolic function has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether LV longitudinal strain (LS) is predictive of cardiovascular (CV) outcomes in HFpEF beyond clinical and conventional echocardiographic measures. Methods and Results LS was assessed by 2D speckle-tracking echocardiography at baseline in 447 HFpEF patients enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 (IQR 1.5–3.9) years, 115 patients experienced the primary composite outcome of CV death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS<15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted HR 2.14, 95% CI 1.26–3.66; p=0.005), CV death alone (adjusted HR 3.20, 95% CI 1.44–7.12; p=0.004), and HF hospitalization alone (adjusted HR 2.23, 95% CI 1.16–4.28; p=0.016) after adjusting for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12–18 months demonstrated a trend towards improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia. Conclusions Impaired LV systolic function is a powerful predictor of HF hospitalization, CV death, or aborted cardiac arrest in HFpEF, independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify HFpEF patients at particularly high risk for CV morbidity and mortality. Clinical Trial Registration Information Clinicaltrials.gov. Identifier NCT00094302. PMID:26130119

  13. Prognostic impact of extent of vascular invasion in low-grade encapsulated follicular cell–derived thyroid carcinomas: a clinicopathologic study of 276 cases☆

    PubMed Central

    Xu, Bin; Wang, Laura; Tuttle, R. Michael; Ganly, Ian; Ghossein, Ronald

    2016-01-01

    Summary Continuous controversy surrounds the predictive value of the degree of vascular invasion (VI) in low-grade encapsulated follicular cell–derived thyroid carcinomas (LGEFCs). Some guidelines advocate conservative therapy in LGEFCs with focal VI. There is therefore a need to assess the survival rates of LGEFC patients with various degrees of VI to better stratify patients for subsequent therapy. Furthermore, the prognostic effect of VI within the different histotypes of LGEFCs is not well known. A total of 276 patients with LGEFCs were subjected to a meticulous histopathologic analysis. They were classified as encapsulated papillary thyroid carcinoma, encapsulated follicular carcinoma (EFC), and encapsulated Hurthle cell carcinoma (EHCC). Of the 276 patients, 24 had extensive VI (EVI) (≥4 foci) and 28 displayed focal (<4 foci) VI. EHCC and EFC showed a much higher rate of EVI than encapsulated papillary thyroid carcinoma. Median follow-up was 6 years. All 14 tumors with adverse behavior harbored distant metastases (DMs), of which 9 had DMs at presentation. All 3 patients without EVI who had aggressive carcinomas harbored DMs at presentation. EVI was an independent predictor of poor recurrence-free survival. Excluding cases with DMs at presentation, only patients with EVI had recurrence, and all relapsed cases were EHCC. EVI is an independent predictor of recurrence-free survival in LGEFCs. EHCC with EVI has a particularly high risk of recurrence. When DMs are not found at presentation, patients with focal VI are at a very low risk of recurrence even if not treated with radioactive iodine. PMID:26482605

  14. Prognostic Impact of Baseline High-Sensitivity C-Reactive Protein in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention Based on Body Mass Index

    PubMed Central

    Ahmed, Khurshid; Chakraborty, Rabin; Cho, Kyung Hoon; Sim, Doo Sun; Hong, Young Joon; Ahn, Youngkeun; Hachinohe, Daisuke; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo

    2012-01-01

    Background and Objectives Serum high sensitivity C-reactive protein (hs-CRP) is a marker of inflammation and may lead to the development of atherosclerosis, adversely affecting mortality. The aim of this study was to evaluate the relationship between baseline hs-CRP level and 12-month clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) according to their body mass index (BMI) status. Subjects and Methods Using data from the Korea Acute Myocardial Infarction Registry from November 2005 to September 2008, a total of 8174 consecutive AMI patients were studied. Cox proportional hazard model revealed that higher baseline levels of hs-CRP was associated with 12-month all-cause mortality (p=0.045). To further understand this association, patients were divided into 3 groups based on their body mass index: 1) overweight/obese, 2) normal weight, and 3) underweight patients. Then each group was stratified into quartiles based on their hs-CRP. Results In overweight/obese patients, Cox model showed significant association of hs-CRP with 12-month mortality when adjusted for age and gender (p<0.001), however, after adjustment with multiple covariates, mortality was highest in the 4th quartile {HR 2.382, (1.079-5.259), p=0.032} though statistically insignificant (p=0.172). We observed no significant association of serum hs-CRP with 12-month mortality in normal weight (p=0.681) and underweight (p=0.760) patients. Conclusion Higher baseline hs-CRP level (≥4.08 mg/dL) in overweight/obese AMI patients showed significant association with 12-month all-cause mortality independent of other prognostic markers. PMID:22493611

  15. Biologic features and prognosis of ductal carcinoma in situ are not adversely impacted by initial large body mass.

    PubMed

    Kuerer, Henry M; Lari, Sara A; Arun, Banu K; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A; Albarracin, Constance T; Babiera, Gildy V; Caudle, Abigail S; Wagner, Jamie L; Litton, Jennifer K; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K

    2012-06-01

    Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m(2)), overweight (BMI 25 to <30 kg/m(2)), or of normal weight or underweight (BMI < 25 kg/m(2)). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local-regional recurrence was calculated using the Kaplan-Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66-5.80) or Hispanic (OR, 1.44; CI, 1.02-2.04), be postmenopausal (OR, 1.63; CI, 1.28-2.07), have diabetes (OR, 4.60; CI, 2.60-8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00-192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01-1.80). At a median follow-up time of 4.96 years (range, 1.0-14.34 years), no significant differences in local recurrence rates were detected based on patients' initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS.

  16. Azathioprine therapy and adverse drug reactions in patients with inflammatory bowel disease: impact of thiopurine S-methyltransferase polymorphism.

    PubMed

    Schwab, Matthias; Schäffeler, Elke; Marx, Claudia; Fischer, Christine; Lang, Thomas; Behrens, Christoph; Gregor, Michael; Eichelbaum, Michel; Zanger, Ulrich M; Kaskas, Bernd A

    2002-08-01

    The efficacy of the immunosuppressants azathioprine and 6-mercaptopurine has been well established in the therapy of inflammatory bowel diseases (IBD). However, its use has been complicated by a high incidence of serious adverse drug reactions such as hematotoxicity, hepatotoxicity, pancreatitis and gastrointestinal disturbances. Whereas azathioprine-related pancytopenia has been clearly linked to thiopurine S-methyltransferase (TPMT) polymorphism limited data are available to explain gastrointestinal side effects. In a retrospective analysis of 93 adults with IBD and azathioprine therapy both phenotyping and genotyping was used to explore systematically the relationship between TPMT and azathioprine-related adverse reactions. At time of inclusion, 69 patients were still receiving azathioprine therapy and had never experienced side effects. Azathioprine had been withdrawn in 10 patients for non-medical reasons or lack of response and 14 patients (15%) had stopped medication or were on reduced dose due to severe azathioprine-related side effects. Nine of these 14 patients had developed gastrointestinal side effects (hepatotoxicity, n = 3; pancreatitis, n = 3; others, n = 3), but their normal red blood cell TPMT activities were in accordance to TPMT wild-type. TPMT deficiency in one patient had led to pancytopenia whereas only two of the remaining four patients with hematotoxicity displayed an intermediate phenotype of TPMT. This study demonstrates that azathioprine-related gastrointestinal side effects are independent of the TPMT polymorphism. Nevertheless pharmacogenetic testing for TPMT prior to commencing thiopurine therapy should become routine practice in order to avoid severe hematotoxicity in TPMT deficient patients and lowering the incidence of hematological side effects in individuals heterozygous for TPMT.

  17. Identifying Impacts of Hydropower Regulation on Salmonid Habitats to Guide River Restoration for Existing Schemes and Mitigate Adverse Effects of Future Developments

    NASA Astrophysics Data System (ADS)

    Buddendorf, B.; Geris, J.; Malcolm, I.; Wilkinson, M.; Soulsby, C.

    2015-12-01

    A decrease in longitudinal connectivity in riverine ecosystems resulting from the construction of transverse barriers has been identified as a major threat to biodiversity. For example, Atlantic Salmon (Salmo salar) have a seasonal variety of hydraulic habitat requirements for their different life stages. However, hydropower impoundments impact the spatial and temporal connectivity of natural habitat along many salmon rivers in ways that are not fully understood. Yet, these changes may affect the sustainability of habitat at local and regional scales and so ultimately the conservation of the species. Research is therefore needed both to aid the restoration and management of rivers impacted by previous hydropower development and guide new schemes to mitigate potentially adverse effects. To this end we assessed the effects of hydropower development on the flow related habitat conditions for different salmon life stages in Scottish rivers at different spatial scales. We used GIS techniques to map the changes in structural connectivity at regional scales, applying a weighting for habitat quality. Next, we used hydrological models to simulate past and present hydrologic conditions that in turn drive reach-scale hydraulic models to assess the impacts of regulation on habitat suitability in both space and time. Preliminary results indicate that: 1) impacts on connectivity depend on the location of the barrier within the river network; 2) multiple smaller barriers may have a potentially lower impact than a single larger barrier; 3) there is a relationship between habitat and connectivity where losing less but more suitable habitat potentially has a disproportionally large impact; 4) the impact of flow regulation can lead to a deterioration of habitat quality, though the effects are spatially variable and the extent of the impact depends on salmon life stage. This work can form a basis for using natural processes to perform targeted and cost-effective restoration of rivers.

  18. Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: a cohort study of an urban, minority sample in the U.S.

    PubMed

    Mersky, J P; Topitzes, J; Reynolds, A J

    2013-11-01

    Research has shown that adverse childhood experiences (ACEs) increase the risk of poor health-related outcomes in later life. Less is known about the consequences of ACEs in early adulthood or among diverse samples. Therefore, we investigated the impacts of differential exposure to ACEs on an urban, minority sample of young adults. Health, mental health, and substance use outcomes were examined alone and in aggregate. Potential moderating effects of sex were also explored. Data were derived from the Chicago Longitudinal Study, a panel investigation of individuals who were born in 1979 or 1980. Main-effect analyses were conducted with multivariate logistic and OLS regression. Sex differences were explored with stratified analysis, followed by tests of interaction effects with the full sample. Results confirmed that there was a robust association between ACEs and poor outcomes in early adulthood. Greater levels of adversity were associated with poorer self-rated health and life satisfaction, as well as more frequent depressive symptoms, anxiety, tobacco use, alcohol use, and marijuana use. Cumulative adversity also was associated with cumulative effects across domains. For instance, compared to individuals without an ACE, individuals exposed to multiple ACEs were more likely to have three or more poor outcomes (OR range=2.75-10.15) and four or more poor outcomes (OR range=3.93-15.18). No significant differences between males and females were detected. Given that the consequences of ACEs in early adulthood may lead to later morbidity and mortality, increased investment in programs and policies that prevent ACEs and ameliorate their impacts is warranted.

  19. Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: A cohort study of an urban, minority sample in the U.S.

    PubMed Central

    Topitzes, J.; Reynolds, A.J.

    2014-01-01

    Research has shown that adverse childhood experiences (ACEs) increase the risk of poor health-related outcomes in later life. Less is known about the consequences of ACEs in early adulthood or among diverse samples. Therefore, we investigated the impacts of differential exposure to ACEs on an urban, minority sample of young adults. Health, mental health, and substance use outcomes were examined alone and in aggregate. Potential moderating effects of sex were also explored. Data were derived from the Chicago Longitudinal Study, a panel investigation of individuals who were born in 1979 or 1980. Main-effect analyses were conducted with multivariate logistic and OLS regression. Sex differences were explored with stratified analysis, followed by tests of interaction effects with the full sample. Results confirmed that there was a robust association between ACEs and poor outcomes in early adulthood. Greater levels of adversity were associated with poorer self-rated health and life satisfaction, as well as more frequent depressive symptoms, anxiety, tobacco use, alcohol use, and marijuana use. Cumulative adversity also was associated with cumulative effects across domains. For instance, compared to individuals without an ACE, individuals exposed to multiple ACEs were more likely to have three or more poor outcomes (OR range = 2.75–10.15) and four or more poor outcomes (OR range = 3.93–15.18). No significant differences between males and females were detected. Given that the consequences of ACEs in early adulthood may lead to later morbidity and mortality, increased investment in programs and policies that prevent ACEs and ameliorate their impacts is warranted. PMID:23978575

  20. Biologic features and prognosis of ductal carcinoma in situ are not adversely impacted by initial large body mass

    PubMed Central

    Lari, Sara A.; Arun, Banu K.; Hu, Chung-Yuan; Brewster, Abenaa; Mittendorf, Elizabeth A.; Albarracin, Constance T.; Babiera, Gildy V.; Caudle, Abigail S.; Wagner, Jamie L.; Litton, Jennifer K.; Bedrosian, Isabelle; Meric-Bernstam, Funda; Lucci, Anthony; Hunt, Kelly K.

    2013-01-01

    Obesity is associated with adverse biologic features and poor outcome in patients with invasive breast cancer, yet this relationship has not been evaluated in patients with ductal carcinoma in situ (DCIS). From 1996 to 2009, body mass index (BMI) was recorded at initial diagnosis for 1,885 patients with DCIS treated at our institution. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI 25 to<30 kg/m2), or of normal weight or underweight (BMI <25 kg/m2). Logistic regression was used to examine associations between BMI and patient, clinical, and pathologic features and treatment. Local–regional recurrence was calculated using the Kaplan–Meier method. All statistical tests were two-sided. Of the 1,885 patients, 514 (27.7%) were obese, 510 (27.5%) were overweight, and 831 (44.8%) were normal/underweight. In multivariate analysis, overweight and obese patients were significantly more likely to be African American (odds ratio [OR], 3.93; 95% confidence interval [CI], 2.66–5.80) or Hispanic (OR, 1.44; CI, 1.02–2.04), be postmenopausal (OR, 1.63; CI, 1.28–2.07), have diabetes (OR, 4.60; CI, 2.60–8.12), have estrogen-receptor-positive DCIS (OR, 1.39; CI, 1.00–192), and present with a radiologic abnormality rather than clinical symptoms (OR, 1.35; CI, 1.01–1.80). At a median follow-up time of 4.96 years (range, 1.0–14.34 years), no significant differences in local recurrence rates were detected based on patients’ initial BMI category. Furthermore, there was no significant difference in risk of recurrence between diabetic patients receiving metformin or not. In conclusion, higher BMI is not associated with adverse biologic features or prognosis in patients with DCIS. PMID:22392043

  1. The Adverse Impact of High Stakes Testing on Minority Students: Evidence from 100 Years of Test Data.

    ERIC Educational Resources Information Center

    Madaus, George F.; Clarke, Marguerite

    This paper examines four aspects of current high stakes testing that impact minority students and others traditionally underserved by American education. Data from research conducted at Boston College over 30 years highlight 4 issues: high stakes, high standards tests do not have a markedly positive effect on teaching and learning; high stakes…

  2. Modeling dropout from adverse event data: impact of dosing regimens across pregabalin trials in the treatment of generalized anxiety disorder.

    PubMed

    Lalovic, Bojan; Hutmacher, Matt; Frame, Bill; Miller, Raymond

    2011-05-01

    Dizziness represents a major determinant of dropout in the treatment of generalized anxiety disorder with pregabalin. Titration (dose escalation) regimens based on clinical judgment were implemented to mitigate this adverse event and reduce patient dropout across clinical trials. Dropout is an important treatment failure endpoint, which can be analyzed using time-to-event models that incorporate daily dosing or other time-varying information. A parametric discrete-time dropout model with daily dizziness severity score as a covariate afforded a systematic, model-based assessment of titration dosing strategies, with model predictions evaluated against corresponding nonparametric estimates. A Gompertz hazard function adequately described the decreasing dropout hazard over time for individuals with severe or moderate dizziness and a lower, constant hazard for individuals reporting no dizziness or mild dizziness. Predictive performance of the model was adequate based on external validation with an independent trial and other goodness-of-fit criteria. Prospective simulations highlight the utility of this approach in reducing dropout based on examination of untested titration scenarios for future generalized anxiety disorder or other trials.

  3. The impact of arbuscular mycorrhizal fungi in mitigating salt-induced adverse effects in sweet basil (Ocimum basilicum L.).

    PubMed

    Elhindi, Khalid M; El-Din, Ahmed Sharaf; Elgorban, Abdallah M

    2017-01-01

    Salinity is one of the serious abiotic stresses adversely affecting the majority of arable lands worldwide, limiting the crop productivity of most of the economically important crops. Sweet basil (Osmium basilicum) plants were grown in a non-saline soil (EC = 0.64 dS m(-1)), in low saline soil (EC = 5 dS m(-1)), and in a high saline soil (EC = 10 dS m(-1)). There were differences between arbuscular mycorrhizal (Glomus deserticola) colonized plants (+AMF) and non-colonized plants (-AMF). Mycorrhiza mitigated the reduction of K, P and Ca uptake due to salinity. The balance between K/Na and between Ca/Na was improved in +AMF plants. Growth enhancement by mycorrhiza was independent from plant phosphorus content under high salinity levels. Different growth parameters, salt stress tolerance and accumulation of proline content were investigated, these results showed that the use of mycorrhizal inoculum (AMF) was able to enhance the productivity of sweet basil plants under salinity conditions. Mycorrhizal inoculation significantly increased chlorophyll content and water use efficiency under salinity stress. The sweet basil plants appeared to have high dependency on AMF which improved plant growth, photosynthetic efficiency, gas exchange and water use efficiency under salinity stress. In this study, there was evidence that colonization with AMF can alleviate the detrimental salinity stress influence on the growth and productivity of sweet basil plants.

  4. Unbalanced international collaboration affects adversely the usefulness of countries' scientific output as well as their technological and social impact.

    PubMed

    Zanotto, Sonia R; Haeffner, Cristina; Guimarães, Jorge A

    2016-01-01

    The unbalanced international scientific collaboration as cause of misleading information on the country's contribution to the scientific world output was analyzed. ESI Data Base (Thomson Reuters' InCites), covering the scientific production of 217 active countries in the period 2010-2014 was used. International collaboration implicates in a high percentage (33.1 %) of double-counted world articles, thus impacting qualitative data as citations, impact and impact relative to word. The countries were divided into three groups, according to their individual contribution to the world publications: Group I (24 countries, at least 1 %) representing 83.9 % of the total double-counted world articles. Group II (40 countries, 0.1-0.99 % each). Group III, 153 countries (70.5 %) with <0.1 % and altogether 1.9 % of the world. Qualitative characteristics of each group were also analyzed: percentage of the country's GNP applied in R&D, proportion of Scientists and Engineers per million inhabitants and Human Development Index. Average international collaboration were: Group I, 43.0 %; Group II, 55.8 % and Group III, 85.2 %. We concluded that very high and unbalanced international collaboration, as presented by many countries, misrepresent the importance of their scientific production, technological and social outputs. Furthermore, it jeopardizes qualitative outputs of the countries themselves, artificially increasing their scientific impact, affecting all fields and therefore, the whole world. The data confirm that when dealing with the qualitative contribution of countries, it is necessary to take in consideration the level of international cooperation because, as seen here, it can and in fact it does create false impression of the real contribution of countries.

  5. Impact of High-Normal Blood Pressure Measured in Emergency Room on Adverse Cardiac Events in Acute Myocardial Infarction

    PubMed Central

    Yoon, Nam Sik; Ahn, Youngkeun; Kim, Jong Hyun; Chae, Shung Chull; Kim, Young Jo; Hur, Seung Ho; Seong, In Whan; Hong, Taek Jong; Choi, Donghoon; Cho, Myeong Chan; Kim, Chong Jin; Seung, Ki Bae; Chung, Wook Sung; Jang, Yang Soo; Cho, Jeong Gwan; Park, Seung Jung

    2012-01-01

    Background and Objectives Prehypertension according to JNC7 is common and is associated with increased vascular mortality. The importance of management in high-normal blood pressure (BP) is underemphasized. Subjects and Methods We analyzed major adverse cardiac events (MACEs) in the Korea Acute Myocardial Infarction Registry in normal BP (group I) and high-normal BP (group II) patients. Results Among 14871 patients, 159 (61±12.3 years, 122 males) satisfied the study indication. Six-month and one-year clinical follow-up rate was 88.9% and 85.8%, respectively. Group I had 78 patients (60.9±12.4 years). Group II had 81 patients (61.6±12.5 years). Demographics of patients were not different between groups. Treatment strategy was not different. Initial Thrombolysis in Myocardial Infarction flow grade 0 was less frequent in group II (n=32, 47.1%) than in group I (n=16, 21.9%) (p=0.001). Successful intervention rate was not different between group II (93.8%) and group I (97.1%) (p=0.590). Six-month MACE occurred in 3 patients in group I (4.4%) and 10 in group II (15.6%) (p=0.031). Compared with normal BP, the odds ratio for patients with high-normal BP was 1.147 (p=0.045, 95% confidence interval 1.011-1.402) for 6-month MACE. Conclusion Even though high-normal BP patients had a better baseline clinical status, the prognosis was poorer than patients with normal BP. Therapeutic BP target goal for the patients with acute myocardial infarction should be <140/90 mm Hg, which is recommended in JNC7. PMID:22701132

  6. A Possible Paradigm for the Mitigation of the Adverse Impacts of Natural Hazards in the Developing Countries

    NASA Astrophysics Data System (ADS)

    Aswathanarayana, U.

    2001-05-01

    The proneness of a country or region to a given natural hazard depends upon its geographical location, physiography, geological and structural setting, landuse/landcover situation, and biophysical and socioeconomic environments (e.g. cyclones and floods in Bangladesh, earthquakes in Turkey, drought in Sub-Saharan Africa). While the natural hazards themselves cannot be prevented, it is possible to mitigate their adverse effects, by a knowledge-based, environmentally-sustainable approach, involving the stakeholder communities: (i) by being prepared: on the basis of the understanding of the land conditions which are prone to a given hazard and the processes which could culminate in damage to life and property (e.g. planting of dense-rooted vegetation belts to protect against landslides in the earthquake-prone areas), (ii) by avoiding improper anthropogenic activities that may exacerbate a hazard (e.g. deforestation accentuating the floods and droughts), and (iii) by putting a hazard to a beneficial use, where possible (groundwater recharging of flood waters), etc. Mitigation strategies need to be custom-made for each country/region by integrating the biophysical and socioeconomic components. The proposed paradigm is illustrated in respect of Extreme Weather Events (EWEs), which is based on the adoption of three approaches: (i) Typology approach, involving the interpretation of remotely sensed data, to predict (say) temporal and spatial distribution of precipitation, (ii) "black box" approach, whereby the potential environmental consequences of an EWE are projected on the basis of previously known case histories, and (iii) Information Technology approach, to translate advanced technical information in the form of "virtual" do-it-yourself steps understandable to lay public.

  7. Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis.

    PubMed

    Roberge, Stéphanie; Demers, Suzanne; Berghella, Vincenzo; Chaillet, Nils; Moore, Lynne; Bujold, Emmanuel

    2014-11-01

    A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, which compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-layer closure, which had shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4; P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1; P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8; P < .001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between single- vs double-layer closure for uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness.

  8. Prognostic Impact of Combined Contrast-Induced Acute Kidney Injury and Hypoxic Liver Injury in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results from INTERSTELLAR Registry

    PubMed Central

    Suh, Young Ju; Kim, Tae-Hoon; Jang, Ho-Jun; Suh, Jon; Park, Hyun Woo; Oh, Pyung Chun; Shin, Sung-Hee; Woo, Seong-Il; Kim, Dae-Hyeok; Kwan, Jun; Kang, WoongChol

    2016-01-01

    Background Besides contrast-induced acute kidney injury(CI-AKI), adscititious vital organ damage such as hypoxic liver injury(HLI) may affect the survival in patients with ST-elevation myocardial infarction (STEMI). We sought to evaluate the prognostic impact of CI-AKI and HLI in STEMI patients who underwent primary percutaneous coronary intervention (PCI). Methods A total of 668 consecutive patients (77.2% male, mean age 61.3±13.3 years) from the INTERSTELLAR STEMI registry who underwent primary PCI were analyzed. CI-AKI was defined as an increase of ≥0.5 mg/dL in serum creatinine level or 25% relative increase, within 48h after the index procedure. HLI was defined as ≥2-fold increase in serum aspartate transaminase above the upper normal limit on admission. Patients were divided into four groups according to their CI-AKI and HLI states. Major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of all-cause mortality, non-fatal MI, non-fatal stroke, ischemia-driven target lesion revascularization and target vessel revascularization were recorded. Results Over a mean follow-up period of 2.2±1.6 years, 94 MACCEs occurred with an event rate of 14.1%. The rates of MACCE and all-cause mortality were 9.7% and 5.2%, respectively, in the no organ damage group; 21.3% and 21.3% in CI-AKI group; 18.5% and 14.6% in HLI group; and 57.7% and 50.0% in combined CI-AKI and HLI group. Survival probability plots of composite MACCE and all-cause mortality revealed that the combined CI-AKI and HLI group was associated with the worst prognosis (p<0.0001 for both). Conclusion Combined CI-AKI after index procedure and HLI on admission is associated with poor clinical outcomes in patients with STEMI who underwent primary PCI. (INTERSTELLAR ClinicalTrials.gov number, NCT02800421.) PMID:27415006

  9. Increased biomass burning due to the economic crisis in Greece and its adverse impact on wintertime air quality in Thessaloniki.

