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Sample records for major prognostic impact

  1. IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

    PubMed Central

    Wang, Xiao-Wei; Ciccarino, Pietro; Rossetto, Marta; Marie, Yannick; Desestret, Virginie; 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 IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H 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. PMID:24877111

  2. 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.

  3. Prognostic Impact of Cerebral Small Vessel Disease on Stroke Outcome

    PubMed Central

    Kim, Beom Joon

    2015-01-01

    Cerebral small vessel disease (SVD), which includes white matter hyperintensities (WMHs), silent brain infarction (SBI), and cerebral microbleeds (CMBs), develops in a conjunction of cumulated injuries to cerebral microvascular beds, increased permeability of blood-brain barriers, and chronic oligemia. SVD is easily detected by routine neuroimaging modalities such as brain computed tomography or magnetic resonance imaging. Research has revealed that the presence of SVD markers may increase the risk of future vascular events as well as deteriorate functional recovery and neurocognitive trajectories after stroke, and such an association could also be applied to hemorrhagic stroke survivors. Currently, the specific mechanistic processes leading to the development and manifestation of SVD risk factors are unknown, and further studies with novel methodological tools are warranted. In this review, recent studies regarding the prognostic impact of WMHs, SBI, and CMBs on stroke survivors and briefly summarize the pathophysiological concepts underlying the manifestation of cerebral SVD. PMID:26060797

  4. 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.

  5. Lunar highlands breccias generated by major impacts

    NASA Technical Reports Server (NTRS)

    James, O. B.

    1977-01-01

    The processes that may have been involved in the formation of most of the major types of lunar breccias are discussed. Some of the types of highlands breccias that may have originated in large impacts are identified.

  6. Prognostic impact of atrial fibrillation on clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease

    PubMed Central

    Patel, Nileshkumar J; Patel, Aashay; Agnihotri, Kanishk; Pau, Dhaval; Patel, Samir; Thakkar, Badal; Nalluri, Nikhil; Asti, Deepak; Kanotra, Ritesh; Kadavath, Sabeeda; Arora, Shilpkumar; Patel, Nilay; Patel, Achint; Sheikh, Azfar; Patel, Neil; Badheka, Apurva O; Deshmukh, Abhishek; Paydak, Hakan; Viles-Gonzalez, Juan

    2015-01-01

    Atrial fibrillation (AF) is the most common type of sustained arrhythmia, which is now on course to reach epidemic proportions in the elderly population. AF is a commonly encountered comorbidity in patients with cardiac and major non-cardiac diseases. Morbidity and mortality associated with AF makes it a major healthcare burden. The objective of our article is to determine the prognostic impact of AF on acute coronary syndromes, heart failure and chronic kidney disease. Multiple studies have been conducted to determine if AF has an independent role in the overall mortality of such patients. Our review suggests that AF has an independent adverse prognostic impact on the clinical outcomes of acute coronary syndromes, heart failure and chronic kidney disease. PMID:26225200

  7. 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. PMID:26910046

  8. Lunar highlands breccias generated by major impacts

    NASA Technical Reports Server (NTRS)

    James, O. B.

    1974-01-01

    Lunar missions are reported which have returned a variety of different types of breccias. These rocks differ greatly in their mechanisms of formation, source materials, and histories after formation; but all are related in that all were generated by impact processes. The impact processes involved in the formation of several major types of breccias are discussed. Some types that may have originated in large impacts are identified. Such breccias are extremely important. The impacts that formed them penetrated deeply into, and perhaps through the lunar crust and brought up materials that had previously experienced little or no impact modification. Detailed studies of such breccias can permit partial reconstruction of their preimpact source terranes and yield information on the nature of the early lunar crust (and possibly the upper mantle as well).

  9. Hedgehog pathway aberrations and gastric cancer; evaluation of prognostic impact and exploration of therapeutic potentials.

    PubMed

    Abdel-Rahman, Omar

    2015-03-01

    Gastric cancer is an important cause for mortality and morbidity worldwide; it lies in the fourt rank as a cause of cancer-related death in males and in the fifth rank of cancer-related death in women. The prognosis of advanced/metastatic gastric cancer cases looks poor with the majority of available therapeutics. Thus, novel therapeutic strategies in this setting have been considered a priority for leading cooperative oncology groups. Hedgehog(Hh) pathway aberrations have sparked particular interest as prognostic markers with data from multiple studies showing consistent evidence of a poor prognostic value of Gli over expression in gastric cancer while on the other hand the prognostic significance of Hh protein over expression (particularly SHH) was not consistent among different studies. This review article revises the prognostic and potential therapeutic opportunities in the targeting of hedgehog pathway in gastric cancer. PMID:25680409

  10. Prognostic Impact of Cytogenetic Abnormalities in Multiple Myeloma

    PubMed Central

    Jian, Yuan; Chen, Xiaolei; Zhou, Huixing; Zhu, Wanqiu; Liu, Nian; Geng, Chuanying; Chen, Wenming

    2016-01-01

    Abstract The identification of specific cytogenetic abnormalities by interphase fluorescence in situ hybridization (i-FISH) has become a routine procedure for prognostic stratification of multiple myeloma (MM) patients. In this study, the prognostic significance of cytogenetic abnormalities detected by interphase fluorescence in situ hybridization (iFISH) in 229 newly diagnosed multiple myeloma patients was retrospectively analyzed. Results showed that del (17p), t(4;14), and 1q21 gain were adverse predictors of progression-free survival (PFS). Patients who carried these cytogenetic abnormalities were more likely to have more adverse biological parameters and lower response rate. Multivariate analysis showed that del (17p), t(4;14), and 1q21 gain were statistically independent predictors of PFS, whereas del (17p) was also adverse predictor of overall survival. Multiple coexisting cytogenetic abnormalities also had a negative correlation with PFS. Bortezomib-based therapy could improve the rate and depth of response in patients with t(4;14) translocation and 1q21 gain. Autologous stem cell transplantation could improve, but not overcome the adverse prognostic effect of high-risk cytogenetic abnormalities. These results demonstrate that MM patients with iFISH abnormalities, especially del (17p), are more likely to have a poor prognosis. PMID:27175647

  11. Prognostic impact of mutation profiling in patients with stage II and III colon cancer

    PubMed Central

    Shen, Yinchen; Han, Xiaohong; Wang, Jianfei; Wang, Shuai; Yang, Hongying; Lu, Shih-Hsin; Shi, Yuankai

    2016-01-01

    Development of colorectal cancer (CRC) associates with accumulation of genetic mutations include the epidermal growth factor receptor (EGFR) signaling pathway. However, whether mutations in KRAS together with downstream factors BRAF, PIK3CA and NRAS impact prognosis is still unclear for stage II-III colon cancer. In the present study a total of 228 stage II-III colon cancer samples were retrospectively collected, KRAS (codons 12, 13 and 61), BRAF (exon 11 and exon 15), PIK3CA (exon 9 and exon 20) and NRAS (codons 12, 13 and 61) status was detected by Sanger sequencing, 37.89% (86/227) tumors harbored a KRAS mutation, 7.02% (16/228) harbored a BRAF mutation, 13.18% (29/220) harbored a PIK3CA mutation and 0.89% (2/224) harbored a NRAS mutation. NRAS mutations existed only in stage II colon cancer. Older groups harbored a higher KRAS and BRAF mutation (P < 0.05), PIK3CA (exon9) mutations appeared more common in worse differentiation tumors (P = 0.032). Moreover, PIK3CA (E545K) mutation was significantly associated with tumor recurrence (P = 0.031) and acted independently prognostic for poor OS (P = 0.044), while only in stage III colon cancer. KRAS, BRAF and NRAS mutations do not have major prognostic value in stage II and III colon cancer, subtypes of gene mutations should be further investigated for a better understanding in CRC. PMID:27074743

  12. The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas

    PubMed Central

    Chang, Li-Yun; Liu, Li-Yu D.; Roth, Don A.; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Chang, King-Jen; Hsieh, Fon-Jou

    2015-01-01

    Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(−) and ER(−)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(−) breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature. PMID:26366408

  13. Prognostic impact of breast cancer subtypes in elderly patients.

    PubMed

    Bergen, E S; Tichy, C; Berghoff, A S; Rudas, M; Dubsky, P; Bago-Horvath, Z; Mader, R M; Exner, R; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2016-05-01

    We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65-74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75-84 years among the old-old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %); p < 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %); p = 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2-11.4; p < 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9-6.4; p < 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease-not TNBC-featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted. PMID:27107570

  14. 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

  15. 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.

  16. 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

  17. Prognostic value of imbalanced interhemispheric functional coordination in early therapeutic efficacy in major depressive disorder.

    PubMed

    Hou, Zhenghua; Song, Xiaopeng; Jiang, Wenhao; Yue, Yingying; Yin, Yingying; Zhang, Yuqun; Liu, Yijun; Yuan, Yonggui

    2016-09-30

    This study aims to explore the early response of antidepressant therapy by measuring the voxel-mirrored homotopic connectivity (VMHC) in major depressive disorder (MDD). Eighty-two MDD patients [n=42 treatment-responsive depression (RD) and n=40 non-responding depression (NRD)] and n=50 normal controls (NC) underwent clinical measures and a magnetic resonance imaging scan, and the VMHC values were calculated. Receiver operating characteristic (ROC) curve analysis was applied to determine the capability of altered VMHC to distinguish NRD. The NRD showed significantly decreased VMHC in bilateral precuneus (PCU) and inferior temporal gyrus (ITG), and increased VMHC in middle frontal gyrus (MFG) and caudate nucleus as compared to RD. When compared with NC, the NRD exhibited reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral gyrus. Moreover, VHMC in medial frontal gyrus, postcentral gyrus and precentral gyrus were significantly decreased in RD. Correlation analysis showed that reduced VMHC in PCU was negatively correlated with the baseline HAMD score of the NRD group. The ROC curve indicated that the combined changes of the three regional VMHC (PCU, ITG and MFG) could effectively identify NRD. The current study suggests that interhemispheric asynchrony may represents a novel neural trait underlying the prediction of early therapeutic outcome in MDD. PMID:27497214

  18. Reduced impact of nodal metastases as a prognostic factor for tonsil cancer in the HPV era.

    PubMed

    Vila, Peter M; Stucken, Chaz L; Morris, Luc G T; Posner, Marshall R; Genden, Eric M; Boffetta, Paolo; Sikora, Andrew G

    2014-09-01

    Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 were obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988 to 1997 as the pre-HPV cohort (N = 752), and 1998-2007 as the HPV-predominant cohort (N = 2,755). Comparing the two cohorts, Kaplan-Meier 5-year overall survival (OS) for tonsil SCC improved from 54.0 to 74.3 % (p < 0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9 % (p < 0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7 %, p < 0.0001), two to three (54.2 vs. 75.9 %, p < 0.0001), four to eight (40.3 vs. 68.9 %, p < 0.0001), and greater than eight positive nodes (25.5 vs. 41.9 %, p < 0.0001). While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from "classical" OPC, with unique prognostic features. PMID:24190760

  19. Reduced Impact of Nodal Metastases as a Prognostic Factor for Tonsil Cancer in the HPV Era

    PubMed Central

    Vila, Peter M.; Stucken, Chaz L.; Morris, Luc G.T.; Posner, Marshall R.; Genden, Eric M.; Boffetta, Paolo; Sikora, Andrew G.

    2013-01-01

    Objective Metastatic lymph nodes (LN) are an adverse prognostic factor in head and neck squamous cell carcinoma (SCC). In this study, we tested the hypothesis that nodal metastases have reduced impact on survival in tonsil cancer in the HPV-predominant era. Methods Incidence and mortality data of tonsil and oral cavity SCC between 1988 and 2007 was obtained from the SEER database. Based on published literature, we considered cases of tonsil cancer from 1988–1997 the pre-HPV cohort (N=752), and 1998–2007 as the HPV-predominant cohort (N=2,755). Results Comparing the two cohorts, Kaplan-Meier five-year overall survival (OS) for tonsil SCC improved from 54.0% to 74.3% (p<0.0001), and cancer-specific survival (CSS) improved from 66.0 to 82.9% (p<0.0001). Stratifying by LN involvement showed improved OS in the HPV-predominant cohort with one (63.6 vs. 79.7%, p<0.0001), two to three (54.2 vs. 75.9%, P<0.0001), four to eight (40.3 vs. 68.9%, p<0.0001), and greater than eight positive nodes (25.5 vs. 41.9%, p<0.0001). Conclusion While metastatic LNs still negatively affect prognosis, their impact on OPC survival has diminished in the HPV-predominant era. This finding provides a rationale for additional studies of the prognostic significance of LN metastases in OPC cohorts of defined HPV status, and supports the concept that HPV-related OPC is a disease distinct from “classical” OPC, with unique prognostic features. PMID:24190760

  20. TERT promoter mutations and rs2853669 polymorphism: prognostic impact and interactions with common alterations in glioblastomas.

    PubMed

    Nencha, Umberto; Rahimian, Amithys; Giry, Marine; Sechi, Andrea; Mokhtari, Karima; Polivka, Marc; Schmitt, Yohann; Di Stefano, Anna-Luisa; Alentorn, Agusti; Labussière, Marianne; Sanson, Marc

    2016-02-01

    TERT promoter (TERTp) mutation is the most common mutation in glioblastomas. It creates a putative binding site for Ets/TCF transcription factors, enhancing telomerase expression and activity, whereas the rs2853669 variant disrupts another Ets/TCF binding. We explore here the interaction between these two alterations, tumor genomic profile and the impact on prognosis. The TERTp and rs2853669 statuses were determined and confronted with the outcome and molecular profile, i.e., loss of chromosome 10q, CDKN2A deletion, IDH mutation, EGFR amplification, MGMT promoter methylation. 651 glioblastomas were selected (sex ratio = 1.35, median age 60.4 years, median survival 13.5 months). The TERTp mutation found in 481 patients (74 %) was independent from rs2853669 genotypes. TERTp mutation, but not rs2853669 status, was associated with older age (61.4 vs. 52.8 years). rs2853669 status had no impact on overall survival (OS) either in mutated TERTp or wild-type TERTp. Neither rs2736100 (TERT, 5q15.33) nor rs192011116 (TERC, 3q26.2) status had any impact on survival or showed any association with a TERTp mutation. The TERTp mutation was associated with EGFR amplification chromosome 10q loss, CDKN2A deletion and IDH wt. EGFR amplification was associated with a better outcome in TERTp mutated GBM, and a worse outcome in TERTp WT. This study-the largest analyzing the TERTp mutation and the rs2853669 polymorphism-fails to find any prognostic impact of rs2853669. It confirms the dual prognostic impact of EGFR amplification depending on TERTp status. PMID:26608520

  1. 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

  2. Unique cytogenetic findings confirmed by FISH in a rare case of infant MDS with major prognostic implications

    SciTech Connect

    Sutcliffe, M.J.; Haag, M.M.; Dumont, D.P.

    1994-09-01

    An extremely rare finding in the young, the myelodysplastic syndrome (MDS) refractory anemia with excess blasts (RAEB), is distinguished by blood cytopenia, trilineage dyspoiesis and an increase in peripheral and bone marrow blasts. A 3-year-old male presented with arm pain of one week duration followed by progressive bruising, high fever and severe headaches. Bone marrow pathology revealed dysmyelopoietic granulocytic hyperplasia, marked reduction in megakaryocytes and increased blastosis suggestive of RAEB. Peripheral blood smear confirmed leukoerythroblastic anemia, reticulocytopenia and thyrombocytopenia. Cytogenetic bone marrow evaluation showed the majority of cells with ring (11), monosomies No. 17 and No. 20 and a derivative No. 12 chromosome. Due to the structural complexity and diagnostic and prognostic implications of accurate interpretation, analysis was confirmed using FISH COATASOME probes No. 11, No. 12 and No. 20 (Oncor, Inc.). The rearranged chromosome comprised chromosomes 12 and 20. Breakpoints in No. 12 were at p13 and q24.3. The breakpoint in chromosome 20 at q11.2 resulted in attachment of the distal 20q11.2 fragment to 12q and the centromere and p arm to 12p. C-banding confirmed two centromeres. Progression to ANLL is observed in 15-30% of patients with MDS. Distinction between RAEB and ANLL challenges diagnosis and patient management. Clonal chromosomal abnormalities due to RAEB and nonrandom ANLL changes also show considerable overlap, emphasizing their basic pathobiological similarity. However, r(11) has been described in ANLL and although the structurally rearranged No. 12 is believed to be a unique finding, the breakpoints were considered diagnostically significant. The presence of unusual cytogenetic findings may herald progression of MDS to acute leukemia before morphological classification is evident, emphasing the importance of clarifying structural abnormalities that may provide powerful evidence for clinical management.

  3. 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.

  4. Career Cruising Impact on the Self Efficacy of Deciding Majors

    ERIC Educational Resources Information Center

    Smother, Anthony William

    2012-01-01

    The purpose of this study was to analyze the impact of "Career Cruising"© on self-efficacy of deciding majors in a university setting. The use of the self-assessment instrument, "Career Cruising"©, was used with measuring the career-decision making self-efficacy in a pre and post-test with deciding majors. The independent…

  5. Prognostic impact of FLT3-ITD load in NPM1 mutated acute myeloid leukemia.

    PubMed

    Schnittger, S; Bacher, U; Kern, W; Alpermann, T; Haferlach, C; Haferlach, T

    2011-08-01

    High FLT3-ITD/wildtype (wt) load in FLT3-ITD-mutated AML has been associated with adverse impact on outcome in several studies. To clarify whether FLT3-ITD load as expressed as FLT3-ITD/wt ratio is also relevant in patients with NPM1 mutated AML, we assessed the FLT3-ITD mutation status and FLT3-ITD/wt ratio by fragment analysis in 638 NPM1mut AML (339 females; 299 males; 17.8-88.0 years), and analyzed its prognostic relevance in 355 patients. FLT3-ITD of various length and load were detected in 243/638 cases (38.1%). Median EFS (19.3 vs 9.7 months, P<0.001) and median 2-year survival rate (72.0 vs 52.7%, P=0.006) was better in FLT3wt (n=212 with available follow-up data) than FLT3-ITD (n=143). A higher FLT3-ITD/wt ratio as continuous variable was correlated with a shorter EFS (P=0.028). When patients were separated into subgroups according to the FLT3-ITD mutation load, only a FLT3-ITD/wt ratio 0.5 conferred an independent adverse impact on EFS and OS, and retained its prognostic significance also in multivariate analysis (P=0.009 for EFS, P=0.008 for OS). In conclusion, for risk estimation in NPM1 mutated AML not only the FLT3-ITD status, but also the FLT3-ITD load has to be taken into account. These data might contribute to clinical decision making in AML. PMID:21537333

  6. Epidemiology and clinical impact of major comorbidities in patients with COPD

    PubMed Central

    Smith, Miranda Caroline; Wrobel, Jeremy P

    2014-01-01

    Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival. There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes. Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD. Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication. The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities. Unfortunately, comorbidities are often under-recognized and under-treated. This review focuses on the epidemiology of ten major comorbidities in patients with COPD. Further, we emphasize the clinical impact upon prognosis and management considerations. This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. PMID:25210449

  7. Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Hagag, Adel A; Badraia, Ibrahim M; Hassan, Samir M; Abd El-Lateef, Amal E

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, thorough clinical examination and laboratory investigations including; complete blood count, LDH, BM aspiration, cytochemistry, immunophenotyping, FISH technique for detection of t(12;21) and t(9;22) and assessment of WT-1 Gene by real-time PCR in BM samples at time of diagnosis. Results Positive WT-1 gene expression was found in 22 cases (55%) and negative expression in 18 cases (45%). Positive WT-1 gene expression group (n=22) includes 14 males and 8 females with mean age at presentation of 5.261 ± 0.811 while negative WT-1 gene expression group (n=18) includes 12 males and 6 females with mean age at diagnosis of 9.669 ± 3.731 with significantly older age in negative WT-1 gene expression group but no significant differences between positive and negative WT-1 gene expression groups regarding sex and clinical presentations. There were no significant differences in platelets and WBCs counts, hemoglobin and LDH levels and the number of peripheral blood and BM blast cells at diagnosis between positive and negative WT-1 gene expression groups but after induction therapy there were significantly lower BM blast cells in positive WT-1 gene expression group. There were no statistically significant differences between positive and negative WT-1 gene expression groups regarding immunophenotyping and chromosomal translocations including t(12;21) and t(9;22). There were a significantly higher relapse and death rate and a lower rate of CR, DFS, and OAS in negative WT-1 gene expression

  8. External validation of the CRASH and IMPACT prognostic models in severe traumatic brain injury.

    PubMed

    Han, Julian; King, Nicolas K K; Neilson, Sam J; Gandhi, Mihir P; Ng, Ivan

    2014-07-01

    An accurate prognostic model is extremely important in severe traumatic brain injury (TBI) for both patient management and research. Clinical prediction models must be validated both internally and externally before they are considered widely applicable. Our aim is to independently externally validate two prediction models, one developed by the Corticosteroid Randomization After Significant Head injury (CRASH) trial investigators, and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) group. We used a cohort of 300 patients with severe TBI (Glasgow Coma Score [GCS] ≤8) consecutively admitted to the National Neuroscience Institute (NNI), Singapore, between February 2006 and December 2009. The CRASH models (base and CT) predict 14 day mortality and 6 month unfavorable outcome. The IMPACT models (core, extended, and laboratory) estimate 6 month mortality and unfavorable outcome. Validation was based on measures of discrimination and calibration. Discrimination was assessed using the area under the receiving operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. In the NNI database, the overall observed 14 day mortality was 47.7%, and the observed 6 month unfavorable outcome was 71.0%. The CRASH base model and all three IMPACT models gave an underestimate of the observed values in our cohort when used to predict outcome. Using the CRASH CT model, the predicted 14 day mortality of 46.6% approximated the observed outcome, whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to 0.89, and good overall calibration. We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI. PMID:24568201

  9. Different Mid-Term Prognostic Predictors of Major Adverse Events in Diabetic and Nondiabetic Peripheral Artery Disease Presenting With Critical Limb Ischemia.

    PubMed

    Liang, Kae-Woei; Kuo, Hsun-Nan; Lee, Wen-Lieng; Liu, Tsun-Jui; Lin, Wei-Wen; Tsao, Chen-Rong; Ting, Chih-Tai; Wang, Kuo-Yang

    2016-03-01

    We compared midterm prognostic predictors of peripheral artery disease (PAD) with or without diabetes mellitus (DM) presenting with critical lower limb ischemia (CLI). A total of 172 patients with PAD (109 DM; 63 non-DM) were enrolled. The major adverse events (MAEs) were death or amputation. The diabetic group had a higher MAE rate (39% vs 22%, P = .042) with a mean follow-up duration of 30 ± 19 months. In a multivariate binary logistic regression analysis, revascularization (odds ratio = 0.289, P = .006) and higher serum cholesterol (odds ratio=0.988, P = .027) predicted a lower MAE rate in the DM group. In contrast, the presence of severe chronic kidney disease (stage 4 or 5, odds ratio = 5.238, P = .025) was a positive predictor of MAEs in the nondiabetic group. In conclusion, the prognostic predictors of MAE in diabetic and nondiabetic patients with PAD and CLI were different. PMID:23389094

  10. Long-term prognostic impact of the attenuated plaque in patients with acute coronary syndrome.

    PubMed

    Okura, Hiroyuki; Kataoka, Toru; Yoshiyama, Minoru; Yoshikawa, Junichi; Yoshida, Kiyoshi

    2016-01-01

    Several intravascular ultrasound studies have reported that culprit lesion-attenuated plaque (AP) is related to slow flow/no reflow after percutaneous coronary intervention (PCI). Long-term prognostic impact of the AP is unknown. The aim of this study was to investigate acute and long-term clinical impact of the AP in patients with acute coronary syndrome (ACS). A total of 110 ACS patients who underwent successful PCI were enrolled. Acute and long-term clinical outcomes were compared between patients with AP (AP group: n = 73) and those without AP (non-AP group: n = 37). Long-term cardiac event was defined as a composite of death and ACS. Baseline characteristics in 2 groups were similar. AP was associated with higher TIMI frame count immediately after the first balloon inflation. After thrombectomy and intracoronary drug administration, final TIMI frame count became similar between AP and non-AP group. Although AP was associated with higher incidence of fatal arrhythmia during hospitalization, in-hospital mortality did not differ between the 2 groups. During follow-up (median 6.2 years), cardiac event-free survival did not differ between the 2 groups. Despite the initial unfavorable effect on coronary reflow, presence of AP did not affect acute as well as long-term clinical outcome in patients with ACS. PMID:25183306

  11. Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer.