    PubMed

    Saffari, Arian; Daher, Nancy; Samara, Constantini; Voutsa, Dimitra; Kouras, Athanasios; Manoli, Evangelia; Karagkiozidou, Olga; Vlachokostas, Christos; Moussiopoulos, Nicolas; Shafer, Martin M; Schauer, James J; Sioutas, Constantinos

    2013-01-01

    The recent economic crisis in Greece resulted in a serious wintertime air pollution episode in Thessaloniki. This air quality deterioration was mostly due to the increased price of fuel oil, conventionally used as a source of energy for domestic heating, which encouraged the residents to burn the less expensive wood/biomass during the cold season. A wintertime sampling campaign for fine particles (PM2.5) was conducted in Thessaloniki during the winters of 2012 and 2013 in an effort to quantify the extent to which the ambient air was impacted by the increased wood smoke emissions. The results indicated a 30% increase in the PM2.5 mass concentration as well as a 2-5-fold increase in the concentration of wood smoke tracers, including potassium, levoglucosan, mannosan, and galactosan. The concentrations of fuel oil tracers (e.g., Ni and V), on the other hand, declined by 20-30% during 2013 compared with 2012. Moreover, a distinct diurnal variation was observed for wood smoke tracers, with significantly higher concentrations in the evening period compared with the morning. Correlation analysis indicated a strong association between reactive oxygen species (ROS) activity and the concentrations of levoglucosan, galactosan, and potassium, underscoring the potential impact of wood smoke on PM-induced toxicity during the winter months in Thessaloniki.

  10. Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

    PubMed Central

    Guenounou, Sarah; Borel, Cécile; Bérard, Emilie; Yon, Edwige; Fort, Marylise; Mengelle, Catherine; Bertoli, Sarah; Sarry, Audrey; Tavitian, Suzanne; Huguet, Françoise; Attal, Michel; Récher, Christian; Huynh, Anne

    2016-01-01

    Abstract Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors. Myeloablative and reduced-intensity conditioning regimen were given to 71 and 65 patients, respectively. Including CMV reactivations, at least 1 viral reactivation was recorded in 76 patients. Viral reactivations were associated with a lower risk of relapse (adjusted HR 0.14; 95% CI 0.07–0.30; P < 0.01), better disease-free survival (aHR 0.29; 95% CI 0.16–0.54; P < 0.01) but higher non relapse mortality. This translated into a better overall survival (aHR 0.44; 95%CI 0.25–0.77; P < 0.01) in patients who experienced viral reactivation. Thus, viral reactivations, including but not limited to CMV reactivation, are associated with a better outcome particularly with regard to the risk of relapse in AML patients undergoing alloSCT. New guidelines regarding the choice of donor according to the CMV serostatus are needed. PMID:27902595

  11. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment.

    PubMed

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.

  12. Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy.

    PubMed

    Aoki, Masahiko; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Fujioka, Ichitaro; Tanaka, Mitsuki; Ono, Shuichi; Takai, Yoshihiro

    2016-07-01

    The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5-10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.

  13. Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

    PubMed Central

    2013-01-01

    Introduction Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. Methods Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up. Results Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. Conclusions A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases. PMID:23302110

  14. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment

    PubMed Central

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels. PMID:26469350

  15. Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy

    PubMed Central

    Aoki, Masahiko; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Fujioka, Ichitaro; Tanaka, Mitsuki; Ono, Shuichi; Takai, Yoshihiro

    2016-01-01

    The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45–60 Gy in 5–10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5–54.5 months). The median value of the average iodine density was 1.86 mg/cm3 (range, 0.40–9.27 mg/cm3). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors. PMID:26826198

  16. The impact of adverse health events on consumption: Understanding the mediating effect of income transfers, wealth, and health insurance.

    PubMed

    Babiarz, Patryk; Yilmazer, Tansel

    2017-03-21

    Using data from the Panel Study of Income Dynamics for years 1999-2013, we investigate the impact of physical and mental illnesses on household consumption and financial status. In comparison to severe physical health problems, mental illnesses lead to larger decreases in labor income. Increases in public and private transfers following the onset of a mental illness do not completely offset the decline in labor income. Consequently, we find a significant decrease in consumption expenditures after the household head experiences a mental problem. On the other hand, public and private transfers and accumulated wealth offset the relatively smaller decline in labor income and enable households with severe physical problems to smooth their consumption. Health insurance helps to prevent larger drops in consumption after the onset of a mental health problem.

  17. Medical and Genetic Differences in the Adverse Impact of Sleep Loss on Performance: Ethical Considerations for the Medical Profession

    PubMed Central

    Czeisler, Charles A.

    2009-01-01

    without unacceptably compromising patient safety? Moreover, once it is possible to identify reliably those most vulnerable to the adverse effects of sleep loss on performance, will academic medical centers have an obligation to evaluate the proficiency of both residents and staff physicians under conditions of acute and chronic sleep deprivation? Should work-hour policy limits be modified to ensure that they are not hazardous for the patients of the most vulnerable quartile of physicians, or should the limits be personalized to enable the most resistant quartile to work longer hours? Given that the prevalence of sleep disorders has increased in our society overall, and increases markedly with age, how should fitness for extended duration work hours be monitored over a physician's career? In the spirit of the dictum to do no harm, advances in understanding the medical and genetic basis of inter-individual differences in the performance vulnerability to sleep loss should be incorporated into the development of work-hour policy limits for both physicians and surgeons. PMID:19768182

  18. Medical and genetic differences in the adverse impact of sleep loss on performance: ethical considerations for the medical profession.

    PubMed

    Czeisler, Charles A

    2009-01-01

    without unacceptably compromising patient safety? Moreover, once it is possible to identify reliably those most vulnerable to the adverse effects of sleep loss on performance, will academic medical centers have an obligation to evaluate the proficiency of both residents and staff physicians under conditions of acute and chronic sleep deprivation? Should work-hour policy limits be modified to ensure that they are not hazardous for the patients of the most vulnerable quartile of physicians, or should the limits be personalized to enable the most resistant quartile to work longer hours? Given that the prevalence of sleep disorders has increased in our society overall, and increases markedly with age, how should fitness for extended duration work hours be monitored over a physician's career? In the spirit of the dictum to do no harm, advances in understanding the medical and genetic basis of inter-individual differences in the performance vulnerability to sleep loss should be incorporated into the development of work-hour policy limits for both physicians and surgeons.

  19. Prognostic utility of coronary computed tomographic angiography

    PubMed Central

    Otaki, Yuka; Berman, Daniel S.; Min, James K.

    2013-01-01

    Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a noninvasive method that enables accurate detection and exclusion of anatomically obstructive coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. There are numerous potential advantages of CCTA beyond simply luminal stenosis assessment including quantification of atherosclerotic plaque volume as well as assessment of plaque composition, extent, location and distribution. In recent years, an array of studies has evaluated the prognostic utility of CCTA findings of CAD for the prediction of major adverse cardiac events, all-cause death and plaque instability. This prognostic information enhances risk stratification and, if properly acted upon, may improve medical therapy and/or behavioral changes that may enhance event-free survival. The goal of the present article is to summarize the current status of the prognostic utility of CCTA findings of CAD. PMID:23809386

  20. The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

    PubMed Central

    Wong, Li-Fan; Lee, Jang-Ming

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793

  1. A clean-burning biofuel as a response to adverse impacts of woodsmoke and coalsmoke on Navajo health

    SciTech Connect

    Shultz, E.B. Jr.; Bragg, W.G.; Whittier, J.

    1994-12-31

    Because over 60% of Navajo households are heated with woodfuel and coal, and indoor air pollution from woodsmoke and coalsmoke is problematic, most Navajos are probably at risk of respiratory and other smoke-induced illnesses. A previous study has shown that Navajo children living in homes heated by a wood/coal stove are nearly five times more likely to contract acute lower respiratory tract infections than children from homes that do not use those fuels. Stove and flue improvements to reduce leakage of smoke into the home would help. So would clean-burning solid fuels in replacement of woodfuel and coal. The authors describe a clean-burning fast-growing carbohydrate biofuel, prepared by sun-drying the roots of a wild southwestern gourd plant, Cucurbita foetidissima. They call it {open_quotes}rootfuel.{close_quotes} A test plot is growing during the 1994 season at the NMSU Agricultural Science Center on the Navajo Nation, near Farmington, New Mexico. Irrigation requirements are being measured. In the Fall, a preliminary needs assessment will be conducted to learn more about how fuel usage impacts Navajo health. The acceptability of rootfuel in selected homes will be tested during the upcoming heating season.

  2. Trading places - an innovative SO{sub 2} trading program to mitigate potential adverse impacts on Class I areas: part I. impacts

    SciTech Connect

    Louis Militana; Cindy Huber; Christopher Colbert; Chris Arrington; Don Shepherd

    2005-07-01

    Published in two parts, this article describes a new emissions cap-and-trade program to reduce acid deposition and visibility impacts in four Class I areas (e.g. wildernesses and national parks) from the proposed Longview Power coal-fired power plant to be located in Maidsville, WV. Part I discusses the air quality impacts of the proposed project. 5 refs., 2 figs., 5 tabs.

  3. Prognostics for Microgrid Components

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  4. Adverse impacts of pasture abandonment in Himalayan protected areas: Testing the efficiency of a Natural Resource Management Plan (NRMP)

    SciTech Connect

    Nautiyal, Sunil . E-mail: sunil.nautiyal@zalf.de; Kaechele, Harald

    2007-03-15

    The high elevational areas in the Himalayas of India are dominated by forests and alpine pastures. There are many protected areas in the region, including Nanda Devi Biosphere Reserve (NDBR) and Valley of Flowers (VOF) where natural resource management plan (NRMP) has been implemented for the conservation of biodiversity. This has affected the traditional animal husbandry system, as well as the vegetation dynamics of alpine pastures. An integrated approach to studying the impact of NRMP in the region has been applied by us. First, a survey was conducted regarding livestock management, data pertaining the livestock husbandry, the role of animal husbandry in economics of rural household, and socioeconomics. Second, field based study on phytosociology of some important alpine herbs was done to enumerate the density and species richness in different land mark of the region. Thereafter, satellite data and Geographic Information System (GIS) were used to develop a land cover map of the area and to note changes in the landscape over time after implementation of NRMP. From an economic point of view the implementation of such plan is a setback to the rural economy. However, the ecological perspective of such models is a threat to the diversity of alpine pastures. The invasion of bushes/thorny bushes/shrubs and weeds with their luxuriant growth is changing the vegetation index and dynamics. Consequently, the diversity of herbs in alpine pastures of the Himalayan Mountains is in jeopardy. Overall, the situation is leading to landscape change in the region. This study is helpful for generating useful outcomes and strategies considering the question or debate 'is grazing good or bad for pasture ecosystems in the Himalayas?'.

  5. Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

    NASA Technical Reports Server (NTRS)

    Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2013-01-01

    A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

  6. New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.

    PubMed

    Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H

    2014-09-01

    Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.

  7. Projected 21st Century Impacts of Climate Change on the Performance of the Los Angeles Aqueduct and Adaptation Measures to Mitigate Adverse Impacts

    NASA Astrophysics Data System (ADS)

    Mills, B.; Sayenko, K.; Roy, S. B.; Lew, C.

    2011-12-01

    One of the largest sources of drinking water to the City of Los Angeles (the City) comes from snow melt from the Eastern Sierra Nevada Mountains that drain into Owens Valley and Mono Basin. Much of this water is then transported to the City via the Los Angeles Aqueduct (LAA) originally built in 1913. During the 1980s and earlier, up to 500,000 acre-feet (af) of water was conveyed annually, but more recently less water has been transported due to increasing usage in Owens Valley, and due to a series of dry years.The City is concerned about potential impacts of climate change on this water supply, and commissioned the authors to perform a study to evaluate these potential impacts on both the infrastructure of the LAA and water supply to the City. This presentation focuses on the water supply issue, which has the potential to impact millions of customers. The study results presented here are part of a larger study where 16 global climate models were downscaled and applied to the Owens Valley and Mono Basin watersheds. This presentation begins by assuming base-of-mountain runoff is known from the 16 GCMs, and does not focus on the GCMs or downscaling.The results of the study described in this presentation are those of the authors and not of the LADWP. One of the most consequential findings of the study is the projected decrease in runoff from the watershed over the 21st century. While wet years are still dispersed between dry years, over the 21st century the loss in runoff is equivalent to approximately five years of historical average runoff. In addition to climate change impacts, water usage in the Owens valley is projected to increase over the 21st century and that increasing usage is projected to be comparable to climate change impacts. Eight adaptation options were identified to mitigate potential impacts. These included increasing storage volume of reservoirs in Owens Valley, changing operational rules for releasing water, construction of surface storage or

  8. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204

  9. Toward IVHM Prognostics

    NASA Technical Reports Server (NTRS)

    Walsh, Kevin; Venti, Mike

    2007-01-01

    This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

  10. The Impact of Inherited Thrombophilia Types and Low Molecular Weight Heparin Treatment on Pregnancy Complications in Women with Previous Adverse Outcome

    PubMed Central

    Aracic, Nada; Roje, Damir; Jakus, Ivana Alujevic; Bakotin, Marinela

    2016-01-01

    Purpose To assess the distribution of births and spontaneous abortions, first-trimester abortion (FTA) and mid-trimester abortion (MTA), in untreated (n=128) and low molecular weight heparin (LMWH) treated pregnancies (n=50) of the same women with inherited thrombophilias and adverse pregnancy outcome (APO) in previous pregnancies. We particularly investigated the impact of LMWH on reducing the pregnancy complications in two thrombophilia types, "Conventional" and "Novel". Materials and Methods 50 women with inherited thrombophilia (26 Conventional and 24 Novel) and APO in previous pregnancies were included in the study. Conventional group included factor V Leiden (FVL), prothrombin G20210A (PT) mutations and antithrombin (AT), protein S (PS), and protein C (PC) deficiency, while the Novel group included methylentetrahydrofolate-reductase (MTHFR), plasminogen activator inhibitor-1 (PAI-1), and angiotensin converting enzyme (ACE) polymorphism. APO was defined as one of the following: preterm birth (PTB), fetal growth restriction (FGR), preeclampsia (PE), intrauterine fetal death (IUFD), placental abruption (PA) and deep venous thrombosis (DVT). Results There was no difference in distribution of births and spontaneous abortions between Conventional and Novel thrombophilia in untreated pregnancies (χ2=2.7; p=0.100) and LMWH treated pregnancies (χ2=0.442; p=0.506). In untreaed pregnancies thrombophilia type did not have any impact on the frequency of FTA and MTA (χ2=0.14; p=0.711). In birth-ended pregnancies LMWH treatement reduced the incidence of IUFD (p=0.011) in Conventional and FGR, IUFD, and PTB in Novel thrombophilia group. Conclusion The equal impact of two thrombophilia types on the pregnancy outcomes and a more favorable effect of LMWH therapy on pregnancy complications in Novel thrombophilia group point the need for Novel thrombophilias screening and the future studies on this issue should be recommended. PMID:27401656

  11. Incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with neuromuscular scoliosis: A STROBE-compliant retrospective observational analysis.

    PubMed

    Jia, Rui; Li, Na; Xu, Bi-Yun; Zhang, Wei; Gu, Xiao-Ping; Ma, Zheng-Liang

    2017-03-01

    Factors influencing massive blood loss for neuromuscular scoliosis (NMS) patients.Despite advances in surgical and anesthetic techniques, scoliosis surgery is still associated with intraoperative massive blood loss, which can result in postoperative mortality and morbidity. The aim of this study was to assess the incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with NMS.A retrospective review of adolescents who underwent posterior spinal instrumentation and fusion for NMS was performed. Perioperative variables and data were recorded. Massive blood loss was defined as an estimated blood loss that exceeds 30% of total blood volume.We obtained data for 114 patients, of whom 63 (55%) had intraoperative massive blood loss. Compared with those without, patients with massive blood loss were more likely to be older, have lower body mass indexes (BMIs), larger Cobb angles, more fused levels, more osteotomy procedures, and prolonged duration of operation. Logistic regression analysis identified the number of fused levels to be more than 12 (P = 0.003, odds ratio = 6.614, 95% confidence interval [CI]: 1.891-23.131), BMI lower than 16.8 kg/m (P = 0.025, odds ratio = 3.293, 95% CI: 1.159-9.357), age greater than 15 years (P = 0.014, odds ratio = 3.505, 95% CI: 1.259-9.761), and duration of operation longer than 4.4 hours (P = 0.016, odds ratio = 3.746, 95% CI: 1.428-9.822) as influencing factors. Patients with massive blood loss are associated with more intraoperative colloids infusion and blood transfusions (red blood cell and fresh frozen plasma), as well as postoperative drainage volume.In adolescents with NMS who underwent posterior spinal instrumentation and fusion operations, intraoperative massive blood loss is common. The number of fused levels, BMI, age, and duration of operation are factors influencing intraoperative massive blood loss.

  12. Prognostic impact of history of follicular lymphoma, induction regimen and stem cell transplant in patients with MYC/BCL2 double hit lymphoma

    PubMed Central

    Li, Shaoying; Saksena, Annapurna; Desai, Parth; Xu, Jie; Zuo, Zhuang; Lin, Pei; Tang, Guilin; Yin, C. Cameron; Seegmiller, Adam; Jorgensen, Jeffrey L.; Miranda, Roberto N.; Reddy, Nishitha M; Bueso-Ramos, Carlos; Medeiros, L. Jeffrey

    2016-01-01

    MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma. Patients received induction chemotherapy regimens including 61 R-CHOP, 31 R-EPOCH, 29 R-Hyper-CVAD, and 23 other regimens. Thirty-nine patients received a stem cell transplant (SCT) including 31 autologous and 8 allogeneic. Sixty-two patients achieved complete remission (CR) after induction chemotherapy. Median overall survival (OS) was 19 months. Clinicopathologic features were similar between patients with de novo tumors versus those with a history of FL (P > 0.05). Using multivariate analysis, achieving CR, undergoing SCT, stage and the International Prognostic Index were independent prognostic factors for OS. Stem cell transplantion was associated with improved OS in patients who failed to achieve CR, but not in patients who achieved CR after induction chemotherapy. In conclusion, patients with MYC/BCL2 DHL who present with de novo disease and patients with a history of FL have a similarly poor prognosis. Achievement of CR, regardless of the induction chemotherapy regimen used, is the most important independent prognostic factor. Patients who do not achieve CR after induction chemotherapy may benefit from SCT. PMID:27203548

  13. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... technology available for minimizing adverse environmental impact be established for my Phase II existing... technology available to minimize adverse environmental impact for your facility in accordance with paragraphs... technology available for minimizing adverse environmental impact. This determination must be based...

  14. Protection of palak (Beta vulgaris L. var Allgreen) plants from ozone injury by ethylenediurea (EDU): roles of biochemical and physiological variations in alleviating the adverse impacts.

    PubMed

    Tiwari, Supriya; Agrawal, Madhoolika

    2009-06-01

    Ameliorative effects of ethylenediurea (N-[2-(2-oxo-1-imidazolinidyl) ethyl]-N' phenylurea, abbreviated as EDU) against ozone stress were studied on selected growth, biochemical, physiological and yield characteristics of palak (Beta vulgaris L. var Allgreen) plants grown in field at a suburban site of Varanasi, India. Mean eight hourly ozone concentration varied from 52 to 73 ppb which was found to produce adverse impacts on plant functioning and growth characteristics. The palak plants were treated with 300 ppm EDU at 10 days after germination at 10 days interval up to the plant maturity. Lipid peroxidation in EDU treated plants declined significantly as compared to non-EDU treated ones. Significant increment in F(v)/F(m) ratio in EDU treated plants as compared to non-EDU treated ones was recorded. EDU treated plants showed significant increment in ascorbic acid contents and reduction in peroxidase activity as compared to non-EDU treated ones. As a result of the protection provided by EDU against ozone induced stress on biochemical and physiological characteristics of palak, the morphological parameters also responded positively. Significant increments were recorded in shoot length, number of leaves plant(-1), leaf area and root and shoot biomass of EDU treated plants as compared to non-EDU treated ones. Contents of Na, K, Ca, Mg and Fe were higher in EDU treated plants as compared to non-EDU treated ones. The present investigation proves the usefulness of EDU in partially ameliorating ozone injury in ambient conditions.

  15. Quality of life in patients with schizophrenia: the impact of socio-economic factors and adverse effects of atypical antipsychotics drugs.

    PubMed

    de Araújo, Aurigena Antunes; de Araújo Dantas, Diego; do Nascimento, Gemma Galgani; Ribeiro, Susana Barbosa; Chaves, Katarina Melo; de Lima Silva, Vanessa; de Araújo, Raimundo Fernandes; de Souza, Dyego Leandro Bezerra; de Medeiros, Caroline Addison Carvalho Xavier

    2014-09-01

    This cross-sectional study compared the effects of treatment with atypical antipsychotic drugs on quality of life (QoL) and side effects in 218 patients with schizophrenia attending the ambulatory services of psychiatric in Rio Grande do Norte, Brazil. Socio-economic variables were compared. The five-dimension EuroQoL (EQ-5D) was used to evaluate QoL, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ (2) test and Student's t test, with a significance level of 5 %. Average monthly household incomes in the medication groups were 1.1-2.1 minimum wages ($339-$678). UKU Scale scores showed significant differences in side effects, mainly, clozapine, quetiapine and ziprasidone (p < 0.05). EQ-5D scores showed that all drugs except olanzapine significantly impacted mobility (p < 0.05), and proportions of individuals reporting problems in other dimensions were high: 63.6 % of clozapine users reported mobility problems, 63.7 and 56.3 % of clozapine and ziprasidone users, respectively, had difficulties with usual activities, 68.8 and 54.5 % of ziprasidone and clozapine users, respectively, experienced pain and/or discomfort, and 72.8 % of clozapine users reported anxiety and/or depression. Psychiatric, neurological, and autonomous adverse effects, as well as other side effects, were prevalent in users of atypical antipsychotic drugs, especially clozapine and ziprasidone. Olanzapine had the least side effects. QoL was impacted by side effects and economic conditions in all groups. Thus, the effects of these antipsychotic agents appear to have been masked by aggravating social and economic situations.

  16. A Comprehensive Prognostics Approach for Predicting Gas Turbine Engine Bearing Life

    DTIC Science & Technology

    2004-06-01

    PROGNOSTICS APPROACH FOR PREDICTING GAS TURBINE ENGINE BEARING LIFE Rolf Orsagh, Michael Roemer, Jeremy Sheldon Impact Technologies, LLC 125...Wright-Patterson AFB, OH 45433 ABSTRACT Development of practical and verifiable prognostic approaches for gas turbine engine bearings will play...unnecessary maintenance on engines that operate under unusually mild conditions. A comprehensive engine bearing prognostic approach is presented

  17. The Expression and Prognostic Impact of CD95 Death Receptor and CD20, CD34 and CD44 Differentiation Markers in Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    M. Kamazani, Fatemeh; Bahoush-Mehdiabadi, Gholamreza; Aghaeipour, Mahnaz; Vaeli, Shahram; Amirghofran, Zahra

    2014-01-01

    Objective: This study investigated the expression and prognostic significance of the CD95 death receptor and CD20, a B cell-lineage associated marker, along with CD34 and CD44 non-lineage associated molecules in Iranian children with acute lymphoblastic leukemia (ALL). Methods: We performed immunophenotyping for expressions of the molecules in blood samples from children diagnosed with ALL by using a panel of monoclonal antibodies for flow cytometry analysis. The expression of markers was evaluated in relation to clinical and paraclinical features as well as response to treatment in the patients. Findings : CD95 showed a higher expression in T-ALL compared to B-ALL (P<0.001). Analysis of the clinical and laboratory findings at diagnosis in the group of B-ALL patients revealed an association between CD95 expression with lower white blood cell (WBC) numbers and bone marrow blasts (P<0.05). We detected a positive correlation between the expressions of CD95 and CD44 (r=0.445, P<0.01) in B-ALL patients. There was an association between CD20 expression and several poor prognostic factors that included increased extramedullary involvement (EMI) and decreased platelet numbers (P<0.008). The mean expression of CD34 in B-ALL was higher than T-ALL (P=0.004). At follow-up, complete remission duration (CRD) and survival duration did not significantly differ between patients who were positive or negative for each marker. Conclusion: Association of the studied molecules with several prognostic factors implies the significance of CD95 molecule as favorable and CD20 as unfavorable prognostic markers for childhood ALL. PMID:25755857

  18. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    PubMed

    Pinheiro, Dammy; Chang, Yu-Mei; Bryant, Hannah; Szladovits, Balazs; Dalessandri, Tim; Davison, Lucy J; Yallop, Elizabeth; Mills, Emily; Leo, Chiara; Lara, Ana; Stell, Anneliese; Polton, Gerry; Garden, Oliver A

    2014-01-01

    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  19. Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

    PubMed Central

    Fujimoto, Daichi; Kato, Ryoji; Morimoto, Takeshi; Shimizu, Ryoko; Sato, Yuki; Kogo, Mariko; Ito, Jiro; Teraoka, Shunsuke; Nagata, Kazuma; Nakagawa, Atsushi; Otsuka, Kojiro; Tomii, Keisuke

    2016-01-01

    Background Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently lacking. Methods We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital. Results A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09–2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3–7.2 months). Conclusions Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC. PMID:28006019

  20. Evolving transcriptomic fingerprint based on genome‐wide data as prognostic tools in prostate cancer

    PubMed Central

    Schliekelman, Mark; Shin, Heesun; Erho, Nicholas; Davicioni, Elai

    2015-01-01

    Background Information Prostate cancer (PCa) is a common disease but only a small subset of patients are at risk of developing metastasis and lethal disease, and identifying which patients will progress is challenging because of the heterogeneity underlying tumour progression. Understanding this heterogeneity at the molecular level and the resulting clinical impact is a critical step necessary for risk stratification. Defining genomic fingerprint elucidates molecular variation and may improve PCa risk stratification, providing more accurate prognostic information of tumour aggressiveness (or lethality) for prognostic biomarker development. Therefore, we explored transcriptomic differences between patients with indolent disease outcome and patients who developed metastasis post‐radical prostatectomy using genome‐wide expression data in the post radical prostatectomy clinical space before metastatic spread. Results Based on differential expression analysis, patients with adverse pathological findings who are at higher risk of developing metastasis have a distinct transcriptomic fingerprint that can be detected on surgically removed prostate specimens several years before metastasis detection. Nearly half of the transcriptomic fingerprint features were non‐coding RNA highlighting their pivotal role in PCa progression. Protein‐coding RNA features in the fingerprint are involved in multiple pathways including cell cycle, chromosome structure maintenance and cytoskeleton organisation. The metastatic transcriptomic fingerprint was determined in independent cohorts verifying the association between the fingerprint and metastatic patients. Further, the fingerprint was confirmed in metastasis lesions demonstrating that the fingerprint represents early metastatic transcriptomic changes, suggesting its utility as a prognostic tool to predict metastasis and provide clinical value in the early radical prostatectomy setting. Conclusions Here, we show that transcriptomic

  1. Impact of Hyperglycemia on Survival and Infection-Related Adverse Events in Patients with Metastatic Colorectal Cancer Who Were Receiving Palliative Chemotherapy

    PubMed Central

    Hong, Yong Joo; Han, Hye-Suk; Jeong, Yusook; Jeong, Jiwon; Lim, Sung-Nam; Choi, Hyung Jin; Jeon, Hyun-Jung; Oh, Tae-Keun; Lee, Sang-Jeon; Lee, Ki Hyeong

    2014-01-01

    Purpose Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. Materials and Methods We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. Results The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). Conclusion Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy. PMID:25038764

  2. Excellent Outcomes and Lack of Prognostic Impact of Cell of Origin for Localized Diffuse Large B-cell Lymphoma in the Rituximab Era

    PubMed Central

    Kumar, Anita; Lunning, Matthew A.; Zhang, Zhigang; Migliacci, Jocelyn C.; Moskowitz, Craig H.; Zelenetz, Andrew D.

    2015-01-01

    Summary Therapeutic options for limited-stage diffuse large B cell lymphoma (DLBCL) include short- or full-course R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) +/- radiotherapy. The optimal treatment remains unclear. The prognostic value of cell-of-origin (COO) in early stage DLBCL is unknown. Patients with limited-stage DLBCL (stage I or stage II, non-bulky) treated with R-CHOP +/- involved field radiotherapy (IFRT) from 1999 – 2012 were included. COO by the Hans algorithm was analysed in a subset of patients. Of 261 patients, 30% were stage I (N=82), 37% Stage IE (N=96), <1% stage IXEE (N=1), 18% stage II (N=46) and 14% Stage IIE (N=37). The stage-modified IPI stratified patients into prognostically relevant groups. There was no significant difference in progression-free survival (PFS) or overall survival (OS) for patients in the germinal centre B-cell-like (GCB; n=65) and non-GCB cohorts (n=22). Seventeen patients received R-CHOP x 3-4 cycles (Arm A), 147 received R-CHOP x 3-4 cycles + IFRT (Arm B), 48 received R-CHOP x6 cycles (Arm C), and 50 received R-CHOP x6 cycles +IFRT (Arm D). The outcomes were excellent, with 5-year PFS of 82% and 5-year OS of 93%, and were similar across the 4 treatment groups. In the rituximab era, outcomes for limited-stage DLBCL, regardless of treatment approach, were excellent. Baseline COO was not a significant prognostic factor in patients treated with short-course R-CHOP + IFRT. PMID:26456939

  3. Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer

    PubMed Central

    Hwang, Seong Bae; Lee, Hye Yoon; Kim, Hoon Yub

    2012-01-01

    Purpose Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. Methods We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. Results CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). Conclusion CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer. PMID:22493626

  4. Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

    PubMed Central

    Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella

    2014-01-01

    Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk. PMID:25373410

  5. Geospatial Strategy for Adverse Impact of Urban Heat Island in upper atmospheres of the earth Mountain Areas using LANDSAT ETM+ Sensors

    NASA Astrophysics Data System (ADS)

    Kumar, Amit; Vandana, Vandana

    2016-07-01

    We are living in the age of the rapidly growing population and changing environmental conditions with advanced technical capacity. This has been resulting in widespread land cover change. Among several human-induced environmental and urban thermal problems are reported to be negatively affecting urban residents in many ways. Urban Heat Islands exist in many large cities especially metropolitan cities and can significantly affect the permafrost layer in mountain areas. The adverse effect of urban heat island has become the subject of numerous studies in recent decades and is reflected in many major mountain cities around the world. The built-up structures in urbanized areas considerably alter land cover thereby affecting thermal energy flow which leads to the development of elevated surface and air temperature. The phenomenon Urban Heat Island implies 'island' of high temperature in cities, surrounded by relatively lower temperature in rural areas. The Urban Heat Island for the temporal period is estimated using geospatial techniques which are then utilized for the impact assessment of the climate of the surrounding regions and how it reduce the sustainability of the natural resources like air, vegetation. The knowledge of surface temperature is important for the study of urban climate and human health. The rapid growth of industries in peri-urban areas results in excessive warming and variations in weather conditions. It leads to soil degradation in frozen areas due to high temperature which leads to melting of snow in mountain areas Remotely sensed data of thermal infrared band in the region of 10.4-12.5 µm of EMR spectrum, available from LANDSAT- ETM+ is proved to be very helpful to identify urban heat islands. Thermal infrared data acquired during the daytime and night time can be used to monitor the heat island associated with urban areas as well as atmospheric pollution. The present paper describes the methodology and resolution dynamic urban heat island

  6. Ki-67 and PCNA Expression in Canine Mammary Tumors and Adjacent Nonneoplastic Mammary Glands: Prognostic Impact by a Multivariate Survival Analysis.

    PubMed

    Carvalho, M I; Pires, I; Prada, J; Lobo, L; Queiroga, F L

    2016-11-01

    The assessment of tumor proliferation has been considered a determining prognostic factor in canine mammary tumors (CMTs). However, no studies have assessed the prognostic importance of proliferation in adjacent nonneoplastic mammary glands. We included 64 CMTs (21 benign and 43 malignant) and studied the proliferation index (PI) of Ki-67 and proliferating cell nuclear antigen (PCNA) together with several clinicopathological characteristics. A positive and statistically significant correlation between the PI of Ki-67 and PCNA in tumors and adjacent nonneoplastic mammary glands was observed in benign and malignant tumors. Tumor size, skin ulceration, histological type, mitotic index, nuclear grade, differentiation grade, histological grade of malignancy, lymph node metastasis, Ki-67, and PCNA expression in tumors and adjacent nonneoplastic mammary glands were statistically associated with overall survival by univariate analysis in malignant cases (n = 43). Histological grade of malignancy and high intratumoral PCNA retained their significance by multivariate analysis arising as independent predictors of overall survival. Interestingly, the PI of Ki-67 and PCNA of adjacent nontumoral mammary glands were associated with clinicopathological features of tumor aggressiveness and shorter overall survival, demonstrating the need to better explore this adjacent non-neoplastic tissue.

  7. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  8. Prognostics of Power MOSFET

    NASA Technical Reports Server (NTRS)

    Celaya, Jose Ramon; Saxena, Abhinav; Vashchenko, Vladislay; Saha, Sankalita; Goebel, Kai Frank

    2011-01-01

    This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as a precursor of failure due to its dependence on junction temperature. The experimental data is augmented with a finite element analysis simulation that is based on a two-transistor model. The simulation assists in the interpretation of the degradation phenomena and SOA (safe operation area) change.

  9. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  10. Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with a Prognostic Impact on Survival and Those of Viral Origin

    PubMed Central

    Herman, Ana; Gruden, Kristina; Blejec, Andrej; Podpečan, Vid; Motaln, Helena; Rožman, Primož; Hren, Matjaž; Zupančič, Klemen; Veber, Matija; Verbovšek, Urška; Lah Turnšek, Tamara; Porčnik, Andrej; Koršič, Marjan; Knežević, Miomir; Jeras, Matjaž

    2015-01-01

    Background Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis in spite of a plethora of established diagnostic and prognostic biomarkers and treatment modalities. Therefore, the current goal is the detection of novel biomarkers, possibly detectable in the blood of GBM patients that may enable an early diagnosis and are potential therapeutic targets, leading to more efficient interventions. Experimental Procedures MicroRNA profiling of 734 human and human-associated viral miRNAs was performed on blood plasma samples from 16 healthy individuals and 16 patients with GBM, using the nCounter miRNA Expression Assay Kits. Results We identified 19 miRNAs with significantly different plasma levels in GBM patients, compared to the healthy individuals group with the difference limited by a factor of 2. Additionally, 11 viral miRNAs were found differentially expressed in plasma of GBM patients and 24 miRNA levels significantly correlated with the patients’ survival. Moreover, the overlap between the group of candidate miRNAs for diagnostic biomarkers and the group of miRNAs associated with survival, consisted of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa miR 592 and hsa miR 514a 3p have not been previously described in GBM and represent novel candidates for selective biomarkers. The possible signalling, induced by the revealed miRNAs is discussed, including those of viral origin, and in particular those related to the impaired immune response in the progression of GBM. Conclusion The GBM burden is reflected in the alteration of the plasma miRNAs pattern, including viral miRNAs, representing the potential for future clinical application. Therefore proposed biomarker candidate miRNAs should be validated in a larger study of an independent cohort of patients. PMID:25950799

  11. Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

    SciTech Connect

    Selz, Jessica; Stevens, Denise; Jouanneau, Ludivine; Labib, Alain; Le Scodan, Romuald

    2012-12-01

    Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

  12. Explaining Disproportionately High Rates of Adverse Birth Outcomes among African Americans: The Impact of Stress, Racism, and Related Factors in Pregnancy

    ERIC Educational Resources Information Center

    Giscombe, Cheryl L.; Lobel, Marci

    2005-01-01

    Compared with European Americans, African American infants experience disproportionately high rates of low birth weight and preterm delivery and are more than twice as likely to die during their 1st year of life. The authors examine 5 explanations for these differences in rates of adverse birth outcomes: (a) ethnic differences in health behaviors…

  13. Adverse events in healthcare: learning from mistakes.

    PubMed

    Rafter, N; Hickey, A; Condell, S; Conroy, R; O'Connor, P; Vaughan, D; Williams, D

    2015-04-01

    Large national reviews of patient charts estimate that approximately 10% of hospital admissions are associated with an adverse event (defined as an injury resulting in prolonged hospitalization, disability or death, caused by healthcare management). Apart from having a significant impact on patient morbidity and mortality, adverse events also result in increased healthcare costs due to longer hospital stays. Furthermore, a substantial proportion of adverse events are preventable. Through identifying the nature and rate of adverse events, initiatives to improve care can be developed. A variety of methods exist to gather adverse event data both retrospectively and prospectively but these do not necessarily capture the same events and there is variability in the definition of an adverse event. For example, hospital incident reporting collects only a very small fraction of the adverse events found in retrospective chart reviews. Until there are systematic methods to identify adverse events, progress in patient safety cannot be reliably measured. This review aims to discuss the need for a safety culture that can learn from adverse events, describe ways to measure adverse events, and comment on why current adverse event monitoring is unable to demonstrate trends in patient safety.

  14. [Clinical survey of tizanidine-induced adverse effects--impact of concomitant drugs providing cytochrome P450 1A2 modification--].

    PubMed

    Momo, Kenji; Homma, Masato; Matsumoto, Sayaka; Sasaki, Tadanori; Kohda, Yukinao

    2013-01-01

    The drug-drug interactions of tizanidine and cytochrome (CYP) P450 1A2 inhibitors, which potentially alter the hepatic metabolism of tizanidine, were investigated by retrospective survey of medical records with regard to prescription. One thousand five hundred sixty-three patients treated with tizanidine at University of Tsukuba Hospital were investigated. Of those, 713 patients (45.6%) were treated with coadministration of tizanidine and CYP1A2 inhibitors (37 drugs). The patients who received a combination of tizanidine and CYP1A2 inhibitors were characterized as elderly, having multiple diseases, and taking a large number of comedications (over 10 drugs) for a long period as compared with the patients who did not receive CYP1A2 inhibitors. Tizanidine-induced adverse effects were examined in 100 patients treated with coadministration of tizanidine and 8 CYP1A2 inhibitors. Adverse effects (e.g., drowsiness: 10 patients; low blood pressure: 9 patients; low heart rate: 9 patients) were observed in 23 patients (23%) 8±10 days after CYP1A2 inhibitors were coadministered. The patients with tizanidine-induced adverse effects were of older age (64.3±9.8 vs. 57.5±18.1 years, p<0.05) and received a higher daily dose of tizanidine (3.00±0.74 vs. 2.56±0.86 mg/day, p<0.05) than the patients without adverse effects. The present results suggest that coadministration of tizanidine and CYP1A2 inhibitors enhances tizanidine-induced adverse effects, especially in elderly patients treated with a higher dose of tizanidine.

  15. Significance Analysis of Prognostic Signatures

    PubMed Central

    Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

    2013-01-01

    A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated

  16. Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis.

    PubMed

    Fujimoto, Daichi; Ueda, Hiroyuki; Shimizu, Ryoko; Kato, Ryoji; Otoshi, Takehiro; Kawamura, Takahisa; Tamai, Koji; Shibata, Yumi; Matsumoto, Takeshi; Nagata, Kazuma; Otsuka, Kyoko; Nakagawa, Atsushi; Otsuka, Kojiro; Katakami, Nobuyuki; Tomii, Keisuke

    2014-06-01

    Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1-93) versus 2 (1-32) median (range), P = 0.023; bone, 3 (1-43) versus 2 (1-27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17-3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37-3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS.

  17. GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

    PubMed

    Mosaad, Youssef M; Elashery, Rasha; Darwish, Ahmad; Sharaf Eldein, Omar A; Barakat, Tarek; Marouf, Samy; Abou El-Khier, Noha T; Youssef, Laila F; Fawzy, Iman M

    2017-03-01

    To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.

  18. Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

    SciTech Connect

    Lopez Guerra, Jose Luis; Zhuang, Yan; Hong, David S.; Heymach, John V.; Swisher, Stephen G.; Lin, Steven H.; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    2012-09-01

    Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed better overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.

  19. Whole genome expression profiling of blood cells in ovarian cancer patients -prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14.

    PubMed

    Isaksson, Helena S; Sorbe, Bengt; Nilsson, Torbjörn K

    2014-06-30

    Ovarian cancer patients with different tumor stages and cell differentiation might be distinguished from each other by gene expression profiles in whole blood cell mRNA by the Affymetrix Human Gene 1.0 ST Array. We also examined if there is any association with other clinical variables, response to therapy, and residual tumor burden after surgery. Patients were divided into two groups, one with poor prognosis, advanced stage and poorly differentiated tumors (n = 22), and one group with good prognosis, early stage and well- to medium differentiated tumors (n = 11). Six genes were found to be differentially expressed: the PDIA3, LYAR, NOP14, NCALD and MTSS1 genes were down-regulated and the CYP1B1 gene expression was up-regulated in the poor prognosis group, all with p value <0.05, adjusted for mass comparison. In survival analyses, CYP1B1, MTSS1, NCALD and NOP14 remained significantly different (p<0.05). Patient groups did not differ in any transcript related to acute phase or immune responses. This minimal gene expression signature of prognostic ovarian cancer-related genes opens up an avenue for more practicable monitoring of ovarian cancer patients by simple peripheral blood tests, which may evolve into a tool to guide selection of curative and postoperative supportive therapies.

  20. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  1. Prognostic impact of polymorphism of matrix metalloproteinase-2 and metalloproteinase tissue inhibitor-2 promoters in breast cancer in Tunisia: case-control study.

    PubMed

    Ben Néjima, Dalel; Ben Zarkouna, Yosr; Gammoudi, Amor; Manai, Mohamed; Boussen, Hamouda

    2015-05-01

    Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) polymorphism in Tunisian breast cancer patients. MMP-2 genotypes were determined by real-time polymerase chain reaction (RT-PCR), and TIMP-2 genotypes were identified using a PCR-restriction fragment length polymorphism (RFLP) method in 210 breast cancer patients and 250 frequency-matched control women. Association of the clinicopathological parameters and the genetic markers with risk of breast cancer was assessed using univariate analyses. We found that the variant MMP-2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.49; 95 % confidence interval (95 % CI), 0.033-0.73], compared with the CC genotype. For TIMP-2, a moderately reduced risk of the cancer (OR, 0.57; 95 % CI, 0.37-0.87) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, polymorphisms in both genes seem to have additive effects and the highest risk for breast cancer has been observed in those with MMP-2 CC genotype and TIMP-2 GC or CC genotype (p = 0.006). A significant association was also found between the CC genotype and the aggressive forms of breast cancer as defined by advanced stages at the time of diagnosis and metastasis. This is the first report on the association of MMP-2 and TIMP-2 gene polymorphisms in breast cancer in Tunisian population. Our results suggest that the presence of the variant allele in the promoter of MMP-2 or TIMP-2 may be a protective factor for the development of breast cancer.

  2. Prognostic impact of human leukocyte antigen class I expression and association of platinum resistance with immunologic profiles in epithelial ovarian cancer.

    PubMed

    Mariya, Tasuku; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Asano, Takuya; Kuroda, Takafumi; Yasuda, Kazuyo; Mizuuchi, Masahito; Sonoda, Tomoko; Saito, Tsuyoshi; Sato, Noriyuki

    2014-12-01

    Epithelial ovarian cancer (EOC) is one of the most deadly carcinomas in females. Immune systems can recognize EOCs; however, a defect of human leukocyte antigen (HLA) class I expression is known to be a major mechanism for escape from immune systems, resulting in poor prognosis. The purpose of this study is to identify novel correlations between immunologic responses and other clinical factors. We investigated the expression of immunologic components in 122 cases of EOCs for which surgical operations were performed between 2001 and 2011. We immunohistochemically stained EOC specimens using an anti-pan HLA class I monoclonal antibody (EMR8-5) and anti-CD3, -CD4, and -CD8 antibodies, and we analyzed correlations between immunologic parameters and clinical factors. In multivariate analysis that used the Cox proportional hazards model, independent prognostic factors for overall survival in advanced EOCs included low expression level of HLA class I [risk ratio (RR), 1.97; 95% confidence interval (CI), 1.01-3.83; P = 0.046] and loss of intraepithelial cytotoxic T lymphocyte (CTL) infiltration (RR, 2.11; 95% CI, 1.06-4.20; P = 0.033). Interestingly, almost all platinum-resistant cases showed a significantly low rate of intraepithelial CTL infiltration in the χ(2) test (positive vs. negative: 9.0% vs. 97.7%; P < 0.001). Results from a logistic regression model revealed that low CTL infiltration rate was an independent factor of platinum resistance in multivariate analysis (OR, 3.77; 95% CI, 1.08-13.12; P = 0.037). Platinum-resistant EOCs show poor immunologic responses. The immune escape system of EOCs may be one of the mechanisms of platinum resistance.

  3. Prognostic Impact of the Presence and Absence of Angina on Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Stable Coronary Artery Disease

    PubMed Central

    Dagenais, Gilles R.; Lu, Jiang; Faxon, David P.; Bogaty, Peter; Adler, Dale; Fuentes, Francisco; Escobedo, Jorge; Krishnaswami, Ashok; Slater, James; Frye, Robert L.

    2013-01-01

    Objectives The purpose of this analysis was to assess in patients with type 2 diabetes and stable coronary artery disease (CAD) whether the risk of all-cause mortality and cardiovascular events varied according to the presence or absence of angina and angina equivalent symptoms. Background Data on the prognostic value of symptoms in these patients are limited. Methods Post-hoc analysis was performed in 2,364 patients with type 2 diabetes and documented CAD enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial to determine the occurrence of death and composite of death, myocardial infarction, and stroke during a 5-year follow-up according to cardiac symptoms at baseline. Results There were 1,434 patients with angina (A), 506 with angina equivalents (E), and 424 with neither of these (N). The cumulative death rates (total 316) were 12% in A, 14% in E, and 10% in N (p = 0.3), and cardiovascular composite rates (total 548) were 24% in A, 24% in E, and 21% in N (p =0.5). Compared with N, the hazard ratios adjusted for confounders were not different for death in A (1.11; 99% CI: 0.81 to 1.53) and E (1.17; 99% CI: 0.81 to 1.68) or for cardiovascular events in A (1.17; 99% CI: 0.92 to 1.50) and E (1.11; 99% CI: 0.84 to 1.48). Conclusions Whatever their symptom status, patients with type 2 diabetes and stable CAD were at similar risk of cardiovascular events and death. These findings suggest that these patients may be similarly managed in terms of risk stratification and preventive therapies. (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) PMID:23410541

  4. Prognostic impact of hormone receptor- and HER2-defined subtypes in inflammatory breast cancer treated with high-dose chemotherapy: a retrospective study

    PubMed Central

    Boudin, Laurys; Gonçalves, Anthony; Sfumato, Patrick; Sabatier, Renaud; Bertucci, François; Tarpin, Carole; Provansal, Magali; Houvenaeghel, Gilles; Lambaudie, Eric; Tallet, Agnes; Resbeut, Michel; Charafe-Jauffret, Emmanuelle; Calmels, Boris; Lemarie, Claude; Boher, Jean-Marie; Extra, Jean-Marc; Viens, Patrice; Chabannon, Christian

    2016-01-01

    Purpose: Studies examining high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC-AHSCT) strategies in inflammatory breast cancer (IBC), showed encouraging results in terms of disease-free survival (DFS), and overall survival (OS). The lack of data regarding HER2 status in all of these studies prevented any prognostic analysis involving breast cancer subtypes. Methods: All consecutive female patients treated for IBC with HDC and AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. Since 2005, trastuzumab was included in initial treatment. Patient, tumor and treatment characteristics were collected. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: Luminal, (HR+/HER2-), HER2 (HER2+, any HR), and triple negative (TN) (HER2- and HR-). The main objective was the analysis of OS according to the IHC subtypes. Results: Sixty-seven patients were included. Eleven patients received trastuzumab. Median follow up was 80.04 months (95% CI 73.2-88.08). Five-year OS and DFS for the whole population patients were 74% (95% CI 61-83) and 65 % (95% CI 52-75), respectively. OS differed across subtypes (p=0.057) : HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89% (95% CI 64-97) compared to 57% (95% CI 33-76) for the TN subgroup (HR 5.38, 95% CI 1.14-25.44; p=0.034). Conclusions: In IBC patients receiving HDC-AHSCT, OS favorably compares with data available in the literature on similar groups of patients. TN patients carried the least favourable OS and HER2 patients, half of them also receiving trastuzumab, had the best outcome. These findings provide additional information and options for patients with IBC and who could potentially benefit of HDC-AHSCT. PMID:27877223

  5. Clinical Outcome of Breast Conservation Therapy for Breast Cancer in Hong Kong: Prognostic Impact of Ipsilateral Breast Tumor Recurrence and 2005 St. Gallen Risk Categories

    SciTech Connect

    Yau, T.-K. . E-mail: tkokyau@gmail.com; Soong, Inda S.; Chan, K.; Chan, M.; Cheung, P.; Lau, H.W.; Chang, Amy T.Y.; Lee, Anne W.M.