    PubMed

    Berntsson, Jonna; Nodin, Björn; Eberhard, Jakob; Micke, Patrick; Jirström, Karin

    2016-09-01

    Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p < 0.001, p < 0.001, and p = 0.006, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.53, 95% CI 0.36-0.78), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study. PMID:27074317

  12. 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

  13. Differential Prognostic Impacts of Diabetes over Time Course after Acute Myocardial Infarction

    PubMed Central

    Kim, Hack-Lyoung; Kang, Si-Hyuck; Yoon, Chang-Hwan; Cho, Young-Seok; Youn, Tae-Jin; Cho, Goo-Yeong; Chae, In-Ho; Kim, Hyo-Soo; Chae, Shung-Chull; Cho, Myeong-Chan; Kim, Young-Jo; Kim, Ju Han; Ahn, Youngkeun; Jeong, Myung Ho

    2013-01-01

    This study was performed to evaluate the effects of diabetes on short- and mid-term clinical outcomes in patients with acute myocardial infarction (AMI). Between October 2005 and December 2009, a total of 22,347 patients with AMI from a nationwide registry was analyzed. At the time point of the day 30 after AMI onset, landmark analyses were performed for the development of major adverse cardiovascular events (MACEs), including death, re-infarction and revascularization. In this cohort, 6,131 patients (27.4%) had diabetes. Short-term MACEs, which occurred within 30 days of AMI onset, were observed in 1,364 patients (6.1%). Among the 30-day survivors (n = 21,604), mid-term MACEs, which occurred between 31 and 365 days after AMI onset, were observed in 1,181 patients (5.4%). After adjustment for potential confounders, diabetes was an independent predictor of mid-term MACEs (HR, 1.25; 95% CI, 1.08-1.45; P = 0.002), but not of short-term MACEs (HR: 1.16; 95% CI: 0.93-1.44; P = 0.167). Diabetes is a poor prognostic factor for mid-term clinical outcomes but not for short-term outcomes in AMI patients. Careful monitoring and intensive care should be considered in diabetic patients, especially following the acute stage of AMI. PMID:24339704

  14. Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer

    PubMed Central

    Goeppert, B; Frauenschuh, L; Zucknick, M; Stenzinger, A; Andrulis, M; Klauschen, F; Joehrens, K; Warth, A; Renner, M; Mehrabi, A; Hafezi, M; Thelen, A; Schirmacher, P; Weichert, W

    2013-01-01

    Background: Biliary tract cancers (BTC) are relatively rare malignant tumours with poor prognosis. It is known from other solid neoplasms that antitumour inflammatory response has an impact on tumour behaviour and patient outcome. The aim of this study was to provide a comprehensive characterisation of antitumour inflammatory response in human BTC. Methods: Tumour-infiltrating T lymphocytes (CD4+, CD8+, and Foxp3+), natural killer cells (perforin+), B lymphocytes (CD20+), macrophages (CD68+) as well as mast cells (CD117+) were assessed by immunohistochemistry in 375 BTC including extrahepatic (ECC; n=157), intrahepatic (ICC; n=149), and gallbladder (GBAC; n=69) adenocarcinomas. Overall and intraepithelial quantity of tumour-infiltrating immune cells was analysed. Data were correlated with clinicopathological variables and patient survival. Results: The most prevalent inflammatory cell type in BTC was the T lymphocyte. Components of the adaptive immune response decreased, whereas innate immune response components increased significantly in the biliary intraepithelial neoplasia – primary carcinoma – metastasis sequence. BTC patients with intraepithelial tumour-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes showed a significantly longer overall survival. Number of total intraepithelial tumour-infiltrating Foxp3+ regulatory T lymphocytes (HR: 0.492, P=0.002) and CD4+ T lymphocytes (HR: 0.595, P=0.008) were tumour grade- and UICC-stage-independent prognosticators. The subtype-specific evaluation revealed that the tumour-infiltrating lymphocytic infiltrate is a positive outcome predictor in ECC and GBAC but not in ICC. Conclusion: Our findings characterise the immune response in cholangiocarcinogenesis and identify inflammatory cell types that influence the outcome of BTC patients. Further, we show that BTC subtypes show relevant differences with respect to density, quality of inflammation, and impact on patient survival. PMID:24136146

  15. Changes in environmental impacts of major crops in the US

    NASA Astrophysics Data System (ADS)

    Yang, Yi; Suh, Sangwon

    2015-09-01

    As with life cycle assessment (LCA) studies in general, agricultural LCAs often rely on static and outdated inventory data, but literature suggests that agricultural systems may be highly dynamic. Here, we applied life cycle impact assessment methods to investigate the trends and underlying drivers of changes in non-global environmental impacts of major crops in the US. The results show that the impact per hectare corn and cotton generated on the ecological health of freshwater systems decreased by about 50% in the last decade. This change is mainly due to the use of genetically modified (GM) crops, which has reduced the application of insecticides and relatively toxic herbicides such as atrazine. However, the freshwater ecotoxicity impact per hectare soybean production increased by 3-fold, mainly because the spread of an invasive species, soybean aphid, has resulted in an increasing use of insecticides. In comparison, other impact categories remained relatively stable. By evaluating the relative ecotoxicity potential of a large number of pesticides, our analysis offers new insight into the benefits associated with GM crops. Our study also implies that because different impact categories show different degrees of changes, it is worthwhile focusing on the rapidly changing categories when updating agricultural LCA databases under time and resource constraints.

  16. Prognostic impact of bone marrow fibrosis in primary myelofibrosis. A study of the AGIMM group on 490 patients.

    PubMed

    Guglielmelli, Paola; Rotunno, Giada; Pacilli, Annalisa; Rumi, Elisa; Rosti, Vittorio; Delaini, Federica; Maffioli, Margherita; Fanelli, Tiziana; Pancrazzi, Alessandro; Pieri, Lisa; Fjerza, Rajmonda; Pietra, Daniela; Cilloni, Daniela; Sant'Antonio, Emanuela; Salmoiraghi, Silvia; Passamonti, Francesco; Rambaldi, Alessandro; Barosi, Giovanni; Barbui, Tiziano; Cazzola, Mario; Vannucchi, Alessandro M

    2016-09-01

    The prognostic significance of bone marrow (BM) fibrosis grade in patients with primary myelofibrosis (PMF) is still debated. A fibrosis grade greater than 1 was shown to associate with higher risk of death, and addition of fibrosis grade to IPSS score resulted in a more accurate prediction of survival. The aim of this study was to analyze the prognostic impact of BM fibrosis in 490 patients with PMF, evaluated at diagnosis, molecularly annotated and with extensive follow-up information. We found that fibrosis grade 2 and greater on a 0-3 scale was associated with clinical characteristics indicative of a more advanced disease, such as anemia, leukopenia, thrombocytopenia, constitutional symptoms, larger splenomegaly and a higher IPSS risk category. Patients with higher grade of fibrosis were also more likely to have additional somatic mutations in ASXL1 and EZH2, that are prognostically adverse. Median survival was significantly reduced in patients with grade 2 and 3 fibrosis as compared with grade 1; this effect was maintained when analysis was restricted to younger patients. In multivariate analysis, fibrosis grade independently predicted for survival regardless of IPSS variables and mutational status; the adverse impact of fibrosis was noticeable especially in lower IPSS risk categories. Overall, results indicate that higher grades of fibrosis correlate with unique clinical and molecular aspects and represent an independent adverse variable in patients with PMF; these observations deserve confirmation in prospectively designed series of patients. Am. J. Hematol. 91:918-922, 2016. © 2016 Wiley Periodicals, Inc. PMID:27264006

  17. Novel prognostic gene mutations identified in chronic lymphocytic leukemia and their impact on clinical practice.

    PubMed

    Campregher, Paulo Vidal; Hamerschlak, Nelson

    2014-08-01

    Chronic lymphocytic leukemia (CLL) is a lymphoid malignancy characterized by progressive accumulation of mature lymphocytes in the peripheral blood, bone marrow, liver, and lymphoid organs. Although most patients with CLL have an insidious clinical course, a subset of cases present with fast evolution and chemotherapy resistance, leading to high morbidity and mortality. Few clinically validated prognostic markers, such as TP53, are available for use in clinical practice to guide treatment decisions. Recently, several novel prognostically relevant molecular markers have been identified in CLL. We conducted a narrative literature review of the latest findings to evaluate the potential inclusion of these markers in the management of CLL cases. PMID:24548608

  18. Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Nomura, Motoo; Shitara, Kohei; Kodaira, Takeshi; Hatooka, Shunzo; Mizota, Ayako; Kondoh, Chihiro; Yokota, Tomoya; Takahari, Daisuke; Ura, Takashi; Muro, Kei

    2012-02-01

    Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.

  19. Environmental impacts of Major Flood Events: Hurricane Katrina

    NASA Astrophysics Data System (ADS)

    Reible, D. D.

    2008-05-01

    The flooding of New Orleans by Hurricane Katrina provides many lessons for the environmental and engineering communities and raises serious public policy questions about risk management. Although serious environmental and waste management concerns were highlighted as a result of the flooding, many were not observed in the extensive environmental sampling that occurred. The potential environmental consequences were of concern because of the many chemical plants, petroleum facilities, and contaminated sites, including Superfund sites, in the areas covered by floodwaters. The potential sources of toxics and environmental contaminants included metal-contaminated soils typical of old urban areas. Compounding these concerns is the presence of hazardous chemicals commonly stored in households and commercial establishments and the fuel and motor oil in approximately 350,000 flooded automobiles. Uncontrolled biological wastes from both human and animal sources also contributed to the pollutant burden. There were concerns associated with the immediate impacts of the flooding, the disposal of the debris and wastes in the aftermath, as well as the long- term legacy associated with contaminants in homes and yards. This discussion focuses on successes and failures in responding to each of these concerns as well as lessons learned for future major flooding events. Special attention is paid to some of the unique hazards posed by Katrina, including water quality impacts associated with debris disposal, high indoor concentrations of contaminants due to fractionation from outdoor soils, and mold.

  20. Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

    PubMed

    Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

    2016-03-01

    The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS. PMID:26432331

  1. The prognostic impact of clinical and molecular features in hairy cell leukaemia variant and splenic marginal zone lymphoma.

    PubMed

    Hockley, Sarah L; Else, Monica; Morilla, Alison; Wotherspoon, Andrew; Dearden, Claire; Catovsky, Daniel; Gonzalez, David; Matutes, Estella

    2012-08-01

    Hairy cell leukaemia variant (HCL-variant) and splenic marginal zone lymphoma (SMZL) are disorders with overlapping features. We investigated the prognostic impact in these disorders of clinical and molecular features including IGH VDJ rearrangements, IGHV gene usage and TP 53 mutations. Clinical and laboratory data were collected before therapy from 35 HCL-variant and 68 SMZL cases. End-points were the need for treatment and overall survival. 97% of HCL-variant and 77% of SMZL cases required treatment (P = 0·009). Survival at 5 years was significantly worse in HCL-variant [57% (95% confidence interval 38-73%)] compared with SMZL [84% (71-91%); Hazard Ratio 2·25 (1·20-4·25), P = 0·01]. In HCL-variant, adverse prognostic factors for survival were older age (P = 0·04), anaemia (P = 0·01) and TP 53 mutations (P = 0·02). In SMZL, splenomegaly, anaemia and IGHV genes with >98% homology to the germline predicted the need for treatment; older age, anaemia and IGHV unmutated genes (100% homology) predicted shorter survival. IGHV gene usage had no impact on clinical outcome in either disease. The combination of unfavourable factors allowed patients to be stratified into risk groups with significant differences in survival. Although HCL-variant and SMZL share some features, they have different outcomes, influenced by clinical and biological factors. PMID:22594855

  2. Major osteoporotic fragility fractures: Risk factor updates and societal impact

    PubMed Central

    Pisani, Paola; Renna, Maria Daniela; Conversano, Francesco; Casciaro, Ernesto; Di Paola, Marco; Quarta, Eugenio; Muratore, Maurizio; Casciaro, Sergio

    2016-01-01

    Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence. PMID:27004165

  3. Major osteoporotic fragility fractures: Risk factor updates and societal impact.

    PubMed

    Pisani, Paola; Renna, Maria Daniela; Conversano, Francesco; Casciaro, Ernesto; Di Paola, Marco; Quarta, Eugenio; Muratore, Maurizio; Casciaro, Sergio

    2016-03-18

    Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence. PMID:27004165

  4. Prognostic Impact of Ultrasonography Features and 18F-Fluorodeoxyglucose Uptake in Patients With Papillary Thyroid Microcarcinoma

    PubMed Central

    Seo, Ji Won; Hwang, Sang Hyun; Cho, Arthur; Lee, Hye Sun; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kwak, Jin Young

    2016-01-01

    Objectives To evaluate the prognostic impact of ultrasonography (US) features and 18F-fluorodeoxyglucose (18F-FDG) uptake in patients with papillary thyroid microcarcinoma (PTMC). Methods This study included 74 patients with a single PTMC diagnosed pathologically. Patients underwent total thyroidectomy, or near-total thyroidectomy and staging thyroid US and positron emission tomography (PET) were performed prior to surgery. US features of thyroid nodules were reviewed retrospectively and the maximum standard uptake value (SUV) of nodules was semiquantitatively analyzed on 18F-FDG PET/computed tomography (CT). Patients were followed-up for recurrence, which was defined as PTC on cytology results, elevated serum thyroglobulin (Tg) or anti-Tg antibody levels, or uptake on whole-body scintigraphy. We used univariate and multivariate analyses to evaluate whether poor prognostic outcomes were associated with US features or SUV values derived from PET/CT of nodules. In addition, subjects were divided into 2 groups for subgroup analyses: one with nodules equal to or larger than 5 mm and one with nodules smaller than 5 mm. Results Among the 74 patients, there was no recurrence. Thus we evaluated the correlation between SUV value and US features with poor prognostic factors of PTMC which included extrathyroid extension, central and lateral lymph node (LN) metastasis. However no clinicopathologic factors were associated with extrathyroid extension, central LN metastasis, or lateral LN metastasis. Conclusion In patients with PTMC, US features and SUV values on FDG-PET were not related to extrathyroid extension or LN metastasis. However, future studies with a larger sample size and longer follow-up should be performed to verify the results of this study. PMID:26976029

  5. 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

  6. Impact of major volcanic eruptions on stratospheric water vapour

    NASA Astrophysics Data System (ADS)

    Löffler, M.; Brinkop, S.; Jöckel, P.

    2015-12-01

    Volcanic eruptions can have significant impact on the earth's weather and climate system. Besides the subsequent tropospheric changes also the stratosphere is influenced by large eruptions. Here changes in stratospheric water vapour after the two major volcanic eruptions of El Chichón in Mexico in 1982 and Mount Pinatubo on the Philippines in 1991 are investigated with chemistry-climate model simulations. This study is based on two simulations with specified dynamics of the EMAC model, performed within the Earth System Chemistry integrated Modelling (ESCiMo) project, of which only one includes the volcanic forcing through prescribed aerosol optical properties. The results show a significant increase in stratospheric water vapour after the eruptions, resulting from increased heating rates and the subsequent changes in stratospheric and tropopause temperatures in the tropics. The tropical vertical advection and the South Asian summer monsoon are identified as important sources for the additional water vapour in the stratosphere. Additionally, volcanic influences on the tropospheric water vapour and ENSO are evident.

  7. Impact of major volcanic eruptions on stratospheric water vapour

    NASA Astrophysics Data System (ADS)

    Löffler, Michael; Brinkop, Sabine; Jöckel, Patrick

    2016-05-01

    Volcanic eruptions can have a significant impact on the Earth's weather and climate system. Besides the subsequent tropospheric changes, the stratosphere is also influenced by large eruptions. Here changes in stratospheric water vapour after the two major volcanic eruptions of El Chichón in Mexico in 1982 and Mount Pinatubo on the Philippines in 1991 are investigated with chemistry-climate model simulations. This study is based on two simulations with specified dynamics of the European Centre for Medium-Range Weather Forecasts Hamburg - Modular Earth Submodel System (ECHAM/MESSy) Atmospheric Chemistry (EMAC) model, performed within the Earth System Chemistry integrated Modelling (ESCiMo) project, of which only one includes the long-wave volcanic forcing through prescribed aerosol optical properties. The results show a significant increase in stratospheric water vapour induced by the eruptions, resulting from increased heating rates and the subsequent changes in stratospheric and tropopause temperatures in the tropics. The tropical vertical advection and the South Asian summer monsoon are identified as sources for the additional water vapour in the stratosphere. Additionally, volcanic influences on tropospheric water vapour and El Niño-Southern Oscillation (ENSO) are evident, if the long-wave forcing is strong enough. Our results are corroborated by additional sensitivity simulations of the Mount Pinatubo period with reduced nudging and reduced volcanic aerosol extinction.

  8. Prognostic impact of persistent cytogenetic abnormalities at complete remission in adult patients with acute lymphoblastic leukemia.

    PubMed

    Short, Nicholas J; Kantarjian, Hagop M; Jabbour, Elias J; O'Brien, Susan M; Faderl, Stefan; Burger, Jan A; Garris, Rebecca; Qiao, Wei; Huang, Xuelin; Jain, Nitin; Konopleva, Marina; Kadia, Tapan M; Daver, Naval; Borthakur, Gautam; Cortes, Jorge E; Ravandi, Farhad

    2016-06-01

    In acute myelogenous leukemia, the persistent detection of abnormal cytogenetics at complete remission (ACCR) is associated with inferior outcomes. However, the prognostic significance of ACCR in adult patients with acute lymphoblastic leukemia (ALL) is unknown. We evaluated 272 adult patients with ALL and abnormal cytogenetics at baseline who were treated with frontline induction chemotherapy, achieved complete remission (CR) and had cytogenetic analysis performed at the time of CR. ACCR was observed in 26 patients (9.6%). Median relapse-free survival was 22 months (95% CI, 12 months to not reached) for patients with ACCR vs. 48 months (range, 30-125 months) in patients with normal cytogenetics at CR (NCCR; P = 0.31). Median overall survival also did not differ significantly between the ACCR (99 months [range, 17 months to not reached]) and NCCR groups (67 months [range, 47 months to not reached], P = 0.86). The specificity of ACCR for minimal residual disease (MRD) positivity by multi-parameter flow cytometry (MFC) was 43%, and there was overall poor correlation between these two methods for the detection of residual disease. When patients were stratified by MRD status, the presence or absence of persistent cytogenetic abnormalities at CR did not add additional prognostic information. This study suggests that there is poor association between MRD assessment by MFC and the presence or absence of cytogenetic abnormalities at CR in adult patients with ALL. ACCR was not associated with adverse outcomes in ALL and did not add additional prognostic information when MRD status by MFC was known. PMID:26800008

  9. Diffuse Large B-cell lymphoma: Prognostic markers and their impact on therapy.

    PubMed

    Jamil, Muhammad O; Mehta, Amitkumar

    2016-05-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin lymphoma (NHL). DLBCL is clinically, pathologically and molecularly heterogeneous disease. Various clinical, pathological and molecular markers have been developed to characterize the disease. Based on these characterizations, new targeted agents are being investigated to optimize the treatment and improve the outcomes of DLBCL. Enhanced molecular understanding, invention of targeted agents and immunotherapy has opened the doors for improvement in the treatment of DLBCL. In this review, we will discuss various prognostic markers of DLBCL and their potential therapeutic implications. PMID:26808217

  10. Clinical impact of CD200 expression in patients with acute myeloid leukemia and correlation with other molecular prognostic factors

    PubMed Central

    Damiani, Daniela; Tiribelli, Mario; Raspadori, Donatella; Sirianni, Santina; Meneghel, Alessia; Cavalllin, Margherita; Michelutti, Angela; Toffoletti, Eleonora; Geromin, Antonella; Simeone, Erica; Bocchia, Monica; Fanin, Renato

    2015-01-01

    CD200, a protein belonging to the immunoglobulin superfamily, has been associated with a poor prognosis in lymphoproliferative disorders and in acute leukemia. We studied the expression of CD200 in a series of 244 patients with diagnosis of acute myeloid leukemia (AML), to evaluate its impact on outcome and its possible association with other known prognostic factors. CD200 was found in 136/244 (56%) patients, in 41 of whom (30%) with high intensity of expression (MFI ≥ 11). CD200 was more frequent in secondary compared to de novo leukemia (p = 0.0006), in CD34 positive cases (p = 0.00001), in Bcl2 overexpressing cases (p = 0.01), in those wild-type Flt3 (p = 0.004) and with favorable or unfavorable compared to intermediate karyotype (p = 0.0003). CD200+ patients have a two-fold lower probability to attain complete remission, both in univariate (p = 0.006) and multivariate (p = 0.04) analysis. The negative impact of CD200 was found also in overall survival (p = 0.02) and was correlated with the intensity of expression of the molecule (p = 0.024). CD200 has an additive negative impact on survival in patients with unfavorable cytogenetic (p = 0.046) and in secondary leukemia (p = 0.05), and is associate with a worsening of outcome in patients with favorable biological markers, such as mutated NPM (p = 0.02), wild-type Flt3 (p = 0.034), negativity of CD34 (p = 0.03) and of CD56 (p = 0.03). In conclusion, CD200 is emerging as both a prognostic factor and a potential target of novel therapeutic approaches for AML, aiming to reverse the “do not eat me” signal of CD200 or to manipulate the suppressive immune microenvironment induced by CD200 binding to its receptor. PMID:26338961

  11. Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer

    PubMed Central

    Holzinger, Daniel; Danilovic, Ivan; Seemann, Rudolf; Kornek, Gabriela; Engelmann, Johannes; Pillerstorff, Robert; Holawe, Simone; Psyrri, Amanda; Erovic, Boban M.; Farwell, Gregory; Perisanidis, Christos

    2016-01-01

    Background We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan–Meier curves were used for survival analyses. Results Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09–2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11–2.86, p = 0.016). Conclusion Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC. PMID:27362659

  12. Histological examination has a major impact on macroscopic necropsy diagnoses

    PubMed Central

    Bernardi, F D C; Saldiva, P H N; Mauad, T

    2005-01-01

    Background: Necropsy is the gold standard for clinicopathological discrepancy studies and epidemiological surveys. Inadequate sampling or lack of tissue may hamper the final interpretation and quality of the necropsy. Aim: To compare the histological and gross necropsy diagnoses of different organs. Methods: A retrospective comparison of the provisional reports (gross findings only) and the final reports (after histological examination) of the necropsies performed at the department of pathology of the Hospital das Clínicas, Sao Paulo University, Brazil, a large tertiary care complex, in 2001. The total number of diagnoses listed for the lungs, heart, liver, pancreas, kidneys, and spleen were calculated. Findings were categorised into concordant/refined diagnosis, discordant/additional diagnosis, histology needed, and inconclusive. Results: Three hundred and seventy one postmortem reports were analysed. There were 214 men and 157 women, with a mean age of 50.3 years, ranging from 1 to 92. The lung received the highest number (954) and the pancreas the lowest number (390) of diagnoses. The highest frequencies of discrepancies between the gross and microscopic findings were found in the lung and the liver: 38.7% and 35.1%, respectively. The brain had the lowest frequency of discrepancies. In a small number of cases, the final diagnosis could only be achieved through microscopic analysis, with the highest frequency being found in the kidneys (8.5%). Conclusions: Histological analysis has a major impact on previously performed gross diagnosis at necropsy, especially in the lungs, liver, and kidneys. Adequate sampling and histological analysis are important for necropsy quality. PMID:16311344

  13. Acute myeloid leukemia in patients older than 75: prognostic impact of FLT3-ITD and NPM1 mutations.

    PubMed

    Hirsch, Pierre; Qassa, Ghazi; Marzac, Christophe; Tang, Ruoping; Perrot, Jean-Yves; Isnard, Françoise; Mohty, Mohamad; Marie, Jean Pierre; Legrand, Ollivier

    2015-01-01

    The benefit associated with chemotherapy in older patients with acute myeloid leukemia (AML) is debated. The prognostic impact of molecular mutations in these patients is unknown. We identified 79 patients with AML aged 75 years or over. Forty-two received chemotherapy and 37 supportive care only. In intensively treated patients, overall survival was longer (p < 0.001). Achieving complete remission was associated with longer survival (p < 0.001). NPM1 mutations tended to be associated with a higher complete remission rate (p = 0.12). In multivariate analysis, FLT3-ITD was associated with poorer survival (p = 0.049). Patients harboring FLT3-ITD and no NPM1 mutation had a poorer prognosis than others (p = 0.02). Intensive treatments can benefit a portion of elderly patients. FLT3-ITD and NPM1 mutational status might be useful for prognosis stratification. PMID:24724782

  14. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention

    PubMed Central

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID:26885226

  15. 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

  16. 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

  17. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC

    PubMed Central

    Hirsch, Pierre; Tang, Ruoping; Marzac, Christophe; Perrot, Jean-Yves; Fava, Fanny; Bernard, Chantal; Jeziorowska, Dorota; Marie, Jean Pierre; Legrand, Ollivier

    2012-01-01

    ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication. PMID:22058196

  18. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC.

    PubMed

    Hirsch, Pierre; Tang, Ruoping; Marzac, Christophe; Perrot, Jean-Yves; Fava, Fanny; Bernard, Chantal; Jeziorowska, Dorota; Marie, Jean Pierre; Legrand, Ollivier

    2012-02-01

    ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication. PMID:22058196

  19. 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

  20. An analysis of the impact of tumor amount on the predictive power of a prostate biopsy prognostic assay

    NASA Astrophysics Data System (ADS)

    Khan, Faisal M.; Fogarasi, Stephen I.; Powell, Douglas; Fernandez, Gerardo; Mesa-Tejada, Ricardo; Donovan, Michael J.

    2011-03-01

    The Prostate Px prognostic assay offered by Aureon Biosciences is designed to predict progression post primary treatment for prostate cancer patients based on their diagnostic biopsy specimen. The assay is driven by the automated image analysis of a diagnostic prostate needle biopsy (PNB) and incorporates pathologist acquired and digitally masked images which reflect the morphometric (Hematoxylin and Eosin, H&E) and protein expression (immunofluorescence, IF) properties of the PNB. Up to 9 images (3 H&E and 6 IF) from each of 1027 patients, with varying amounts of tumor content were included in the study. We wanted to understand what was the minimal tumor volume required to maintain assay predictive robustness as a result of overall PNB tumor content and assess the impact of pathologist tumor masking variability. 232 patients were selected who had a minimum of 80% tumor volume in a 20x magnification image. In each of the three imaging domains (2 different multiplex (Mplex) IF images and one H&E), the tumor volume was artificially reduced in increments from 80% to 2.5% of the original image area. This simulated decreasing amounts of tumor as well as variations in digital tumor masking. The univariate predictive power of individual imaging domains remained robust down to the 10% tumor level, whereas the total assay was robust through the 20% to 10% tumor level. This work presents one of the first assessments of the variety in tumor amounts on the predictive power of a commercially available prognostic assay that is reliant on multiple bioimaging domains.

  1. 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.

  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. Prognostic Impact of Changes in Adipose Tissue Areas after Colectomy in Colorectal Cancer Patients.