    2007-07-01

    Purpose: The aim of this study was to evaluate the clinical outcome of breast conservation therapy (BCT) for invasive breast cancers in our predominantly Chinese population. Methods and Materials: Clinical outcomes of 412 T1-2 invasive breast cancers treated by wide local excision and external radiotherapy from 1994 to 2003 were retrospectively analyzed. Only 7% lesions were first detected by mammograms. Adjuvant tamoxifen and chemotherapy were added in 74% and 45% patients, respectively. Results: The median follow-up was 5.4 years. The 5-year actuarial ipsilateral breast tumor recurrence (IBTR) rate, distant failure-free survival, cause-specific survival, and overall survival were 4%, 92%, 96%, and 98%, respectively. The 5-year distant failure-free survival for the low-risk, intermediate-risk, and high-risk categories (2005 St. Gallen) were 98%, 91%, and 80%, respectively (p 0.0003). Cosmetic results were good to excellent in more than 90% of the assessable patients. Grade 3 histology (hazard ratio [HR], 4.461; 95% CI, 1.216-16.360; p = 0.024), age (HR, 0.915; 95% CI, 0.846-0.990; p = 0.027), and close/positive final margins (HR, 3.499; 95% CI, 1.141-10.729; p = 0.028) were significant independent risk factors for IBTR. Both St. Gallen risk categories (p = 0.003) and IBTR (HR, 5.885; 95% CI, 2.494-13.889; p < 0.0005) were independent prognostic factors for distant failure-free survival. Conclusions: Despite the low percentage of mammographically detected lesions, the overall clinical outcome of BCT for invasive breast cancers in the Chinese population is comparable to the Western series. The 2005 St. Gallen risk category is a promising clinical tool, but further validation by large studies is warranted.

  6. Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy

    PubMed Central

    Mordhorst, Louise Bohr; Ahlin, Cecilia; Sorbe, Bengt

    2016-01-01

    Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined. Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining. The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis. PMID:27577083

  7. Prognostic models in acute pulmonary embolism: a systematic review and meta-analysis

    PubMed Central

    Elias, Antoine; Mallett, Susan; Daoud-Elias, Marie; Poggi, Jean-Noël; Clarke, Mike

    2016-01-01

    Objective To review the evidence for existing prognostic models in acute pulmonary embolism (PE) and determine how valid and useful they are for predicting patient outcomes. Design Systematic review and meta-analysis. Data sources OVID MEDLINE and EMBASE, and The Cochrane Library from inception to July 2014, and sources of grey literature. Eligibility criteria Studies aiming at constructing, validating, updating or studying the impact of prognostic models to predict all-cause death, PE-related death or venous thromboembolic events up to a 3-month follow-up in patients with an acute symptomatic PE. Data extraction Study characteristics and study quality using prognostic criteria. Studies were selected and data extracted by 2 reviewers. Data analysis Summary estimates (95% CI) for proportion of risk groups and event rates within risk groups, and accuracy. Results We included 71 studies (44 298 patients). Among them, 17 were model construction studies specific to PE prognosis. The most validated models were the PE Severity Index (PESI) and its simplified version (sPESI). The overall 30-day mortality rate was 2.3% (1.7% to 2.9%) in the low-risk group and 11.4% (9.9% to 13.1%) in the high-risk group for PESI (9 studies), and 1.5% (0.9% to 2.5%) in the low-risk group and 10.7% (8.8% to12.9%) in the high-risk group for sPESI (11 studies). PESI has proved clinically useful in an impact study. Shifting the cut-off or using novel and updated models specifically developed for normotensive PE improves the ability for identifying patients at lower risk for early death or adverse outcome (0.5–1%) and those at higher risk (up to 20–29% of event rate). Conclusions We provide evidence-based information about the validity and utility of the existing prognostic models in acute PE that may be helpful for identifying patients at low risk. Novel models seem attractive for the high-risk normotensive PE but need to be externally validated then be assessed in impact studies. PMID

  8. Prognostic impact of the tumor-infiltrating regulatory T-cell (Foxp3+)/activated cytotoxic T lymphocyte (granzyme B+) ratio on resected left-sided pancreatic cancer

    PubMed Central

    Hwang, Ho Kyoung; Kim, Hyoung-Il; Kim, Se Hoon; Choi, Junjeong; Kang, Chang Moo; Kim, Kyung Sik; Lee, Woo Jung

    2016-01-01

    Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B+) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)+] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study. TIL subsets were enumerated by immunohistochemical staining for cluster of differentiation (CD)3, CD4, CD8, Foxp3 and granzyme B in the intra-tumoral areas of tissue blocks. Patients were divided into two groups according to the median value of the absolute counts and relative ratios of TIL subsets. In the univariate analysis, age, gender, tumor size, nodal stage, tumor differentiation and lymphovascular/perineural invasion were not significantly associated with survival outcome. However, low levels of preoperative cancer antigen (CA) 19–9 were associated with a longer overall survival (OS), although the association was not significant (37 vs. 18 months; P=0.061). A high level of granzyme B+ was associated with enhanced disease-free survival (DFS) (25 vs. 10 months; P=0.023), and a low Foxp3+/granzyme B+ ratio was associated with a favorable prognosis in terms of DFS (25 vs. 8 months; P=0.008) and OS (47 vs. 17 months; P=0.003). In the multivariate analysis, the ratio of Foxp3+/granzyme B+ was an independent prognostic factor for determining DFS [Exp(B), 3.060; 95% confidence interval (CI), 1.259–47.436; P=0.014] and OS [Exp(B), 3.580; 95% CI, 1.460–8.780; P=0.005]. Among the clinicopathological factors, low levels of CA 19–9 were significantly associated with a low Foxp3+/granzyme B+ ratio (P=0.016). The results of the present study suggested that a low Foxp3

  9. Are food insecurity's health impacts underestimated in the U.S. population? Marginal food security also predicts adverse health outcomes in young U.S. children and mothers.

    PubMed

    Cook, John T; Black, Maureen; Chilton, Mariana; Cutts, Diana; Ettinger de Cuba, Stephanie; Heeren, Timothy C; Rose-Jacobs, Ruth; Sandel, Megan; Casey, Patrick H; Coleman, Sharon; Weiss, Ingrid; Frank, Deborah A

    2013-01-01

    This review addresses epidemiological, public health, and social policy implications of categorizing young children and their adult female caregivers in the United States as food secure when they live in households with "marginal food security," as indicated by the U.S. Household Food Security Survey Module. Existing literature shows that households in the US with marginal food security are more like food-insecure households than food-secure households. Similarities include socio-demographic characteristics, psychosocial profiles, and patterns of disease and health risk. Building on existing knowledge, we present new research on associations of marginal food security with health and developmental risks in young children (<48 mo) and health in their female caregivers. Marginal food security is positively associated with adverse health outcomes compared with food security, but the strength of the associations is weaker than that for food insecurity as usually defined in the US. Nonoverlapping CIs, when comparing odds of marginally food-secure children's fair/poor health and developmental risk and caregivers' depressive symptoms and fair/poor health with those in food-secure and -insecure families, indicate associations of marginal food security significantly and distinctly intermediate between those of food security and food insecurity. Evidence from reviewed research and the new research presented indicates that households with marginal food security should not be classified as food secure, as is the current practice, but should be reported in a separate discrete category. These findings highlight the potential underestimation of the prevalence of adverse health outcomes associated with exposure to lack of enough food for an active, healthy life in the US and indicate an even greater need for preventive action and policies to limit and reduce exposure among children and mothers.

  10. Exposure of Particulate Matters PM10 and PM2.5 to Pregnant Ladies during First Trimester and its Impact on Adverse Birth Outcomes in Delhi, India

    NASA Astrophysics Data System (ADS)

    Kumar, S.; Goyal, P.

    2015-12-01

    The incessant exposure to criteria air pollutants at different level of concentrations is associated with adverse birth outcomes. The present study advocates the importance of the early period of pregnancy (first trimester) for association between growth in term of small gestational age (SGA) and birth weight (BW) with PM2.5 and PM10 for megacity Delhi. The association of PM10 and PM2.5 average concentration, SGA, pre term birth (PTB) and lower birth weight (LBW < 2500g or 5.5 pounds) outcomes have been investigated among 1749 live births in a large hospital during the year 2012 New Delhi, India. The air pollutants PM2.5 and PM10 have been used in single pollutant logistic regression models to estimate odds ratios (OR) for these outcomes. Growth in term of SGA is associated with PM2.5 levels (OR = 0.99, confidence interval (CI) = 0.99 - 1.0) and PM10 levels (OR= 0.99, CI= 0.99 - 1.001) in the first trimester of pregnancy. Birth weight outcome in terms of lower birth weight (LBW) has been found to be significantly associated with PM2.5 (OR= 0.99, CI = 0.98 - 1.00) exposure in the first trimester. A very significant decrease of 0.1% has been observed in growth of infant in terms of SGA with per 10 mg/m3 increase in PM2.5. Also, 0.1 % statistically significant adverse association of BW in terms of LBW has been found with per 10 mg/m3 increased vulnerability of PM2.5 during first trimester of gestation.

  11. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis.

    PubMed

    Ocio, E M; Schop, R F J; Gonzalez, B; Van Wier, S A; Hernandez-Rivas, J M; Gutierrez, N C; Garcia-Sanz, R; Moro, M J; Aguilera, C; Hernandez, J; Xu, R; Greipp, P R; Dispenzieri, A; Jalal, S M; Lacy, M Q; Gonzalez-Paz, N; Gertz, M A; San Miguel, J F; Fonseca, R

    2007-01-01

    Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.

  12. Synergistic childhood adversities and complex adult psychopathology.

    PubMed

    Putnam, Karen T; Harris, William W; Putnam, Frank W

    2013-08-01

    Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.

  13. Tourism Impacts of Three Mile Island and Other Adverse Events: Implications for Lincoln County and Other Rural Counties Bisected by Radioactive Wastes Intended for Yucca Mountain.

    ERIC Educational Resources Information Center

    Himmelberger, Jeffery J.; And Others

    1995-01-01

    Summarizes key research implications of Three Mile Island and other major hazard events as related to tourism. Examines how the proposed Yucca Mountain nuclear waste repository system will impact tourism in southern Nevada and other visitor-oriented rural counties bisected by planned waste transportation corridors. (AIM)

  14. [Prognostic factors in acute nonlymphoid leukemias].

    PubMed

    Capelli, D; Tedeschi, A; Montillo, M; Corvatta, L; Bartocci, C; Montroni, M; Leoni, P

    1996-10-01

    Our retrospective study was aimed at assessing parameters affecting the prognosis of acute non lymphoid leukemia (ANLL). Since 1988 to 1994 we observed 84 patients: 52 males, 32 females. For each patient we considered at diagnosis: age, fever, performance status, platelets, hemoglobin and white blood cell count, extramidollary disease, bone marrow blastosis, phenotype and cytogenetic abnormalities of blasts cells. All the parameters listed above were correlated with the time to achieve the complete remission (CR), CR duration and the overall survival. Statistical tests as t-student and chi square test were used. Statistical analysis of the parameters considered revealed that the only value affecting the achievement of a CR was the age. The prognostic significance of immunophenotyping in ANLL has been a controversial issue, with a number of conflicting reports. In our study only the terminal deoxynucleotidyl transferase was significantly associated with prognosis. Our study, as data reported in literature, confirms that the prognostic impact of the various parameters in ANLL is controversial. The study of prognostic factors and of the immunophenotype is important to identify the clinical and the biologic profile of the disease and to evaluate the optimal post-remission treatment.

  15. Trading places - an innovative SO{sub 2} trading program to mitigate potential adverse impacts on class I areas: part II. Mitigation plan

    SciTech Connect

    Louis Militana; Cindy Huber; Christopher Colbert; Chris Arrington; Don Shepherd

    2005-08-01

    This is the second of two articles describing a plan that was developed to mitigate the effects of acid deposition and visibility impairment in four Class I areas from the proposed Longview Power Project. Part I (published in July 2005) discussed the air quality impacts of the proposed coal-fired power plant. Part II discusses the mitigation plan. 2 refs., 1 fig., 3 tabs.

  16. Machine perfusion following static cold storage preservation in kidney transplantation: donor-matched pair analysis of the prognostic impact of longer pump time.

    PubMed

    Ciancio, Gaetano; Gaynor, Jeffrey J; Sageshima, Junichiro; Roth, David; Kupin, Warren; Guerra, Giselle; Tueros, Lissett; Zarak, Alberto; Hanson, Lois; Ganz, Susan; Chen, Linda; Ruiz, Phillip; Livingstone, Alan S; Burke, George W

    2012-01-01

    The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar's test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared. Mean ± SD pump times for paired recipients with first and second kidneys were 22.7 ± 7.3 h and 31.2 ± 7.9 h, respectively (mean difference: 8.5 ± 4.5 h, P < .000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post-transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom-from-BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor-matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes.

  17. Prognostic Scores for Acute Pulmonary Embolism.

    PubMed

    Morillo, Raquel; Moores, Lisa; Jiménez, David

    2017-02-06

    Rapid and accurate risk stratification is critical in determining the optimal treatment strategy for patients with acute pulmonary embolism (PE). Early identification of patients with normal blood pressure and a favorable prognosis (low-risk PE) might select a subset of patients for outpatient treatment, which is associated with reduced cost and improved patient satisfaction, and has been shown to be effective and safe. Alternatively, identification of normotensive patients deemed as having a high risk for PE-related adverse clinical events (intermediate-high-risk PE) might select a subset of patients for close observation and consideration of escalation of therapy. Clinical prognostic scores have been gaining importance in the classification of patients into these categories. They should be derived and validated following strict methodological standards, and their use in clinical practice should be encouraged.

  18. Drug-induced blood consumption: the impact of adverse drug reactions on demand for blood components in German departments of internal medicine.

    PubMed

    Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Thuermann, Petra A; Hasford, Joerg

    2012-10-01

    Therapy for adverse drug reactions (ADRs) often results in the application of blood components. This study aims to assess the demand for blood components and the resulting economic burden (hospital perspective) in German hospitals induced by ADRs leading to admissions to departments of internal medicine. In this prospective study, ADRs leading to hospitalization were surveyed in four regional pharmacovigilance centres in Germany during the years 2000-2007. ADRs assessed as 'possible', 'likely' or 'very likely' were included. Market prices for blood components and hospitalization data were determined by desktop research. A probabilistic sensitivity analysis was performed. A total of 6099 patients were admitted to internal medicine departments because of an outpatient ADR of whom 1165 patients (19.1%; mean age, 73.0 ± 13.0 years) required treatment with blood components owing to major bleeding events. Overall consumption was 4185 erythrocyte concentrates (EC), 426 fresh frozen plasma (FFP) and 48 thrombocyte (TC) units. On the basis of statistical hospital data, we estimated a nationwide demand of approximately 132,020 EC, 13,440 FFP and 1515 TC units, resulting in total costs of €12.66 million per year for all German hospitals. Some 19.2% of all ADR cases were assessed as preventable. Theoretically, a nationwide decreased demand for blood components and a savings potential of €2.43 million per year could be achieved by preventing ADRs in Germany. Blood components are used in one-fifth (mainly gastrointestinal bleeding) of all ADRs, leading to hospitalizations in internal medicine departments. Both blood demand and hospital procurement costs can be significantly lowered by preventing ADRs.

  19. [Immune response and digestive cancers: Prognostic and therapeutic implications].

    PubMed

    Bibeau, Frédéric; Bazille, Céline; Svrcek, Magali; Pierson, Rémi; Lagorce-Pagès, Christine; Cohen, Romain; André, Thierry

    2017-02-01

    The aim of this article is to emphasize the impact of the immune response in digestive cancers, especially from colorectal (CRC) origin. In this setting, an adaptive lymphocytic infiltrate underlines the prognostic impact of the immune response, because it is associated to a favorable outcome. The next challenge will be to validate, in a prospective therapeutic trial, the integration of the immune response as decisional parameter for adjuvant therapy. The immune response is also a predictive parameter in microsatellite instable metastatic CRC, characterized by an adaptive lymphocytic infiltrate, leading to a very high response rate to immune therapies. However, prognostic and predictive biomarkers still need to be optimized in order to better select patients. These data are also valuable for digestive non-colorectal cancers, which are briefly analyzed. The methodology for the assessment of these prognostic and predictive biomarkers, which represents an important issue in precision medicine, is also discussed.

  20. [Clinical usefulness of ondansetron hydrochloride for nausea and vomiting during repeated courses of chemotherapy for malignant lymphoma--impact of prognosis announcement on anti-emetic effect and evaluation of patient perception of chemotherapy-associated adverse events].

    PubMed

    Kodama, Fumio; Mohri, Hiroshi; Motomura, Shigeki; Fukawa, Hitoshi; Tanabe, Juichi; Koharasawa, Hideyuki; Kanamori, Heiwa; Hashimoto, Yoshimi; Harano, Hiroshi; Sakai, Rika; Tomita, Naoto; Fujimaki, Katsumichi; Takemura, Sachiya; Hattori, Michiko

    2002-02-01

    We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.

  1. D-Dimer elevation and adverse outcomes.

    PubMed

    Halaby, Rim; Popma, Christopher J; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel Z; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, C Michael

    2015-01-01

    D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

  2. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  3. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients

    PubMed Central

    Nattenmüller, Johanna; Wochner, Raoul; Muley, Thomas; Steins, Martin; Hummler, Simone; Teucher, Birgit; Wiskemann, Joachim; Kauczor, Hans-Ulrich; Wielpütz, Mark Oliver; Heussel, Claus Peter

    2017-01-01

    Introduction Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. Methods In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. Results We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05–0.001), while there were decreases in MA, MD and BMI (p<0.05–0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001). Conclusions After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity. PMID

  4. Prognostic Biomarkers in Ovarian Cancer

    PubMed Central

    Huang, Jie; Hu, Wei; Sood, Anil K

    2014-01-01

    Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID:22045356

  5. Comparison of three prognostic scoring systems in a series of 146 cases of chronic myelomonocytic leukemia (CMML): MD Anderson prognostic score (MDAPS), CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model. A detailed review of prognostic factors in CMML.

    PubMed

    Calvo, Xavier; Nomdedeu, Meritxell; Santacruz, Rodrigo; Martínez, Núria; Costa, Dolors; Pereira, Arturo; Estrada, Natalia; Xicoy, Blanca; Esteve, Jordi; Nomdedeu, Benet

    2015-07-23

    Although specific prognostic models for chronic myelomonocytic leukemia (CMML) exist, few are based on large series of patients. MD Anderson prognostic score (MDAPS) has been the most useful for CMML risk assessment. Due to recent emergence of CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model, we compared the three scores. One hundred forty-six CMML patients diagnosed between 1998 and 2014 were retrospectively analyzed. Univariate analysis was performed to assess prognostic impact on overall survival (OS) and leukemia-free survival (LFS) of the variables composing the scores and all items showed prognostic value on OS with the exception of the presence of circulating immature myeloid cells. Regarding LFS, only CPSS variables, bone marrow blast ≥10% and an absolute monocyte count >10×10(9)/L had an impact. When the scores were applied, all showed an impact on OS and retained their significance in multivariate analysis. By using ROC curves and C-index, CPSS showed a slightly better predictive value for mortality and leukemia transformation. Variables composing the three indexes were compared in multivariate analysis and only CPSS parameters and platelets<100×10(9)/L retained their significance. Based on these findings, by adding platelet count to CPSS, a new score was implemented (CPSS-P) showing the best risk prediction capability in our series. This study reinforces the validity of the tested scores.

  6. Current United States Department of Agriculture-Agricultural Research Service research on understanding agrochemical fate and transport to prevent and mitigate adverse environmental impacts.

    PubMed

    Hapeman, Cathleen J; McConnell, Laura L; Rice, Clifford P; Sadeghi, Ali M; Schmidt, Walter F; McCarty, Gregory W; Starr, James L; Rice, Pamela J; Angier, Jonathan T; Harman-Fetcho, J A

    2003-01-01

    Environmentally and economically viable agriculture requires a variety of cultivation practices and pest management options as no one system will be appropriate for every situation. Agrochemicals are some of the many pest control tools used in an integrated approach to pest management. They are applied with the intent of maximizing efficacy while minimizing off-site movement; however, their judicious use demands a practical knowledge of their fate and effects in agricultural and natural ecosystems. Agrochemical distribution into environmental compartments is influenced by the physical and chemical properties of the agrochemical and environmental conditions, ie soil type and structure, and meteorological conditions. Agricultural Research Service (ARS) researchers working in the area of agrochemical fate have focused on accurately describing those processes that govern the transport, degradation and bioavailability of these chemicals under conditions reflecting actual agronomic practices. Results from ARS research concerning the environmental fate and effects of agrochemicals have led to the development of science-based management practices that will protect vulnerable areas of the ecosystem. The new challenge is to identify these vulnerable areas and the temporal and spatial variations prior to use of the chemical by predicting how it will behave in environmental matrices, and using that information, predict its transport and transformation within an air- or watershed. With the development of better predictive tools and GIS (Geographic Information System)-based modeling, the risks of agricultural management systems can be assessed at the watershed and basin levels, and management strategies can be identified that minimize negative environmental impacts.

  7. Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

    PubMed Central

    2013-01-01

    Background Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Methods Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. Results The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. Conclusion The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL. PMID:23638998

  8. Review and Analysis of Algorithmic Approaches Developed for Prognostics on CMAPSS Dataset

    NASA Technical Reports Server (NTRS)

    Ramasso, Emannuel; Saxena, Abhinav

    2014-01-01

    Benchmarking of prognostic algorithms has been challenging due to limited availability of common datasets suitable for prognostics. In an attempt to alleviate this problem several benchmarking datasets have been collected by NASA's prognostic center of excellence and made available to the Prognostics and Health Management (PHM) community to allow evaluation and comparison of prognostics algorithms. Among those datasets are five C-MAPSS datasets that have been extremely popular due to their unique characteristics making them suitable for prognostics. The C-MAPSS datasets pose several challenges that have been tackled by different methods in the PHM literature. In particular, management of high variability due to sensor noise, effects of operating conditions, and presence of multiple simultaneous fault modes are some factors that have great impact on the generalization capabilities of prognostics algorithms. More than 70 publications have used the C-MAPSS datasets for developing data-driven prognostic algorithms. The C-MAPSS datasets are also shown to be well-suited for development of new machine learning and pattern recognition tools for several key preprocessing steps such as feature extraction and selection, failure mode assessment, operating conditions assessment, health status estimation, uncertainty management, and prognostics performance evaluation. This paper summarizes a comprehensive literature review of publications using C-MAPSS datasets and provides guidelines and references to further usage of these datasets in a manner that allows clear and consistent comparison between different approaches.

  9. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  10. Paradoxical effects of kisspeptin: it enhances oocyte in vitro maturation but has an adverse impact on hatched blastocysts during in vitro culture.

    PubMed

    Saadeldin, Islam M; Koo, Ok Jae; Kang, Jung Taek; Kwon, Dae Kee; Park, Sol Ji; Kim, Su Jin; Moon, Joon Ho; Oh, Hyun Ju; Jang, Goo; Lee, Byeong Chun

    2012-01-01

    Kisspeptin (Kp) is best known as a multifunctional peptide with roles in reproduction, the cardiovascular system and cancer. In the present study the expression of kisspeptin hierarchy elements (KISS1, GNRH1 and LHB) and their receptors (KISS1R, GNRHR and LHCGR, respectively) in porcine ovary and in cumulus-oocyte complexes (COCs) were investigated, as were its effects on the in vitro maturation (IVM) of oocytes and their subsequent ability to sustain preimplantation embryo competence after parthenogenetic electrical activation. Kp system elements were expressed and affected IVM of oocytes when maturation medium was supplemented with 10(-6)M Kp. Oocyte maturation, maternal gene expression (MOS, GDF9 and BMP15), blastocyst formation rate, blastocyst hatching and blastocyst total cell count were all significantly increased when oocytes were matured in medium containing Kp compared with the control group (without Kp). A Kp antagonist (p234) at 4×10(-6)M interfered with this hierarchy but did not influence the threshold effect of gonadotrophins on oocyte maturation. FSH was critical and permissive to Kp action on COCs by increasing the relative expression of KISS1R. In contrast, Kp significantly increased apoptosis, the expression of pro-apoptotic gene, BAK1, and suppressed trophoblast outgrowths from hatched blastocysts cultured on feeder cells. The present study provides the first functional evidence of the Kp hierarchy in porcine COCs and its role in enhancing oocyte maturation and subsequent developmental competence in an autocrine-paracrine manner. However, Kp supplementation may have a harmful impact on cultured hatched blastocysts reflecting systemic or local regulation during the critical early period of embryonic development.

  11. Advanced Methods for Determining Prediction Uncertainty in Model-Based Prognostics with Application to Planetary Rovers

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew J.; Sankararaman, Shankar

    2013-01-01

    Prognostics is centered on predicting the time of and time until adverse events in components, subsystems, and systems. It typically involves both a state estimation phase, in which the current health state of a system is identified, and a prediction phase, in which the state is projected forward in time. Since prognostics is mainly a prediction problem, prognostic approaches cannot avoid uncertainty, which arises due to several sources. Prognostics algorithms must both characterize this uncertainty and incorporate it into the predictions so that informed decisions can be made about the system. In this paper, we describe three methods to solve these problems, including Monte Carlo-, unscented transform-, and first-order reliability-based methods. Using a planetary rover as a case study, we demonstrate and compare the different methods in simulation for battery end-of-discharge prediction.

  12. Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates1

    PubMed Central

    Kwok, Man Leung; Yuen, Hon; Lai, Sik To

    2003-01-01

    Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates. PMID:14519241

  13. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  14. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

  15. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology.

    PubMed

    Bujak, Kamil; Wasilewski, Jarosław; Osadnik, Tadeusz; Jonczyk, Sandra; Kołodziejska, Aleksandra; Gierlotka, Marek; Gąsior, Mariusz

    2015-01-01

    Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization.

  16. Towards Prognostics of Electrolytic Capacitors

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai

    2011-01-01

    A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.

  17. The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Li, Ya-Jun; Jiang, Wen-Qi; Huang, Jia-Jia; Xia, Zhong-Jun; Huang, Hui-Qiang; Li, Zhi-Ming

    2013-05-01

    The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score including C-reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T-cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T-cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression-free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low-risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL.

  18. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

    SciTech Connect

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet; Mul, Veronique; Dam, Go van; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-03-15

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.

  19. Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion

    PubMed Central

    Waked, Imam; Berhane, Sarah; Toyoda, Hidenori; Chan, Stephen L; Stern, Nicholas; Palmer, Daniel; Tada, Toshifumi; Yeo, Winnie; Mo, Frankie; Bettinger, Dominik; Kirstein, Martha M; Iñarrairaegui, Mercedes; Gomaa, Asmaa; Vogel, Arndt; Meyer, Tim; Sangro, Bruno; Lai, Paul; Kumada, Takashi; Johnson, Philip J

    2017-01-01

    Background: Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI). Methods: In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival. Results: Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI. Conclusions: The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown. PMID:28125820

  20. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.

  1. VNN1 overexpression is associated with poor response to preoperative chemoradiotherapy and adverse prognosis in patients with rectal cancers

    PubMed Central

    Chai, Chi-Yung; Zhang, Yimin; Song, Junlong; Lin, Shih-Chun; Sun, Shengrong; Chang, I-Wei

    2016-01-01

    Background: Colorectal cancer is prevalent worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a public dataset of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that VNN1 was the most significantly upregulated gene among those related to nitrogen compound metabolic process (GO:0006807). Therefore, we analyzed the clinicopathological correlation and prognostic impact of VNN1 protein (pantetheinase), which encoded by VNN1 gene. Methods: VNN1 immunostaining was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by surgery, which were bisected into high- and low-expression subgroups. Furthermore, statistical analyses were performed to correlate the relationship between VNN1 immunoreactivity and clinicopathological features, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: High VNN1 immunoexpression was significantly associated with advanced pre-treatment and post-treatment disease and poor response to CCRT (all P ≤ .026). In addition, VNN1 overexpression was linked to adverse DSS, LRFS and MeFS in univariate analysis and served as an independent prognosticator indicating worse DSS and LRFS in multivariate analysis (all P ≤ .019). Conclusion: VNN1 may play a crucial role in rectal cancer progression and responsiveness to CCRT, and serve as a novel prognostic biomarker. Additional studies to clarify the molecular pathway are essential for developing potential VNN1-targeted therapies for rectal cancer. PMID:27830030

  2. Childhood Adversities and Adult Cardiometabolic Health: Does the Quantity, Timing, and Type of Adversity Matter?

    PubMed Central

    Friedman, Esther M.; Montez, Jennifer Karas; Sheehan, Connor McDevitt; Guenewald, Tara L.; Seeman, Teresa E.

    2015-01-01

    Objective Adverse events in childhood can indelibly influence adult health. While evidence for this association has mounted, a fundamental set of questions about how to operationalize adverse events has been understudied. Method We used data from the National Survey of Midlife Development in the United States to examine how quantity, timing, and types of adverse events in childhood are associated with adult cardiometabolic health. Results The best-fitting specification of quantity of events was a linear measure reflecting a dose–response relationship. Timing of event mattered less than repeated exposure to events. Regarding the type of event, academic interruptions and sexual/physical abuse were most important. Adverse childhood events elevated the risk of diabetes and obesity similarly for men and women but had a greater impact on women’s risk of heart disease. Discussion Findings demonstrate the insights that can be gleaned about the early-life origins of adult health by examining operationalization of childhood exposures. PMID:25903978

  3. Environmental adversity and uncertainty favour cooperation

    PubMed Central

    Andras, Peter; Lazarus, John; Roberts, Gilbert

    2007-01-01

    Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher) or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies. PMID:18053138

  4. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    PubMed Central

    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

  5. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  6. Adverse cutaneous drug reaction.

    PubMed

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.

  7. Adverse Environments and Children's Creativity Development: Transforming the Notion of "Success in Adversity" in China

    ERIC Educational Resources Information Center

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications…

  8. Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

    PubMed Central

    Han, Wonshik; Kim, Jongjin; Moon, Hyeong-Gon; Oh, Sohee; Song, Yun Seon; Kim, Young A; Chang, Mee Soo; Noh, Dong-Young

    2017-01-01

    Purpose We aimed to reveal the prognostic influence of B-cell CLL/lymphoma 2 (BCL2) on molecular subtypes of breast cancer. Methods We analyzed 9,468 patients with primary breast cancer. We classified molecular subtypes according to the National Comprehensive Cancer Network (NCCN) and St. Gallen guidelines, mainly on the basis of the expression of hormonal receptor (HR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Results Regarding NCCN classification, BCL2 was a strong favorable prognostic factor in the HR(+)/HER2(–) subtype (p<0.001) and a marginally significant favorable prognosticator in the HR(+)/HER2(+) subtype (p=0.046). BCL2 had no prognostic impact on HR(–)/HER2(+) and HR(–)/HER2(–) subtypes. In relation to St. Gallen classification, BCL2 was a strong favorable prognosticator in luminal A and luminal B/HER2(–) subtypes (both p<0.001). BCL2 was a marginally significant prognosticator in the luminal B/HER2(+) subtype (p=0.046), and it was not a significant prognosticator in HER2 or triple negative (TN) subtypes. The prognostic effect of BCL2 was proportional to the stage of breast cancer in HR(+)/HER2(–), HR(+)/HER2(+), and HR(–)/HER2(–) subtypes, but not in HR(–)/HER2(+) subtype. BCL2 was not a prognostic factor in TN breast cancer regardless of epidermal growth factor receptor expression. Conclusion The prognostic influence of BCL2 was different across molecular subtypes of breast cancer, and it was largely dependent on HR, HER2, Ki-67, and the stage of cancer. BCL2 had a strong favorable prognostic impact only in HR(+)/HER2(–) or luminal A and luminal B/HER2(–) subtypes, particularly in advanced stages. Further investigations are needed to verify the prognostic influence of BCL2 on molecular subtypes of breast cancer and to develop clinical applications for prognostication using BCL2. PMID:28382095

  9. Prognostic biomarkers in acute coronary syndrome

    PubMed Central

    Pavan, Chiara

    2016-01-01

    The acute coronary syndrome (ACS) is a leading cause of death around the globe. Beside a still high mortality rate, additional complications of ACS include arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure (HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac rupture. Despite many prognostic tools have been developed over the past decades, efforts are still ongoing to identify reliable and predictive biomarkers, which may help predict the prognosis of these patients and especially the risk of HF. Recent evidence suggests that the value of a discrete number of biomarkers of myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2 (sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with ACS. Interestingly, the already promising predictive value of these biomarkers when measured alone was shown to be consistently magnified when combined with other and well-established cardiac biomarkers such natriuretic peptides and cardiac troponins. This article is hence aimed to review the current knowledge about cardiac biomarkers of fibrosis and adverse remodeling. PMID:27500159

  10. From NDE to Prognostics: A Revolution in Asset Management for Generation IV Nuclear Power Plants

    SciTech Connect

    Bond, Leonard J.; Doctor, Steven R.

    2007-06-01

    For Generation IV nuclear power plants (NPP) to achieve operational goals it is necessary to adopt new on-line monitoring and prognostic methodologies, giving operators better plant situational awareness and reliable predictions of remaining service life. Such techniques can improve plant economics, reduce unplanned outages, improve safety and provide probabilistic risk assessments. This paper reviews the state of the art and the potential impact from monitoring, diagnostics and prognostics on advanced NPP, with a focus on the needs of Generation IV systems.

  11. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  12. Prognostics for Ground Support Systems: Case Study on Pneumatic Valves

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew; Goebel, Kai

    2011-01-01

    Prognostics technologies determine the health (or damage) state of a component or sub-system, and make end of life (EOL) and remaining useful life (RUL) predictions. Such information enables system operators to make informed maintenance decisions and streamline operational and mission-level activities. We develop a model-based prognostics methodology for pneumatic valves used in ground support equipment for cryogenic propellant loading operations. These valves are used to control the flow of propellant, so failures may have a significant impact on launch availability. Therefore, correctly predicting when valves will fail enables timely maintenance that avoids launch delays and aborts. The approach utilizes mathematical models describing the underlying physics of valve degradation, and, employing the particle filtering algorithm for joint state-parameter estimation, determines the health state of the valve and the rate of damage progression, from which EOL and RUL predictions are made. We develop a prototype user interface for valve prognostics, and demonstrate the prognostics approach using historical pneumatic valve data from the Space Shuttle refueling system.

  13. A framework for quantifying net benefits of alternative prognostic models.

    PubMed

    Rapsomaniki, Eleni; White, Ian R; Wood, Angela M; Thompson, Simon G

    2012-01-30

    New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks.

  14. Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

    PubMed Central

    Barcelo, Antonia; Bauça, Josep Miquel; Yañez, Aina; Fueyo, Laura; Gomez, Cristina; de la Peña, Monica; Pierola, Javier; Rodriguez, Alberto; Sanchez-de-la-Torre, Manuel; Abad, Jorge; Mediano, Olga; Amilibia, Jose; Masdeu, Maria Jose; Teran, Joaquin; Montserrat, Josep Maria; Mayos, Mercè; Sanchez-de-la-Torre, Alicia; Barbé, Ferran

    2016-01-01

    Background Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. Methods A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. Results Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. Conclusions The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. Trial Registration ClinicalTrials.gov NCT01335087 PMID:26930634

  15. Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

    NASA Technical Reports Server (NTRS)

    Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2011-01-01

    Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

  16. Towards Prognostics for Electronics Components

    NASA Technical Reports Server (NTRS)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  17. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  18. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    PubMed Central

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  19. Prognostic models in obstetrics: available, but far from applicable.

    PubMed

    Kleinrouweler, C Emily; Cheong-See, Fiona M; Collins, Gary S; Kwee, Anneke; Thangaratinam, Shakila; Khan, Khalid S; Mol, Ben Willem J; Pajkrt, Eva; Moons, Karel G M; Schuit, Ewoud

    2016-01-01

    Health care provision is increasingly focused on the prediction of patients' individual risk for developing a particular health outcome in planning further tests and treatments. There has been a steady increase in the development and publication of prognostic models for various maternal and fetal outcomes in obstetrics. We undertook a systematic review to give an overview of the current status of available prognostic models in obstetrics in the context of their potential advantages and the process of developing and validating models. Important aspects to consider when assessing a prognostic model are discussed and recommendations on how to proceed on this within the obstetric domain are given. We searched MEDLINE (up to July 2012) for articles developing prognostic models in obstetrics. We identified 177 papers that reported the development of 263 prognostic models for 40 different outcomes. The most frequently predicted outcomes were preeclampsia (n = 69), preterm delivery (n = 63), mode of delivery (n = 22), gestational hypertension (n = 11), and small-for-gestational-age infants (n = 10). The performance of newer models was generally not better than that of older models predicting the same outcome. The most important measures of predictive accuracy (ie, a model's discrimination and calibration) were often (82.9%, 218/263) not both assessed. Very few developed models were validated in data other than the development data (8.7%, 23/263). Only two-thirds of the papers (62.4%, 164/263) presented the model such that validation in other populations was possible, and the clinical applicability was discussed in only 11.0% (29/263). The impact of developed models on clinical practice was unknown. We identified a large number of prognostic models in obstetrics, but there is relatively little evidence about their performance, impact, and usefulness in clinical practice so that at this point, clinical implementation cannot be recommended. New efforts should be directed

  20. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  1. Generic Software Architecture for Prognostics (GSAP) User Guide

    NASA Technical Reports Server (NTRS)

    Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

    2016-01-01

    The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

  2. Specimen banks for cancer prognostic factor research.

    PubMed

    Burke, H B; Henson, D E

    1998-10-01

    Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues. This paper presents an overview of some of the issues related to the use of specimen banks in prognostic factor research.

  3. Diagnosis of potential stressors adversely affecting benthic ...

    EPA Pesticide Factsheets

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

  4. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    PubMed

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  5. Distilling the Verification Process for Prognostics Algorithms

    NASA Technical Reports Server (NTRS)

    Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

    2013-01-01

    The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

  6. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... technology available for minimizing adverse environmental impact be established for my Phase II existing... environmental impact be established for my Phase II existing facility? (a) Compliance alternatives. You must... for minimizing adverse environmental impact at your facility: (1)(i)You may demonstrate to...

  7. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... technology available for minimizing adverse environmental impact be established for my Phase II existing... environmental impact be established for my Phase II existing facility? (a) Compliance alternatives. You must... for minimizing adverse environmental impact at your facility: (1)(i)You may demonstrate to...

  8. 40 CFR 125.94 - How will requirements reflecting best technology available for minimizing adverse environmental...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... technology available for minimizing adverse environmental impact be established for my Phase II existing... environmental impact be established for my Phase II existing facility? (a) Compliance alternatives. You must... for minimizing adverse environmental impact at your facility: (1)(i)You may demonstrate to...

  9. Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS)

    PubMed Central

    Hamilton, Robert J.; Abdallah, Kald; Pintilie, Melania; Joshua, Anthony M.

    2017-01-01

    Background Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity. Methods We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC). The prognostic effects of concomitant medications and PSA response were assessed by Cox proportional hazards models. One year tAUC was calculated for multivariable prognostic model optimized to our data. Conditional logistic regression models were used to assess associations with grade 3/4 adverse events (G3/4 AE) at baseline and after cycle 1 of treatment. Results Despite limitations of the PDS data set, the existing model was validated; one year AUC, was 0.68 (95% CI 95% CI, .66 to .71) to 0.78 (95%CI, .74 to .81) depending on the subset of datasets used. A new model was constructed with an AUC of .74 (.72 to .77). Concomitant medications low molecular weight heparin and warfarin were associated with poorer survival, Metformin and Cox2 inhibitors were associated with better outcome. PSA response was associated with survival, the effect of which was greatest early in follow-up. Age was associated with baseline risk of G3/4 AE. The odds of experiencing G3/4 AE later on in treatment were significantly greater for subjects who experienced a G3/4 AE in their first cycle (OR 3.53, 95% CI 2.53–4.91, p < .0001). Conclusion Despite heterogeneous data collection protocols, PDS provides access to large datasets for novel outcomes analysis. In this paper, we demonstrate its utility for validating existing models and novel model generation including the utility of concomitant medications in

  10. Prognostic relevance of minimal residual disease in colorectal cancer

    PubMed Central

    Bork, Ulrich; Grützmann, Robert; Rahbari, Nuh N; Schölch, Sebastian; Distler, Marius; Reissfelder, Christoph; Koch, Moritz; Weitz, Jürgen

    2014-01-01

    Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options. PMID:25132746

  11. Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

    PubMed

    Cheng, Li; Tan, Mei; Liu, Zhengkui

    2015-01-01

    China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy.

  12. Hybrid Bearing Prognostic Test Rig

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Certo, Joseph M.; Handschuh, Robert F.; Dimofte, Florin

    2005-01-01

    The NASA Glenn Research Center has developed a new Hybrid Bearing Prognostic Test Rig to evaluate the performance of sensors and algorithms in predicting failures of rolling element bearings for aeronautics and space applications. The failure progression of both conventional and hybrid (ceramic rolling elements, metal races) bearings can be tested from fault initiation to total failure. The effects of different lubricants on bearing life can also be evaluated. Test conditions monitored and recorded during the test include load, oil temperature, vibration, and oil debris. New diagnostic research instrumentation will also be evaluated for hybrid bearing damage detection. This paper summarizes the capabilities of this new test rig.

  13. Prognostic value of procalcitonin in hospitalized patients with lower respiratory tract infections

    PubMed Central

    Nobre, Vandack; Borges, Isabela

    2016-01-01

    Lower respiratory tract infections are common and potentially lethal conditions and are a major cause of inadequate antibiotic prescriptions. Characterization of disease severity and prognostic prediction in affected patients can aid disease management and can increase accuracy in determining the need for and place of hospitalization. The inclusion of biomarkers, particularly procalcitonin, in the decision taken process is a promising strategy. This study aims to present a narrative review of the potential applications and limitations of procalcitonin as a prognostic marker in hospitalized patients with lower respiratory tract infections. The studies on this topic are heterogeneous with respect to procalcitonin measurement techniques, cutoff values, clinical settings, and disease severity. The results show that procalcitonin delivers moderate performance for prognostic prediction in patients with lower respiratory tract infections; its predictive performance was not higher than that of classical methods, and knowledge of procalcitonin levels is most useful when interpreted together with other clinical and laboratory results. Overall, repeated measurement of the procalcitonin levels during the first days of treatment provides more prognostic information than a single measurement; however, information on the cost-effectiveness of this procedure in intensive care patients is lacking. The results of studies that evaluated the prognostic value of initial procalcitonin levels in patients with community-acquired pneumonia are more consistent and have greater potential for practical application; in this case, low procalcitonin levels identify those patients with a low risk of adverse outcomes. PMID:27305038

  14. Cutaneous adverse reactions to lenalidomide.

    PubMed

    Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S

    2015-01-01

    Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide.

  15. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  16. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  17. [Prognostic study of liver abscess].

    PubMed

    Nouira, Ramzi; Bedoui, Riadh; Miaadi, Naoufel; Guesmi, Fethi; Ben Achour, Jamel; Hani, Mohamed; Daghfous, Mounir; Ben Osman, Samia; Zoghlami, Ayoub; Najah, Nabil

    2003-04-01

    The objective of this work is to study factors of prognostic of mortality of abscesses of the liver. We have treated between 1990 and 2000 in our service, 38 patient for abscess of the liver. The symptoms are dominated by the pain of the right hypochondria (37 cases) and the fever (34 cases). An unique abscess has been recovered in 25 cases. Some multiple localizations have been observed in 12 cases. 21 patients have been operated. The bacteriological study at all patients revealed the presence of germ in 27 cases. In 6 cases, there were two germs. It was a bacillus negative gram in 26 cases and a cocci positive gram in 7 cases. Six complications have been observed at the operated patients. In 5 cases, it was a septic shock having leads to the death. After survey univariate and multivariate the only factor of bad prognostic recovered is the septic shock. The aetiology was identified in only 9 cases; it was abscess cholangiotis.

  18. Commentary: Childhood Exposure to Environmental Adversity and the Well-Being of People with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Emerson, E.

    2013-01-01

    People with intellectual disabilities have poorer health than their non-disabled peers. They are also more likely to be exposed to a wide range of environmental adversities in childhood. Research undertaken in the general population has demonstrated that exposure to environmental adversity in childhood can have an adverse impact on health and…

  19. Prognostic Analysis System and Methods of Operation

    NASA Technical Reports Server (NTRS)

    MacKey, Ryan M. E. (Inventor); Sneddon, Robert (Inventor)

    2014-01-01

    A prognostic analysis system and methods of operating the system are provided. In particular, a prognostic analysis system for the analysis of physical system health applicable to mechanical, electrical, chemical and optical systems and methods of operating the system are described herein.

  20. Distributed Prognostics based on Structural Model Decomposition

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

    2014-01-01

    Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

  1. Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

    PubMed

    Hiwase, Devendra K; Singhal, Deepak; Strupp, Corinna; Chhetri, Rakchha; Kutyna, Monika M; Wee, L Amilia; Harrison, Peter B; Nath, Shriram V; Wickham, Nicholas; Hui, Chi-Hung; Gray, James X; Bardy, Peter; Ross, David M; Lewis, Ian D; Reynolds, John; To, L Bik; Germing, Ulrich

    2017-03-01

    RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.

  2. Adverse effects of public health interventions: a conceptual framework.

    PubMed

    Lorenc, Theo; Oliver, Kathryn

    2014-03-01

    Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.

  3. Model-Based Prognostics of Hybrid Systems

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal

    2015-01-01

    Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.

  4. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.

    PubMed

    Loghavi, Sanam; Al-Ibraheemi, Alyaa; Zuo, Zhuang; Garcia-Manero, Guillermo; Yabe, Mariko; Wang, Sa A; Kantarjian, Hagop M; Yin, Cameron C; Miranda, Roberto N; Luthra, Raja; Medeiros, L Jeffrey; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-10-01

    Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = <0·001). Expression of TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F.

  5. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    PubMed

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network.

  6. Adverse Outcome Pathway (AOP) Network Development for ...

    EPA Pesticide Factsheets

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

  7. Serious Adverse Events After Cataract Surgery

    PubMed Central

    Stein, Joshua D.