    PubMed

    Choe, Eun Kyung; Park, Kyu Joo; Ryoo, Seung Bum; Moon, Sang Hui; Oh, Heung Kwon; Han, Eon Chul

    2016-10-01

    There have been few studies assessing the changes in the body components of patients after colectomy in colorectal cancer (CRC). The purpose of this study was to verify the trends in the adipose tissue areas of CRC patients before and after surgery and to determine their clinical relevance. Computed tomography (CT)-assessed subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas were recorded before and after curative resection in stage I to III CRC patients. Changes in the adipose tissue were assessed by calculating the difference in the adipose tissue area between preoperative CT and the most recent postoperative CT, which is disease-free state. Regarding obesity before surgery, there were no prognostic effect of body mass index (BMI), VAT and SAT, and 47.3% of patients had increases in VAT after colectomy. By multivariate analysis, adjusting sex, age, stage, differentiation, VAT change was the only obesity related factor to predict the prognosis, that patients who had increase in VAT after colectomy had better overall survival (HR, 0.557; 95% CI, 0.317-0.880) and disease-free survival (HR, 0.602; 95% CI, 0.391-0.927). BMI and SAT change had no significant association. In subgroup analysis of stage III CRC patients, VAT change had significance for prognosis only in patients who had adjuvant chemotherapy but not in those who did not receive postoperative chemotherapy. Increase in visceral adipose tissue after surgery is a favorable predictor of prognosis for CRC patients. PMID:27550485

  4. Major intrinsic proteins (MIPs) in plants: a complex gene family with major impacts on plant phenotype.

    PubMed

    Forrest, Kerrie L; Bhave, Mrinal

    2007-10-01

    The ubiquitous cell membrane proteins called aquaporins are now firmly established as channel proteins that control the specific transport of water molecules across cell membranes in all living organisms. The aquaporins are thus likely to be of fundamental significance to all facets of plant growth and development affected by plant-water relations. A majority of plant aquaporins have been found to share essential structural features with the human aquaporin and exhibit water-transporting ability in various functional assays, and some have been shown experimentally to be of critical importance to plant survival. Furthermore, substantial evidence is now available from a number of plant species that shows differential gene expression of aquaporins in response to abiotic stresses such as salinity, drought, or cold and clearly establishes the aquaporins as major players in the response of plants to conditions that affect water availability. This review summarizes the function and regulation of these genes to develop a greater understanding of the response of plants to water insufficiency, and particularly, to identify tolerant genotypes of major crop species including wheat and rice and plants that are important in agroforestry. PMID:17562090

  5. Prognostic Value of Major Cardiac Event Risk Score Estimated With Gated Myocardial Perfusion Imaging in Japanese Patients With Coronary Artery Disease.

    PubMed

    Yoda, Shunichi; Nakanishi, Kanae; Tano, Ayako; Hori, Yusuke; Hayase, Misa; Mineki, Takashi; Suzuki, Yasuyuki; Matsumoto, Naoya; Hirayama, Atsushi

    2016-07-27

    We published a cardiac event risk score (CERS) predicting the risk of major cardiac events (MCEs) within 3 years. The purpose of this study was to verify the prognostic value of the CERS before and after treatment in Japanese patients with coronary artery disease.We retrospectively investigated 612 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2013 and who had a significant stenosis with ≥ 75% narrowing of the arterial diameter detected by coronary angiography performed after confirmation of ≥ 5% ischemia with the SPECT. The patients underwent treatment including revascularization and medication, and thereafter, were re-evaluated with SPECT during a chronic phase and followed-up to confirm prognosis for ≥ 1 year. The endpoint was the onset of MCEs during the follow-up.During the follow-up (36.7 ± 14.5 months), 50 patients (8.7%) experienced MCEs comprising cardiac death (n = 16), non-fatal myocardial infarction (n = 4), and unstable angina pectoris (n = 30). The multivariate Cox proportional hazards regression model analysis for the actual occurrence of MCEs showed the summed difference score % and MCE risks estimated with the CERS after treatment to be significant independent variables. Ischemic reduction after treatment contributed significantly to a decrease in the MCE risks. The MCE risks estimated with the CERS after treatment were generally consistent with the incidence of the MCEs actually observed.The CERS after treatment is a valuable formula for predicting prognosis in Japanese patients with coronary artery disease. PMID:27357436

  6. Relocation Impacts of a Major Release from SRTC

    SciTech Connect

    Blanchard, A.

    1999-05-17

    The relocation impacts of an accidental release, scenario 1-RD-3 , are evaluated for the Savannah River Technology Center. The extent of the area potentially contaminated to a level that would result in doses exceeding the relocation protective action guide is calculated.

  7. The Impact of New Major Offerings on Student Retention

    ERIC Educational Resources Information Center

    Sauer, Paul L.; O'Donnell, Joseph B.

    2006-01-01

    A strategy used by industry to retain customers and remain competitive is the design and launch of new products. One might then question whether the launch of new courses and new majors by colleges and universities has the potential of reducing student attrition. Combining survey data from matriculating freshmen with administrative data taken from…

  8. Prevalence and prognostic impact of kidney disease on heart failure patients

    PubMed Central

    Löfman, Ida; Szummer, Karolina; Hagerman, Inger; Dahlström, Ulf; Lund, Lars H; Jernberg, Tomas

    2016-01-01

    Objectives The aim was to determine the prevalence of different degrees of kidney dysfunction and to examine their association with short-term and long-term outcomes in a large unselected contemporary heart failure population and some of its subgroups. We examined to what extent the different cardiac conditions and their severity contribute to the prognostic value of kidney dysfunction in heart failure. Design We studied 47 716 patients in the Swedish Heart Failure Registry. Patients were divided into five renal function strata based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. The adjusted association between kidney function and outcome was examined by Cox regression. Results 51% of the patients had eGFR <60 mL/min/1.73 m2 and 11% had eGFR <30. There was increasing mortality with decreasing kidney function regardless of age, presence of diabetes, New York Heart Association NYHA class, duration of heart failure and haemoglobin levels. The risk HR (95% CI) persisted after adjusting for differences in baseline characteristics, severity of heart disease, and medical treatment: eGFR 60–89: 0.86 (0.79 to 0.95); eGFR 30–59: 1.13 (1.03 to 1.24); eGFR 15–29: 1.85 (1.67 to 2.07); and eGFR <15: 2.96 ([2.53 to –3.47)], compared with eGFR ≥90. Conclusions Kidney dysfunction is common and strongly associated with short-term and long-term outcomes in patients with heart failure. This strong association was evident in all age groups, regardless of NYHA class, duration of heart failure, haemoglobin level, and presence/absence of diabetes mellitus. After adjusting for differences in baseline data, aetiology and severity of heart disease and treatment, the strong association remained. PMID:26848393

  9. Predicting Outcome after Traumatic Brain Injury: Development of Prognostic Scores Based on the IMPACT and the APACHE II

    PubMed Central

    Siironen, Jari; Kivisaari, Riku; Hernesniemi, Juha; Skrifvars, Markus B.

    2014-01-01

    Abstract Prediction models are important tools for heterogeneity adjustment in clinical trials and for the evaluation of quality of delivered care to patients with traumatic brain injury (TBI). We sought to improve the predictive performance of the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials) prognostic model by combining it with the APACHE II (Acute Physiology and Chronic Health Evaluation II) for 6-month outcome prediction in patients with TBI treated in the intensive care unit. A total of 890 patients with TBI admitted to a large urban level 1 trauma center in 2009–2012 comprised the study population. The IMPACT and the APACHE II scores were combined using binary logistic regression. A randomized, split-sample technique with secondary bootstrapping was used for model development and internal validation. Model performance was assessed by discrimination (by area under the curve [AUC]), calibration, precision, and net reclassification improvement (NRI). Overall 6-month mortality was 22% and unfavorable neurological outcome 47%. The predictive power of the new combined IMPACT–APACHE II models was significantly superior, compared to the original IMPACT models (AUC, 0.81–0.82 vs. 0.84–0.85; p<0.05) for 6-month mortality prediction, but not for unfavorable outcome prediction (AUC, 0.81–0.82 vs. 0.83; p>0.05). However, NRI showed a significant improvement in risk stratification of patients with unfavorable outcome by the IMPACT–APACHE II models, compared to the original models (NRI, 5.4–23.2%; p<0.05). Internal validation using split-sample and resample bootstrap techniques yielded equivalent results, indicating low grade of overestimation. Our findings show that by combining the APACHE II with the IMPACT, improved 6-month outcome predictive performance is achieved. This may be applicable for heterogeneity adjustment in forthcoming TBI studies. PMID:24836936

  10. Chemical consequences of major impact events on earth

    NASA Technical Reports Server (NTRS)

    Lewis, J. S.; Watkins, G. H.; Hartman, H.; Prinn, R. G.

    1982-01-01

    Violent cometary or asteroidal impact events comparable to that which terminated the Cretaceous era must produce large amounts of nitrogen oxides, sufficient to provide NOx mole fractions much larger than 100 ppm over areas of millions of square kilometers. Rapid production of NO2, and subsequent rainout of HNO3 and other strong acids can acidify surface waters, selectively destroying CaCO3 shells. This scenario holds the promise of explaining both the scope of Cretaceous biological extinctions and their extraordinary selectivity.

  11. Impact Constraints on Major Events in Early Mars History

    NASA Technical Reports Server (NTRS)

    Frey, H. V.

    2004-01-01

    MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

  12. Relocation impacts of a major release from SRTC

    SciTech Connect

    Blanchard, A.; Thompson, E.A.; Thompson, J.M.

    1999-06-01

    The relocation impacts of an accidental release, scenario 1-RD-3 , are evaluated for the Savannah River Technology Center. The extent of the area potentially contaminated to a level that would result in doses exceeding the relocation protective action guide(PAG)is calculated. The maximum calculated distance downwind from the accident at which the relocation PAG is exceeded is also determined. The consequences of the particulate portion of the release are evaluated using the HOTSPOT model and an EXCEL spreadsheet. The consequences of the tritium release are evaluated using UFOTRI.

  13. An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies

    PubMed Central

    Padron, E; Garcia-Manero, G; Patnaik, M M; Itzykson, R; Lasho, T; Nazha, A; Rampal, R K; Sanchez, M E; Jabbour, E; Al Ali, N H; Thompson, Z; Colla, S; Fenaux, P; Kantarjian, H M; Killick, S; Sekeres, M A; List, A F; Onida, F; Komrokji, R S; Tefferi, A; Solary, E

    2015-01-01

    Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication. PMID:26230957

  14. Major coastal impact induced by a 1000-year storm event

    PubMed Central

    Fruergaard, Mikkel; Andersen, Thorbjørn J.; Johannessen, Peter N.; Nielsen, Lars H.; Pejrup, Morten

    2013-01-01

    Extreme storms and storm surges may induce major changes along sandy barrier coastlines, potentially causing substantial environmental and economic damage. We show that the most destructive storm (the 1634 AD storm) documented for the northern Wadden Sea within the last thousand years both caused permanent barrier breaching and initiated accumulation of up to several metres of marine sand. An aggradational storm shoal and a prograding shoreface sand unit having thicknesses of up to 8 m and 5 m respectively were deposited as a result of the storm and during the subsequent 30 to 40 years long healing phase, on the eroded shoreface. Our results demonstrate that millennial-scale storms can induce large-scale and long-term changes on barrier coastlines and shorefaces, and that coastal changes assumed to take place over centuries or even millennia may occur in association with and be triggered by a single extreme storm event.

  15. Comparison of diagnostic accuracy, time dependency, and prognostic impact of abnormal Q waves, combined electrocardiographic criteria, and ST segment abnormalities in right ventricular infarction.

    PubMed Central

    Zehender, M; Kasper, W; Kauder, E; Schönthaler, M; Olschewski, M; Just, H

    1994-01-01

    OBJECTIVE--To determine the diagnostic and prognostic impact of abnormal Q waves in comparison to or in combination with ST segment abnormalities in the right precordial and inferior leads as indicators of right ventricular infarction during the acute phase of inferior myocardial infarction. DESIGN--Prospective study of a consecutive series of 200 patients with acute inferior myocardial infarction with and without right ventricular infarction. SETTING--Department of internal medicine, university clinic. RESULTS--Right ventricular infarction was diagnosed in 106 (57%) out of 187 patients from the results of coronary angiography, technetium pyrophosphate scanning, and measurement of haemodynamic variables or at necropsy, or both. In the acute phase of inferior infarction ST segment elevation > or = 0.1 mV in any of the right precordial leads V4-6R was the most reliable criterion for right ventricular infarction (sensitivity, 89%; specificity, 83%). Abnormal Q waves in the right precordial leads, the most specific criterion (91%) for right ventricular infarction, were superior to ST segment elevation in patients admitted > 12 hours after the onset of symptoms. Both ST segment elevation in leads V4-6R (increase in in hospital mortality, 6.2-times; P < 0.001; major complications, 2.3-times; P < 0.01) and abnormal Q waves (2.3-times, P < 0.05; 1.8-times, P < 0.05) on admission were highly predictive of a worse outcome during the in hospital period. In the presence of inferior myocardial infarction previously proposed combined electrocardiographic criteria were not better diagnostically or prognostically than ST segment abnormalities and abnormal Q waves alone. CONCLUSIONS--During the first 24 hours of inferior myocardial infarction ST segment elevation and abnormal Q waves derived from the right precordial leads are complementary rather than competitive criteria for reliably diagnosing right ventricular infarction, both indicating a worse in hospital course for the

  16. The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment

    PubMed Central

    Warfvinge, Carl Fredrik; Elebro, Jacob; Heby, Margareta; Nodin, Björn; Krzyzanowska, Agnieszka; Bjartell, Anders; Leandersson, Karin; Eberhard, Jakob; Jirström, Karin

    2016-01-01

    Background Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Methods Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). Results High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29–0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). Conclusion This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers. PMID:27275582

  17. Microsatellite instability and ploidy status define three categories with distinctive prognostic impact in endometrioid endometrial cancer

    PubMed Central

    Bilbao-Sieyro, Cristina; Ramírez-Moreno, Raquel; Rodríguez-González, Germán; Falcón, Orlando; León, Laureano; Torres, Santiago; Fernández, Leandro; Alonso, Sergio; Díaz-Chico, Nicolás; Perucho, Manuel; Díaz-Chico, Juan Carlos

    2014-01-01

    Microsatellite instability (MSI) and aneuploidy are inversely related phenomena. We tested whether ploidy status influences the clinical impact of MSI in endometrioid endometrial cancer (EEC). We analyzed 167 EECs for MSI and ploidy. Tumors were classified in three categories according to MSI and ploidy status. Associations with clinicopathological and molecular variables, survival, and treatment response were assessed. All MSI tumors (23%) were scored as diploid, and 14% of microsatellite stable (MSS) tumors presented aneuploidy. MSI tumors associated with older age at diagnosis, non-obesity, high histological grade, and advanced surgical stage. MSS-aneuploid tumors also associated with higher grade and advanced stage. In multivariate survival analysis MSI did not influence disease-free survival (DFS) or cancer-specific survival (CSS). However, when just diploid tumors were considered for the analysis, MSI significantly contributed to worse DFS and CSS, and the same was observed for aneuploidy when MSS tumors were analyzed alone. In diploid tumors, a differential response to postoperative radiotherapy (RT) was observed according to MSI, since it predicted poor DFS and CSS in the multivariate analysis. We conclude that ploidy status influences the clinical impact of MSI in EEC. Among diploid tumors those with MSI have poor clinical outcome and respond worse to RT. PMID:25026289

  18. Prognostic impact of immunophenotypic complete response in patients with multiple myeloma achieving better than complete response.

    PubMed

    Fukumoto, Kota; Fujisawa, Manabu; Suehara, Yasuto; Narita, Ken-Taro; Usui, Yoshiaki; Takeuchi, Masami; Matsue, Kosei

    2016-08-01

    To investigate the impact of immunophenotypic complete response [iCR, ≤10(-4) multiple myeloma (MM) cells defined by multicolor flow cytometry (MFC)] on survival in patients with MM, we retrospectively analyzed 78 patients that obtained conventional CR at our hospital. Survivals were landmarked at achievement of CR. The rate of stringent CR (sCR) among patients with CR was 88%, and iCR for CR and sCR patients were 44% and 49%, respectively. Achievement of iCR was associated with significantly longer disease-free survival (DFS) not only in CR patients (p = 0.009) but also in sCR patients (p = 0.002), while sCR attainment per se did not have statistically significant impact on DFS (p = 0.06) or overall survival (OS) (p = 0.587). Univariate and multivariate analyses indicated that attainment of iCR was independently associated with longer 2-year DFS in addition to creatinine (≤2.0 mg/dL) and maintenance therapy. This study highlights the importance of pursuing iCR even in patients with sCR. PMID:26764045

  19. 40 CFR 1502.4 - Major Federal actions requiring the preparation of environmental impact statements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... preparation of environmental impact statements. 1502.4 Section 1502.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY ENVIRONMENTAL IMPACT STATEMENT § 1502.4 Major Federal actions requiring the preparation of environmental impact statements. (a) Agencies shall make sure the proposal which is the subject of...

  20. 40 CFR 1502.4 - Major Federal actions requiring the preparation of environmental impact statements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... preparation of environmental impact statements. 1502.4 Section 1502.4 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY ENVIRONMENTAL IMPACT STATEMENT § 1502.4 Major Federal actions requiring the preparation of environmental impact statements. (a) Agencies shall make sure the proposal which is the subject of...

  1. Prognostic Impact of mRNA Expression Levels of HER1–4 (ERBB1–4) in Patients with Locally Advanced Rectal Cancer

    PubMed Central

    Kripp, Melanie; Merx, Kirsten; Wirtz, Ralph Markus; Gaiser, Timo; Eidt, Sebastian; Schwaab, Juliana; Post, Stefan; Wenz, Frederik; Hochhaus, Andreas

    2016-01-01

    Background. No predictive or prognostic biomarker is available for patients with locally advanced rectal cancer (LARC) undergoing perioperative chemoradiotherapy (CRT). Members of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases EGFR (HER1, ERBB1), HER2 (ERBB2), HER3 (ERBB3), and HER4 (ERBB4) are therapeutic targets in several cancers. The analysis was performed to assess expression levels and study the potential prognostic impact for disease-free and overall survival in patients with LARC. Patients and Methods. ERBB1–4 mRNA expression and tumor proliferation using Ki-67 (MKI67) mRNA were evaluated using RT-quantitative PCR in paraffin-embedded tumor samples from 86 patients (median age: 63) treated with capecitabine or 5-fluorouracil-based CRT within a phase 3 clinical trial. Results. A positive correlation of HER4 and HER2, HER3 and HER2, and HER4 and HER3 with each other was observed. Patients with high mRNA expression of ERBB1 (EGFR, HER1) had significantly increased risk for recurrence and death. Patients with high mRNA expression of MKI67 had reduced risk for relapse. Conclusion. This analysis suggests a prognostic impact of both ERBB1 and MKi67 mRNA expression in LARC patients treated with capecitabine or fluorouracil-based chemoradiotherapy. PMID:27610130

  2. Meta-Analysis of the Prognostic Impact of Anemia in Patients Undergoing Percutaneous Coronary Intervention.

    PubMed

    Kwok, Chun Shing; Tiong, Denise; Pradhan, Ashish; Andreou, Andreas Y; Nolan, James; Bertrand, Olivier F; Curzen, Nick; Urban, Philip; Myint, Phyo K; Zaman, Azfar G; Loke, Yoon K; Mamas, Mamas A

    2016-08-15

    Anemia is common in patients undergoing percutaneous coronary intervention (PCI), and current guidelines fail to offer recommendations for its management. This review aims to examine the relation between baseline anemia and mortality, major adverse cardiovascular events (MACE), and major bleeding in patients undergoing PCI. We searched MEDLINE and EMBASE for studies that evaluated mortality and adverse outcomes in anemic and nonanemic patients who underwent PCI. Data were collected on study design, participant characteristics, definition of anemia, follow-up, and adverse outcomes. Random effects meta-analysis of risk ratios was performed using inverse variance method. A total of 44 studies were included in the review with 230,795 participants. The prevalence of baseline anemia was 26,514 of 170,914 (16%). There was an elevated risk of mortality and MACE with anemia compared with no anemia-pooled risk ratio (RR) 2.39 (2.02 to 2.83), p <0.001 and RR 1.51 (1.34 to 1.71), p <0.001, respectively. The risk of myocardial infarction and bleeding with anemia compared with no anemia was elevated, pooled RR 1.33 (1.07 to 1.65), p = 0.01 and RR 1.97 (1.03 to 3.77), p <0.001, respectively. The risk of mortality per unit incremental decrease in hemoglobin (g/dl) was RR 1.19 (1.09 to 1.30), p <0.001 and the risk of mortality, MACE, and reinfarction per 1 unit incremental decrease in hematocrit (%) was RR 1.07 (1.05 to 1.10), p = 0.04, RR 1.09 (1.08 to 1.10) and RR 1.06 (1.03 to 1.10), respectively. The prevalence of anemia in contemporary cohorts of patients undergoing PCI is significant and is associated with significant increases in postprocedural mortality, MACE, reinfarction, and bleeding. The optimal strategy for the management of anemia in such patients remains uncertain. PMID:27342283

  3. Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy.

    PubMed

    Vacchelli, Erika; Semeraro, Michaela; Enot, David P; Chaba, Kariman; Poirier Colame, Vichnou; Dartigues, Peggy; Perier, Aurelie; Villa, Irene; Rusakiewicz, Sylvie; Gronnier, Caroline; Goéré, Diane; Mariette, Christophe; Zitvogel, Laurence; Kroemer, Guido

    2015-08-28

    Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy. PMID:26369701

  4. Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma.

    PubMed

    Shindoh, Junichi; Sugawara, Yasuhiko; Nagata, Rihito; Kaneko, Junichi; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Tanaka, Tomohiro; Kokudo, Norihiro

    2014-04-01

    Tumor markers [alpha-fetoprotein (AFP) or des-gamma-carboxyprothrombin (DCP)] and neutrophil/lymphocyte ratio (NLR) reportedly correlate with long-term outcomes for hepatocellular carcinoma (HCC). However, no standardized method has been established for evaluating the pretransplant data. One hundred and twenty-four patients who underwent living donor liver transplantation (LDLT) were retrospectively reviewed. The best predictive parameters for tumor recurrence were maximum values for AFP or DCP and 90-day mean values for NLR, respectively, and multivariate analysis confirmed these values were correlated with tumor recurrence. However, receiver operating characteristic analysis revealed that discriminative powers were sufficient only in maximum AFP [area under the curve (AUC) 0.88, P < 0.001] and maximum DCP (AUC 0.76, P < 0.001), while mean NLR was less predictive (AUC 0.62, P = 0.20). When incorporating AFP and DCP to the Tokyo criteria (≤5 tumors with each tumor ≤ 5 cm), the presence of at least two of the following factors: (i) beyond the Tokyo criteria, (ii) AFP>250 ng/ml, and (iii) DCP > 450 mAu/ml (>450 ng/ml), was correlated with a worse 5-year disease-free survival rate (20.0% vs. 96.8%, P < 0.001) and 5-year overall survival rate (20.0% vs. 84.0%, P < 0.001). The prognosis of patients undergoing LDLT for HCC strongly relies on maximum AFP or DCP values before transplantation, while the prognostic impact of NLR is limited. PMID:24472068

  5. AGR3 in Breast Cancer: Prognostic Impact and Suitable Serum-Based Biomarker for Early Cancer Detection

    PubMed Central

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

    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. PMID:25875093

  6. Prognostic Impact of Microsatellite Instability in Colorectal Cancer Presenting With Mucinous, Signet-Ring, and Poorly Differentiated Cells

    PubMed Central

    Jung, Sang Hun; Kim, Jae Hwang

    2016-01-01

    Purpose Mucinous cells (MUCs), signet-ring cells (SRCs), and poorly differentiated cells (PDCs) are uncommon histologic types and have been associated with advanced tumor stage and poor prognosis. However, MUCs, SRCs, and PDCs are commonly observed in cancers with high microsatellite instability (MSI), which have favorable outcomes compared with cancers with microsatellite stability (MSS). The purpose of this study was to evaluate the prognostic impact of high-MSI in patients with sporadic colorectal cancer presenting with MUCs, SRCs, and/or PDCs. Methods Between January 2006 and December 2012, 176 with proven microsatellite status who also presented with MUCs, SRCs, and PDCs were selected for this study and were divided into 2 groups, high-MSI and MSS; their outcomes were analyzed. Results Of the 176 patients, 56 and 120, respectively, had high-MSI and MSS cancers. High-MSI cancers had larger tumors, proximal tumor location, and a lower TNM stage. The recurrence rate was lower in the high-MSI group (13.7% vs. 35.4%, P = 0.006). Common patterns of distant metastasis for MUC, SRC, PDC cancers were peritoneal spread (46.9%) and hematogenous metastasis (46.4%). The 5-year CSS rates were 88.2% and 61.2% for patients with high-MSI and MSS cancers, respectively (P < 0.0001). In the multivariate analysis, except for stage-IV cancer, MSI status was an independent risk factor for cancer-specific survival (MSS: hazard ratio, 4.34; 95% confidence interval, 1.68-11.21). Conclusion In patients with colorectal cancer presenting with MUCs, SRCs, and/or PDCs, those with high-MSI cancers had better outcomes. PMID:27218096

  7. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study.

    PubMed

    Bochtler, Tilmann; Hegenbart, Ute; Kunz, Christina; Benner, Axel; Kimmich, Christoph; Seckinger, Anja; Hose, Dirk; Goldschmidt, Hartmut; Granzow, Martin; Dreger, Peter; Ho, Anthony D; Jauch, Anna; Schönland, Stefan O

    2016-07-28

    Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%. Translocation t(11;14) as the most prevalent aberration (59%) led to an improved CR rate after high-dose therapy (41.2% vs 20.0%; P = .02), translating into a prolonged hematologic event-free survival (hemEFS; median, 46.1 vs 28.1 months; P = .05) and a trend for better overall survival (median, not reached vs 93.7 months; P = .07). In multivariate analysis, t(11;14) was confirmed as a favorable prognostic factor regarding hemEFS along with lower values for the difference between involved and uninvolved free light chains. Conversely, deletion 13q14, gain of 1q21, and hyperdiploidy had no significant prognostic impact. The high-risk cytogenetic aberrations t(4;14), t(14;16), and del(17p13) conferred an unfavorable prognosis, although statistical significance was reached only for univariate CR analysis in this small group of 9 patients. Thus, t(11;14) positivity in HDM-treated AL patients conferred superior CR rates and hemEFS. In view of the reduced response of t(11;14) to bortezomib, this highlights the impact of therapy on the prognostic role of cytogenetic aberrations. PMID:27257181

  8. 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

  9. Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group.