    2013-01-01

    Purpose Over the past several decades there have been many advances in the equipment, instrumentation and techniques of performing cataract surgery. This review will address the impact of these advances on the safety profile of cataract surgery. Recent Findings Recent studies have demonstrated a decline in the risk of serious postoperative adverse events (endophthalmitis, suprachoroidal hemorrhage, retinal detachment) following cataract surgery. Factors that increase the risk of serious complications from cataract surgery include patient-related factors (male sex, concomitant diabetic retinopathy, same day cataract surgery combined with another intraocular surgery, tamsulosin use) and surgeon-related factors (low surgical volume, limited experience, operating on patients who are most prone to adverse events). Summary Cataract surgery continues to be a very safe surgical procedure with few patients experiencing serious sight-threatening adverse events. Studies in the literature have helped surgeons identify patients who are at high risk for surgical complications and to develop strategies to limit surgical complications when operating on these patients. As multifocal intraocular lenses, femtosecond laser technology, and other surgical innovations continue to gain popularity, it will be interesting in the coming years to determine whether there will be a continued reduction in complications of cataract surgery. PMID:22450221

  8. Combating adverse selection in secondary PC markets.

    PubMed

    Hickey, Stewart W; Fitzpatrick, Colin

    2008-04-15

    Adverse selection is a significant contributor to market failure in secondary personal computer (PC) markets. Signaling can act as a potential solution to adverse selection and facilitate superior remarketing of second-hand PCs. Signaling is a means whereby usage information can be utilized to enhance consumer perception of both value and utility of used PCs and, therefore, promote lifetime extension for these systems. This can help mitigate a large portion of the environmental impact associated with PC system manufacture. In this paper, the computer buying and selling behavior of consumers is characterized via a survey of 270 Irish residential users. Results confirm the existence of adverse selection in the Irish market with 76% of potential buyers being unwilling to purchase and 45% of potential vendors being unwilling to sell a used PC. The so-called "closet affect" is also apparent with 78% of users storing their PC after use has ceased. Results also indicate that consumers place a higher emphasis on specifications when considering a second-hand purchase. This contradicts their application needs which are predominantly Internet and word-processing/spreadsheet/presentation applications, 88% and 60% respectively. Finally, a market solution utilizing self monitoring and reporting technology (SMART) sensors for the purpose of real time usage monitoring is proposed, that can change consumer attitudes with regard to second-hand computer equipment.

  9. Adverse effects of isolation in hospitalised patients: a systematic review.

    PubMed

    Abad, C; Fearday, A; Safdar, N

    2010-10-01

    The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.

  10. Adverse childhood experiences and health anxiety in adulthood.

    PubMed

    Reiser, Sarah J; McMillan, Katherine A; Wright, Kristi D; Asmundson, Gordon J G

    2014-03-01

    Childhood experiences are thought to predispose a person to the development of health anxiety later in life. However, there is a lack of research investigating the influence of specific adverse experiences (e.g., childhood abuse, household dysfunction) on this condition. The current study examined the cumulative influence of multiple types of childhood adversities on health anxiety in adulthood. Adults 18-59 years of age (N=264) completed a battery of measures to assess adverse childhood experiences, health anxiety, and associated constructs (i.e., negative affect and trait anxiety). Significant associations were observed between adverse childhood experiences, health anxiety, and associated constructs. Hierarchical multiple regression analysis indicted that adverse childhood experiences were predictive of health anxiety in adulthood; however, the unique contribution of these experience were no longer significant following the inclusion of the other variables of interest. Subsequently, mediation analyses indicated that both negative affect and trait anxiety independently mediated the relationship between adverse childhood experiences and health anxiety in adulthood. Increased exposure to adverse childhood experiences is associated with higher levels of health anxiety in adulthood; this relationship is mediated through negative affect and trait anxiety. Findings support the long-term negative impact of cumulative adverse childhood experiences and emphasize the importance of addressing negative affect and trait anxiety in efforts to prevent and treat health anxiety.

  11. Prognostic value of sarcopenia in liver surgery.

    PubMed

    Cornet, M; Lim, C; Salloum, C; Lazzati, A; Compagnon, P; Pascal, G; Azoulay, D

    2015-11-01

    Current knowledge indicates that malnutrition increases the rate of post-operative complications, particularly respiratory and infectious, after major surgery. Almost all liver surgery is performed in patients with cancer, a factor that increases the risk of malnutrition. The primary risk factors for post-operative complications are pre-operative hypo-albuminemia and a body mass index less than 20 kg/m(2). To improve the prediction of complications in these patients, some teams have suggested measurement of muscle thickness by computed tomography. Muscular mass can thus be quantified by measuring the total surface of the psoas muscle or the total surface of all muscles (i.e. external and internal oblique, transverse, psoas and paravertebral muscles) seen on an axial CT slice at L3. As well, data exist suggesting that sarcopenia is an independent predictive factor of post-operative morbidity and poor long-term survival after resection for cancer. Nonetheless, the literature on the subject is limited, there are no standardized definitions for sarcopenia, and the need of special software to calculate the surfaces limits its usefulness. Lastly, there are little if any data concerning the nutritional or pharmacologic means to treat sarcopenia. This update, based on a literature review, deals with the value and the prognostic impact of sarcopenia in surgery for liver tumors. The current definition of sarcopenia, validated internationally, the methods of measurement, and the consequences of sarcopenia on the outcome of liver resections are detailed in this review.

  12. No impact of concomitant methotrexate use on serious adverse event and serious infection risk in patients with rheumatoid arthritis treated with bDMARDs: a systematic literature review and meta-analysis

    PubMed Central

    Baradat, Claire; Degboé, Yannick; Constantin, Arnaud; Cantagrel, Alain; Ruyssen-Witrand, Adeline

    2017-01-01

    Objectives To compare the risk of serious adverse events, serious infections and death caused by methotrexate and biological disease-modifying antirheumatic drug (bDMARD) combination therapy versus a bDMARD prescribed as monotherapy in rheumatoid arthritis (RA). Methods A systematic literature review was conducted until February 2016 in PubMed, Embase and Cochrane Library databases by selecting randomised controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy in RA. The meta-analysis compared the occurrence of (1) serious adverse events, (2) serious infections and (3) death among these groups by the Mantel-Haenszel method. Results The literature review selected 16 controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy. After meta-analysis comparing patients under monotherapy to those under combination therapy: (1) the risk of occurrence of serious adverse events was comparable in 12 trials: RR (95% CI) 0.92 (0.78 to 1.08). (2) No significant difference was observed in the risk of occurrence of serious infections in 13 trials: RR (95% CI) 1.15 (0.84 to 1.58). We noted a trend, although insignificant, towards a high risk of the occurrence of tuberculosis in 10 studies: RR (95% CI) 1.78 (0.63 to 4.99). (3) The risk of death was comparable in 12 trials: RR (95% CI) 0.73 (0.40 to 1.35). Conclusions The results showed no significant difference between the two groups, confirming that the use of methotrexate and bDMARD combination therapy in RA does not cause an increased risk of serious adverse events or serious infections or death compared with bDMARD monotherapy. PMID:28270933

  13. An Integrated Approach for Gear Health Prognostics

    NASA Technical Reports Server (NTRS)

    He, David; Bechhoefer, Eric; Dempsey, Paula; Ma, Jinghua

    2012-01-01

    In this paper, an integrated approach for gear health prognostics using particle filters is presented. The presented method effectively addresses the issues in applying particle filters to gear health prognostics by integrating several new components into a particle filter: (1) data mining based techniques to effectively define the degradation state transition and measurement functions using a one-dimensional health index obtained by whitening transform; (2) an unbiased l-step ahead RUL estimator updated with measurement errors. The feasibility of the presented prognostics method is validated using data from a spiral bevel gear case study.

  14. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  15. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  16. Reverse engineering adverse outcome pathways.

    PubMed

    Perkins, Edward J; Chipman, J Kevin; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  17. Adverse childhood experience and asthma onset: a systematic review.

    PubMed

    Exley, Daniel; Norman, Alyson; Hyland, Michael

    2015-06-01

    Adverse childhood experiences such as abuse and neglect are associated with subsequent immune dysregulation. Some studies show an association between adverse childhood experiences and asthma onset, although significant disparity in results exists in the published literature. We aimed to review available studies employing a prospective design that investigates associations between adverse childhood experience and asthma. A search protocol was developed and studies were drawn from four electronic journal databases. Studies were selected in accordance with pre-set inclusion criteria and relevant data were extracted. 12 studies, assessing data from a total of 31 524 individuals, were identified that investigate the impact of a range of adverse childhood experiences on the likelihood of developing asthma. Evidence suggests that chronic stress exposure and maternal distress in pregnancy operate synergistically with known triggers such as traffic-related air pollution to increase asthma risk. Chronic stress in early life is associated with an increased risk of asthma onset. There is evidence that adverse childhood experience increases the impact of traffic-related air pollution and inconsistent evidence that adverse childhood experience has an independent effect on asthma onset.

  18. Prognostic markers of acute decompensated heart failure: the emerging roles of cardiac biomarkers and prognostic scores.

    PubMed

    Cohen-Solal, Alain; Laribi, Said; Ishihara, Shiro; Vergaro, Giuseppe; Baudet, Mathilde; Logeart, Damien; Mebazaa, Alexandre; Gayat, Etienne; Vodovar, Nicolas; Pascual-Figal, Domingo A; Seronde, Marie-France

    2015-01-01

    Rapidly assessing outcome in patients with acute decompensated heart failure is important but prognostic factors may differ from those used routinely for stable chronic heart failure. Multiple plasma biomarkers, besides the classic natriuretic peptides, have recently emerged as potential prognosticators. Furthermore, prognostic scores that combine clinical and biochemical data may also be useful. However, compared with the scores used in chronic heart failure, scores for acute decompensated heart failure have not been validated. This article reviews potential biomarkers, with a special focus on biochemical biomarkers, and possible prognostic scores that could be used by the clinician when assessing outcome in patients with acute heart failure.

  19. The neurobiological Correlates of Childhood Adversity and Implications for Treatment

    PubMed Central

    Tyrka, Audrey R.; Burgers, Darcy E.; Philip, Noah S.; Price, Lawrence H.; Carpenter, Linda L.

    2013-01-01

    Objective This paper provides an overview of research on the neurobiological correlates of childhood adversity and a selective review of treatment implications. Method Findings from a broad array of human and animal studies of early adversity were reviewed. Results Topics reviewed include neuroendocrine, neurotrophic, neuroimaging, and cognitive effects of adversity, as well as genetic and epigenetic influences. Effects of early life stress on treatment outcome are considered, and development of treatments designed to address the neurobiological abnormalities is discussed. Conclusion Early adversity is associated with abnormalities of several neurobiological systems that are implicated in the development of psychopathology and other medical conditions. Early life stress negatively impacts treatment outcome and individuals may require treatments that are specific to this condition. PMID:23662634

  20. Diagnostic and Prognostic Biomarkers in Melanoma

    PubMed Central

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan

    2014-01-01

    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  1. Impact of Obstetrician/Gynecologist Hospitalists on Quality of Obstetric Care (Cesarean Delivery Rates, Trial of Labor After Cesarean/Vaginal Birth After Cesarean Rates, and Neonatal Adverse Events).

    PubMed

    Iriye, Brian K

    2015-09-01

    Care via obstetric hospitalists continues to expand, quickly becoming an integral part of labor and delivery management in urban and suburban areas. Overall lower cesarean delivery rates have been found with obstetric hospitalist care. Continuous 24-hour coverage of labor units has displayed lower rates of neonatal adverse events and likely reduces time in decision to delivery. Further study is needed on maternal and neonatal outcomes to corroborate earlier observations, and to closely examine the type of obstetric hospitalist model being observed to aid in planning the ideal deployment of providers in this workforce of the future.

  2. Prognostic Impact of External Beam Radiation Therapy in Patients Treated With and Without Extended Surgery and Intraoperative Electrons for Locally Recurrent Rectal Cancer: 16-Year Experience in a Single Institution

    SciTech Connect

    Calvo, Felipe A.; Sole, Claudio V.; Alvarez de Sierra, Pedro; Gómez-Espí, Marina; Blanco, Jose; and others

    2013-08-01

    Purpose: To analyze prognostic factors associated with survival in patients after intraoperative electrons containing resective surgical rescue of locally recurrent rectal cancer (LRRC). Methods and Materials: From January 1995 to December 2011, 60 patients with LRRC underwent extended surgery (n=38: multiorgan [43%], bone [28%], soft tissue [38%]) or nonextended (n=22) surgical resection, including a component of intraoperative electron-beam radiation therapy (IOERT) to the pelvic recurrence tumor bed. Twenty-eight (47%) of these patients also received external beam radiation therapy (EBRT) (range, 30.6-50.4 Gy). Survival outcomes were estimated by the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: The median follow-up time was 36 months (range, 2-189 months), and the 1-year, 3-year, and 5-year rates for locoregional control (LRC) and overall survival (OS) were 86%, 52%, and 44%; and 78%, 53%, 43%, respectively. On multivariate analysis, R1 resection, EBRT at the time of pelvic rerecurrence, no tumor fragmentation, and non-lymph node metastasis retained significance with regard to LRR. R1 resection and no tumor fragmentation showed a significant association with OS after adjustment for other covariates. Conclusions: EBRT treatment integrated for rescue, resection radicality, and not involved fragmented resection specimens are associated with improved LRC in patients with locally recurrent rectal cancer. Additionally, tumor fragmentation could be compensated by EBRT. Present results suggest that a significant group of patients with LRRC may benefit from EBRT treatment integrated with extended surgery and IOERT.

  3. Influence of Prognostic Factors for Recurrence of Adenocarcinoma of the Stomach

    PubMed Central

    Mehmedagic, Indira; Hasukic, Sefik; Agic, Mirha; Kadric, Nedzad; Hasukic, Ismar

    2016-01-01

    Introduction: Gastric cancer is the second most important neoplasm in the world. Surgical resection is the treatment of choice for gastric cancer, and recognized by the International Union against Cancer (International Union Against Cancer – UICC) TNM classification of the parameters of the tumor and lymph node. Prognostic factors related to characteristics of the tumor by histopathologic findings have an impact on the planning of the operation. According to the results of most studies it is possible to predict survival and recurrence based on histological type and TNM classification of tumors on the one hand and the surgical procedure on the other. Aim: The aim of the research was to analyze prognostic factors that influenced the frequency of recurrence in gastric surgery patients. Patients and methods: The five year study covered a population of 100 treated patients of adenocarcinoma of the stomach at the Department of Surgery, University Clinical Center Tuzla. The first group were characteristics of tumors in patients with gastric adenocarcinoma. Lymphadenectomy and splenectomy, types of surgery were the second group of prognostic factors. Results: Histological type and TNM stage of tumor as prognostic factors had a significant impact on local tumor recurrence. The type of surgery had no statistically significant value for tumor recurrence (p = 0.7520). Conclusion: Statistical analysis of prognostic factors related to histopathologic characteristics of tumors and the type of surgery gave the results that had an impact on recurrence in gastric surgery patients. The most important prognostic factors were TNM stage of tumor and histological type of tumor that influenced the incidence of recurrence. PMID:28210017

  4. Metrics for Offline Evaluation of Prognostic Performance

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

    2010-01-01

    Prognostic performance evaluation has gained significant attention in the past few years. Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

  5. Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

    NASA Technical Reports Server (NTRS)

    Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

    2013-01-01

    This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.

  6. On Applying the Prognostic Performance Metrics

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

    2009-01-01

    Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.

  7. Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma

    PubMed Central

    Yue, Dongsheng; Li, Kai; Jiang, Richeng

    2016-01-01

    Background Adenosquamous carcinoma is a rare and aggressive form of lung cancer. The prognostic and predictive value of preoperative serum tumor markers and frequency of EGFR mutations in adenosquamous lung carcinoma are unclear. Methods We retrospectively analyzed data and samples collected from 106 radically resected adenosquamous lung carcinoma patients with pathological stage I-IIIA between 2008 and 2013. Correlations between serum tumor marker levels and EGFR mutations as well as survival parameters were analyzed and prognostic factors were identified. Results Of the 106 adenosquamous lung carcinoma patients, 29 (27.4%) harbored EGFR mutations. By univariate analysis, advanced clinical stage (P = 0.009 for disease-free survival [DFS]; P = 0.046 for overall survival [OS]), larger tumor size (P = 0.001 for DFS; P = 0.002 for OS), regional lymph node metastasis (P = 0.024 for DFS; P = 0.030 for OS), higher NSE level (P = 0.002 for DFS; P < 0.001 for OS), and higher TMI (tumor marker index) (P = 0.009 for OS) were significantly correlated with a worse prognosis. By multivariate analysis, NSE (P = 0.014) was confirmed as independent predictor for DFS, while NSE (P = 0.001) and TMI (P = 0.038) were independent prognostic factors for OS. Conclusion Adenosquamous lung carcinoma is an aggressive malignancy with relatively high EGFR mutation frequency. Elevated preoperative NSE level and TMI are adverse predictive and prognostic indicators. PMID:27623437

  8. Adverse drug reactions: part II.

    PubMed

    Wooten, James M

    2010-11-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

  9. Adverse drug reactions: Part I.

    PubMed

    Wooten, James M

    2010-10-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.

  10. A review of the scientific literature related to the adverse impact of physical restraint: gaining a clearer understanding of the physiological factors involved in cases of restraint-related death.

    PubMed

    Barnett, Richard; Stirling, Chris; Pandyan, Anand D

    2012-07-01

    Deaths occurring during and/or in close proximity to physical restraint have been attributed to positional asphyxia, a conclusion primarily based on opinion and reviews of case studies. This review sought to identify the current scientific evidence available in regard to the aetiology of adverse events or death occurring during or in close proximity to physical restraint. A systematic search of electronic databases (SPORTDiscus, AMED, CINAHL, MEDLINE, PsycINFO) for papers published in English, between 1980 and 2011, using keywords that related to restraint, restraint position and cardiovascular function resulted in 11 experimental papers being found for review. The term positional asphyxia as a mechanism for sudden death is poorly understood. The literature shows that restraint position has the ability to impede life-maintaining physiological functions, but that the imposed impediment is not uniform across all restraint positions/techniques. Further research is required to ascertain the risks posed by struggling during restraint for more prolonged periods of time and in different positions using varied techniques of restraint. This research should seek to and rank known or future risk factors of adverse events occurring during restraint, seeking to understand the interactions and if present the cumulative effect of these risk factors. Finally, future research should focus on populations other than apparently healthy male adults.

  11. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  12. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  13. Cryocooler Prognostic Health Management System

    NASA Astrophysics Data System (ADS)

    Shah, A.; Penswick, L.; Dodson, C.; Roberts, T.

    2008-03-01

    High performance sensors are playing an increasingly important role in all aspects of all critical DoD missions. There is a family of sensors that operate with improved sensitivities if cooled to very low (cryogenic) temperatures. For these sensors, a healthy and reliable mechanical refrigeration system (cryocooler) is required. The ability to accurately predict the "health" or remaining useful life of the cryocooler has significant benefits from the viewpoint of ensuring that mission critical functions can be carried out with a high probability of success. The paper provides an overview and approaches used for the development of a Cryocooler Prognostic Health Management System (CPHMS) capable of assessing the cryocooler "health" from the viewpoint of the level of performance degradation and/or the potential for near term failure. Additionally, it quantifies the reliable remaining useful life of the cryocooler. While the proposed system is focused on the specific application to linear drive cryocoolers, especially for DoD, many of the attributes of the system can be applied to other specialized system hardware in both commercial and U.S. Government agency for situations where it is critical that all aspects of the hardware "health" and "remaining useful life" be fully understood. Several benefits of the health monitoring system are also described in the paper.

  14. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  15. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

  16. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  17. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  18. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  19. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental...

  20. Stimulant Treatment over Five Years: Adherence, Effectiveness, and Adverse Effects.

    ERIC Educational Resources Information Center

    Charach, Alice; Ickowicz, Abel; Schachar, Russell

    2004-01-01

    Objective: To evaluate the impact of adherence and medication status on effectiveness and adverse effects of stimulant use in children with attention-deficit/hyperactivity disorder (ADHD) over 5 years. Method: Seventy-nine of 91 participants in a 12-month randomized controlled trial of methylphenidate and parent groups enrolled in a follow-up…

  1. Immunomodulatory drugs: Oral and systemic adverse effects

    PubMed Central

    Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.

    2014-01-01

    Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016

  2. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  3. Infarct volume after glioblastoma surgery as an independent prognostic factor

    PubMed Central

    Bette, Stefanie; Wiestler, Benedikt; Kaesmacher, Johannes; Huber, Thomas; Gerhardt, Julia; Barz, Melanie; Delbridge, Claire; Ryang, Yu-Mi; Ringel, Florian; Zimmer, Claus; Meyer, Bernhard; Boeckh-Behrens, Tobias; Kirschke, Jan S.; Gempt, Jens

    2016-01-01

    Postoperative ischemia is associated with reduced functional independence measured by karnofsky performance score (KPS), which correlates well with overall survival. Other studies suggest that postoperative hypoxia might initiate infiltrative tumor growth. Therefore, aim of this study was to analyze the impact of infarct volume on overall survival and progression free survival (PFS) of glioblastoma patients. 251 patients with surgery for a newly diagnosed glioblastoma (WHO IV) were retrospectively assessed. Pre- and postoperative KPS, date of death/last follow-up and histopathological markers were recorded. Pre- and postoperative tumor volume and the volume of postoperative infarction were manually segmented. A significant correlation of infarct volume with postoperative KPS decrease (P = 0.001) was observed. Infarct volume showed a significant impact on overall survival (P = 0.014), but not on PFS (P = 0.112) in univariate analysis. This effect increased in the subgroup of patients with near-total tumor resection (> 90%) (overall survival: P = 0.006, PFS: P = 0.066). Infarct volume remained as an independent prognostic factor for overall survival in multivariate analysis (HR 1.013 [1.000–1.026], P = 0.042) including other prognostic factors (age, extent of resection, postoperative KPS). Postoperative infarct volume significantly correlates as an independent factor with overall survival after glioblastoma surgery. Besides the influence of perioperative infarction on postoperative KPS, postoperative hypoxia might also have an effect on tumor biology initiating infiltrative growth and therefore impaired survival. PMID:27566556

  4. Stage Separation Failure: Model Based Diagnostics and Prognostics

    NASA Technical Reports Server (NTRS)

    Luchinsky, Dmitry; Hafiychuk, Vasyl; Kulikov, Igor; Smelyanskiy, Vadim; Patterson-Hine, Ann; Hanson, John; Hill, Ashley

    2010-01-01

    Safety of the next-generation space flight vehicles requires development of an in-flight Failure Detection and Prognostic (FD&P) system. Development of such system is challenging task that involves analysis of many hard hitting engineering problems across the board. In this paper we report progress in the development of FD&P for the re-contact fault between upper stage nozzle and the inter-stage caused by the first stage and upper stage separation failure. A high-fidelity models and analytical estimations are applied to analyze the following sequence of events: (i) structural dynamics of the nozzle extension during the impact; (ii) structural stability of the deformed nozzle in the presence of the pressure and temperature loads induced by the hot gas flow during engine start up; and (iii) the fault induced thrust changes in the steady burning regime. The diagnostic is based on the measurements of the impact torque. The prognostic is based on the analysis of the correlation between the actuator signal and fault-induced changes in the nozzle structural stability and thrust.

  5. Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases.

    PubMed

    Kahlert, Christoph; Klupp, Fee; Brand, Karsten; Lasitschka, Felix; Diederichs, Sven; Kirchberg, Johanna; Rahbari, Nuh; Dutta, Shamik; Bork, Ulrich; Fritzmann, Johannes; Reissfelder, Christoph; Koch, Moritz; Weitz, Juergen

    2011-10-01

    The tumor edge of colorectal cancer and its adjacent peritumoral tissue is characterized by an invasion front-specific expression of genes that contribute to angiogenesis or epithelial-to-mesenchymal transition. Dysregulation of these genes has a strong impact on the invasion behavior of tumor cells. However, the invasion front-specific expression of microRNA (miRNA) still remains unclear. Therefore, the aim of the present study was to investigate miRNA expression patterns at the invasion front of colorectal liver metastases. Laser microdissection of colorectal liver metastases was performed to obtain separate tissue compartments from the tumor center, tumor invasion front, liver invasion front and pure liver parenchyma. Microarray expression analysis revealed 23 miRNA downregulated in samples from the tumor invasion front with respect to the same miRNA in the liver, the liver invasion front or the tumor center. By comparing samples from the liver invasion front with samples from pure liver parenchyma, the tumor invasion front and the tumor center, 13 miRNA were downregulated. By quantitative RT-PCR, we validated the liver invasion front-specific downregulation of miR-19b, miR-194, let-7b and miR-1275 and the tumor invasion front-specific downregulation of miR-143, miR- 145, let-7b and miR-638. Univariate analysis demonstrated that enhanced expression of miR-19b and miR-194 at the liver invasion front, and decreased expression of let-7 at the tumor invasion front, is an adverse prognostic marker of tumor recurrence and overall survival. In conclusion, the present study suggests that invasion front-specific downregulation of miRNA in colorectal liver metastases plays a pivotal role in tumor progression.

  6. [Prognostic value of beta-2-microglobulin in Hodgkin disease in young adults].

    PubMed

    Fleury, J; Tortochaux, J; Legros, M; Cure, H; Kwiatkowski, F; Ferrière, J P; Travade, P; Dionet, C; Gaillard, G; Chassagne, J

    1994-07-01

    From 1977 to 1989, we measured serum beta-2-microglobulin (beta 2-MG) levels from 64 unselected and untreated patients, between 18 to 50-year-old, affected by Hodgkin's disease. Serum beta 2-MG level was measured by radioimmunoassay (Phadebas beta 2 microtest). Then, all patients received a chemotherapy such as MOPP or alternating MOPP/ABVD followed or not by radiotherapy. Elevated serum beta 2-MG level (> 2.4 mg/l) is associated with advanced stage disease (stage III-IV), presence of systemic symptoms and bulky tumor. Nevertheless, a multivariate analysis shows that the serum beta 2-MG level is the most significant prognostic indicator for disease free survival. The prognostic value of serum beta 2-MG is demonstrated for myeloma and non Hodgkin's lymphoma. A few authors have evaluated the prognostic impact of serum beta 2-MG in Hodgkin's disease. This study requires confirmation by multicentric and prospective trial.

  7. Changing Medicine and Building Community: Maine’s Adverse Childhood Experiences Momentum

    PubMed Central

    Forstadt, Leslie; Cooper, Sally; Andrews, Sue Mackey

    2015-01-01

    Physicians are instrumental in community education, prevention, and intervention for adverse childhood experiences. In Maine, a statewide effort is focusing on education about adverse childhood experiences and ways that communities and physicians can approach childhood adversity. This article describes how education about adversity and resilience can positively change the practice of medicine and related fields. The Maine Resilience Building Network brings together ongoing programs, supports new ventures, and builds on existing resources to increase its impact. It exemplifies the collective impact model by increasing community knowledge, affecting medical practice, and improving lives. PMID:25902346

  8. Prognostic Disclosures to Children: A Historical Perspective

    PubMed Central

    Sisk, Bryan A.; Bluebond-Langner, Myra; Wiener, Lori; Mack, Jennifer; Wolfe, Joanne

    2016-01-01

    Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Prior to 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a “protective” approach to disclosure, where children were shielded from the harms of bad news. We identified four main arguments in the literature at this time supporting this “protective” approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more “open” approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this “open” approach. Then by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from “never tell” to “always tell”. In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple “black and white” recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight four categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. PMID:27561728

  9. Are Food Insecurity’s Health Impacts Underestimated in the U.S. Population? Marginal Food Security Also Predicts Adverse Health Outcomes in Young U.S. Children and Mothers123

    PubMed Central

    Cook, John T.; Black, Maureen; Chilton, Mariana; Cutts, Diana; Ettinger de Cuba, Stephanie; Heeren, Timothy C.; Rose-Jacobs, Ruth; Sandel, Megan; Casey, Patrick H.; Coleman, Sharon; Weiss, Ingrid; Frank, Deborah A.

    2013-01-01

    This review addresses epidemiological, public health, and social policy implications of categorizing young children and their adult female caregivers in the United States as food secure when they live in households with “marginal food security,” as indicated by the U.S. Household Food Security Survey Module. Existing literature shows that households in the US with marginal food security are more like food-insecure households than food-secure households. Similarities include socio-demographic characteristics, psychosocial profiles, and patterns of disease and health risk. Building on existing knowledge, we present new research on associations of marginal food security with health and developmental risks in young children (<48 mo) and health in their female caregivers. Marginal food security is positively associated with adverse health outcomes compared with food security, but the strength of the associations is weaker than that for food insecurity as usually defined in the US. Nonoverlapping CIs, when comparing odds of marginally food-secure children’s fair/poor health and developmental risk and caregivers’ depressive symptoms and fair/poor health with those in food-secure and -insecure families, indicate associations of marginal food security significantly and distinctly intermediate between those of food security and food insecurity. Evidence from reviewed research and the new research presented indicates that households with marginal food security should not be classified as food secure, as is the current practice, but should be reported in a separate discrete category. These findings highlight the potential underestimation of the prevalence of adverse health outcomes associated with exposure to lack of enough food for an active, healthy life in the US and indicate an even greater need for preventive action and policies to limit and reduce exposure among children and mothers. PMID:23319123

  10. The prognostic factors for patients with hematological malignancies admitted to the intensive care unit.

    PubMed

    Cheng, Qian; Tang, Yishu; Yang, Qing; Wang, Erhua; Liu, Jing; Li, Xin

    2016-01-01

    Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.

  11. Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

    PubMed

    Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

    2015-07-30

    A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points).

  12. The association of chronic adversity with psychiatric disorder and disorder severity in adolescents.

    PubMed

    Benjet, Corina; Borges, Guilherme; Méndez, Enrique; Fleiz, Clara; Medina-Mora, Maria Elena

    2011-09-01

    The purpose of this paper is to estimate the impact of chronic adversity on psychopathology in adolescents, taking into account the type of adversity, number of adversities experienced and type of psychiatric disorder, as well as to estimate the impact on severity of the disorder. A total of 3,005 male and female adolescents from the Mexican Adolescent Mental Health Survey aged 12-17 years were interviewed in a stratified multistage general population probability survey. Assessment of 20 DSM-IV disorders, disorder severity and 12 chronic childhood adversities were assessed with the adolescent version of the World Mental Health Composite International Diagnostic Interview (WMH-CIDI-A). Family dysfunction adversities including abuse presented the most consistent associations between chronic adversity and psychopathology and their impact was generally non-specific with regard to the type of disorder. Parental divorce, parental death and economic adversity were not individually associated with psychopathology. Among those with a psychiatric disorder, sexual abuse and family violence were associated with having a seriously impairing disorder. The odds of having a psychiatric disorder and a serious disorder increased with increasing numbers of adversities; however, each additional adversity increased the odds at a decreasing rate. While the study design does not allow for conclusions regarding causality, these findings suggest general pathways from family dysfunction to psychopathology rather than specific associations between particular adversities and particular disorders, and provide further evidence for the importance of family-focused intervention and prevention efforts.

  13. Adverse responses to local anaesthetics.

    PubMed

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  14. Adverse Outcomes in Group Psychotherapy

    PubMed Central

    Roback, Howard B.

    2000-01-01

    Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735

  15. Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

    PubMed Central

    Zhu, Jia-yu; Liu, Cheng-cheng; Wang, Liang; Zhong, Mei; Tang, Hai-lin; Wang, Hua

    2017-01-01

    The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

  16. Treatment related toxicity in BRCA1-associated epithelial ovarian cancer – is DNA repairing impairment associated with more adverse events?

    PubMed Central

    Budryk, Magdalena; Nowara, Elżbieta; Starzyczny-Słota, Danuta

    2016-01-01

    Aim of the study The presence of BRCA germline mutations in patients with ovarian cancer has been shown to have predictive and prognostic significance, including increased platinum-sensitivity. The aim of the study was to evaluate if patients with BRCA1-associated ovarian cancer have more treatment related adverse events and, if so, does it have impact on chemotherapy outcomes. Material and methods We conducted a retrospective analysis of medical records of 172 patients with newly diagnosed epithelial ovarian cancer, treated in Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch between 2007 and 2013. Ninety-six of these patients have known BRCA mutation status – 21 patients were BRCA1(+) and 75 BRCA1(–). Analysed treatment related adverse events (AE’s) were: haematological toxicity, nausea/vomiting, neuropathy and mucositis. Results Grade 3–4 haematological AE’s were significantly more common among BRCA1(+) patients (OR = 3.86; 95% CI: 1.14–13.23; p = 0.02). There was no association between BRCA1 mutation status and neuropathy (p = 0.73) or nausea/vomiting (p = 0.91). Occurrence of above mentioned AE’s has no significant association with PFS (p = 0.75, 0.64, 0.97 respectively) and OS (p = 0.64, 0.69, 0.73 respectively). Conclusions Among patients with BRCA1-associated epithelial ovarian cancer we observed significantly more grade 3–4 haematological complications after chemotherapy. However, occurrence of AE’s did not correlate with better outcomes in this subgroup.

  17. A Distributed Prognostic Health Management Architecture

    NASA Technical Reports Server (NTRS)

    Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

    2009-01-01

    This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current state-of-the-art PHM systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to loss of functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become unsuitable for successful deployment, and efficient distributed architectures are required. A distributed architecture though, is not effective unless there is an algorithmic framework to take advantage of its unique abilities. The health management paradigm envisaged here incorporates a heterogeneous set of system components monitored by a varied suite of sensors and a particle filtering (PF) framework that has the power and the flexibility to adapt to the different diagnostic and prognostic needs. Both the diagnostic and prognostic tasks are formulated as a particle filtering problem in order to explicitly represent and manage uncertainties; however, typically the complexity of the prognostic routine is higher than the computational power of one computational element ( CE). Individual CEs run diagnostic routines until the system variable being monitored crosses beyond a nominal threshold, upon which it coordinates with other networked CEs to run the prognostic routine in a distributed fashion. Implementation results from a network of distributed embedded devices monitoring a prototypical aircraft electrical power system are presented, where the CEs are Sun Microsystems Small Programmable Object Technology (SPOT) devices.

  18. Evaluating Algorithm Performance Metrics Tailored for Prognostics

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

    2009-01-01

    Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

  19. Prognostic Value of Serum Free Light Chains Measurements in Multiple Myeloma Patients

    PubMed Central

    Bermudo Guitarte, Carmen; Menéndez Valladares, Paloma; Rojas Noboa, Johanna Carolina; Kestler, Krysta; Duro Millán, Rafael

    2016-01-01

    Background The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment. Materials and Methods 180 patients with a median age of 69 years were followed-up for a median time of 35 (18–61) months. The sFLC ratio (sFLCR) was calculated using the monoclonal sFLC as numerator. Patients were divided in two groups according to a sFLCR cut-off based on ROC analysis. The primary endpoints were the Overall Survival (OS) and the Progression-free Survival (PFS). Additionally, thirty-six MM patients treated with novel agents (Bortezomib/Dexamethasone) that achieved Complete Response (CR) or stringent CR (sCR) before autologous stem cell transplantation were studied to assess the impact of sCR in Disease Free Survival (DFS) and OS. Results During follow-up there were 72 disease-related deaths. The 5-years OS for the whole group was 51%. However, separate analysis of patients with sFLCR above (group “high”) or below (groups “low”) the cut-off value of 47 shows an OS of 23% and 73%, respectively (HR = 5.03, 95%CI 2.99–8.50, p<0.001). In addition, analysis by ISS stage, showed that the presence of high sFLCR was always significantly associated with a worse OS. Multivariate analysis identified sFLCR (HR = 4.42, 95%CI 2.57–7.60, p<0.001) and beta-2-microglobulin (B2M) (HR = 3.04, 95%IC 1.75–5.31, p<0.001) as independent risk factors for adverse outcome. A new risk stratification model based on sFLCR≥47 and B2M>3.5 mg/L provided a statistically more significant result for this cohort

  20. Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

    PubMed Central

    Gu, Liangyou; Ma, Xin; Li, Hongzhao; Chen, Luyao; Xie, Yongpeng; Zhao, Chaofei; Luo, Guoxiong; Zhang, Xu

    2016-01-01

    To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50–11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC. PMID:27035802

  1. Management of Cattle Exposed to Adverse Environmental Conditions.

    PubMed

    Mader, Terry L; Griffin, Dee

    2015-07-01

    During periods of adverse weather, optimum conditions for animal comfort and performance are compromised. Use of alternative supplementation programs need to be considered for livestock challenged by adverse environmental conditions. Use of additional water for consumption and cooling, shade, and/or alternative management strategies need to be considered to help livestock cope with heat stress. For animals reared outside during winter, strategies that increase animal space and environmental buffers need to be used to minimize effects of mud, wet conditions, and windchill. There are ample opportunities for livestock producers to enhance animal welfare and minimize the impact of environmental stress.

  2. Algorithm development for Prognostics and Health Management (PHM).

    SciTech Connect

    Swiler, Laura Painton; Campbell, James E.; Doser, Adele Beatrice; Lowder, Kelly S.

    2003-10-01

    This report summarizes the results of a three-year LDRD project on prognostics and health management. System failure over some future time interval (an alternative definition is the capability to predict the remaining useful life of a system). Prognostics are integrated with health monitoring (through inspections, sensors, etc.) to provide an overall PHM capability that optimizes maintenance actions and results in higher availability at a lower cost. Our goal in this research was to develop PHM tools that could be applied to a wide variety of equipment (repairable, non-repairable, manufacturing, weapons, battlefield equipment, etc.) and require minimal customization to move from one system to the next. Thus, our approach was to develop a toolkit of reusable software objects/components and architecture for their use. We have developed two software tools: an Evidence Engine and a Consequence Engine. The Evidence Engine integrates information from a variety of sources in order to take into account all the evidence that impacts a prognosis for system health. The Evidence Engine has the capability for feature extraction, trend detection, information fusion through Bayesian Belief Networks (BBN), and estimation of remaining useful life. The Consequence Engine involves algorithms to analyze the consequences of various maintenance actions. The Consequence Engine takes as input a maintenance and use schedule, spares information, and time-to-failure data on components, then generates maintenance and failure events, and evaluates performance measures such as equipment availability, mission capable rate, time to failure, and cost. This report summarizes the capabilities we have developed, describes the approach and architecture of the two engines, and provides examples of their use. 'Prognostics' refers to the capability to predict the probability of

  3. Weight-of-evidence evaluation of an adverse outcome ...

    EPA Pesticide Factsheets

    Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

  4. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  5. Diagnosis, progression patterns and prognostication in mastocytosis.

    PubMed

    Sperr, Wolfgang R; Valent, Peter

    2012-06-01

    Mastocytosis is a heterogeneous group of disorders defined by abnormal growth and accumulation of clonal mast cells. CM is the predominant variant in childhood, whereas the majority of adult patients present with systemic mastocytosis. In over 80% of the latter patients, the KIT mutation D816V is detectable. Whereas childhood mastocytosis often resolves spontaneously before adolescence and has a good prognosis, in most adult patients mastocytosis is a persistent systemic disorder. The course and prognosis in these patients are variable; in indolent variants, the clinical course remains stable over years or even decades. In advanced mastocytosis, the prognosis is less favorable despite novel drugs counteracting growth of neoplastic mast cells. Although WHO criteria are clearly separating prognostic subsets of mastocytosis, little is known about specific prognostic factors predicting the outcome in individual patients. In this article, we review current concepts in mastocytosis, including prognostic parameters for indolent and advanced systemic mastocytosis.

  6. Prognostic Awareness and Communication of Prognostic Information in Malignant Glioma: A Systematic Review

    PubMed Central

    Diamond, Eli L.; Corner, Geoffrey W.; DeRosa, Antonio; Breitbart, William; Applebaum, Allison J.

    2016-01-01

    Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients’ and caregivers’ prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25% to 100% of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed. PMID:24874468

  7. Prognostic awareness and communication of prognostic information in malignant glioma: a systematic review.

    PubMed

    Diamond, Eli L; Corner, Geoffrey W; De Rosa, Antonio; Breitbart, William; Applebaum, Allison J

    2014-09-01

    Malignant glioma (MG) is a devastating neurological disease with a uniformly poor prognosis and a clinical course characterized by progressive functional and cognitive impairment. A small body of literature addresses patients' and caregivers' prognostic awareness (PA), or understanding of prognosis in patients with cancer. Studies that examine PA and desire for prognostic information among patients with MG are limited. We sought to review the existing literature on PA and communication of prognostic information to patients with MG. Fourteen studies examining PA or experience and preferences regarding communication of prognostic information were included. The definition and measurement of PA across studies varied, and the prevalence of accurate PA ranged from 25 to 100 % of participants. There is likely a subset of patients who do not desire accurate prognostic information, although the patient and disease characteristics that predict this preference are currently unknown. This review suggests that patients with MG desire prognostic information communicated in a manner that preserves hope. Systematic investigation to define communication needs for prognostic information in the unique clinical setting of MG is needed.

  8. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    ERIC Educational Resources Information Center

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  9. The international serious adverse events consortium.

    PubMed

    Holden, Arthur L; Contreras, Jorge L; John, Sally; Nelson, Matthew R

    2014-11-01

    The International Serious Adverse Events Consortium is generating novel insights into the genetics and biology of drug-induced serious adverse events, and thereby improving pharmaceutical product development and decision-making.

  10. Prognostic Factors in Childhood Leukemia (ALL or AML)

    MedlinePlus

    ... Diagnosis, and Types Prognostic Factors in Childhood Leukemia (ALL or AML) Certain factors that can affect a ... myelogenous leukemia (AML). Prognostic factors for children with ALL Children with ALL are often divided into risk ...

  11. Adverse reactions to drug additives.

    PubMed

    Simon, R A

    1984-10-01

    There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

  12. Early life adversity: Lasting consequences for emotional learning.

    PubMed

    Krugers, Harm J; Arp, J Marit; Xiong, Hui; Kanatsou, Sofia; Lesuis, Sylvie L; Korosi, Aniko; Joels, Marian; Lucassen, Paul J

    2017-02-01

    The early postnatal period is a highly sensitive time period for the developing brain, both in humans and rodents. During this time window, exposure to adverse experiences can lastingly impact cognitive and emotional development. In this review, we briefly discuss human and rodent studies investigating how exposure to adverse early life conditions - mainly related to quality of parental care - affects brain activity, brain structure, cognition and emotional responses later in life. We discuss the evidence that early life adversity hampers later hippocampal and prefrontal cortex functions, while increasing amygdala activity, and the sensitivity to stressors and emotional behavior later in life. Exposure to early life stress may thus on the one hand promote behavioral adaptation to potentially threatening conditions later in life -at the cost of contextual memory formation in less threatening situations- but may on the other hand also increase the sensitivity to develop stress-related and anxiety disorders in vulnerable individuals.

  13. Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

    PubMed

    Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

    2015-01-01

    Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

  14. HVPG signature: A prognostic and predictive tool in hepatocellular carcinoma

    PubMed Central

    Xiang, Yi; Chen, Jinjun; Zhao, Jianbo; Li, Jing; Qi, Fu-Zhen; Xu, Yong

    2016-01-01

    Hepatic venous pressure gradient (HVPG) measurement provides independent prognostic value in patients with cirrhosis, and the prognostic and predictive role of HVPG in hepatocellular carcinoma (HCC) also has been explored. The management of HCC is limited to the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) guidelines that consider that HVPG≥10 mmHg to be a contraindication for hepatic resection (HR), otherwise other treatment modalities are recommended. Current studies show that a raised HVPG diagnosed directly or indirectly leads to a negative prognosis of patients with HCC and cirrhosis, but HVPG greater than 10 mmHg should not be regarded as an absolute contraindication for HR. Selecting direct or surrogate measurement of HVPG is still under debate. Only several studies reported the impact of HVPG in negative prognosis of HCC patients after liver transplantation (LT) and the value of HVPG in the prediction of HCC development, which need to be further validated. PMID:27566593

  15. Prognostics Health Management for Advanced Small Modular Reactor Passive Components

    SciTech Connect

    Meyer, Ryan M.; Ramuhalli, Pradeep; Coble, Jamie B.; Mitchell, Mark R.; Wootan, David W.; Hirt, Evelyn H.; Berglin, Eric J.; Bond, Leonard J.; Henager, Charles H.

    2013-10-18

    In the United States, sustainable nuclear power to promote energy security is a key national energy priority. Advanced small modular reactors (AdvSMR), which are based on modularization of advanced reactor concepts using non-light-water reactor (LWR) coolants such as liquid metal, helium, or liquid salt may provide a longer-term alternative to more conventional LWR-based concepts. The economics of AdvSMRs will be impacted by the reduced economy-of-scale savings when compared to traditional LWRs and the controllable day-to-day costs of AdvSMRs are expected to be dominated by operations and maintenance costs. Therefore, achieving the full benefits of AdvSMR deployment requires a new paradigm for plant design and management. In this context, prognostic health management of passive components in AdvSMRs can play a key role in enabling the economic deployment of AdvSMRs. In this paper, the background of AdvSMRs is discussed from which requirements for PHM systems are derived. The particle filter technique is proposed as a prognostics framework for AdvSMR passive components and the suitability of the particle filter technique is illustrated by using it to forecast thermal creep degradation using a physics-of-failure model and based on a combination of types of measurements conceived for passive AdvSMR components.

  16. Prognosis Research Strategy (PROGRESS) 2: prognostic factor research.

    PubMed

    Riley, Richard D; Hayden, Jill A; Steyerberg, Ewout W; Moons, Karel G M; Abrams, Keith; Kyzas, Panayiotis A; Malats, Núria; Briggs, Andrew; Schroter, Sara; Altman, Douglas G; Hemingway, Harry

    2013-01-01

    Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.

  17. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  18. Loss of ALCAM expression is linked to adverse phenotype and poor prognosis in breast cancer: a TMA-based immunohistochemical study on 2,197 breast cancer patients.

    PubMed

    Burandt, Eike; Bari Noubar, Tanaz; Lebeau, Annette; Minner, Sarah; Burdelski, Christoph; Jänicke, Fritz; Müller, Vollkmar; Terracciano, Luigi; Simon, Ronald; Sauter, Guido; Wilczak, Waldemar; Lebok, Patrick

    2014-12-01

    Activated leukocyte cell adhesion molecule (ALCAM) is a membranous cell adhesion protein that is often expressed in breast cancer. Data on the prognostic impact of ALCAM expression is highly controversial in this cancer. To evaluate the clinical impact of ALCAM expression in a sufficiently large patient cohort, we utilized a tissue microarray (TMA) containing more than 2,100 primary breast cancers with clinical follow-up data by immunohistochemistry. TMA spots containing normal breast epithelium showed moderate to strong membranous ALCAM staining. ALCAM staining was strong in 66.2%, moderate in 10.9%, weak in 11.1% and absent in 11.8% of 1,778 (80.9%) interpretable breast cancer tissue spots. Decreased ALCAM expression was significantly associated with advanced tumor size (p=0.0017), unfavorable tumor grade (p<0.0001), negative ER and PR status (p<0.0001 each) as well as high Ki67 labeling index (p<0.0001). Cancers with ACLAM expression loss had a significantly poorer overall (p<0.0001) and disease-specific survival (p=0.0088). This association also held true in the subset of nodal positive cancers (p<0.0001). In conclusion, these data demonstrate that ALCAM is generally expressed in normal and cancerous breast epithelium and that a marked reduction of ALCAM expression characterizes a subset of breast cancer patients with adverse tumor characteristics and unfavorable clinical outcome.

  19. Misuse of topical corticosteroids: A clinical study of adverse effects

    PubMed Central

    Dey, Vivek Kumar

    2014-01-01

    Background: Misuse of topical corticosteroids is a widespread phenomenon among young people in India, especially women. The practice is associated with significant adverse effects and poor awareness of these effects among the general public. Aim: This study was conducted to examine the misuse and adverse effects of topical corticosteroids among the people in Bastar region in Chhattisgarh state of India. Materials and Methods: Data collected from patients presenting with at least one of the adverse effects of topical corticosteroids as the chief complaint, from November 2010 to October 2011. Results: Out of the 6723 new patients, 379 (5.63%) had presented with misuse and adverse effects of topical corticosteroids, of whom 78.89% were females. More than 65% of the patients were in the age group 10-29 years. The main reason for using the topical corticosteroids was to lighten skin colour and treat melasma and suntan. Acne (37.99%) and telangiectasia (18.99%) were the most common adverse effects noted. Conclusions: Misuse of topical corticosteroids has a huge impact on dermatological practice, leading to a significant proportion of visits to the dermatologist. This hydra-headed problem needs multi-dimensional interventions, involving educational, legal and managerial approaches with cooperation from different sectors of society. PMID:25396124

  20. Towards the regulation of aerosol emissions by their potential health impact: Assessing adverse effects of aerosols from wood combustion and ship diesel engine emissions by combining comprehensive data on the chemical composition and their toxicological effects on human lung cells

    NASA Astrophysics Data System (ADS)

    Zimmermann, R.; Streibel, T.; Dittmar, G.; Kanashova, T.; Buters, J.; Öder, S.; Paur, H. R.; Dilger, M.; Weiss, C.; Harndorf, H.; Stengel, B.; Hirvonen, M. R.; Jokiniemi, J.; Hiller, K.; Sapcariu, S.; Sippula, O.; Orasche, J.; Müller, L.; Rheda, A.; Passig, J.; Radischat, C.; Czech, H.; Tiita, P.; Jalava, P.; Kasurinen, S.; Schwemer, T.; Yli-Prilä, P.; Tissari, J.; Lamberg, H.; Schnelle-Kreis, J.