    PubMed

    Bertoli, Sarah; Bories, Pierre; Béné, Marie C; Daliphard, Sylvie; Lioure, Bruno; Pigneux, Arnaud; Vey, Norbert; Delaunay, Jacques; Leymarie, Vincent; Luquet, Isabelle; Blanchet, Odile; Cornillet-Lefebvre, Pascale; Hunault, Mathilde; Bouscary, Didier; Fegueux, Nathalie; Guardiola, Philippe; Dreyfus, François; Harousseau, Jean Luc; Cahn, Jean Yves; Ifrah, Norbert; Récher, Christian

    2014-01-01

    Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard "7+3" only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patients, 795 (96.6%) were evaluable. Five hundred and forty-five patients (68.6%) had less than 5% d15-blasts. Predictive factors for high d15-blasts were white blood cell count (P<0.0001) and cytogenetic risk (P<0.0001). Patients with fewer than 5% d15-blasts had a higher complete response rate (91.7% vs. 69.2%; P<0.0001) and a lower induction death rate (1.8% vs. 6.8%; P=0.001). Five-year event-free (48.4% vs. 25%; P<0.0001), relapse-free (52.7% vs. 36.9%; P=0.0016) and overall survival (55.3% vs. 36.5%; P<0.0001) were significantly higher in patients with d15-blasts lower than 5%. Multivariate analyses identified d15-blasts and cytogenetic risk as independent prognostic factors for the three end points. Failure to achieve early blast clearance remains a poor prognostic factor even after early salvage. By contrast, early responding patients have a favorable outcome without any additional induction course. (ClinicalTrials.gov identifier NCT01015196). PMID:23975179

  10. Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group

    PubMed Central

    Bertoli, Sarah; Bories, Pierre; Béné, Marie C.; Daliphard, Sylvie; Lioure, Bruno; Pigneux, Arnaud; Vey, Norbert; Delaunay, Jacques; Leymarie, Vincent; Luquet, Isabelle; Blanchet, Odile; Cornillet-Lefebvre, Pascale; Hunault, Mathilde; Bouscary, Didier; Fegueux, Nathalie; Guardiola, Philippe; Dreyfus, François; Harousseau, Jean Luc; Cahn, Jean Yves; Ifrah, Norbert; Récher, Christian

    2014-01-01

    Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard “7+3” only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patients, 795 (96.6%) were evaluable. Five hundred and forty-five patients (68.6%) had less than 5% d15-blasts. Predictive factors for high d15-blasts were white blood cell count (P<0.0001) and cytogenetic risk (P<0.0001). Patients with fewer than 5% d15-blasts had a higher complete response rate (91.7% vs. 69.2%; P<0.0001) and a lower induction death rate (1.8% vs. 6.8%; P=0.001). Five-year event-free (48.4% vs. 25%; P<0.0001), relapse-free (52.7% vs. 36.9%; P=0.0016) and overall survival (55.3% vs. 36.5%; P<0.0001) were significantly higher in patients with d15-blasts lower than 5%. Multivariate analyses identified d15-blasts and cytogenetic risk as independent prognostic factors for the three end points. Failure to achieve early blast clearance remains a poor prognostic factor even after early salvage. By contrast, early responding patients have a favorable outcome without any additional induction course. (ClinicalTrials.gov identifier NCT01015196) PMID:23975179

  11. Predicting Outcomes after Severe and Moderate Traumatic Brain Injury: An External Validation of Impact and Crash Prognostic Models in a Large Spanish Cohort.

    PubMed

    Castaño-Leon, Ana M; Lora, David; Munarriz, Pablo M; Cepeda, Santiago; Paredes, Igor; de la Cruz, Javier; Gómez Lopez, Pedro A; Lagares, Alfonso

    2016-09-01

    Prognostic models that were developed by the International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) study group and the Corticosteroid Randomization After Signification Head injury (CRASH) collaborators are the most commonly used prognostic models for outcome after traumatic brain injury (TBI). Although they have been considered to be useful tools in clinical practice, a continuous process of external validation in recent cohorts of different populations is necessary. The objective of this study was to determine the external validity and compare the IMPACT and CRASH-refitted models for prediction of outcomes after moderate or severe TBI in a non-selected 1301-patient Spanish cohort. We studied discrimination, calibration, and overall fit as external validation measures. Excellent discrimination was indicated (area under the curve [AUC] 0.78-0.87) by the higher values in the validation than in the development sample for both models and outcomes. Calibration revealed that IMPACT models, in general, predict lower probabilities of both outcomes (mortality and disability). In contrast, CRASH-refitted models provided higher predicted probabilities than those observed. We can conclude that both models demonstrate an adequate performance in our representative traumatic brain Mediterranean population. Therefore, these models can be sensibly applied in our clinical practice so long as their limitations are observed during individual outcome prediction. PMID:26982260

  12. Prevalence and prognostic impact of chronic kidney disease in STEMI from a gender perspective: data from the SWEDEHEART register, a large Swedish prospective cohort

    PubMed Central

    Sederholm Lawesson, Sofia; Alfredsson, Joakim; Szummer, Karolina; Fredrikson, Mats; Swahn, Eva

    2015-01-01

    Objectives Gender differences in prevalence and prognostic impact of chronic kidney disease (CKD) in ST segment elevation myocardial infarction (STEMI) have been poorly evaluated. In STEMI, female gender has been independently associated with an increased risk of mortality. CKD has been found to be an important prognostic marker in myocardial infarction. The aim of this study was to evaluate gender differences in prevalence and prognostic impact of CKD on short-term and long-term mortality. Design Prospective observational cohort study. Setting The national quality register SWEDEHEART was used. In the beginning of the study period, 94% of the Swedish coronary care units contributed data to the register, which subsequently increased to 100%. The glomerular filtration rate was estimated (eGFR) according to Modification of Diet in Renal Disease Study (MDRD) and Cockcroft-Gault (CG). Participants All patients with STEMI registered in SWEDEHEART from the years 2003–2009 were included (37 991 patients, 66% men). Main results Women had 1.6 (MDRD) to 2.2 (CG) times higher multivariable adjusted risk of CKD. Half of the women had CKD according to CG. CKD was associated with 2–2.5 times higher risk of in-hospital mortality and approximately 1.5 times higher risk of long-term mortality in both genders. Each 10 mL/min decline of eGFR was associated with an increased risk of in-hospital and long-term mortality (22–33% and 9–16%, respectively) and this did not vary significantly by gender. Both in-hospital and long-term mortality were doubled in women. After multivariable adjustment including eGFR, there was no longer any gender difference in early outcome and the long-term outcome was better in women. Conclusions Among patients with STEMI, female gender was independently associated with CKD. Reduced eGFR was a strong independent risk factor for short-term and long-term mortality without a significant gender difference in prognostic impact and seems to be an

  13. Diagnostic and prognostic impact of cytochemically assessed nuclear DNA contents in human adenocarcinomas of the mammary gland.

    PubMed

    Askensten, U

    1988-01-01

    Cytochemical assessments of the nuclear DNA contents in carcinomas of the breast can be used for both prognostic and diagnostic purposes. Two main techniques are currently being used, viz. flow cytometry (FCM) and microspectrophotometry (MSP). An account of their advantages and disadvantages is given. In addition, an old, rather crude, cytophotometric technique can be used for histopathological sections of paraffin-embedded specimens. The principal sampling procedures are fine-needle aspiration biopsy and the so-called imprint technique, where the specimens are made from the cut surface of the freshly excised operation specimen. Paraffin-embedded histopathological material can also be used, applying a newly developed MSP procedure, where isolated nuclei from deparaffinized/disintegrated specimens are analyzed. Most important is that intact cell nuclei, representative for the whole tumour nodule, can be obtained. The simultaneous use of FCM and MSP is also of utmost importance for the reliability in the interpretation of the results. Then, a kind of "DNA malignancy grading" is obtained that in several investigations has proven itself to be an excellent prognosticating tool that can be used for making an adequate choice of therapy for the individual patient. The diagnostic value of the results of the cytochemically assessed nuclear DNA distribution patterns is not so high as the prognostic one. Tumours with a diploid type of nuclear DNA content can be found both among benign and malignant neoplasms. However, a neoplasm with an aneuploid DNA distribution pattern can almost certainly be considered highly malignant. PMID:3066302

  14. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism.

    PubMed

    Batista, Rui; Cruvinel-Carloni, Adriana; Vinagre, João; Peixoto, Joana; Catarino, Telmo A; Campanella, Nathalia Cristina; Menezes, Weder; Becker, Aline Paixão; de Almeida, Gisele Caravina; Matsushita, Marcus M; Clara, Carlos; Neder, Luciano; Viana-Pereira, Marta; Honavar, Mrinalini; Castro, Lígia; Lopes, José Manuel; Carvalho, Bruno; Vaz, Rui Manuel; Máximo, Valdemar; Soares, Paula; Sobrinho-Simões, Manuel; Reis, Rui Manuel; Lima, Jorge

    2016-07-15

    Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients carrying the rs2853669 A allele and not in those carrying the G allele. In conclusion, the presence of TERTp mutations was associated with worse prognosis in GBM patients, although such association depended on the status of the rs2853669 SNP. The status of the rs2853669 SNP should be taken in consideration when assessing the prognostic value of TERTp mutations in GBM patients. TERTp mutations and the rs2853669 SNP can be used in the future as biomarkers of glioma prognosis. PMID:26914704

  15. Crustal evolution of the early earth: The role of major impacts

    NASA Technical Reports Server (NTRS)

    Frey, H.

    1979-01-01

    The role of major impact basins (such as those which formed on the moon before 4 billion years ago) is examined to determine the effects of such impacts on the early crustal evolution of the earth. Specifically addressed is the fundamental problem of what is the origin of the earth's fundamental crustal dichotomy of low density continental and high density oceanic crust and its relationship to the superficially similar highlands/maria crustal dichotomies of the moon, Mercury and Mars.

  16. Lexical Collocations and Their Impact on the Online Writing of Taiwanese College English Majors and Non-English Majors

    ERIC Educational Resources Information Center

    Hsu, Jeng-yih

    2007-01-01

    The present study investigates the use of English lexical collocations and their relation to the online writing of Taiwanese college English majors and non-English majors. Data for the study were collected from 41 English majors and 21 non-English majors at a national university of science and technology in southern Taiwan. Each student was asked…

  17. Impact of familial risk and mammography screening on prognostic indicators of breast disease among women from the Ontario site of the Breast Cancer Family Registry.

    PubMed

    Walker, Meghan J; Mirea, Lucia; Cooper, Kristine; Nabavi, Mitra; Glendon, Gord; Andrulis, Irene L; Knight, Julia A; O'Malley, Frances P; Chiarelli, Anna M

    2014-06-01

    Although several studies have found screen-detected cancers in women with familial breast cancer risk have favorable prognostic features compared with symptomatic cancers, the impact of level of familial risk is unknown. A cohort of 899 first-degree female relatives of cases of breast cancer from the Ontario site of the Breast Cancer Family Registry was followed for 2 years. Logistic regression analyses compared diagnoses of breast cancer or benign breast disease (BBD) between women at high (n = 258, 28.7 %) versus low/moderate (n = 641, 71.3 %) familial risk. Similar analyses compared prognostic features of invasive cancers and BBD by level of familial risk and mammography screening status. Among 899 women, 44 (4.9 %) were diagnosed with invasive breast cancer and/or ductal carcinoma in situ, and 56 (6.2 %) with BBD. Women with high familial risk were significantly more likely to be diagnosed with breast cancer [odds ratio (OR) = 2.84, 95 % confidence interval (CI) 1.50-5.38] than low/moderate risk women, particularly if diagnosed at age ≥50 (OR = 2.99, 95 % CI 1.37-6.56) or screened with mammography (OR = 3.33, 95 % CI 1.54-7.18). High risk women were more likely to be diagnosed with BBD (OR = 1.94, 95 % CI 1.03-3.66). Level of familial risk was not associated with prognostic features. Cancers among unscreened women were larger (OR = 9.72, 95 % CI 1.01-93.61) and diagnosed at stage II or above (OR = 7.80, 95 % CI 1.18-51.50) compared with screen-detected cancers. Screening mammography may be effective for women with a first-degree family history of breast cancer, irrespective of level of familial risk. PMID:24097051

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

    PubMed Central

    OHARA, MASAHIRO; AKIMOTO, ETSUSHI; NOMA, MIDORI; MATSUURA, KAZUO; DOI, MIHOKO; KAGAWA, NAOKI; ITAMOTO, TOSHIYUKI

    2015-01-01

    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/m2 (high, H) or <25 kg/m2 (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. PMID:26722327

  19. Impact of a Sophomore Seminar on the Desire of STEM Majors to Pursue a Science Career

    ERIC Educational Resources Information Center

    Sweeder, Ryan D.; Strong, Philip E.

    2012-01-01

    This study focuses on the impact of a sophomore seminar on STEM majors desire to pursue a science career. This seminar was a component in a broader scholarship program and focused on helping students gain a broader understanding of the process of science, expose students to a range of career options and provide opportunities for outside of class…

  20. 40 CFR 1502.4 - Major Federal actions requiring the preparation of environmental impact statements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Major Federal actions requiring the preparation of environmental impact statements. 1502.4 Section 1502.4 Protection of Environment COUNCIL ON..., could significantly affect the quality of the human environment. Statements shall be prepared on...

  1. 40 CFR 1502.4 - Major Federal actions requiring the preparation of environmental impact statements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Major Federal actions requiring the preparation of environmental impact statements. 1502.4 Section 1502.4 Protection of Environment COUNCIL ON..., could significantly affect the quality of the human environment. Statements shall be prepared on...

  2. Apollo 16 impact-melt splashes - Petrography and major-element composition

    NASA Technical Reports Server (NTRS)

    See, Thomas H.; Horz, Friedrich; Morris, Richard V.

    1986-01-01

    Petrographic and major-element analyses are applied to 50 Apollo 16 impact-melt splash (IMS) samples in order to determine their origin and assess the nature of the subregolith source. The macroscopic analyses reveal that the IMSs exhibit a glassy appearance, but the textures range from holohyaline to hyalopilitic. Schlieren-rich glasses dominate the holohyaline areas, and the crystalline areas are mainly spherulitic. It is observed that most IMSs contain feldspathic monomineralic and lithic clasts and no regolithic materials. It is detected that the chemistry of most IMSs is not like the local regolith and appears to represent varied mixtures of VHA impact-melt breccias and anorthosite; the host rocks are mainly dimict breccias. It is concluded that the Cayley Formation is a polymict deposit composed of VHA impact-melt breccias and anorthosites. Tables revealing the macroscopic characteristics of the IMSs and the major-element composition of IMSs and various host rock are presented.

  3. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

    PubMed Central

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Íñigo; Novelli, Silvana; Briones, Javier; Mate, José L.; Salamero, Olga; Sancho, Juan M.; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

    2013-01-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters. PMID:23716551

  4. Prognostic Impact of Modulators of G proteins in Circulating Tumor Cells from Patients with Metastatic Colorectal Cancer

    PubMed Central

    Barbazan, Jorge; Dunkel, Ying; Li, Hongying; Nitsche, Ulrich; Janssen, Klaus-Peter; Messer, Karen; Ghosh, Pradipta

    2016-01-01

    The consequence of a loss of balance between G-protein activation and deactivation in cancers has been interrogated by studying infrequently occurring mutants of trimeric G-protein α-subunits and GPCRs. Prior studies on members of a newly identified family of non-receptor guanine nucleotide exchange factors (GEFs), GIV/Girdin, Daple, NUCB1 and NUCB2 have revealed that GPCR-independent hyperactivation of trimeric G proteins can fuel metastatic progression in a variety of cancers. Here we report that elevated expression of each GEF in circulating tumor cells (CTCs) isolated from the peripheral circulation of patients with metastatic colorectal cancer is associated with a shorter progression-free survival (PFS). The GEFs were stronger prognostic markers than two other markers of cancer progression, S100A4 and MACC1, and clustering of all GEFs together improved the prognostic accuracy of the individual family members; PFS was significantly lower in the high-GEFs versus the low-GEFs groups [H.R = 5, 20 (95% CI; 2,15–12,57)]. Because nucleotide exchange is the rate-limiting step in cyclical activation of G-proteins, the poor prognosis conferred by these GEFs in CTCs implies that hyperactivation of G-protein signaling by these GEFs is an important event during metastatic progression, and may be more frequently encountered than mutations in G-proteins and/or GPCRs. PMID:26916336

  5. Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD

    PubMed Central

    de Jonge, Hendrik J.M.; Valk, Peter J.M.; de Bont, Eveline S.J.M.; Schuringa, Jan Jacob; Ossenkoppele, Gert; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    Background High white blood cell count at presentation is an unfavorable prognostic factor for treatment outcome in intermediate cytogenetic risk acute myeloid leukemia. Since the impact of white blood cell count on outcome of subgroups defined by the molecular markers NPMc+ and FLT3-internal tandem duplication (ITD) is unknown, we addressed this issue. Design and Methods We studied the effect of white blood cell count on outcome in a clinically and molecularly well-defined cohort of 525 patients with acute myeloid leukemia using these molecular markers. In addition, since an increased white blood cell count has been associated with an increased FLT3-ITD/FLT3 (wild-type) ratio, we investigated whether the effect of white blood cell count on outcome could be explained by the FLT3-ITD/FLT3 ratio. Results This analysis revealed that white blood cell count had no impact on outcome in patients with the genotypic combinations ‘NPMc+ without FLT3-ITD’ and ‘NPM1 wild-type with or without FLT3-ITD’. In contrast, white blood cell count had a significant impact on complete remission rate (P=0.034), event-free survival (P=0.009) and overall survival (P<0.001) in patients with the genotypic combination ‘NPMc+ with FLT3-ITD’. A FLT3-ITD/FLT3 ratio greater than 1 was also associated with a reduced complete remission rate (P=0.066) and significantly reduced event-free survival (P= 0.001) and overall survival (P=0.001) in patients with the genotypic combination ‘NPMc+ with FLT3-ITD’. Multivariable analysis revealed that white blood cell count and FLT3-ITD/FLT3 ratio were independent prognostic indicators for outcome in the subgroup with the genotypic combination ‘NPMc+ with FLT3-ITD’. Conclusions Our results demonstrate that both high white blood cell count and FLT3-ITD/FLT3 ratio are prognostic factors in patients with acute myeloid leukemia with the genotypic combination ‘NPMc+ with FLT3-ITD'. PMID:21606167

  6. The prognostic value of the plasma N-terminal pro-brain natriuretic peptide level on all-cause death and major cardiovascular events in a community-based population

    PubMed Central

    Zhu, Qiwei; Xiao, Wenkai; Bai, Yongyi; Ye, Ping; Luo, Leiming; Gao, Peng; Wu, Hongmei; Bai, Jie

    2016-01-01

    Background Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value for patients with cardiovascular disease, chronic kidney disease, etc, the prognostic significance of NT-proBNP levels in the general population has not been established. The aim of this study was to evaluate the clinical significance of NT-proBNP in a community population. Methods This is a community-based prospective survey of residents from two communities in Beijing conducted for a routine health status checkup. Out of 1,860 individuals who were eligible for inclusion from 2007 to 2009, 1,499 completed a follow-up and were assessed for the prognostic value of NT-proBNP in 2013. A questionnaire was used for end point events. Anthropometry and blood pressure were measured. Plasma NT-proBNP, creatinine, lipids, and glucose were determined. Results A total of 1,499 subjects with complete data were included in the analysis. Participants were divided into four groups according to baseline NT-proBNP levels (quartile 1, <19.8 pg/mL; quartile 2, 19.8–41.6 pg/mL; quartile 3, 41.7–81.8 pg/mL; quartile 4, ≥81.9 pg/mL). During a median 4.8-year follow-up period, the all-cause mortality rate rose from 0.8% in the lowest concentration NT-proBNP group (<19.8 pg/mL) to 7.8% in the highest NT-proBNP group (≥81.9 pg/mL; P<0.001). The incidence of major adverse cardiovascular events (MACEs) increased from 3.1% in the lowest NT-proBNP group to 18.9% in the highest group (P<0.001). Individuals in the highest NT-proBNP group (≥81.9 pg/mL) were associated with higher risk of all-cause death and MACEs compared with the lowest NT-proBNP group using Kaplan–Meier survival curves and the Cox proportional hazard model after adjusting for age, sex, and traditional risk factors. Conclusion The plasma NT-proBNP level is a strong and independent prognosis factor for all-cause death and MACEs in the community population. The NT-proBNP cut-point for the

  7. Concussions experienced by Major League Baseball catchers and umpires: field data and experimental baseball impacts.

    PubMed

    Beyer, Jeffrey A; Rowson, Steven; Duma, Stefan M

    2012-01-01

    Some reports have shown that head injuries in baseball may comprise up to 18.5% of all competitive sports-related head injuries. The objective of this study was to evaluate the response of catcher and umpire masks to impacts at these different regions to discover the impact conditions that represent the greatest risk of injury. A series of 10 events in which a catcher or umpire in Major League Baseball, who experienced a foul ball to the mask that resulted in a concussion, were analyzed through video and data on pitch characteristics. It was found that the impacts were distributed across the face, and the median plate speed was approximately 38 m/s (84 mph). To determine the relative severity of each identified impact location, an instrumented Hybrid III head outfitted with a catcher or umpire mask was impacted with baseballs. Testing at 27 and 38 m/s (60 and 84 mph) suggested that impacts to the center-eyebrow and chin locations were the most severe. Peak linear and rotational accelerations were found to be lower than the suggested injury thresholds. While impacts to a mask result in head accelerations which are near or below levels commonly associated with the lower limits for head injury, the exact injury mechanism is unclear, as concussions are still experienced by the mask wearers. PMID:22012084

  8. 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

  9. Prognostic impact of chemotherapy-induced amenorrhea on premenopausal breast cancer: a meta-analysis of the literature

    PubMed Central

    Zhou, Qiong; Yin, Wenjin; Du, Yueyao; Shen, Zhenzhou; Lu, Jingsong

    2015-01-01

    Abstract Objective: We conducted this meta-analysis of published data to assess the exact prognostic value of adjuvant chemotherapy-induced amenorrhea (CIA) as a prognostic factor for premenopausal breast cancer. Methods: We searched for all relevant studies published before May 2014 in the PubMed, OVID, and EMBASE databases. Relative risks (RRs) were used to estimate the association between CIA and various survival outcomes, including disease-free survival (DFS) and overall survival (OS). Results: This meta-analysis identified 13 eligible studies including 5,513 cases and 2,008 controls for DFS and 5 eligible studies including 2,331 cases and 776 controls for OS. Results demonstrated that CIA is associated with improved DFS (RR, 0.67; 95% CI, 0.61-0.74; P < 0.001) and OS (RR, 0.60; 95% CI, 0.50-0.72; P < 0.001). In subgroup analyses, CIA was found to affect DFS (RR, 0.73; 95% CI, 0.61-0.88; P = 0.001) in estrogen receptor (ER)–positive patients; however, similar results were not observed in ER-negative patients (for DFS: RR, 0.97; 95% CI, 0.66-1.41; P = 0.858). Participants with CIA achieved a significantly better prognosis than participants without CIA, irrespective of nodal status, chemotherapy regimen, endocrine therapy, or publication year. Conclusions: This meta-analysis clarifies that CIA contributes to improved prognosis in premenopausal women with ER-positive breast cancer and is at least partially responsible for the benefits of adjuvant chemotherapy in these women, which induce chemical castration. PMID:25783467

  10. Climate changes impacts on the hydrology of major rivers in the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Su, F.; Zhang, L.; Ou, T.; Chen, D.

    2013-05-01

    Major Asian rivers including Indus, Ganges, Brahmaputra, Irrawaddy, Salween, Mekong, Yellow, and Yangtze originate from the Tibetan Plateau (TP). Changes of climate factors may have substantial impacts on the hydrological cycle in the TP. Therefore, quantifying the potential impacts of future climate changes over the TP is essential to assist policy-makers and water managers in adopting strategies reflecting the state of scientific understanding of the likelihood. In this work, temperature and precipitation projected by 20 general circulation models (GCMs) in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) from emission scenarios rcp2.6, rcp4.5, and rcp8.5 were used to characterize the potential climate changes over the TP for 2011-2040 and 2041-2070 relative to 1971-2000. Outputs from the 20 GCMs were downscaled by using the delta method, and were used to force a land surface hydrology model. The hydrology model was applied to investigate the potential impacts of climate changes on the hydrology of upstream of six major river basins in the TP -the Yellow, Yangtze, Mekong, Salween, Brahmaputra, and Indus. Precipitation and streamflow regimes vary among the river basins in the TP. The investigation of climate change impacts was focused on the precipitation-dominated and melting water-dominated river basins.

  11. Impacts of future climate changes on the hydrology of major rivers in the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Su, F.; Zhang, L.; Ou, T.; Chen, D.

    2012-12-01

    Major Asian rivers including Indus, Ganges, Brahmaputra, Irrawaddy, Salween, Mekong, Yellow, and Yangtze originate from the Tibetan Plateau (TP). These rivers support billions of people downstream, and the TP is therefore considered as the water tower of Asia. Changes of climate factors (e.g., temperature and precipitation) may have substantial impacts on the hydrological cycle in the TP. Therefore, quantifying the potential impacts of future climate changes over the TP is essential to assist policy-makers and water managers in adopting strategies reflecting the state of scientific understanding of the likelihood. In this work, temperature and precipitation projected by 20 general circulation models (GCMs) in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) from emission scenarios rcp2.6, rcp4.5, and rcp8.5 were used to characterize the potential climate changes over the TP for 2013-2065. Outputs from the 20 GCMs were downscaled by using the delta method, and were used to force a land surface hydrology model. The hydrology model was applied to investigate the potential impacts of climate changes on the hydrology of upstream of six major river basins in the TP -the Yellow, Yangtze, Mekong, Salween, Brahmaputra, and Indus. Precipitation and streamflow regimes vary among the river basins in the TP. The investigation of climate change impacts was focused on the precipitation-dominated and melting water-dominated river basins.