    2014-12-01

    Ship engine emissions are important regarding lung and cardiovascular diseases in coastal regions worldwide. Bio mass burning is made responsible for adverse health effects in many cities and rural regions. The Virtual Helmholtz Institute-HICE (www.hice-vi.eu) addresses chemical & physical properties and health effects of anthropogenic combustion emissions. Typical lung cell responses to combustion aerosols include inflammation and apoptosis, but a molecular link with the specific chemical composition in particular of ship emissions has not been established. Through an air-liquid interface exposure system (ALI), we exposed human lung cells at-site to exhaust fumes from a ship engine running on common heavy fuel oil (HFO) and cleaner-burning diesel fuel (DF) as well as to emissions of wood combustion compliances. A special field deployable ALI-exposition system and a mobile S2-biological laboratory were developed for this study. Human alveolar basal epithelial cells (A549 etc.) are ALI-exposed to fresh, diluted (1:40-1:100) combustion aerosols and subsequently were toxicologically and molecular-biologically characterized. Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling to characterise the cellular responses. The HFO ship emissions contained high concentrations of toxic compounds (transition metals, organic toxicants) and particle masses. The cellular responses included inflammation and oxidative stress. Surprisingly, the DF ship emissions, which predominantly contain rather "pure" carbonaceous soot and much less known toxicants, induced significantly broader biological effects, affecting essential cellular pathways (e.g., mitochondrial function and intracellular transport). Therefore the use of distillate fuels for shipping (this is the current emission reduction strategy of the IMO) appears insufficient for diminishing health effects. The study suggests rather reducing the particle emissions

  1. The preoperative sensitive-modified Glasgow prognostic score is superior to the modified Glasgow prognostic score in predicting long-term survival for esophageal squamous cell carcinoma

    PubMed Central

    Tian, Rui; Zhang, Fei; Sun, Peng; Wu, Jing; Yan, Hong; Wu, Ai-Ran; Zhang, Min; Jiang, Yu-Lu; Lu, Yan-Hong; Xu, Qiu-Yan; Zhan, Xiao-Hong; Zhang, Rong-Xin; Qian, Li-Ting; He, Jie

    2016-01-01

    The present study was designed to investigate the prognostic significance of the preoperative sensitive-modified Glasgow prognostic score (S-mGPS) and its superiority in esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative albumin and C-reactive protein (CRP) levels were retrospectively collected in 442 patients who underwent transthoracic esophagectomy. The S-mGPS was calculated before surgery based on optimal cutoff values of 45.6 g/L for albumin and 10.0 mg/L for CRP. 360, 74 and 8 cases were assigned an mGPS of 0, 1 and 2, respectively. In contrast, the S-mGPS was 0 in 114, 1 in 258 and 2 in 70 patients. Of the 360 patients with an mGPS of 0, 246 migrated to the S-mGPS-1 group. Both mGPS and S-mGPS were significantly correlated with tumor length, depth of invasion, pathological tumor-node-metastasis (pTNM) stage and adjuvant treatment. In addition, they were significantly associated with disease free survival (DFS) and overall survival (OS) in univariate analysis. Furthermore, multivariate Cox regression analysis identified S-mGPS as an independent prognostic indicator for both DFS [hazard ratio (HR), 1.577; 95% confidence interval (CI), 1.149-2.163; P = 0.005] and OS (HR, 1.762; 95% CI, 1.250-2.484; P = 0.001), but not mGPS (HR, 0.957; 95% CI, 0.692-1.323; P = 0.790 for DFS and HR, 1.089; 95% CI, 0.781-1.517; P = 0.615 for OS, respectively). Moreover, subgroup analysis revealed that the prognostic impact of the S-mGPS was especially striking in pTNM stage II patients. The preoperative S-mGPS is superior to the mGPS as a prognostic predictor in patients with resectable ESCC. PMID:27528228

  2. Advanced Ground Systems Maintenance Prognostics Project

    NASA Technical Reports Server (NTRS)

    Harp, Janicce Leshay

    2014-01-01

    The project implements prognostics capabilities to predict when a component, system or subsystem will no longer meet desired functional or performance criteria, called the "end of life." The capability also provides an assessment of the "remaining useful life" of a hardware component.

  3. Requirements Flowdown for Prognostics and Health Management

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Saxena, Abhinav; Roychoudhury, Indranil; Celaya, Jose R.; Saha, Bhaskar; Saha, Sankalita

    2012-01-01

    Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by providing a reliable estimate of future system states. This estimate is a key for planning and decision making in an operational setting. While technology solutions have made considerable advances, the tie-in into the systems engineering process is lagging behind, which delays fielding of PHM-enabled systems. The derivation of specifications from high level requirements for algorithm performance to ensure quality predictions is not well developed. From an engineering perspective some key parameters driving the requirements for prognostics performance include: (1) maximum allowable Probability of Failure (PoF) of the prognostic system to bound the risk of losing an asset, (2) tolerable limits on proactive maintenance to minimize missed opportunity of asset usage, (3) lead time to specify the amount of advanced warning needed for actionable decisions, and (4) required confidence to specify when prognosis is sufficiently good to be used. This paper takes a systems engineering view towards the requirements specification process and presents a method for the flowdown process. A case study based on an electric Unmanned Aerial Vehicle (e-UAV) scenario demonstrates how top level requirements for performance, cost, and safety flow down to the health management level and specify quantitative requirements for prognostic algorithm performance.

  4. Prognostic Analysis of the Tactical Quiet Generator

    SciTech Connect

    Hively, Lee M

    2008-09-01

    The U.S. Army needs prognostic analysis of mission-critical equipment to enable condition-based maintenance before failure. ORNL has developed and patented prognostic technology that quantifies condition change from noisy, multi-channel, time-serial data. This report describes an initial application of ORNL's prognostic technology to the Army's Tactical Quiet Generator (TQG), which is designed to operate continuously at 10 kW. Less-than-full power operation causes unburned fuel to accumulate on internal components, thereby degrading operation and eventually leading to failure. The first objective of this work was identification of easily-acquired, process-indicative data. Two types of appropriate data were identified, namely output-electrical current and voltage, plus tri-axial acceleration (vibration). The second objective of this work was data quality analysis to avoid the garbage-in-garbage-out syndrome. Quality analysis identified more than 10% of the current data as having consecutive values that are constant, or that saturate at an extreme value. Consequently, the electrical data were not analyzed further. The third objective was condition-change analysis to indicate operational stress under non-ideal operation and machine degradation in proportion to the operational stress. Application of ORNL's novel phase-space dissimilarity measures to the vibration power quantified the rising operational stress in direct proportion to the less-than-full-load power. We conclude that ORNL's technology is an excellent candidate to meet the U.S. Army's need for equipment prognostication.

  5. The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction

    PubMed Central

    Cho, Jung Sun; Youn, Ho-Joong; Her, Sung-Ho; Park, Maen Won; Kim, Chan Joon; Park, Gyung-Min; Cho, Jae Yeong; Ahn, Youngkeun; Kim, Kye Hun; Park, Jong Chun; Seung, Ki Bae; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo; Han, Kyoo Rok; Kim, Hyo Soo

    2015-01-01

    The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR. PMID:26130953

  6. The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction.

    PubMed

    Cho, Jung Sun; Youn, Ho-Joong; Her, Sung-Ho; Park, Maen Won; Kim, Chan Joon; Park, Gyung-Min; Jeong, Myung Ho; Cho, Jae Yeong; Ahn, Youngkeun; Kim, Kye Hun; Park, Jong Chun; Seung, Ki Bae; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo; Han, Kyoo Rok; Kim, Hyo Soo

    2015-07-01

    The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.

  7. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted.

  8. Regional Longitudinal Myocardial Deformation Provides Incremental Prognostic Information in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Jensen, Jan Skov; Pedersen, Sune H.; Galatius, Søren; Fritz-Hansen, Thomas; Bech, Jan; Olsen, Flemming Javier; Mogelvang, Rasmus

    2016-01-01

    Background Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information. Method In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE). Results During a median-follow-up of 5.3 (IQR 2.5–6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters). Conclusion Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse

  9. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  10. Rethinking the Measurement of Adversity.

    PubMed

    Mersky, Joshua P; Janczewski, Colleen E; Topitzes, James

    2017-02-01

    Research on adverse childhood experiences (ACEs) has unified the study of interrelated risks and generated insights into the origins of disorder and disease. Ten indicators of child maltreatment and household dysfunction are widely accepted as ACEs, but further progress requires a more systematic approach to conceptualizing and measuring ACEs. Using data from a diverse, low-income sample of women who received home visiting services in Wisconsin ( N = 1,241), this study assessed the prevalence of and interrelations among 10 conventional ACEs and 7 potential ACEs: family financial problems, food insecurity, homelessness, parental absence, parent/sibling death, bullying, and violent crime. Associations between ACEs and two outcomes, perceived stress and smoking, were examined. The factor structure and test-retest reliability of ACEs was also explored. As expected, prevalence rates were high compared to studies of more representative samples. Except for parent/sibling death, all ACEs were intercorrelated and associated at the bivariate level with perceived stress and smoking. Exploratory factor analysis confirmed that conventional ACEs loaded on two factors, child maltreatment and household dysfunction, though a more complex four-factor solution emerged once new ACEs were introduced. All ACEs demonstrated acceptable test-retest reliability. Implications and future directions toward a second generation of ACE research are discussed.

  11. Conceptualizing prognostic awareness in advanced cancer: A systematic review

    PubMed Central

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2015-01-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

  12. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    PubMed

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  13. OAE: The Ontology of Adverse Events

    PubMed Central

    2014-01-01

    Background A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. Description The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term ‘adverse event’ denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. Conclusion OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of

  14. The Prognostic Value of Amplitude-Integrated EEG in Full-Term Neonates with Seizures

    PubMed Central

    Liu, Lili; Hou, Xinlin; Sun, Guoyu; Li, Lei; Liu, Yunzhe; Zhou, Congle; Gu, Ruolei; Luo, Yuejia

    2013-01-01

    Neonatal seizures pose a high risk for adverse outcome in survived infants. While the prognostic value of amplitude-integrated electroencephalogram (aEEG) is well established in neonates with encephalopathy and asphyxia, neonatal seizure studies focusing on the direct correlation between early aEEG measurement and subsequent neurologic outcome are scarce. In this study, the prognostic value of aEEG features was systematically analyzed in 143 full-term neonates to identify prognostic indicators of neurodevelopmental outcome. Neonatal aEEG features of background pattern, cyclicity, and seizure activity, as well as the etiology of neonatal seizures, were significantly associated with neurodevelopmental outcome at one year of age. aEEG background pattern was highly associated with neurologic outcomes (χ2 = 116.9), followed by aEEG cyclicity (χ2 = 87.2) and seizure etiology (χ2 = 79.3). Multiple linear regression showed that the four predictors explained 71.2% of the variation in neurological outcome, with standardized β coefficients of 0.44, 0.24, 0.22, and 0.14 for the predictors of aEEG background pattern, cyclicity, etiology, and aEEG seizure activity, respectively. This clinically applicable scoring system based on etiology and three aEEG indices would allow pediatricians to assess the risk for neurodevelopmental impairment and facilitate an early intervention in newborns developing seizures. PMID:24236076

  15. Prognostic Value of Epicardial Fat Volume Measurements by Computed Tomography: A Systematic Review of the Literature

    PubMed Central

    Spearman, James V.; Renker, Matthias; Schoepf, U. Joseph; Krazinski, Aleksander W.; Herbert, Teri L.; De Cecco, Carlo N.; Nietert, Paul J.; Meinel, Felix G.

    2015-01-01

    Objectives To perform a systematic review of the growing body of literature evaluating the prognostic value of epicardial fat volume (EFV) quantified by cross-sectional imaging for adverse clinical outcomes. Methods Two independent reviewers performed systematic searches on both PubMed and Scopus using search terms developed with a medical librarian. Peer-reviewed articles were selected based on the inclusion of outcome data, utilization of epicardial fat volume and sufficient reporting for analysis. Results A total of 411 studies were evaluated with 9 studies meeting the inclusion criteria. In all, the studies evaluated 10,252 patients. All 9 studies were based on CT measurements. Seven studies evaluated the prognostic value of EFV unadjusted for calcium score, and 6 of these studies found a significant association between EFV and clinical outcomes. Seven studies evaluated the incremental value of EFV beyond calcium scoring, and 6 of these studies found a significant association. Conclusions The majority of studies suggest that EFV quantification is significantly associated with clinical outcomes and provides incremental prognostic value over coronary artery calcium scoring. Future research should use a binary cut-off of 125mL for evaluation of EFV to provide consistency with other research. PMID:25925354

  16. PD-L2: A prognostic marker in chromophobe renal cell carcinoma?

    PubMed

    Erlmeier, Franziska; Weichert, Wilko; Autenrieth, Michael; Wiedemann, Max; Schrader, Andres Jan; Hartmann, Arndt; Ivanyi, Philipp; Steffens, Sandra

    2017-05-01

    In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for PD-L2 expression by immunohistochemistry. Expression data were associated with clinicopathological parameters and overall survival (OS). Twenty-three (28.4%) patients showed a PD-L2 > median (PD-L2 high) staining intensity. No significant association between clinicopathological parameters and PD-L2 expression was identified. A significant difference between 5- and 10-year OS in dependence of PD-L2 expression was found (PD-L2 low 96.4 and 87.7% vs. PD-L2 high 87.1 and 56%; log rank, p = 0.029). However, in multivariate analysis PD-L2 expression failed to be proofed as an independent prognostic factor. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of PD-L2 in a considerably large cohort of chRCC. Our results showed a significant diminished OS in dependence of PD-L2 expression. This implicates that PD-L2 might play a role as prognostic marker in chRCC demanding further evaluation.

  17. Distributed Prognostic Health Management with Gaussian Process Regression

    NASA Technical Reports Server (NTRS)

    Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

    2010-01-01

    Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

  18. Evaluation of etiologic and prognostic factors in neonatal convulsions.

    PubMed

    Yıldız, Edibe Pembegul; Tatlı, Burak; Ekici, Barış; Eraslan, Emine; Aydınlı, Nur; Calışkan, Mine; Ozmen, Meral

    2012-09-01

    This study evaluated etiologic and risk factors affecting long-term prognoses of neurologic outcomes in newborns with neonatal seizures. We enrolled patients at chronologic ages of 23-44 months, referred to the Department of Pediatric Neurology, Istanbul Medical Faculty, from January 1, 2007-December 31, 2009, after manifesting seizures in their first postnatal 28 days. Of 112 newborns, 41 were female, 71 were male, 33 were preterm, and 79 were full-term. Perinatal asphyxia (28.6%) and intracranial hemorrhage (17%) were the most common causes of neonatal seizures. Cerebral palsy developed in 27.6% of patients during follow-up. The incidence of epilepsy was 35.7%. Almost 50% of patients manifested developmental delay in one or more areas. Global developmental delay was the most common (50.8%) neurologic disorder. The correlation between gestational age or birth weight and adverse outcomes was nonsignificant. Etiology, Apgar score, need for resuscitation at birth, background electroencephalogram, neonatal status epilepticus, cranial imaging findings, type/duration of antiepileptic treatment, and response to acute treatment were all strong prognostic factors in neurologic outcomes. Neonatal seizures pose a threat of neurologic sequelae for preterm and full-term infants. Although the number of recognized etiologic factors in neonatal seizures has increased because of improvements in neonatology and diagnostic methods, perinatal asphyxia remains the most common factor.

  19. Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors

    PubMed Central

    Falloon, Judith; Bennett, John E.; Shaw, Pamela A.; Chaitt, Doreen; Baseler, Michael W.; Adelsberger, Joseph W.; Metcalf, Julia A.; Polis, Michael A.; Kovacs, Stephen J.; Kovacs, Joseph A.; Davey, Richard T.; Lane, H. Clifford; Masur, Henry

    2008-01-01

    Idiopathic CD4+ lymphocytopenia (ICL) is a rare non–HIV-related syndrome with unclear natural history and prognosis. This prospective natural history cohort study describes the clinical course, CD4 T lymphocyte kinetics, outcome, and prognostic factors of ICL. Thirty-nine patients (17 men, 22 women) 25 to 85 years old with ICL were evaluated between 1992 and 2006, and 36 were followed for a median of 49.5 months. Cryptococcal and nontuberculous mycobacterial infections were the major presenting opportunistic infections. Seven patients presented with no infection. In 32, CD4 T-cell counts remained less than 300/mm3 throughout the study period and in 7 normalized after an average of 31 months. Overall, 15 (41.6%) developed an opportunistic infection in follow-up, 5 (13.8%) of which were “AIDS-defining clinical conditions,” and 4 (11.1%) developed autoimmune diseases. Seven patients died, 4 from ICL-related opportunistic infections, within 42 months after diagnosis. Immunologic analyses revealed increased activation and turnover in CD4 but not CD8 T lymphocytes. CD8 T lymphocytopenia (< 180/mm3) and the degree of CD4 T cell activation (measured by HLA-DR expression) at presentation were associated with adverse outcome (opportunistic infection-related death; P = .003 and .02, respectively). This trial is registered at http://clinicaltrials.gov as #NCT00001319. PMID:18456875

  20. Prognostic impact of immune status and hematopoietic recovery before and after fludarabine, IV busulfan, and antithymocyte globulins (FB2 regimen) reduced-intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo-SCT).

    PubMed

    Le Bourgeois, Amandine; Lestang, Elsa; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Blin, Nicolas; Clavert, Aline; Tessoulin, Benoit; Dubruille, Viviane; Mahe, Beatrice; Roland, Virginie; Gastinne, Thomas; Le Gouill, Steven; Moreau, Philippe; Mohty, Mohamad; Planche, Lucie; Chevallier, Patrice

    2013-03-01

    This retrospective analysis aimed to assess hematopoietic and immune recovery in a cohort of 53 patients [males: n = 33; median age: 59 yr (range: 22-70)] who received a FB2 (fludarabine 120-150 mg/m² + IV busulfan 6.4 mg/kg + antithymocyte globulin thymoglobulin 5 mg/kg) reduced-intensity conditioning (RIC) allo-stem cells transplantations (SCT). With a median follow-up of 19 months (range: 2-53), the 2-yr overall survival, disease-free survival (DFS), relapse incidence, and non-relapse mortality were 63%, 59.5%, 35%, and 6%, respectively. In univariate analysis, the factors correlated with a significantly higher 2-yr OS and DFS were a higher total circulating lymphocytes count at transplant (>730/mm(3) ; OS: 81% vs. 43%, P = 0.02; DFS: 73% vs. 45.5%, P = 0.03) and a higher recovery of leukocytes (>5300/mm(3) ) (2-yr OS: 81% vs. 44%, P = 0.007; 2-yr DFS: 72% vs. 46%, P = 0.08), neutrophils (>3200/mm(3) ) (2-yr OS: 76% vs. 50%, P = 0.03; 2-yr DFS: 67% vs. 52.0%, P = 0.1), and monocytes (>590/mm(3) ; 2-yr OS: 80% vs. 45%, P = 0.004; 2-yr DFS: 76% vs. 42%, P = 0.01) at day +30 post-transplant. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm(3) ) and a higher monocytes count (>590/mm(3) ) at day +30 post-transplant. These results suggest that immune status and hematopoietic recovery before and after FB2 RIC allo-SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo-SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo-SCT.

  1. Hospital deaths and adverse events in Brazil

    PubMed Central

    2011-01-01

    Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103) and that related to preventable adverse events was 2.3% (25/1103). Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43) and the odds ratio adjusted for patient risk factors (OR 8.23) between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events. PMID:21929810

  2. Prognostic value of the lymphocyte monocyte ratio in patients with colorectal cancer

    PubMed Central

    Song, Wei; Wang, Kai; Zhang, Run-jin; Zou, Shu-bing

    2016-01-01

    Abstract Background: Inflammation plays a critical role in the pathogenesis and progression of cancer. A low lymphocyte-to-monocyte ratio (LMR) is reported be a poor prognostic factor in multiple malignancies. We performed a meta-analysis to evaluate the prognostic role of preoperative LMR in colorectal cancer (CRC). Methods: Studies investigating the prognostic role of preoperative LMR on survival in patients with CRC were systematically searched for in MEDLINE, EMBASE, Cochrane databases from inception up to August 2016. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were calculated using fixed-effects/random-effects models. Results: A total of nine studies comprising 8626 patients with CRC were included in the meta-analysis. The pooled analysis demonstrated that low LMR was significantly associated with decreased OS (HR: 0.63, 95% CI: 0.56–0.70, P < 0.001) and DFS/RFS (HR: 0.76, 95% CI: 0.68–0.84, P < 0.001). The negative prognostic impact of low LMR on OS was observed in patients with different ethnicity, treatment methods, cut-off values, and across disease stages. Conclusions: This meta-analysis demonstrates that low preoperative LMR is associated with worse survival in patients with CRC. PMID:27930549

  3. Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

    PubMed Central

    Marsoni, S.; Torri, V.; Valsecchi, M. G.; Belloni, C.; Bianchi, U.; Bolis, G.; Bonazzi, C.; Colombo, N.; Epis, A.; Favalli, G.

    1990-01-01

    The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed. PMID:2119684

  4. Characterizing "Adversity" of Pathology Findings in ...

    EPA Pesticide Factsheets

    The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

  5. Adverse effects of marijuana use.

    PubMed

    Feeney, Kathleen E; Kampman, Kyle M

    2016-05-01

    Marijuana has consistently been reported as the most commonly used illicit substance in the United States each year. Currently, the legalization of marijuana is up for debate across the nation. While marijuana use is prevalent among the adolescent population, research has shown that there can be devastating effects on health and well-being. A review of the literature shows that marijuana use can have a negative impact on physical health, psychological well-being, and multiple psychosocial outcomes. Adolescents who used marijuana more frequently and began using marijuana at an earlier age experienced worse outcomes and long-lasting effects.

  6. Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.

    PubMed

    Gottardo, Nicholas G; Hoffmann, Katrin; Beesley, Alex H; Freitas, Joseph R; Firth, Martin J; Perera, Kanchana U; de Klerk, Nicolas H; Baker, David L; Kees, Ursula R

    2007-05-01

    In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.

  7. Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

    PubMed Central

    Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

    2016-01-01

    Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

  8. The prognostic value of high sensitivity troponin T 7 weeks after an acute coronary syndrome

    PubMed Central

    Kao, Michelle P C; Dow, Ellie; Lang, Chim; Struthers, Allan

    2012-01-01

    Objective The role of high sensitivity troponin T (hs-TnT) in the convalescence phase after an acute coronary syndrome (ACS) is unknown. The authors aim to assess the prognostic utility of a single hs-TnT level at 7-week post-ACS. Second, the authors evaluated whether any serial changes in hs-TnT between the index admission and 7 weeks post-ACS had any link with the prognosis. Third, the authors assessed whether the prognostic utility of hs-TnT is independent of various echocardiographic abnormalities. Methods The authors measured hs-TnT levels in 326 consecutive patients at 7 weeks after an ACS event. The composite end point of death from any cause or acute myocardial infarction was evaluated over a median duration of 30 months. Results A high 7-week hs-TnT (>14 ng/l) predicted adverse clinical outcomes independent of conventional risk factors, left ventricular dysfunction and left ventricular hypertrophy on echocardiography (adjusted RR: 2.69 (95% CI