  12. Major Impact of Fleet Renewal Over Airports Located in the Most Important Region of Brazil

    NASA Technical Reports Server (NTRS)

    Maters, Rafael Waltz; deRoodeTorres, Roberta; Santo, Respicio A. Espirito, Jr.

    2003-01-01

    The present article discusses and analyses the major impacts of the Brazilian carriers fleet renewal regarding Brazilian airport infrastructure in the most important region of the country, the Southeast (SE). A brief historical overview of the country's airline fleet will be presented, demonstrating the need for its renewal (m fact, Brazilian carriers started a major fleet renewal program m the last five years), while analyzing the periods in which a new breed of aircraft was put into service by the major carriers operating in the SE region. The trend of operating the classic regional jets plus the forthcoming entry into service of the "large regional jets" (LRJ, 70-115 seaters) in several point-to-point routes are presented along with the country's carriers" reality of operating these former aircraft in several high-capacity and medium-range routes. The article will focus on the ability of four of the major Southeast's airports to cope with the fleet modernization, mainly due to the fact that the region studied is the most socioeconomic developed, by far, with the largest demand for air transportation, thus making the impacts much more perceptible for the communities and the airport management involved. With the emergence of these impacts, several new projects and investments are being discussed and pushed forward, despite budgetary constrains being a reality in almost every Brazilian city, even in the SE region. In view of this, the paper presents how the general planning could be carried out in order to adapt the airports' infrastructures in function of the proposed (and in some cases, necessary) fleet renewal. Ultimately, we will present the present picture and two future scenarios m order to determine the level of service in the existent passenger terminal facilities in the wake of the possible operation of several new aircraft. Keywords: Airline fleet planning, Airport planning, Regional development, Regional Jets.

  13. 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. PMID:26796737

  14. The past impact of climate change on the yield of major crops

    NASA Astrophysics Data System (ADS)

    Sakurai, G.; Iizumi, T.; Nishimori, M.; Okada, M.; Yokozawa, M.

    2014-12-01

    Understanding the relationship between climate change and crop production is of paramount importance for food security. Previous statistical analyses of historical data have revealed the important impact of temperature increases on past crop yields. However, the direct effect of the [CO2] increase, known as CO2 fertilization effect, is difficult to estimate by simple statistical analysis because the average atmospheric [CO2] does not vary widely over space and time. Moreover, it is also difficult to estimate each climatic effect on crop yields with completely removing correlation among climatic factors. Although non-statistical approaches using process-based crop models may overcome these problems, the results of simple simulation studies may be misleading because of the uncertainty of the model parameters. In the present study, we applied a Bayesian statistical approach to estimate the parameters of a basic process-based model of crop growth (PRYSBI-2) and the past effect of each climatic factor on yields of major crops. The spatial variability of model parameters was considered by estimating the posterior distribution of the parameters from historical yield data by using the Markov-chain Monte Carlo (MCMC) method. The datasets of maize, soybean, rice, and wheat yields during 1982-2006 with a spatial resolution of 1.125° × 1.125° were used for this purpose (Iizumi et al. 2013). The posterior distributions of model parameters were estimated for each spatial grid with 30 000 MCMC steps of 7 chains. Using this model, we produced maps of the estimated past impact of each climatic factor (including CO2 effect) on crop yields (see Figure for the effect of temperature changes on maize yield as an example). The results suggested large variations of the impact of the change in average temperature on major crop yields. The results also suggested a large impact of CO2 increase on C3 crops such as soybean, rice, and wheat. In some regions, the positive impact of CO2

  15. Comparative impacts of two major hurricane seasons on the Neuse River and western Pamlico Sound ecosystems

    PubMed Central

    Burkholder, JoAnn; Eggleston, David; Glasgow, Howard; Brownie, Cavell; Reed, Robert; Janowitz, Gerald; Posey, Martin; Melia, Greg; Kinder, Carol; Corbett, Reide; Toms, David; Alphin, Troy; Deamer, Nora; Springer, Jeffrey

    2004-01-01

    Ecosystem-level impacts of two hurricane seasons were compared several years after the storms in the largest lagoonal estuary in the U.S., the Albemarle–Pamlico Estuarine System. A segmented linear regression flow model was developed to compare mass-water transport and nutrient loadings to a major artery, the Neuse River Estuary (NRE), and to estimate mean annual versus storm-related volume delivery to the NRE and Pamlico Sound. Significantly less water volume was delivered by Hurricane Fran (1996), but massive fish kills occurred in association with severe dissolved oxygen deficits and high contaminant loadings (total nitrogen, total phosphorus, suspended solids, and fecal bacteria). The high water volume of the second hurricane season (Hurricanes Dennis, Floyd, and Irene in 1999) delivered generally comparable but more dilute contaminant loads, and no major fish kills were reported. There were no discernable long-term adverse impacts on water quality. Populations of undesirable organisms, such as toxic dinoflagellates, were displaced down-estuary to habitats less conducive for growth. The response of fisheries was species-dependent: there was no apparent impact of the hurricanes on commercial landings of bivalve molluscs or shrimp. In contrast, interacting effects of hurricane floodwaters in 1999 and intensive fishing pressure led to striking reductions in blue crabs. Overall, the data support the premise that, in shallow estuaries frequently disturbed by hurricanes, there can be relatively rapid recovery in water quality and biota, and benefit from the scouring activity of these storms. PMID:15199179

  16. Comparative impacts of two major hurricane seasons on the Neuse River and western Pamlico Sound ecosystems.

    PubMed

    Burkholder, JoAnn; Eggleston, David; Glasgow, Howard; Brownie, Cavell; Reed, Robert; Janowitz, Gerald; Posey, Martin; Melia, Greg; Kinder, Carol; Corbett, Reide; Toms, David; Alphin, Troy; Deamer, Nora; Springer, Jeffrey

    2004-06-22

    Ecosystem-level impacts of two hurricane seasons were compared several years after the storms in the largest lagoonal estuary in the U.S., the Albemarle-Pamlico Estuarine System. A segmented linear regression flow model was developed to compare mass-water transport and nutrient loadings to a major artery, the Neuse River Estuary (NRE), and to estimate mean annual versus storm-related volume delivery to the NRE and Pamlico Sound. Significantly less water volume was delivered by Hurricane Fran (1996), but massive fish kills occurred in association with severe dissolved oxygen deficits and high contaminant loadings (total nitrogen, total phosphorus, suspended solids, and fecal bacteria). The high water volume of the second hurricane season (Hurricanes Dennis, Floyd, and Irene in 1999) delivered generally comparable but more dilute contaminant loads, and no major fish kills were reported. There were no discernable long-term adverse impacts on water quality. Populations of undesirable organisms, such as toxic dinoflagellates, were displaced down-estuary to habitats less conducive for growth. The response of fisheries was species-dependent: there was no apparent impact of the hurricanes on commercial landings of bivalve molluscs or shrimp. In contrast, interacting effects of hurricane floodwaters in 1999 and intensive fishing pressure led to striking reductions in blue crabs. Overall, the data support the premise that, in shallow estuaries frequently disturbed by hurricanes, there can be relatively rapid recovery in water quality and biota, and benefit from the scouring activity of these storms. PMID:15199179

  17. Impacts of El Nino Southern Oscillation on the Global Yields of Major Crops

    NASA Technical Reports Server (NTRS)

    Iizumi, Toshichika; Luo, Jing-Jia; Challinor, Andrew J.; Sakurai, Gen; Yokozawa, Masayuki; Sakuma, Hirofumi; Brown, Molly Elizabeth; Yamagata, Toshio

    2014-01-01

    The monitoring and prediction of climate-induced variations in crop yields, production and export prices in major food-producing regions have become important to enable national governments in import-dependent countries to ensure supplies of affordable food for consumers. Although the El Nino/Southern Oscillation (ENSO) often affects seasonal temperature and precipitation, and thus crop yields in many regions, the overall impacts of ENSO on global yields are uncertain. Here we present a global map of the impacts of ENSO on the yields of major crops and quantify its impacts on their global-mean yield anomalies. Results show that El Nino likely improves the global-mean soybean yield by 2.15.4 but appears to change the yields of maize, rice and wheat by -4.3 to +0.8. The global-mean yields of all four crops during La Nina years tend to be below normal (-4.5 to 0.0).Our findings highlight the importance of ENSO to global crop production.

  18. Impacts of El Niño Southern Oscillation on the global yields of major crops.

    PubMed

    Iizumi, Toshichika; Luo, Jing-Jia; Challinor, Andrew J; Sakurai, Gen; Yokozawa, Masayuki; Sakuma, Hirofumi; Brown, Molly E; Yamagata, Toshio

    2014-01-01

    The monitoring and prediction of climate-induced variations in crop yields, production and export prices in major food-producing regions have become important to enable national governments in import-dependent countries to ensure supplies of affordable food for consumers. Although the El Niño/Southern Oscillation (ENSO) often affects seasonal temperature and precipitation, and thus crop yields in many regions, the overall impacts of ENSO on global yields are uncertain. Here we present a global map of the impacts of ENSO on the yields of major crops and quantify its impacts on their global-mean yield anomalies. Results show that El Niño likely improves the global-mean soybean yield by 2.1-5.4% but appears to change the yields of maize, rice and wheat by -4.3 to +0.8%. The global-mean yields of all four crops during La Niña years tend to be below normal (-4.5 to 0.0%). Our findings highlight the importance of ENSO to global crop production. PMID:24827075

  19. Tracking Particulate Organic Matter Characteristics in Major Arctic Rivers: Indicators of Watershed-Scale Climate Impacts

    NASA Astrophysics Data System (ADS)

    McClelland, J. W.; Griffin, C. G.; Holmes, R. M.; Peterson, B. J.; Raymond, P. A.; Spencer, R. G.; Striegl, R. G.; Tank, S. E.

    2015-12-01

    Six large rivers, including the Yukon and Mackenzie in North America and the Yenisey, Ob', Lena, and Kolyma in Eurasia, drain the majority of the watershed area surrounding the Arctic Ocean. Parallel sampling programs were initiated at downstream locations on these rivers in 2003 to improve estimates of fluvial export and track large-scale perturbations associated with climate change. Over a decade later, synthesis of water chemistry data from these ongoing sampling efforts provides an unprecedented opportunity to 1) examine similarities and differences among the major Arctic rivers, and 2) think critically about how changes in various water chemistry parameters may or may not inform us about climate change impacts. River-borne organic matter characteristics may be particularly telling because mass flux values and composition/source indicators vary with hydrology and permafrost coverage. However, separating climate impacts that occur within river corridors from those that occur beyond them may be difficult, especially when considering changes in particulate organic matter (POM) loads. Data on suspended POM yields, C:N ratios, stable isotope ratios, and radiocarbon content in the major Arctic rivers show marked spatial, seasonal, and interannual variability that is helpful for thinking about how climate change effects may manifest in the future, but it will be challenging to separate changes in POM related to bank erosion and suspension/deposition of in situ sediment stocks from changes in POM that may be linked to processes such as permafrost thaw occurring across the broader landscape.

  20. Assessing Climate Change Impacts on the Performance of Major Water Projects over China

    NASA Astrophysics Data System (ADS)

    Tang, Q.; Liu, X.; Yin, Y. Y.; Zhang, C.; Zhang, X.

    2014-12-01

    The terrestrial water cycle has been largely altered by water projects in China. Since 1950, half of the world's large dams over 15 m height have been built in China. The installed hydropower capacity in China was 249 GW in 2012, accounting for about one-fifth of the total installed hydropower capacity of the world. China has also pursued an ambitious effort, the South-North Water Diversion Project, to transfer 44.8 billion m3 of freshwater annually from southern China to the drier north. Climate change is expected to result in changes in land surface hydrology, thus pose a huge challenge to water management. The potential impacts of climate change on the performance of the major water projects are yet to be assessed. We used a land surface hydrological model together with a simple treatment of reservoir operation to assess the impact of hydrological change on the functions of the major water projects under the Intergovernmental Panel on Climate Change (IPCC) climate and socio-economic scenarios. The bias-corrected climate data from global climate models under different Representative Concentration Pathways (RCPs) were used to drive the hydrological model. The operation of 474 major reservoirs was considered with an operating rule to generate maximum possible hydroelectricity and to fulfill water diversion demands. The future socioeconomic conditions, the Shared Socioeconomic Pathways (SSPs), were used to estimate the water requirement and leverage the water diversion. The modeling results suggest that climate change would have negative impacts on hydropower production and water supply reliability in China. This research highlights the need to evaluate the performance change of existing water infrastructures and to develop adaptation strategy in sustainable water management in a changing environment.

  1. Measuring the economic impact of climate change on major South African field crops: a Ricardian approach

    NASA Astrophysics Data System (ADS)

    Gbetibouo, G. A.; Hassan, R. M.

    2005-07-01

    This study employed a Ricardian model to measure the impact of climate change on South Africa's field crops and analysed potential future impacts of further changes in the climate. A regression of farm net revenue on climate, soil and other socio-economic variables was conducted to capture farmer-adapted responses to climate variations. The analysis was based on agricultural data for seven field crops (maize, wheat, sorghum, sugarcane, groundnut, sunflower and soybean), climate and edaphic data across 300 districts in South Africa. Results indicate that production of field crops was sensitive to marginal changes in temperature as compared to changes in precipitation. Temperature rise positively affects net revenue whereas the effect of reduction in rainfall is negative. The study also highlights the importance of season and location in dealing with climate change showing that the spatial distribution of climate change impact and consequently needed adaptations will not be uniform across the different agro-ecological regions of South Africa. Results of simulations of climate change scenarios indicate many impacts that would induce (or require) very distinct shifts in farming practices and patterns in different regions. Those include major shifts in crop calendars and growing seasons, switching between crops to the possibility of complete disappearance of some field crops from some region.

  2. The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype.

    PubMed

    Schneider, Friederike; Hoster, Eva; Unterhalt, Michael; Schneider, Stephanie; Dufour, Annika; Benthaus, Tobias; Mellert, Gudrun; Zellmeier, Evelyn; Kakadia, Purvi M; Bohlander, Stefan K; Feuring-Buske, Michaela; Buske, Christian; Braess, Jan; Heinecke, Achim; Sauerland, Maria C; Berdel, Wolfgang E; Büchner, Thomas; Wörmann, Bernhard J; Hiddemann, Wolfgang; Spiekermann, Karsten

    2012-05-10

    The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level--measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3+1)--on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+ subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML. PMID:22374696

  3. Recycling in the major metal industries: Trends, developments, and regulatory impacts. Information circular/1994

    SciTech Connect

    Foster, R.J.

    1994-01-01

    Public awareness of, and involvement in, recycling has increased significantly in recent years. The actual magnitude and scope of metals recycling in the United States have gone virtually unnoticed. Over time, both the quantitative and qualitative aspects of secondary metals recovery and reuse have changed substantially, while the attendant regulations have become increasingly stringent. This U.S. Bureau of Mines report examines trends and developments in major metal demand and recycling, and analyzes the possible impacts of regulations with regard to recycling activities.

  4. Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia.

    PubMed

    Liang, Jin-Hua; Gao, Rui; Xia, Yi; Gale, Robert Peter; Chen, Rui-Ze; Yang, Yu-Qiong; Wang, Li; Qu, Xiao-Yan; Qiu, Hai-Rong; Cao, Lei; Hong, Min; Wang, Rong; Wang, Yan; Fan, Lei; Chen, Yao-Yu; Hu, Zhi-Bin; Li, Jian-Yong; Xu, Wei

    2016-01-12

    Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems. PMID:26539641

  5. 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

  6. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact.

    PubMed

    Fornara, O; Bartek, J; Rahbar, A; Odeberg, J; Khan, Z; Peredo, I; Hamerlik, P; Bartek, J; Stragliotto, G; Landázuri, N; Söderberg-Nauclér, C

    2016-02-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor. PMID:26138445

  7. Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia

    PubMed Central

    Xia, Yi; Gale, Robert Peter; Chen, Rui-Ze; Yang, Yu-Qiong; Wang, Li; Qu, Xiao-Yan; Qiu, Hai-Rong; Cao, Lei; Hong, Min; Wang, Rong; Wang, Yan; Fan, Lei; Chen, Yao-Yu; Hu, Zhi-Bin; Li, Jian-Yong; Xu, Wei

    2016-01-01

    Epstein-Barr virus (EBV)-DNA is detected in the blood of some persons with chronic lymphocytic leukemia (CLL) at diagnosis. Whether this is important in the development or progression of CLL is controversial. We interrogated associations between blood EBV-DNA copy number and biological and clinical variables in 243 new-diagnosed consecutive subjects with CLL. Quantification of EBV-DNA copies was done by real-time quantitative PCR (RQ-PCR). All subjects had serological evidence of prior EBV-infection. However, only 24 subjects (10%) had a EBV-DNA-positive test at diagnosis. EBV-DNA-positive subjects at diagnosis had lower hemoglobin concentrations and platelet levels, higher thymidine kinase-1 and serum ferritin levels, un-mutated IGHV genes and a greater risk of Richter transformation compared with EBV-DNA-negative subjects. Percent CD20-, CD148- and ZAP70-positive cells and mean fluorescence intensity (MFI) of each cluster designation were also increased in EBV-DNA-positive subjects at diagnosis. EBV-DNA test positivity was associated with a briefer time-to-treatment interval (HR 1.85; [95% confidence interval, 1.13, 3.03]; P=0.014) and worse survival (HR 2.77; [1.18, 6.49]; P=0.019). Reduction in EBV copies was significantly associated with therapy-response. A positive blood EBV-DNA test at diagnosis and sequential testing of EBV copies during therapy were significantly associated with biological and clinical variables, time-to-treatment, therapy-response and survival. If validated these data may be added to CLL prognostic scoring systems. PMID:26539641

  8. Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study

    PubMed Central

    Alessandrino, Emilio Paolo; Porta, Matteo Giovanni Della; Bacigalupo, Andrea; Malcovati, Luca; Angelucci, Emanuele; Van Lint, Maria Teresa; Falda, Michele; Onida, Francesco; Bernardi, Massimo; Guidi, Stefano; Lucarelli, Barbarella; Rambaldi, Alessandro; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Pascutto, Cristiana; Oneto, Rosi; Pirolini, Laura; Fanin, Renato; Bosi, Alberto

    2010-01-01

    Background Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified. Design and Methods We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007. Results Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload. Conclusions Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non

  9. 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

  10. The health and socioeconomic impacts of major multi-sport events: systematic review (1978-2008)

    PubMed Central

    Thomas, Sian; Thomson, Hilary; Scott, John; Hamilton, Val; Hanlon, Phil; Morrison, David S; Bond, Lyndal

    2010-01-01

    Objective To assess the effects of major multi-sport events on health and socioeconomic determinants of health in the population of the city hosting the event. Design Systematic review. Data sources We searched the following sources without language restrictions for papers published between 1978 and 2008: Applied Social Science Index and Abstracts (ASSIA), British Humanities Index (BHI), Cochrane database of systematic reviews, Econlit database, Embase, Education Resources Information Center (ERIC) database, Health Management Information Consortium (HMIC) database, International Bibliography of the Social Sciences (IBSS), Medline, PreMedline, PsycINFO, Sociological Abstracts, Sportdiscus, Web of Knowledge, Worldwide Political Science Abstracts, and the grey literature. Review methods Studies of any design that assessed the health and socioeconomic impacts of major multi-sport events on the host population were included. We excluded studies that used exclusively estimated data rather than actual data, that investigated host population support for an event or media portrayals of host cities, or that described new physical infrastructure. Studies were selected and critically appraised by two independent reviewers. Results Fifty four studies were included. Study quality was poor, with 69% of studies using a repeat cross-sectional design and 85% of quantitative studies assessed as being below 2+ on the Health Development Agency appraisal scale, often because of a lack of comparison group. Five studies, each with a high risk of bias, reported health related outcomes, which were suicide, paediatric health service demand, presentations for asthma in children (two studies), and problems related to illicit drug use. Overall, the data did not indicate clear negative or positive health impacts of major multi-sport events on host populations. The most frequently reported outcomes were economic outcomes (18 studies). The outcomes used were similar enough to allow us to perform a

  11. Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations.

    PubMed

    Boonthimat, Chetsada; Thongnoppakhun, Wanna; Auewarakul, Chirayu U

    2008-10-01

    NPM1 mutations were investigated in 400 Southeast Asian leukemia patients and were detectable in 105 cases (26.25%) of acute myeloid leukemia but in no cases of acute lymphoid leukemia or chronic myeloid leukemia. Eight novel and 5 known mutations were identified. All predicted novel proteins shared the last five amino acids VSLRK with the similar gain of nuclear exporting signal motif as known variants. Older age, high white blood cell and platelet counts, normal cytogenetics, and CD34-negativity were associated with NPM1 mutation. FLT3 mutation was more frequent in mutant NPM1 than wild-type cases (56.8% vs. 25.6%) whereas RAS and AML1 mutations were rarely found. Overall survival analysis based on the NPM1/FLT3 mutational status revealed a better outcome for the NPM1-positive/FLT3-negative subgroup. We conclude that: i) NPM1 mutation represents a common genetic hallmark in Southeast Asian acute myeloid leukemia with a normal karyotype; ii) NPM1 mutants coexisted mainly with FLT3 mutants, but not RAS or AML1; iii) FLT3 mutation had a negative prognostic impact on patients with mutant NPM1. PMID:18641025

  12. Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease.

    PubMed

    Distel, Luitpold V; Fickenscher, Rainer; Dietel, Katrin; Hung, Alexander; Iro, Heiner; Zenk, Johannes; Nkenke, Emeka; Büttner, Maike; Niedobitek, Gerald; Grabenbauer, Gerhard G

    2009-10-01

    he purpose of this study was to evaluate the prognostic influence of various subtypes of tumour infiltrating lymphocytes (TIL) in head and neck cancer, in particular the potential influence of regulatory T cells (Treg) in relation to different treatment modalities was addressed. A total of 115 patients with squamous cell carcinoma of the oro- and hypopharynx were selected. A low-risk group of 62 patients with early disease was treated by primary surgery followed by external radiotherapy. A high-risk group of 53 inoperable patients with advanced disease was treated by primary radiochemotherapy. Two-hundred and forty biopsy samples were evaluated by use of the tissue-micro-array technique employing the following markers: CD3, CD4, CD8, CD20, CD68, FOXP3, Granzyme B. In the low-risk group high CD20+ infiltration was associated with a significantly better NED-survival rate (p=0.02). Contrary, among high-risk patients low CD20+ counts indicated significantly better survival (p=0.03). Additionally, in the low-risk group higher numbers of intraepithelial CD8+ TIL (>66.6 per thousand) led to improved NED-survival of 95% vs. 52% (p=0.005). The impact of TIL on prognosis in patients with head and neck cancer may be affected by type of treatment and stage of disease. This finding will influence future studies on the role of TIL in human cancers. PMID:19576838

  13. The major impacts of James Black's drug discoveries on medicine and pharmacology.

    PubMed

    Walker, Michael J A

    2011-04-01

    James Black has many claims to pharmacological fame as the creator of two new classes of drugs (beta-blockers and H2 antihistamines) and as a tireless innovator in drug discovery strategies and analytical procedures. The latter attributes in particular assisted Black in the invention of the prototypes for the two major classes of drugs for which he is best known, propranolol and cimetidine. The clinical impact of these drugs on both morbidity and mortality has been profound. In addition, the application of his analytical approach to drug discovery and pharmacology led others in the field to create many other new classes of drugs. Shortly before he died in 2010, Black wrote a retrospective review of his research career that provides insight into his innovative thinking and career success. This overview affords readers a very personal picture of the man, his ideas and his contributions. PMID:21414672

  14. Some Analysis of Major Impact of Geothermal Fluid Components in Power Plant Equipment

    NASA Astrophysics Data System (ADS)

    Buzăianu, A.; Csaki, I.; Moţoiu, P.; Leósson, K.; Serghiuţă, S.; Arnbjornsson, A.; Moţoiu, V.; Popescu, G.; Guðlaugsson, S.; Guðmundsson, D.

    2016-06-01

    This paper presents the results from a some analysis and major impact of geothermal fluid composition on the equipment in use in geothermal power plant. The structural analysis of material deposition improve the direct influenced of chemical composition of stem and waters included CaO, MgO, Al2O3 and SiO2 incorporated in the molten phase and the deposits in the scales formed due to equipment. The steam turbine corrosion damage, particularly of blades, discs and pomps, has long been recognized as a leading causes of reduced availability in the geothermal power plant. The corrosion process depends on temperature, pressure, chemisty and vaporous carryover by diversity of impurity. The experimental analysis procedure involves characterization of the fluid geothermal composition. Detailed information about surfaces morphological modification of the power plant components are obtained by electron microprobe analysis EDX and SEM investigation. References selection are obtaining by X-ray diffractometer patterns of the specimen.

  15. The health impact of major nuclear accidents: the case of Greece.

    PubMed

    Kollas, J G

    1993-10-01

    An assessment of the radiological consequences that would result for the population of Greece from postulated major nuclear accidents in the Kozloduy nuclear power station in Bulgaria is performed. Kozloduy lies at a distance of 225 km from the northern borders of Greece and contains six reactors, all of the Russian WWER type. The postulated accidents that are classified as level 7 accidents on the International Nuclear Event Scale, involve significant releases of radioactive materials into the environment, and widespread health and environmental effects. The analysis is performed by the MACCS code. The estimated consequences are compared to the corresponding actual impact of the Chernobyl accident in Greece. The results of the analysis indicate that, under the conservative assumptions adopted, the radiological consequences of the most severe accidents considered would be about 1.5 orders of magnitude larger than the actual radiological consequences of the Chernobyl accident. PMID:8259439

  16. Prognostic impact of chromosomal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemia patients. A study by the spanish group of myelodysplastic syndromes.

    PubMed

    Nomdedeu, Meritxell; Calvo, Xavier; Pereira, Arturo; Carrió, Anna; Solé, Francesc; Luño, Elisa; Cervera, José; Vallespí, Teresa; Muñoz, Concha; Gómez, Cándida; Arias, Amparo; Such, Esperanza; Sanz, Guillermo; Grau, Javier; Insunza, Andrés; Calasanz, María-José; Ardanaz, María-Teresa; Hernández-Rivas, Jesús-María; Azaceta, Gemma; Álvarez, Sara; Sánchez, Joaquín; Martín, María-Luisa; Bargay, Joan; Gómez, Valle; Cervero, Carlos-Javier; Allegue, María-José; Collado, Rosa; Campo, Elías; Esteve, Jordi; Nomdedeu, Benet; Costa, Dolors

    2016-04-01

    Chromosomal translocations are rare in the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). With the exception of t(3q), translocations are not explicitly considered in the cytogenetic classification of the IPSS-R and their impact on disease progression and patient survival is unknown. The present study was aimed at determining the prognostic impact of translocations in the context of the cytogenetic classification of the IPSS-R. We evaluated 1,653 patients from the Spanish Registry of MDS diagnosed with MDS or CMML and an abnormal karyotype by conventional cytogenetic analysis. Translocations were identified in 168 patients (T group). Compared with the 1,485 patients with abnormal karyotype without translocations (non-T group), the T group had a larger proportion of patients with refractory anemia with excess of blasts and higher scores in both the cytogenetic and global IPSS-R. Translocations were associated with a significantly shorter survival and higher incidence of transformation into AML at univariate analysis but both features disappeared after multivariate adjustment for the IPSS-R cytogenetic category. Patients with single or double translocations other than t(3q) had an outcome similar to those in the non-T group in the intermediate cytogenetic risk category of the IPSS-R. In conclusion, the presence of translocations identifies a subgroup of MDS/CMML patients with a more aggressive clinical presentation that can be explained by a higher incidence of complex karyotypes. Single or double translocations other than t(3q) should be explicitly considered into the intermediate risk category of cytogenetic IPSS-R classification. PMID:26690722

  17. Interpersonal impacts mediate the association between personality and treatment response in major depression.

    PubMed

    Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

    2016-07-01

    Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record PMID:27031606

  18. Geographical Detector-Based Identification of the Impact of Major Determinants on Aeolian Desertification Risk.

    PubMed

    Du, Ziqiang; Xu, Xiaoming; Zhang, Hong; Wu, Zhitao; Liu, Yong

    2016-01-01

    Arid and semi-arid areas in North China are facing the challenge of a rising aeolian desertification risk (ADR) due to the intertwined effects of complex natural processes and intensified anthropogenic activities. An accurate quantitative assessment of the relationship between ADR and its determinants is beneficial for understanding the driving mechanisms of aeolian desertification and for controlling future desertification. Previous studies have failed to quantify the relative role of determinants driving ADR and have been limited in assessing their interactive impacts. In this study, a spatial variance analysis-based geographical detector methodology is used to quantify the effects of geological, physical, and human factors on the occurrence of ADR in an area characterized by mountains and hills in northern China. It is found that soil type, precipitation, and wind velocity are the major determinants of ADR, which implies that geological and physical elements (e.g., soil attribute) and climatic factors (e.g., precipitation and wind velocity) rather than human activities have played a greater role in the incidence of ADR. Particularly, the results show that the interaction of various determinants causes significant non-linearly enhanced impacts on the ADR. The findings of our study will assist local inhabitants and policy makers in developing measures for wind prevention and sand control to mitigate the effects of desertification in the region. PMID:26987114

  19. Geographical Detector-Based Identification of the Impact of Major Determinants on Aeolian Desertification Risk

    PubMed Central

    Du, Ziqiang; Xu, Xiaoming; Zhang, Hong; Wu, Zhitao; Liu, Yong

    2016-01-01

    Arid and semi-arid areas in North China are facing the challenge of a rising aeolian desertification risk (ADR) due to the intertwined effects of complex natural processes and intensified anthropogenic activities. An accurate quantitative assessment of the relationship between ADR and its determinants is beneficial for understanding the driving mechanisms of aeolian desertification and for controlling future desertification. Previous studies have failed to quantify the relative role of determinants driving ADR and have been limited in assessing their interactive impacts. In this study, a spatial variance analysis-based geographical detector methodology is used to quantify the effects of geological, physical, and human factors on the occurrence of ADR in an area characterized by mountains and hills in northern China. It is found that soil type, precipitation, and wind velocity are the major determinants of ADR, which implies that geological and physical elements (e.g., soil attribute) and climatic factors (e.g., precipitation and wind velocity) rather than human activities have played a greater role in the incidence of ADR. Particularly, the results show that the interaction of various determinants causes significant non-linearly enhanced impacts on the ADR. The findings of our study will assist local inhabitants and policy makers in developing measures for wind prevention and sand control to mitigate the effects of desertification in the region. PMID:26987114

  20. Impact of obesity on recovery and pulmonary functions of obese women undergoing major abdominal gynecological surgeries.

    PubMed

    Moustafa, Ahmed A M; Abdelazim, Ibrahim A

    2016-06-01

    To determine impact of obesity on recovery parameters and pulmonary functions of women undergoing major abdominal gynecological surgeries. Eighty women undergoing major gynecological surgeries were included in this study. Anesthesia was induced by remifentanil bolus, followed by propofol and cisatracurium to facilitate oro-tracheal intubation and was maintained by balanced anesthesia of remifentanil intravenous infusion and sevoflurane in oxygen and air. Time from discontinuation of maintenance anesthesia to fully awake were recorded at 1-min intervals and time from discontinuation of anesthesia until patient was transferred to post-anesthesia care unit (PACU) and discharged from PACU was also recorded. Pulmonary function tests were performed before surgery and repeated 4 h, days 1, 2 and 3 post-operative for evaluation of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate. Occurrence of post-operative complications, re-admission to ICU, hospital stay and morbidities were also recorded. Induction of anesthesia using remifentanil bolus injection resulted in significant decrease of heart rate and arterial pressures compared to pre-operative and pre-induction values. Recovery times were significantly shorter in obese compared to morbidly obese women. Post-operative pulmonary function tests showed significant deterioration compared to pre-operative measures but showed progressive improvement through first 3 post-operative days. Hospital stay was significantly shorter for obese compared to morbid obese women. Obesity delays recovery from general anesthesia, adversely affects pulmonary functions and increases post-operative complications. Remifentanil infusion and sevoflurane could be appropriate combination for obese and morbidly obese women undergoing major surgeries. PMID:26072156

  1. Impact cratering as a major process in planet formation: Projectile identification of meteorite craters

    NASA Astrophysics Data System (ADS)

    Schmidt, G.; Kratz, K.

    2009-12-01

    Ancient surfaces of solid planets show that impact cratering is a major process in planet formation. Understanding origin and influence of impactors on the chemical composition of planets (core, mantle and crust) it is important to know the relative abundances of highly siderophile elements (Os, Ir, Ru, Pt, Rh, Pd) in the silicate mantle and crust of planets and meteorites. Refractory highly siderophile elements, such as Os and Ir, are abundant in most meteorites but depleted in crustal rocks (low target/meteorite ratios) and thus the most reliable elements for projectile identification. However, target/meteorite ratios are high if target rocks consist of mantle rocks. In such cases elements are enriched in impactites due to relatively high abundances (ng/g level) in target rocks to make the identification of projectile types difficult (e.g., Gardnos impact structure in Norway). The Ru/Ir ratio is the most reliable key ratio that rules out Earth primitive upper mantle (PUM) derived refractory highly siderophile element components in impactites. The well established Ru/Ir ratio of the Earth mantle of 2.0 ± 0.1 (e.g. Schmidt and Kratz 2004) is significantly above the chondritic ratios varying from 1.4 to 1.6. On Earth Rh/Ir, Ru/Ir, Pd/Ir, and Pt/Os derived from PUM match the ratios of group IV irons with fractionated trace element patterns. The question raise if HSE in mantle rocks are added to the accreting Earth by a late bombardment of pre-differentiated objects or the cores of these objects (magmatic iron meteorites as remnants of the first planetesimals, e.g. Kleine et al. 2009) or some unsampled inner solar system materials from the Mercury-Venus formation region, not sampled through meteorite collections (Schmidt 2009). The PGE and Ni systematics of the upper continental crust (UCC) closely resembles group IIIAB iron meteorites with highly fractionated refractory trace element patterns, pallasites, and the evolved suite of Martian meteorites (representing

  2. The Impact of Letter Grades on Student Effort, Course Selection, and Major Choice: A Regression-Discontinuity Analysis

    ERIC Educational Resources Information Center

    Main, Joyce B.; Ost, Ben

    2014-01-01

    The authors apply a regression-discontinuity design to identify the causal impact of letter grades on student effort within a course, subsequent credit hours taken, and the probability of majoring in economics. Their methodology addresses key issues in identifying the causal impact of letter grades: correlation with unobservable factors, such as…

  3. The Impact of Major-Job Mismatch on College Graduates' Early Career Earnings: Evidence from China

    ERIC Educational Resources Information Center

    Zhu, Rong

    2014-01-01

    This paper assesses the impact of the mismatch between a college major and job on college graduates' early career earnings using a sample from China. On average, a major-job mismatched college graduate is found to suffer from an income loss that is much lower than the penalty documented in previous studies. The income losses are also found to…

  4. 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.

  5. Climate-Change Impacts on Major Societal and Environmental Sectors: a National View

    NASA Astrophysics Data System (ADS)

    Melillo, J. M.

    2009-05-01

    The U.S. Climate Change Science Program's Unified Synthesis Product reports on extant and possible future impacts of climate change for seven sectors at the national level - water resources, energy supply and use, transportation, agriculture, ecosystems, human health and society. The sectoral analyses provide an integrated national picture of the climate-change consequences, now and in the future, for society and the environment, albeit a picture with regional texture. Major report findings for each sector will be presented. In addition to the specific sectoral findings, several overarching messages emerge from this component of the synthesis activity. First, it is important to think about interactions between and among sectors with regard to climate impacts. For example, the projected changes in the timing and amount of precipitation, and hence water supply, will very likely have significant implications for other sectors considered in the report. Changes in water supply have the potential to affect hydropower generation, river transportation, crop timing and management, in-stream ecosystem services including fish habitat, and human health issues related to links between heavy rains ad water-borne diseases. Second, the report concludes that climate-change impacts on the sectors must be considered in the context of a range of environmental and social factors including pollution, population growth, over use of resources, and urbanization. The multi-factor analysis provides insight into our understanding of where, when and how climate change combines with other environmental and social changes to affect the sectors. It also provides some understanding of how these interactions can either amplify or dampen climate-change impacts. This message has profound implications for the design of research programs and information systems at the national, regional and local levels. Furthermore, it demands that a true partnership be forged between the natural and social sciences

  6. Observations of the impact of a major Saharan dust storm on the atmospheric radiation balance

    SciTech Connect

    Slingo, A.; Ackerman, Thomas P.; Allan, R. P.; Kassianov, Evgueni I.; McFarlane, Sally A.; Robinson, G. J.; Barnard, James C.; Miller, Mark; Harries, J. E.; Russell, J. E.; Dewitte, S.

    2006-12-01

    Saharan dust storms transport large quantities of material across the African continent and beyond, causing widespread disruption and hazards to health. The dust may be deposited into the Atlantic Ocean, where it provides an important source of nutrients1, and may be carried as far as the West Indies. Such events may also influence the growth of Atlantic tropical cyclones. Satellite observations have enabled estimates to be made of the effect of the dust on the radiation budget seen from space, but only limited in situ observations have hitherto been made at the surface. Here we present the first simultaneous and continuous observations of the effect of a major dust storm in March 2006 on the radiation budget both at the top of the atmosphere (TOA) and at the surface. We combine data from the Geostationary Earth Radiation Budget (GERB) broadband radiometer and the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) on the Meteosat-8 weather satellite with remote sensing and in situ measurements from a new Mobile Facility located in Niamey, Niger (13{sup o} 29'N, 2{sup o} 10'E), operated by the US Atmospheric Radiation Measurement (ARM) program. We show that the dust produced major perturbations to the radiation budget seen from space and from the surface. By combining the two datasets, we estimate the impact on the radiation budget of the atmosphere itself. Using independent data from the Mobile Facility, we derive the optical properties of the dust and input these and other information into radiation codes to simulate the radiative fluxes. Comparisons with the observed fluxes provides a stringent test of the ability of the codes to represent the radiative properties of this important component of the global aerosol burden.

  7. The impact of anesthesia providers on major morbidity following screening colonoscopies

    PubMed Central

    Lubarsky, David A; Guercio, Jason R; Hanna, John W; Abreu, Maria T; Ma, Qianli; Uribe, Claudia; Birnbach, David J; Sinclair, David R; Candiotti, Keith A

    2015-01-01

    Background and aims Few studies evaluate the impact of anesthesia providers during procedures, such as colonoscopy, on low-risk patients. The objective of this study was to compare the effect of anesthesia providers on several outcome variables, including major morbidity, following screening colonoscopies. Methods A propensity-matched cohort study of 14,006 patients who enrolled with a national insurer offering health maintenance organization (HMO), preferred provider organization (PPO), and Medicare Advantage plans for a screening colonoscopy between July 1, 2005 and June 30, 2007 were studied. Records were evaluated for completion of the colonoscopy, new cancer diagnosis (colon, anal, rectal) within 6 months of the colonoscopy, new primary diagnosis of myocardial infarction (MI), new primary diagnosis of stroke, hospital admission within 7 days of the colonoscopy, and adherence to guidelines for use of anesthesia providers. Results The presence of an anesthesia provider did not affect major morbidity or the percent of completed exams. Overall morbidity within 7 days was very low. When an anesthesia provider was present, a nonsignificant trend toward greater cancer detection within 6 months of the procedure was observed. Adherence to national guidelines regarding the use of anesthesia providers for low-risk patients was poor. Conclusion A difference in outcome associated with the presence or absence of an anesthesia provider during screening colonoscopy in terms of MI, stroke, or hospital admission within 7 days of the procedure was not observed. Adherence to published guidelines for the use of anesthesia providers is low. The incidence of completed exams was unaffected by the presence of an anesthesia provider. However, a nonstatistically significant trend toward increased cancer detection requires further study. PMID:26060404

  8. Ligand-receptor dissociated expression explains high TSLP without prognostic impact in human primary head and neck squamous cell carcinoma.

    PubMed

    Guillot-Delost, Maude; Guilleré, Lia; Berger, Frédérique; Ventre, Aurore; Michea, Paula; Sirven, Philémon; Pattarini, Lucia; Scholer-Dahirel, Alix; Kebir, Fatima-Zahra; Huerre, Michel; Chouchane-Mlik, Olfa; Lappartient, Emmanuelle; Rodriguez, José; Jouffroy, Thomas; Klijanienko, Jerzy; Nicolas, André; Sastre-Garau, Xavier; Honorio, Sofia; Mosseri, Véronique; Le Peltier, Nelly; Sablin, Marie-Paule; Le Tourneau, Christophe; Tartour, Éric; Badoual, Cécile; Soumelis, Vassili

    2016-07-01

    Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine expressed by epithelial cells during allergic inflammation, and activating dendritic cells (DC). Its expression and functional role in cancer remain controversial. We conducted retrospective (n = 89), and prospective studies including patients with untreated primary head and neck squamous cell carcinoma (HNSCC). We found that TSLP was overexpressed by HNSCC tumor cells, and associated with a highly differentiated status. However, no significant difference in overall and recurrence-free survival was found between patients bearing a tumor with high and low TSLP levels, respectively. Surprisingly, there was no significant association between the levels of TSLP expression, and the number of tumor-infiltrating mature DCLAMP(+) DC. In order to explain the apparent lack of TSLP-induced DC activation, we performed phenotypic and functional experiments on freshly resected tumors. Tumor-infiltrating immune cells, including DC, did not express the TSLP receptor heterodimer (TSLPR chain, IL-7Ralpha chain). Furthermore, freshly sorted blood CD11c(+) DC from healthy donors cultured with tumor-conditioned supernatant exhibited an activated profile, but this was not affected by an anti-TSLP blocking antibody, suggesting a DC activation pathway independent of tumor-derived TSLP. Overall, our results demonstrate that TSLP is overexpressed in HNSCC but its function is hampered by the lack of TSLPR-expressing cells in the tumor microenvironment. Such a dissociated ligand-receptor expression may impact intercellular communication in other immune activation pathways, and tumor types. PMID:27622034

  9. The Prognostic Impact of High On-Treatment Platelet Reactivity with Aspirin or ADP Receptor Antagonists: Systematic Review and Meta-Analysis

    PubMed Central

    D'Ascenzo, Fabrizio; Barbero, Umberto; Bisi, Marta; Moretti, Claudio; Omedè, Pierluigi; Cerrato, Enrico; Quadri, Giorgio; Zoccai, Giuseppe Biondi; DiNicolantonio, James J.; Gasparini, Mauro; Bangalore, Sripal; Gaita, Fiorenzo

    2014-01-01

    Objective. Negative results of recent randomized clinical trials testing the hypothesis of target therapy for patients with high on-treatment platelet reactivity (HOPR) have questioned its independent impact on clinical outcomes. 26 studies with 28.178 patients were included, with a median age of 66.8 (64–68) and 22.7% (22.4–27.8), of female gender. After a median follow-up of 1 year (0.1–1), cardiac adverse events occurred in 8.3% (3–11; all results are reported as median and interquartile range) of patients. Pooling all studies together, on-treatment platelet reactivity significantly increased the risk of adverse events (OR 1.33 [1.09, 1.64], I2 = 0%). However, a sensitivity analysis showed that HOPR did not increase the risk of adverse events for patients with ACS, AMI, or stable angina as well as patients resistant to aspirin, ADP antagonists, or both. For all studies, publication bias was formally evident; after adjusting for this, HOPR did not significantly increase adverse cardiac events (OR 1.1 : 0.89–1.22, I2 0%). Conclusions. After adjusting for clinical confounders (like risk factors and clinical presentation) and for relevant publication bias, HOPR was not an independent prognostic indicator in unselected patients with both stable and unstable coronary disease for an adverse cardiac event. The clinical importance of HOPR for high-risk populations remains to be assessed. PMID:25374889

  10. New concept of myocardial longitudinal strain reserve assessed by a dipyridamole infusion using 2D-strain echocardiography: the impact of diabetes and age, and the prognostic value

    PubMed Central

    2013-01-01

    Aims Although dipyridamole is a widely used pharmacological stress agent, the direct effects on myocardium are not entirely known. Diabetic cardiomyopathy can be investigated by 2D-strain echocardiography. The aim of this study was to assess myocardial functional reserve after dipyridamole infusion using speckle-tracking echocardiography. Methods Seventy-five patients referred for dipyridamole stress myocardial perfusion gated SPECT (MPGS) were examined by echocardiography to assess a new concept of longitudinal strain reserve (LSR) and longitudinal strain rate reserve (LSRR) respectively defined by the differences of global longitudinal strain (GLS) and longitudinal strain rate between peak stress after dipyridamole and rest. Twelve patients with myocardial ischemia were excluded on the basis of MPGS as gold standard. Results Mean LSR was −2.28±2.19% and was more important in the 28 (44%) diabetic patients (−3.27±1.93%; p = 0.001). After multivariate analyses, only diabetes improved LSR (p = 0.011) after dipyridamole infusion and was not associated with glycaemic control (p = 0.21), insulin therapy (p = 0.46) or duration of the disease (p = 0.80). Conversely, age (p = 0.002) remained associated with a decrease in LSR. LSSR was also correlated to age (p = 0.005). Patients with a LSR < 0% have a better survival after 15 months (log-rank p = 0.0012). Conclusion LSR explored by 2D speckle-tracking echocardiography after dipyridamole infusion is a simple and new concept that provides new insights into the impact of diabetes and age on the myocardium with a potential prognostic value. PMID:23759020

  11. 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. PMID:26826198

  12. 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

  13. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

    PubMed Central

    Deng, Lijuan; Wang, Xiaoxiao; Manyam, Ganiraju C.; Visco, Carlo; Montes-Moreno, Santiago; Zhang, Li; Dybkær, 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.; Parsons, Ben M.; Møller, Michael B.; Piris, Miguel A.; Winter, Jane N.; Medeiros, L. Jeffrey; Hu, Shimin; Young, Ken H.

    2016-01-01

    Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2 and BCL6 in 898 patients with de novo diffuse large B-cell lymphoma treated with standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). Neither BCL6 translocation alone (more frequent in activated B-cell like diffuse large B-cell lymphoma) nor in combination with MYC translocation (observed in 2.0% of diffuse large B-cell lymphoma) predicted poorer survival in diffuse large B-cell lymphoma patients. Diffuse large B-cell lymphoma patients with MYC/BCL6 co-expression did have significantly poorer survival, however, MYC/BCL6 co-expression had no effect on prognosis in the absence of MYC/BCL2 co-expression, and had no additive impact in MYC+/BCL2+ cases. The isolated MYC+/BCL6+/BCL2− subset, more frequent in germinal center B-cell like diffuse large B-cell lymphoma, had significantly better survival compared with the isolated MYC+/BCL2+/BCL6− subset (more frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma needs to be refined based on the specific genetic abnormalities present in these tumors. PMID:26573234

  14. Impact of a major hurricane on surgical services in a university hospital.

    PubMed

    Norcross, E D; Elliott, B M; Adams, D B; Crawford, F A

    1993-01-01

    Hurricane Hugo struck Charleston, South Carolina, on September 21, 1989. This report analyzes the impact this storm had upon surgical care at a university medical center. Although disaster planning began on September 17, hurricane damage by high winds and an 8.7-foot tidal surge led to loss of emergency power and water. Consequently, system failures occurred in air conditioning, vacuum suction, steam and ethylene oxide sterilization, plumbing, central paging, lighting, and refrigeration. The following surgical support services were affected. In the blood bank, lack of refrigeration meant no platelet packs for 2 days. In radiology, loss of electrical power damaged CT/MRI scanners and flooding ruined patient files, resulting in lost information. In the intensive care unit, loss of electricity meant no monitors and hand ventilation was used for 4 hours. In the operating room, lack of temperature and humidity control (steam, water, and suction supply) halted elective surgery until October 2. Ground and air transportation were limited by unsafe landing sites, impassable roads, and personnel exhaustion. Surgical planning for a major hurricane should include: 1) a fail-safe source of electrical power, 2) evacuation of as many critically ill patients as possible before the storm, 3) cancellation of all elective surgery, and 4) augmented ancillary service staffing with some, although limited, physician support. PMID:8480928

  15. Impacts of future climate change on potential yields of major crops in China

    NASA Astrophysics Data System (ADS)

    Yin, Y.; Tang, Q.; Liu, X.

    2014-05-01

    Climate change may affect crop development and yield, and consequently cast a shadow of doubt over China's food self-sufficiency efforts. In this study we used the model projections of a couple of global gridded crop models (GGCMs) to assess the effects of future climate change on the potential yields of the major crops (i.e. wheat, rice, maize and soybean) over China. The GGCMs were forced with the bias-corrected climate data from 5 global climate models (GCMs) under the Representative Concentration Pathways (RCP) 8.5 which were made available by the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP). The results show that the potential yields of rice may increase over a large portion of China. Climate change may benefit food productions over the high-altitude and cold regions where are outside current main agricultural area. However, the potential yield of maize, soybean and wheat may decrease in a large portion of the current main crop planting areas such as North China Plain. Development of new agronomic management strategy may be useful for coping with climate change in the areas with high risk of yield reduction.

  16. The radiative impact of major volcanic eruptions on stratospheric water vapour

    NASA Astrophysics Data System (ADS)

    Löffler, Michael; Brinkop, Sabine; Jöckel, Patrick

    2016-04-01

    Volcanic eruptions can have significant impact on the earth's weather and climate system. Besides the subsequent tropospheric changes also the stratosphere is influenced by large eruptions. Here changes in stratospheric water vapour after the two major volcanic eruptions of El Chichón in Mexico in 1982 and Mount Pinatubo on the Philippines in 1991 are investigated with chemistry-climate model simulations. This study is based on two simulations with specified dynamics of the EMAC model, performed within the Earth System Chemistry integrated Modelling (ESCiMo) project, of which only one includes the volcanic forcing through prescribed aerosol optical properties. The results show a significant increase in stratospheric water vapour after the eruptions, resulting from increased heating rates and the subsequent changes in stratospheric and tropopause temperatures in the tropics. The tropical vertical advection and the South Asian summer monsoon are identified as important sources for the additional water vapour in the stratosphere. Additionally, volcanic influences on the tropospheric water vapour and ENSO are evident.

  17. 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 Central

    Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C.; Sun, Ruifan; 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, Jinfeng; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Pham, Lan V.; Medeiros, L. Jeffrey; Young, Ken H.

    2015-01-01

    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. PMID:26324762

  18. MicroRNAs in heart failure: Small molecules with major impact

    PubMed Central

    Kalozoumi, Georgia; Yacoub, Magdi; Sanoudou, Despina

    2014-01-01

    MicroRNAs (miRNAs) have emerged as potent modulators of mammalian gene expression, thereby broadening the spectrum of molecular mechanisms orchestrating human physiological and pathological cellular functions. Growing evidence suggests that these small non-coding RNA molecules are pivotal regulators of cardiovascular development and disease. Importantly, multiple miRNAs have been specifically implicated in the onset and progression of heart failure, thus providing a new platform for battling this multi-faceted disease. This review introduces the basic concepts of miRNA biology, describes representative examples of miRNAs associated with multiple aspects of HF pathogenesis, and explores the prognostic, diagnostic and therapeutic potential of miRNAs in the cardiology clinic. PMID:25419522

  19. Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas

    PubMed Central

    SORBE, BENGT

    2016-01-01

    The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I–IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors. PMID:26998163

  20. 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.

  1. Socio-economic impacts of major floods in Italy from 1951 to 2003

    NASA Astrophysics Data System (ADS)

    Lastoria, B.; Simonetti, M. R.; Casaioli, M.; Mariani, S.; Monacelli, G.

    2006-03-01

    Meteorological and hydrological monitoring and modeling, with particular regard for extreme hydrological events, represent important activities carried out by the Hydrological and Inland Waters Service of the Italian Agency for Environmental Protection and Technical Services (APAT). Recently, a study on the socio-economic effects of floods was published in the Italian Environmental Data Yearbook by APAT. It is based on processed data related to the major floods (i.e., events with at least a casualty or that have generated economic damages higher than 0.001% of the Gross Domestic Product) striking Italy between 1951 and 2003. Information was gathered from technical reports and/or databases belonging to APAT, Italian Regional Environmental Agencies (ARPAs), central and local authorities, research institutions and newspaper reports. These data are collected in tables reporting the number of flood events and of casualties and the amount of financial resources required for environmental restoration and/or for risk mitigation purposes. For year 2003, when APAT has begun a systematic monitoring of flood events in Italy, data concerning rainfall, number of persons involved, evacuation and urgent measures introduced to face the event (laws and acts) are also included. In this way, it was possible to realize a new database, in which flood events that caused the declaration of the state of emergency have been collected. Because of the difficulties in finding sufficiently reliable data for the period before the II World War, the collection of historical data started from 1951. During this period, about 50% of the flood events examined have caused at least 5 victims each, and about 10% more than 100; these data highlight the considerable social impact of flood events and suggest the importance of creating an integrated database to collect information about flood events involving all Europe. These two databases (the historical and updating archives) could be useful for taking

  2. Impact of anthropogenic emissions from major population centers on global and regional aerosol budgets

    NASA Astrophysics Data System (ADS)

    Kunkel, Daniel; Tost, Holger; Lawrence, Mark

    2013-04-01

    In urban areas, in particular in major population centers (MPCs), anthropogenic pollutants can dominate over natural emissions and cause severe air quality problems. We used emission annihilation scenario simulations in the atmospheric chemistry global circulation model EMAC to study the individual and cumulative impact of four major aerosol species from MPCs on the global and regional aerosol budgets. Black carbon, particulate organic matter, sulphur dioxide (SO2), and nitrogen oxides (NOx) were used to represent emissions of primary aerosols and of precursors gases for secondary aerosols sulphate and nitrate, respectively. Moreover, feedbacks resulting from changed emissions on other atmospheric constituents were assessed and the linearity in the burden changes due to the emission changes was discussed. Aerosol sulphate showed the strongest decrease in the global budget and also the most widespread changes in the tropospheric column density, whereas the smallest global decrease with only local changes was found for particulate organic matter. The maximum reduction was found around the emission sources and in downwind regions. The primary emitted aerosols showed almost no feedback on other species. In contrast, many gas-aerosol equilibria were affected when the SO2 and NOx emissions were reduced. In the case with the reduced MPC-NOx emissions, many species participating in the NOx-ozone (O3) chemistry showed a response in their concentrations. In particular, ozone changed differently in extra-tropical and tropical cities, which is in accordance with findings of Butler and Lawrence (2009). Moreover, the oxidation capacity of the atmosphere was changed. The hydroxyl radical concentration changed similarly to O3, which lead to an increase in the tropospheric carbon monoxide concentration and to locally greater SO2 concentrations. Changes in the emissions for black carbon, particulate organic matter, and SO2 resulted in almost linear responses of the corresponding

  3. Epidemiology and Impact of Knee Injuries in Major and Minor League Baseball Players.

    PubMed

    Dahm, Diane L; Curriero, Frank C; Camp, Christopher L; Brophy, Robert H; Leo, Tony; Meister, Keith; Paletta, George A; Steubs, John A; Mandelbaum, Bert R; Pollack, Keshia M

    2016-01-01

    Few studies have explored the frequency and impact of lower extremity injuries, such as those to the knee, among professional baseball players. The purpose of this study was to detail the epidemiology of knee injuries in Major League Baseball (MLB) and Minor League Baseball (MiLB) players during the 2011-2014 seasons. It was hypothesized that knee injuries are a common occurrence in these athletes, and represent a significant source of time away from play. The MLB Health and Injury Tracking System database was searched to identify all patients diagnosed with knee injuries during the 2011-2014 seasons. All injuries that occurred during the preseason, regular season, and postseason that resulted in time away from play were included. Injury data analyzed included total number of knee injuries, specific diagnoses, injury mechanisms, locations, player positions, and time lost. Descriptive statistics were conducted and injury rates per athlete-exposures were calculated. During the 2011-2014 seasons, a total of 2171 knee injuries occurred in MLB and MiLB players, representing 6.5% of all injuries in professional baseball. The knee injury rate across both the MLB and MiLB was 1.2 per 1000 athlete-exposures. The mean number of days missed per injury across both leagues was 16.2 with a total of 30,449 days of missed play amongst all athletes over the 4 seasons. Injuries to the knee were the fifth most common cause of missed time in all of baseball, and the fourth most common reason for missed games in the MLB alone. Approximately 12% of all injuries required surgical intervention. The most common mechanism of injury was noncontact (44%), and base runners were injured more frequently than any other position (24%). The infield (30%) and home plate (23%) were the most common locations in which injuries occurred. These data can be utilized for targeted injury prevention initiatives. PMID:26991584

  4. Impact of Climate Change on Five Major Crop Fungal Diseases: Building Climatic Indicators of Infection Risk

    NASA Astrophysics Data System (ADS)

    Launay, M.; Caubel, J.; Bourgeois, G.; Huard, F.; Garcia de Cortazar-Atauri, I.

    2013-12-01

    The climate change will modify the severity and occurrence of fungal crop diseases, as the bioclimatic niches of pathogens will shift according to temperature and rainfall patterns evolution. Therefore it becomes necessary to integrate fungal disease pressure assessment into evaluation tools of crop suitability at the regional level. The aim of this study was to build two climatic indicators, the Average Infection Efficiency (AIE) and the Number of Infection Days (NID), quantifying the potential effect of climate on infection intensity and occurrence. A simple and continuous function was developed to calculate them, which is easy to parameterize from experimental measurements, usable on large spatial scales and adaptable to various pathogens. The evolution of those climatic indicators was then studied for five major fungal crop diseases in Northern France, the phoma of oilseed rape, the potato late blight, the downy mildew of grape, the leaf rust of wheat and the net blotch of barley. These indicators were applied on a multisite analysis in Northern France. They were calculated during the crop cycle when the host plant is able to be infected, over the period between 1970 and 2100 for the balanced scenario of climate change A1B. In late spring and summer, higher temperatures combined with lower humidity reduced the risk of infection of potato late blight and downy mildew of grape. In autumn and spring the balance between warmer temperatures and lower humidity determined the risk of infection on oilseed rape and cereals: increased risk in late autumn and early spring, and decreased risk in early autumn and mid-spring when low humidity becomes limiting. This statement highlighted the need for using between year scale for a relevant analysis of climate change impact on infection risk. The indicators we developed are thus useful for land management at regional scale and medium term, in particular for stakeholders who need decision support tools through which they could

  5. 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.

  6. 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

  7. Economic impact of accelerated cleanup on regions surrounding the U.S. DOE's major nuclear weapons sites.

    PubMed

    Greenberg, M; Solitare, L; Frisch, M; Lowrie, K

    1999-08-01

    The regional economic impacts of the U.S. Department of Energy's accelerated environmental cleanup plan are estimated for the major nuclear weapons sites in Colorado, Idaho, New Mexico, South Carolina, Tennessee, and Washington. The analysis shows that the impact falls heavily on the three relatively rural regions around the Savannah River (SC), Hanford (WA), and Idaho National Engineering and Environmental Laboratory (ID) sites. A less aggressive phase-down of environmental management funds and separate funds to invest in education and infrastructure in the regions helps buffer the impacts on jobs, personal income, and gross regional product. Policy options open to the federal and state and local governments are discussed. PMID:10765427

  8. Neurological prognostication after cardiac arrest

    PubMed Central

    Sandroni, Claudio; Geocadin, Romergryko G.

    2016-01-01

    Purpose of review Prediction of neurological prognosis in patients who are comatose after successful resuscitation from cardiac arrest remains difficult. Previous guidelines recommended ocular reflexes, somatosensory evoked potentials and serum biomarkers for predicting poor outcome within 72h from cardiac arrest. However, these guidelines were based on patients not treated with targeted temperature management and did not appropriately address important biases in literature. Recent findings Recent evidence reviews detected important limitations in prognostication studies, such as low precision and, most importantly, lack of blinding, which may have caused a self-fulfilling prophecy and overestimated the specificity of index tests. Maintenance of targeted temperature using sedatives and muscle relaxants may interfere with clinical examination, making assessment of neurological status before 72 h or more after cardiac arrest unreliable. Summary No index predicts poor neurological outcome after cardiac arrest with absolute certainty. Prognostic evaluation should start not earlier than 72 h after ROSC and only after major confounders have been excluded so that reliable clinical examination can be made. Multimodality appears to be the most reasonable approach for prognostication after cardiac arrest. PMID:25922894

  9. The Impact of Employing Brainstorming Strategy on Improving Writing Performance of English Major Students at Balqa Applied University in Jordan

    ERIC Educational Resources Information Center

    Amoush, Kholoud Hussein

    2015-01-01

    The study aimed at identifying the impact of employing brainstorming strategy on improving writing performance of English Major Students at Balqa Applied University in Jordan. The sample of the study which consisted of 80 male and female university students was distributed into two groups; experimental (taught by brainstorming strategy) and…

  10. A review of major factors influencing plant responses to recreation impacts

    NASA Astrophysics Data System (ADS)

    Kuss, Fred R.

    1986-09-01

    This article reviews some of the more important factors found to influence the susceptibility of plants to trampling impacts associated with recreational use of natural areas. A three-way interaction mediates plant responses to impacts: plant x environment x stress level(s). Plant responses vary in part according to the genetic constitution of the plant, life and growth form, the adaptive flexibility of the plant, and anatomical differences inherent to growth habit and morphology. Other factors that influence plant sensitivities to impacts are the habitat environments in which plants grow, since a number of conditions such as moisture excesses or deficiencies, nitrogen or oxygen starvation, late frosts, etc., cause physiological injury and may increase plant sensitivity to impacts. Among the environmental factors that may increase or lessen plant sensitivities to impacts are soil moisture levels, canopy density, elevation, aspect, microclimate, soil drainage, texture, fertility and productivity. Seasonal influences also bear consideration since environmental changes and phonological and physiological events are mediated by time of year. Stresses are caused by both direct and indirect forms of impact and vary according to season of use, frequency and amount of use, and the type of activity. These interactions are further complicated by evidence that inter- and intraspecific competition, antagonism, and commensalism may influence differences in the sensitivity of plant communities to impacts.

  11. Analysis of Chinese emissions trends of major halocarbons in monitoring the impacts of the Montreal Protocol

    NASA Astrophysics Data System (ADS)

    Li, S.; Park, S.; Park, M.; Kim, J.; Muhle, J.; Fang, X.; Stohl, A.; Weiss, R. F.; Kim, K.

    2013-12-01

    In this study we estimate the emission rates of anthropogenic halocarbons, which include CFC-11, CFC-12, HCFC-22, HCFC-141b, HCFC-142b, HFC-23, HFC-134a, HFC-32, HFC-125 and HFC-152a for China during the period of 2008 and 2012 using an interspecies correlation method (Kim et al., 2010; Li et al., 2011), which is a unique 'top-down' approach using in situ high-precision measurements at Gosan, a remote station on Jeju Island, Korea. Mixing ratios of ambient halocarbons have been measured every two hours using a cryogenic pre-concentration system coupled with gas chromatograph and mass selective detector (GC-MSD) as part of the Advanced Global Atmospheric Gases Experiment network. We first separated air-mass segments originating from China using a back-trajectory analysis to identify Chinese emission from the observations, and found that the mixing ratios of most of compounds presented significant correlations against those of HCFC-22. Based on the correlations, we analyzed emission strengths of individual compounds, which correspond to their slopes against HCFC-22 since the slope can be a useful proxy to demonstrate their emission trends with an assumption of relatively constant emission of HCFC-22 during the analysis period. The analysis showed about 14% increase in the emissions strengths of CFCs (mainly due to CFC-12) between 2008 and 2012 in China. Interestingly, HCFC-141b and HCFC-142b that are commonly known to be used for foam blowing agents revealed opposite trends in their emission strengths: ca. 48% increase of HCFC-141b versus ca. 22% decrease of HCFC-142b, suggesting the possibility of other major sources in case of China. The emission strengths of HFCs have been increasing due to significant emissions of HFC-32, HFC-125 and HFC-134a during the analysis period. However, HFC-23 which is a well-known byproduct of HCFC-22 production processes, showed decrease by about 22% in the emission strength. Reduction in HFC-23 emissions is most likely due to the

  12. Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era.

    PubMed

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

    2015-12-01

    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 to 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 International Prognostic Index 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 × 3-4 cycles (Arm A), 147 received R-CHOP × 3-4 cycles + IFRT (Arm B), 48 received R-CHOP × 6 cycles (Arm C), and 50 received R-CHOP × 6 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

  13. Towards standardised evaluative measurement of nature impacts: two spatial planning case studies for major Dutch lakes.

    PubMed

    van Puijenbroek, P J T M; Sijtsma, F J; Wortelboer, F G; Ligtvoet, W; Maarse, M

    2015-02-01

    In the assessment of complex spatial planning projects, the ecological impacts and socio-economic impacts are fundamental to the evaluation. The measurements of ecological impacts of spatial plans have to be integrated in a standardised way. In the present paper, we analyse two Dutch case studies and apply the standardised Threat-Weighted Ecological Quality Area measurement. This measurement is developed to evaluate projects with terrestrial impacts but has not yet been applied for water evaluations. We aim to show how the use of a common measurement tool incorporates both ecological quality and degree of threat on criteria in the EU Water Framework Directive and Nature 2000. The measurements discussed here derive from two cases of cost-benefit analysis: The first case is the Markermeer, the second largest lake of The Netherlands, and a study on water quality improvement and nature restoration; an artificial island will also be the setting for a new residential area. The second case study is on water level management carried out on the IJsselmeer, the largest lake in the country. Results of our analysis show the potential impacts with a standardised method to the spatial distribution and quality of the ecosystems. PMID:24770926

  14. 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 Central

    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. PMID:25119018

  15. The Impact of Extensive Reading on College Business Majors in Taiwan

    ERIC Educational Resources Information Center

    Shih, Ying-Chun

    2015-01-01

    The effects of extensive reading on EFL context have been examined with a variety of studies. This study examined the impact of extensive reading on reading proficiency while the participants were taught reading strategies. Furthermore, this study explored whether there were any differences between intervention and control groups on the reading…

  16. Separating the Air Quality Impact of a Major Highway and Nearby Sources by Nonparametric Trajectory Analysis

    EPA Science Inventory

    Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur di...

  17. The Major Impacts of the Baby Boom Cohort upon American Life, Past, Present and Future.

    ERIC Educational Resources Information Center

    Whaley, Charles E.

    Impacts of the "Baby Boom" generation, the 75 million persons born between 1947 and 1962 in the United States, are analyzed. Factors influencing this unprecedented increase in birth rates included "catching up" by men who had been at war, a higher proportion of women in childbearing years, a decrease in the average marriage age, and the prosperous…

  18. The Major Impacts of the Baby Boom upon American Life, 1945-2050.

    ERIC Educational Resources Information Center

    Vaughan, Jerry L.

    The demographic context of the baby boom in the United States (1946-1964) as well as past and future impacts of this population increase are considered in this review of research. During the 18-year period, over 76,000,000 babies were born, more than the entire population of the United States in 1900. Reasons for the increase are attributed to…

  19. The Impact of Cooperative Quizzes in a Large Introductory Astronomy Course for Non-Science Majors

    ERIC Educational Resources Information Center

    Zeilik, Michael; Morris, Vicky J.

    2004-01-01

    In Astronomy 101 at the University of New Mexico, we carried out a repeated-items experiment on quizzes and tests to investigate the impact of cooperative testing. This trial was the only change in a reformed course format that had been refined over previous semesters. Our research questions were: (1) Did cooperative quizzes result in gains for…

  20. 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

  1. IMPACTS OF TRAFFIC ON AIR QUALITY AND HEALTH EFFECTS NEAR MAJOR ROADWAYS

    EPA Science Inventory

    A growing number of epidemiological studies conducted in Europe, Asia, and North America have identified an increase in occurrence of adverse health effects for populations living near major roads. However, the biological mechanism(s) leading to the adverse effects have not been...

  2. The Impact of Leadership Roles and Internships on Undergraduate Business Major Field Test (MFT) Scores

    ERIC Educational Resources Information Center

    Ward, Chris; Yates, Dan; Song, Joon Young

    2014-01-01

    It is often the goal or mission of higher education to prepare graduates for leadership roles in organizations and the community. Even if we are to assume that leadership skills can be developed, determining the appropriate ways to teach and measure leadership is often debated. Our study used quantitative data from the ETS Business Major Field…

  3. Water quality of four major lakes in Mississippi, USA: Impacts on human and aquatic ecosystem health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Harmful algal blooms (HABs), harmful microorganisms (pathogens) and toxic metals represent three major agents of water quality deterioration. Better water quality is of utmost importance to water bodies that provide recreational opportunities, even better quality is expected in the water bodies that...

  4. Natural Science Majors and Liberal Education: The Impact of a Living-Learning Community

    ERIC Educational Resources Information Center

    Hutt, Chris D.

    2012-01-01

    The purpose of this study was to explore the articulated experiences of natural science majors who were participating in a liberal arts living-learning community. Using the American Association of College and University's (2002) report, "Greater Expectations" as an organizing framework, this study sought to determine how--if at…

  5. Separating the air quality impact of a major highway and nearby sources by nonparametric trajectory analysis.

    PubMed

    Henry, Ronald C; Vette, Alan; Norris, Gary; Vedantham, Ram; Kimbrough, Sue; Shores, Richard C

    2011-12-15

    Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur dioxide concentrations were collected from December 2008 to December 2009. The purpose of the study was to determine the impact of the highway at three downwind monitoring stations using an upwind station to measure background concentrations. NTA was used to precisely determine the contribution of the highway to the average concentrations measured at the monitoring stations accounting for the spatially heterogeneous contributions of other local urban sources. NTA uses short time average concentrations, 5 min in this case, and constructed local back-trajectories from similarly short time average wind speed and direction to locate and quantify contributions from local source regions. Averaged over an entire year, the decrease of concentrations with distance from the highway was found to be consistent with previous studies. For this study, the NTA model is shown to be a reliable approach to quantify the impact of the highway on local air quality in an urban area with other local sources. PMID:22044064

  6. Vascular grading of angiogenesis: prognostic significance in breast cancer

    PubMed Central

    Hansen, S; Grabau, D A; Sørensen, F B; Bak, M; Vach, W; Rose, C

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (κ = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P< 0.0001), node-negative patients (P< 0.0001) and node-positive patients (P< 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P< 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer. © 2000 Cancer Research Campaign PMID:10646886

  7. Prognostic Impact of Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Treated using Intensity-Modulated Radiation Therapy.

    PubMed

    Peng, Hao; Guo, Rui; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    The prognostic value of plasma Epstein-Barr virus (EBV) DNA remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 584 newly diagnosed patients with nonmetastatic and biopsy-proven NPC treated using IMRT. Plasma EBV DNA concentration was measured before therapy (pre-DNA) and within 1 month of completing therapy (post-DNA) using real-time quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curves were generated to identify pre-DNA and post-DNA cut-off values. Prognostic value was assessed using a multivariate Cox proportional hazards model .Three-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free (DMFS) for pre-DNA >2010 vs.≤2010 were 78.1% vs. 93.6% (P < 0.001), 92.3% vs. 98.9% (P < 0.001), 90.9% vs. 96.6% (P = 0.004) and 85.5% vs. 96.6% (P < 0.001), respectively. Three-year DFS, OS, LRRFS and DMFS for post-DNA >0 vs. = 0 were 49.9% vs. 88.5% (P < 0.001), 72.1% vs. 97.5% (P < 0.001), 86.6% vs. 94.3% (P = 0.019), and 60.5% vs. 93.3% (P < 0.001), respectively. Plasma EBV DNA remains a prognostic factor in IMRT era and should be incorporated into TNM staging to guide individualized treatment strategies in NPC. PMID:26924234

  8. Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma.

    PubMed

    Togami, Shinichi; Sasajima, Yuko; Oi, Takateru; Ishikawa, Mitsuya; Onda, Takashi; Ikeda, Shun-Ichi; Kato, Tomoyasu; Tsuda, Hitoshi; Kasamatsu, Takahiro

    2012-05-01

    Uterine papillary serous carcinoma (UPSC) is a rare and aggressive variant of endometrial carcinoma. Little is known about the pathological and biological features of this tumor. Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) expression have an important role in tumor behavior and clinical outcome, but their relevance in UPSC is not clear. In the present study, the immunohistochemical expression of HER2 and HR was assessed in 27 patients with Stage I disease, 13 with Stage II disease, 25 with Stage III disease, and 6 with Stage IV disease. Correlations between HER2 and HR expression and the clinicopathological parameters of UPSC were evaluated using Cox's univariate and multivariate analyses. For all patients, the 5-year recurrence-free survival (RFS) and overall survival (OS) rates were 51% and 66%, respectively; in patients with Stage I, II, III and IV disease, the RFS and OS were 67%/81%, 59%/77%, 43%/54% and 0%/0%, respectively. Of all 71 patients, 14% (10/71) were positive for HER2 and 52% (37/71) were positive for HR. Overexpression of HER2 was correlated with lower OS (P = 0.01), whereas HR overexpression was correlated with higher OS (P = 0.008). In multivariate models, HER2, HR, and histologic subtype were identified as independent prognostic indicators for RFS (P = 0.022, P = 0.018, and P = 0.01, respectively), but HR was the only independent factor associated with OS (P = 0.044). Thus, HER2 and HR are prognostic variables in UPSC, with HR an independent prognostic factor for OS. PMID:22329832

  9. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

    Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  10. Prognostic DNA methylation markers for prostate cancer.

    PubMed

    Strand, Siri H; Orntoft, Torben F; Sorensen, Karina D

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  11. Assessing Resiliency in a Large Lake Receiving Mine Tailings Waste: Impacts of Major Environmental Disturbance.

    NASA Astrophysics Data System (ADS)

    Petticrew, Ellen; Owens, Philip; Albers, Sam

    2016-04-01

    On 4th August 2014, the tailings impoundment of the Mount Polley copper and gold mine in British Columbia failed. Material from the impoundment (surface area = 2.7 km2) flowed into nearby Polley Lake and Hazeltine Creek, before discharging into Quesnel Lake, a large (ca. 100 km long, >500 m deep), relatively pristine lake. Initial estimates suggest that approximately 25 Mm3 of tailings (water and solids) and eroded soils and surficial materials from Hazeltine Creek were delivered to Quesnel Lake, raising the lake by 7.7 cm. Much of this material was deposited at the bottom of Quesnel Lake but a plume of fine-grained sediment (D50 of ca. 1 μm) remained suspended in the water column. The impact of the distribution of this sediment was monitored over the next 15 months using water column profiling for temperature, conductivity, fluorescence and turbidity with depth. The plume movement was regulated by natural processes associated with the physical limnology of this large fjord lake, specifically, seiche events which transferred suspended particles both up-lake, against the flow regime, and down-lake into the Quesnel River. Samples of lake water and bottom sediment taken from the impacted area show elevated levels of total metals and other elements, which may have important ecosystem implications in this watershed. Indeed, the breach occurred at a time when a peak run of sockeye salmon were returning to their natal streams in the Quesnel basin. Zooplankton sampling for metals was initiated in fall 2014 to determine up take of metals into the food web. This poster describes the failure of the impoundment dam and presents results of sampling the aquatic environment over the first fifteen months of impact.

  12. Analysis of the Impact of Major Dust Events on the Aerosols Characteristics over Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Farahat, Ashraf; El-Askary, Hesham; Al-Shaibani, Abdulaziz; Hariri, Mustafa M.

    2015-04-01

    The Kingdom of Saudi Arabia is a major source of atmospheric dust. Frequent dust storms blow up and significantly affect human activities, airports and citizens' health. Aerosols optical and physical characteristics are influenced by major dust storms outbreaks. In this, paper, ground based AERONET measurements are integrated with space-borne sensors, namely MODIS and CALIPSO to analyze aerosols' characteristics during March - May of 2009 where a massive dust storm blew up and caused a widespread heavy atmospheric dust load over Saudi Arabia and the same period during 2010, where less dust activities were reported. The MODIS Deep Blue AOD analysis showed similar aerosols pattern over the land, however a substantial variance in aerosol loading during March - May 2009 compared with the same period in 2010 was observed. The angstrom exponent analysis showed that the majority of aerosol measurements in 2009 and 2010 are dominated by coarse-mode particles with angstrom exponent < 0.5. Detailed analysis of aerosol optical properties shows significant influence of coarse mode particles in the enhanced aerosol loading in 2009. The volume depolarization rations (VDR) derived from CALIPSO backscattering measurements is used to find latitudinal profile of mean aerosol optical depth to indicate the type of particles and to discriminate spherical aerosols with non-spherical particles. Acknowledgement The authors would like to acknowledge the support provided by the King Abdel Aziz City for Science & Technology (KACST) for funding this work under grant No. (MT-32-76). The support provided by the Deanship of Research at King Fahd University of Petroleum & Minerals (KFUPM) is gratefully acknowledged.

  13. Impact of a major meteor storm on Earth's ionosphere: A modeling study

    NASA Astrophysics Data System (ADS)

    McNeil, William J.; Dressler, Rainer A.; Murad, Edmond

    2001-06-01

    A comprehensive model of the effect of a major meteor storm on Earth's ionosphere is presented. The model includes meteor stream mass distributions based on visual magnitude observations, a differential ablation model of major meteoric metals, Fe and Mg, and state-of-the-art modeling of the chemistry and transport of meteoric metal atoms and ions subsequent to deposition. Particular attention is paid to the possibility of direct ionic deposition of metallic species. The model is validated by calculating the effect of annual meteor showers on the background metal atom and ion abundances. A metallic ion density increase of up to 1 order of magnitude is observed, in agreement with in situ measurements during showers. The model is exercised for a hypothetical Leonid meteor storm of the magnitude reported in 1966. The model predicts the formation of a layer of metal ions in the ionospheric E region that reaches peak densities of around 1×105cm-3, corresponding to a 2 order of magnitude increase of the quiescent nighttime E region density. Although sporadic E layers reaching or exceeding this density are relatively common, the effect is different in that it persists on the order of days and would be observed over nearly one-half the globe. The model predictions are consistent with the available 1966 Leonid storm data. In particular, the observation of enhanced, predawn sporadic E activity points to efficient collisional ionization of meteoric metals, as assumed in the model.

  14. Re-plumbing the Terrestrial Hydrosphere: Scope and Impact of Major Inter-basin Water Transfers

    NASA Astrophysics Data System (ADS)

    Shikhmacheva, K. V.; Vorosmarty, C. J.; Fekete, B. M.; Afshari, S.; Aside, B.; Chibisova, Y.; Dopson, I.; Link, H.; Mouden, A.

    2013-12-01

    The availability of water has become one of the main concerns in modern history and it is an important policymaking strategy. Increasing population, agricultural intensification, rapid urbanization, industrial expansion and environmental changes increase water demand on region and global scales. Inter-Basin Water Transfer (IBWT) is an important element of satisfying immediate water requirements. The complex engineering structures divert water flow between watersheds, thus ';re-plumbing' terrestrial hydrosphere. We report here an analysis of inter-basin water transfer for the Northeast region, which is a part of an NSF funded project entitled 'The NorthEast Regional Earth System Model (NE-RESM).' In addition, this work is also a part of a global IBWT study. First, we present the IBWT geo-referenced assembled data set, derived from from maps, published documents and online resources. The information in the data base was classified by project name, diverted volume, source location, usage, status of construction, transport distance and purpose. The key feature of the dataset is geo-location of the projects, that allows further analysis of the hydrologic impact of each of the projects as well as their collective significance. Upon completion of the data-collection phase, the inputs were verified using RiverGIS and ArcGIS software. In addition, we investigated some key measures of IBWT distortion of regional-scale hydrology as well as their socio-economic impacts across the Northeast region. We calculated several indicators to assess these impacts, for example the donor-to-recipient basin flow ratio, which represents the 'gain' and 'loss' of water relative to the natural flow on a basin scale. Elements of the regional IBWT data base will be incorporated into the regional-scale Water Balance Model (WBM), and linked to the operation of reservoirs and dams. While focused on the Northeastern U.S., we believe that this data, its testing and applications will yield broad use

  15. Pomalidomide Shows Significant Therapeutic Activity against CNS Lymphoma with a Major Impact on the Tumor Microenvironment in Murine Models

    PubMed Central

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A.; Moghaddam, Mehran F.; Copland, John A.; Tun, Han W.

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  16. Heart failure prognostic model

    PubMed Central

    Axente, L; Sinescu, C; Bazacliu, G

    2011-01-01

    Heart failure (HF) is a common, costly, disabling and deadly syndrome. Heart failure is a progressive disease characterized by high prevalence in society, significantly reducing physical and mental health, frequent hospitalization and high mortality (50% of the patients survive up to 4 years after the diagnosis, the annual mortality varying from 5% to 75%). The purpose of this study is to develop a prognostic model with easily obtainable variables for patients with heart failure. Methods and Results. Our lot included 101 non–consecutive hospitalized patients with heart failure diagnosis. It included 49,5% women having the average age of 71.23 years (starting from 40 up to 91 years old) and the roughly estimated period for monitoring was 35.1 months (5–65 months). Survival data were available for all patients and the median survival duration was of 44.0 months. A large number of variables (demographic, etiologic, co morbidity, clinical, echocardiograph, ECG, laboratory and medication) were evaluated. We performed a complex statistical analysis, studying: survival curve, cumulative hazard, hazard function, lifetime distribution and density function, meaning residual life time, Ln S (t) vs. t and Ln(H) t vs. Ln (t). The Cox multiple regression model was used in order to determine the major factors that allow the forecasting survival and their regression coefficients: age (0.0369), systolic blood pressure (–0.0219), potassium (0.0570), sex (–0.3124) and the acute myocardial infarction (0.2662). Discussion. Our model easily incorporates obtainable variables that may be available in any hospital, accurately predicting survival of the heart failure patients and enables risk stratification in a few hours after the patients' presentation. Our model is derived from a sample of patients hospitalized in an emergency department of cardiology, some with major life–altering co morbidities. The benefit of being aware of the prognosis of these patients with high risk is

  17. Heart failure prognostic model.

    PubMed

    Axente, L; Sinescu, C; Bazacliu, G

    2011-05-15

    Heart failure (HF) is a common, costly, disabling and deadly syndrome. Heart failure is a progressive disease characterized by high prevalence in society, significantly reducing physical and mental health, frequent hospitalization and high mortality (50% of the patients survive up to 4 years after the diagnosis, the annual mortality varying from 5% to 75%). The purpose of this study is to develop a prognostic model with easily obtainable variables for patients with heart failure. METHODS AND RESULTS. Our lot included 101 non-consecutive hospitalized patients with heart failure diagnosis. It included 49.5% women having the average age of 71.23 years (starting from 40 up to 91 years old) and the roughly estimated period for monitoring was 35.1 months (5-65 months). Survival data were available for all patients and the median survival duration was of 44.0 months. A large number of variables (demographic, etiologic, co morbidity, clinical, echocardiograph, ECG, laboratory and medication) were evaluated. We performed a complex statistical analysis, studying: survival curve, cumulative hazard, hazard function, lifetime distribution and density function, meaning residual life time, Ln S (t) vs. t and Ln(H) t vs. Ln (t). The Cox multiple regression model was used in order to determine the major factors that allow the forecasting survival and their regression coefficients: age (0.0369), systolic blood pressure (-0.0219), potassium (0.0570), sex (-0.3124) and the acute myocardial infarction (0.2662). DISCUSSION. Our model easily incorporates obtainable variables that may be available in any hospital, accurately predicting survival of the heart failure patients and enables risk stratification in a few hours after the patients' presentation. Our model is derived from a sample of patients hospitalized in an emergency department of cardiology, some with major life-altering co morbidities. The benefit of being aware of the prognosis of these patients with high risk is extremely

  18. The Impact of Damage Control Surgery on Major Abdominal Vascular Trauma

    PubMed Central

    Sorrentino, Talia A; Moore, Ernest E; Wohlauer, Max V; Biffl, Walter L; Pieracci, Fredric M; Johnson, Jeffrey L; Barnett, Carlton C; Bensard, Denis D; Burlew, Clay Cothren

    2012-01-01

    Background Thirty years ago we reported our experience with abdominal vascular trauma, highlighting the critical role of hypothermia, acidosis, and coagulopathy. Damage control surgery was subsequently introduced to address this “lethal triad.” The purpose of this study is to evaluate outcomes from our most recent 6-year experience compared to 30 years ago. Methods Patients with major abdominal vascular injuries were examined; the most recent 6-year period was compared with archived data from a similar 6-year period three decades ago. Results The number of patients with major abdominal vascular injuries decreased from 123 patients (1975–1980) to 64 patients (2004–2009). The mean initial pH decreased from 7.21 to 6.96 (1975–1980 vs. 2004–2009]) for patients with overt coagulopathy. In spite of increasingly protracted acidosis, mortality attributable to refractory coagulopathy has decreased from 46% to 19% (1975–1980 vs. 2004–2009, χ2 = 4.36, p = 0.04). There was no significant difference in mortality due to exsanguinating injuries (43% vs. 62%, 1975–1980 vs. 2004–2009, χ2 = 1.96, p = 0.16). Prehospital transport times were unchanged (22 min vs. 20 min, 1975–1980 vs. 2004–2009). Despite the administration of additional clotting factors and the advent of DCS, the overall mortality remains largely unchanged (37% vs. 33%, 1975–1980 vs. 2004–2009, χ2 = 0.385, p = 0.53). Conclusions Adoption of damage control surgery, including the implementation of a massive transfusion protocol, is associated with a reduction in mortality for abdominal vascular injuries due to coagulopathy, however, patients continue to die from exsanguination. PMID:22682716

  19. Impact of a major cyclone on a southeast African estuarine lake system

    NASA Astrophysics Data System (ADS)

    Forbes, A. T.; Cyrus, D. P.

    The St Lucia lake and estuarine system in northern Natal, South Africa was struck by Cyclone Domoina on 31 January 1984. This is the only cyclone known to have traversed part of South Africa. The ensuing flood levels in the St Lucia system (which have been exceeded perhaps only one other time in recorded history) provided an opportunity to assess the effect of a major disturbance on a subtropical estuarine system. Major geomorphological changes occurred in the mouth area where all man-made structures were obliterated. The two river channels were scoured from 2-3 m to 10-14 m in depth and widened by up to 300 m, while the shoreline between the two channels retreated in places up to 100 m. An estimated 16∗10 6 m 3 of sediment were removed from the lower reaches of the system including areas of mangrove and Phragmites australis swamp. One-metre tall mangrove saplings died following inundation lasting days to weeks. Effects on the fauna included redistribution of the tanaid Apseudes digitalis, the mysid Mesopodopsis africana, the copepod Pseudodiaptomus stuhlmanni, the polychaete Scololepis squamata and the bivalve Solen cylindraceus, all typical lake species which appeared in the tidal channel linking the lake with the sea. Responses of other species such as the penaeid prawns, the crab Scylla serrata and the sole Solea bleekeri suggested that physiological tolerance, extended larval or juvenile recruitment periods and prey switching minimized long-term flood effects. No large-scale mortalities were noted, and the absence of a temperature shock is considered to be a significant feature.

  20. 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.

  1. Fire regimes in Russia and their impacts on major biogeochemical cycles

    NASA Astrophysics Data System (ADS)

    Shvidenko, A.; Shchepashchenko, D.; Kraxner, F.; Bartalev, S.

    2015-12-01

    The warming trend in Russia for period of 1976-2014 was more than two times higher than the global one. Change of precipitation was regionally diverse, but on average not enough to compensate the high warming rate. Variability of seasonal weather increased with long dry and warm periods. Severe heat waves are regularly observed in different regions of the country. Three available remote sensing products of spatially explicit distribution of burnt area in Russia (GFED4; Institute of Forest SB RAS, Krasnoyarsk; and Space Research Institute, RAS, Moscow) reported rather consistent average burnt areas for the period of 2000-2010 (from 8.3 to 9.4 x 106 ha year-1); however, the differences for individual years, particularly for 2011-2012 are large. Of the total fire area, about 2/3 were on forest land. A typical feature of fire regimes of recent decades is increasing frequency and severity of mega-fires, which envelope vast regions (up to millions of hectares) with numerous simultaneously burning areas, cause large ecological, economic and social losses and often provide irreversible impacts on forest ecosystems. Such fires occurred in different regions of Russia in 1998 (7.7 x 106 ha of burnt areas), 2002 (8.2), 2003 (16.6), 2005 (8.5), 2006 (12.4), 2007 (8.9), 2008 (16.8), 2009 (10.4), 2010 (7.9), 2011 (8.8 x 106 ha), 2012 (15.8 x 106 ha). We present a full fire carbon budget for 2000-2012 as a proxy of severity of fire regimes, based on 1) a country's Integrated Land Information System, which contains georeferenced land cover, amount of fuel by types and annual burnt areas at resolution of 1km; and 2) regionally distributed models of fire severity. The amount of fuel consumed by fire is estimated at 135 Tg C yr-1 with large interannual variation and uncertainties ~25%. We discuss ecological consequences of fire, its impact on successions, health and productivity of forest ecosystems as well as predicted dynamics of fire regimes over 21st century.

  2. The Impact of Cooperative Quizzes in a Large Introductory Astronomy Course for Non Science Majors

    NASA Astrophysics Data System (ADS)

    Zeilik, Michael; Morris, Vicky J.

    In Astronomy 101 at the University of New Mexico, we carried out a repeated-items experiment on quizzes and tests to investigate the impact of cooperative testing. This trial was the only change in a reformed course format that had been refined over previous semesters. Our research questions were: Did cooperative quizzes result in gains for the class overall? Did these gains "stick" within the semester? In the spring and fall semesters of 2000, students took quizzes individually and in cooperative learning teams, and tests individually. Normalized gain, , on the quizzes averaged about 0.4, and effect size about 0.8 (approximately a 10% increase in class mean score). Repeating selected quiz items on a subsequent test demonstrated that the gain was sustained over a month in both semesters. In addition, we compared demographics of UNM students with those of the National Astronomy Diagnostic Test project. We found that UNM students are similar to the national sample, except in ethnicity (more Hispanic American, fewer White). Based on these results, we judge that our cooperative quiz strategy will likely succeed in other "Astro 101" classes.

  3. Impact of Major Coronal Mass Ejections on Geospace during 2005 September 7-13

    NASA Astrophysics Data System (ADS)

    Wang, Yuming; Xue, Xianghui; Shen, Chenglong; Ye, Pinzhong; Wang, S.; Zhang, Jie

    2006-07-01

    We have analyzed five major CMEs originating from NOAA active region (AR) 808 during the period of 2005 September 7-13, when the AR 808 rotated from the east limb to near solar meridian. Several factors that affect the probability of the CMEs' encounter with the Earth are demonstrated. The solar and interplanetary observations suggest that the second and third CMEs, originating from E67° and E47°, respectively, encountered the Earth, while the first CME originating from E77° missed the Earth, and the last two CMEs, although originating from E39° and E10°, respectively, probably only grazed the Earth. On the basis of our ice cream cone mode and CME deflection model, we find that the CME span angle and deflection are important for the probability of encountering Earth. The large span angles allowed the middle two CMEs to hit the Earth, even though their source locations were not close to the solar central meridian. The significant deflection made the first CME totally miss the Earth even though it also had wide span angle. The deflection may also have made the last CME nearly miss the Earth even though it originated close to the disk center. We suggest that, in order to effectively predict whether a CME will encounter the Earth, the factors of the CME source location, the span angle, and the interplanetary deflection should all be taken into account.

  4. Impact of major coronal mass ejections on geo-space during September 7 -- 13, 2005

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Xue, X.; Shen, C.; Ye, P.; Wang, S.; Zhang, J.

    2006-05-01

    We have analyzed five major CMEs originating from NOAA active region (AR) 808 during the period of September 7 to 13, 2005, when the AR 808 rotated from the east limb to near solar meridian. Several factors that affect the probability of the CMEs' encounter with the Earth are demonstrated. The solar and interplanetary observations suggest that the 2nd and 3rd CMEs, originating from E67 and E47 respectively, encountered the Earth, while the 1st CME originating from E77 missed the Earth, and the last two CMEs, originating from E39 and E10 respectively, probably only grazed the Earth. Based on our ice-cream cone model (Xue et al. 2005a) and CME deflection model (Wang et al. 2004b), we find that the CME span angle and deflection are important for the probability of encountering. The large span angles make middle two CMEs hit the Earth, though their source locations were not close to the solar central meridian. The significant deflection makes the first CME totally missed the Earth though it also had wide span angle. The deflection may also make the last CME nearly missed the Earth though it originated close to the disk center. We suggest that, in order to effectively predict whether a CME will encounter the Earth, the factors of the CME source location, the span angle, and the interplanetary deflection should all be taken into account.

  5. Impacts of biotic and abiotic stress on major quality attributing metabolites of coffee beans.

    PubMed

    Vaddadi, Sridevi; Parvatam, Giridhar

    2015-03-01

    Biotic stress factors such as Rhizopus oligosporus and Aspergillus niger mycelial extracts and abiotic elements methyljasmonate (MJ) and salicylic acid (SA), when administered through floral spray to Coffea canephora, showed significant influence on major bioactive metabolites of beans. Up to 42% caffeine, 39% theobromine and 46% trigonelline, along with 32% cafestol and kahweol content elevation was evident under respective elicitor treatments. Over all, the surge in respective metabolites depends on elicitor stress type and concentration. Abiotic factors MJ and SA were found to be efficient at 1 to 5 microM concentration in augmenting all the metabolites, compared to R. oligosporus and A. niger spray at 0.5-2.0% wherein the response was moderate as compared to abiotic stress, however significant compared to control. Though this elevation in caffeine, theobromine, cafestol and kahweol is not warranted from quality point of view, increase in trigonelline improves coffee quality. Besides increase in metabolites, stress mediated augmentation of bioactive compounds in coffee has a wide scope for studying gene expression pattern. PMID:25895259

  6. Impact of electroconvulsive therapy on magnetoencephalographic correlates of dysfunctional emotional processing in major depression.

    PubMed

    Zwanzger, Peter; Klahn, Anna Luisa; Arolt, Volker; Ruland, Tillmann; Zavorotnyy, Maxim; Sälzer, Johannes; Domschke, Katharina; Junghöfer, Markus

    2016-04-01

    In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses. PMID:26922827

  7. Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity

    PubMed Central

    Li, Li; Shelton, Richard Charles; Chassan, Rachel Ann; Hammond, John Charles; Gower, Barbara Ann; Garvey, Timothy W

    2016-01-01

    Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes. PMID:27274905

  8. The Global Burden of Liver Disease: The Major Impact of China

    PubMed Central

    Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

    2016-01-01

    Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus, HBV), nonalcoholic fatty liver disease and alcoholic liver disease affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines and drug development for liver diseases, and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID:25164003

  9. Impact of STAT/SOCS mRNA Expression Levels after Major Injury

    PubMed Central

    Brumann, M.; Matz, M.; Kusmenkov, T.; Stegmaier, J.; Biberthaler, P.; Kanz, K.-G.; Mutschler, W.; Bogner, V.

    2014-01-01

    Background. Fulminant changes in cytokine receptor signalling might provoke severe pathological alterations after multiple trauma. The aim of this study was to evaluate the posttraumatic imbalance of the innate immune system with a special focus on the STAT/SOCS family. Methods. 20 polytraumatized patients were included. Blood samples were drawn 0 h–72 h after trauma; mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3 were quantified by qPCR. Results. IL-10 mRNA expression increased significantly in the early posttraumatic period. STAT 3 mRNA expressions showed a significant maximum at 6 h after trauma. SOCS 1 levels significantly decreased 6 h–72 h after trauma. SOCS 3 levels were significantly higher in nonsurvivors 6 h after trauma. Conclusion. We present a serial, sequential investigation in human neutrophil granulocytes of major trauma patients evaluating mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3. Posttraumatically, immune disorder was accompanied by a significant increase of IL-10 and STAT 3 mRNA expression, whereas SOCS 1 mRNA levels decreased after injury. We could demonstrate that death after trauma was associated with higher SOCS 3 mRNA levels already at 6 h after trauma. To support our results, further investigations have to evaluate protein levels of STAT/SOCS family in terms of posttraumatic immune imbalance. PMID:24648661

  10. The global burden of liver disease: the major impact of China.

    PubMed

    Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

    2014-12-01

    Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID:25164003

  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. PMID:26476674

  12. Impact of Burden of Thalassemia Major on Health-related Quality of Life in Omani Children.

    PubMed

    Mevada, Surekha T; Al Saadoon, Muna; Zachariah, Mathew; Al Rawas, Abdul H; Wali, Yasser

    2016-07-01

    To improve treatment outcome in young patients with homozygous β-thalassemia, evaluation of factors associated with health-related quality of life (HRQoL) is essential to develop clinical, counseling, social, and school support programs. This study was performed to evaluate HRQoL in Omani children with thalassemia who have not been previously evaluated. All patients with thalassemia (5 to 18 y) on regular hypertransfusion from August 2013 to February 2014 were included. Demographic-clinical information was obtained from electronic patient records. The 23-item Pediatric Quality of Life Inventory (PedsQL) 4.0 with 4 multidimensional scales and 3 summary scores was used to assess HRQoL by both patients and caregivers. Statistical analysis was performed using SPSS version 19. Delayed age at diagnosis and delayed initiation of chelation were independently associated with a negative impact on total PedsQL scores; children with higher pretransfusion hemoglobin and lower serum ferritin levels scored better overall. Patients self-rated their HRQoL scores lower as compared with caregivers. Although physical health was more affected than psychosocial health function from both patients' (72.26±22.34 vs. 74.55±18.25) and caregivers' (69.91±19.86 vs. 78.83±18.45) perspective, school functioning domain (68.05±21.30 and 69.71±18.96) scored the lowest. Low ratings for physical health and school functioning highlight the importance of adequate transfusion together with the need for a multidisciplinary teamwork by health care providers, social workers, counselors, family members, and school authorities to provide psychosocial support to prevent mental issues and improve academic performance in these young patients. PMID:27164523

  13. 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

  14. Air quality impacts of a scheduled 36-h closure of a major highway

    NASA Astrophysics Data System (ADS)

    Quiros, David C.; Zhang, Qunfang; Choi, Wonsik; He, Meilu; Paulson, Suzanne E.; Winer, Arthur M.; Wang, Rui; Zhu, Yifang

    2013-03-01

    Elevated concentrations of ultrafine particles (UFPs, <0.1 μm) are commonly found near roadways. On the July 16-17, 2011 weekend, a section of a major Los Angeles freeway, the I-405, was closed for 36 h. We measured UFPs and other pollutants at two fixed locations, one upwind and one downwind, and at various distances from I-405 using a mobile measurement platform (MMP) on Fridays, Saturdays, and Sundays before, during, and after closure. On the closure Saturday on July 16, I-405 traffic flow was reduced by ˜90% relative to non-closure Saturday observations. Downwind of I-405, fixed-site measurements showed the following reductions: 83% of particle number concentration (PNC), 36% of PM2.5, and 62% of black carbon. Fixed-site measurements showed daily average UFP size distributions were bimodal for non-closure conditions (nucleation modes ˜20 nm, accumulation modes ˜60 nm), but only showed an accumulation mode ˜50 nm during closure. Spatial measurements from the MMP confirmed no nucleation mode was detected at any location 0-300 m downwind during closure. In 2011, non-closure particle emission factors were 5.0, 2.7, and 3.4 × 1013 particles vehicle-1 km-1 for Friday through Sunday respectively. After accounting for instrumental and traffic flow differences, weekday PNC in 2011 was 60% lower than 2001 at the same study location. During the closure event, regional freeway traffic was reduced compared to four selected control Saturdays. Eight stationary monitoring stations throughout the South Coast Air Basin showed PM2.5 was reduced between 18 and 36% relative to the same control days. The outcome of this natural experiment during the I-405 closure confirms that substantial traffic reduction can improve local and regional air quality in sprawled urban regions such as Los Angeles, CA.

  15. The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

    PubMed

    Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

    2015-08-01

    Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. PMID:25861730

  16. René Stet's impact on the study of teleost major histocompatibility genes: evolution from loci to populations.

    PubMed

    Dixon, Brian

    2008-02-01

    René Josephus Maria Stet pursued a 35-year-long scientific career contributing to human immunology, shrimp immunity and teleost immunity. His most significant contributions, however, were to the field of teleost major histocompatibility (MH) gene research from 1988 to 2007, a field in which he was a leader and an innovator. This review will discuss his work on these genes, highlighting the impact he had in three temporally overlapping phases of his career that can be characterized as MH gene discovery, MH gene function and evolution and population dynamics of teleost MH genes. PMID:18193417

  17. Impact of Albumin on Coagulation Competence and Hemorrhage During Major Surgery

    PubMed Central

    Rasmussen, Kirsten C.; Højskov, Michael; Johansson, Pär I.; Kridina, Irina; Kistorp, Thomas; Salling, Lisbeth; Nielsen, Henning B.; Ruhnau, Birgitte; Pedersen, Tom; Secher, Niels H.

    2016-01-01

    Abstract For patients exposed to a massive blood loss during surgery, maintained coagulation competence is important. It is less obvious whether coagulation competence influences bleeding during elective surgery where patients are exposed to infusion of a crystalloid or a colloid. This randomized controlled trial evaluates whether administration of 5% human albumin (HA) or lactated Ringer solution (LR) affects coagulation competence and in turn blood loss during cystectomy due to bladder cancer. Forty patients undergoing radical cystectomy were included to receive either 5% HA (n = 20) or LR (n = 20). Nineteen patients were analyzed in the HA group and 20 patients in the lactated Ringer group. Blinded determination of the blood loss was similar in the 2 groups of patients: 1658 (800–3300) mL with the use of HA and 1472 (700–4330) mL in the lactated Ringer group (P = 0.45). Yet, by thrombelastography (TEG) evaluated coagulation competence, albumin affected clot growth (TEG-angle 69 ± 5 vs 74° ± 3°, P < 0.01) and strength (TEG-MA: 59 ± 6 vs 67 ± 6 mm, P < 0.001) more than LR. Furthermore, by multivariate linear regression analyses reduced TEG-MA was independently associated with the blood loss (P = 0.042) while administration of albumin was related to the changes in TEG-MA (P = 0.029), aPPT (P < 0.022), and INR (P < 0.033). This randomized controlled trial demonstrates that administration of HA does not affect the blood loss as compared to infusion of LR. Also the use of HA did not affect the need for blood transfusion, the incidence of postoperative complications, or the hospital in-stay. Yet, albumin decreases coagulation competence during major surgery and the blood loss is related to TEG-MA rather than to plasma coagulation variables. PMID:26945358

  18. Banking of fresh-frozen prostate tissue using the alternate mirror image protocol: methods, validation, and impact on the pathological prognostic parameters in radical prostatectomy.

    PubMed

    Brimo, Fadi; Sircar, Kanishka; Chevalier, Simone; Saad, Fred; Lacombe, Louis; Têtu, Bernard; Scarlata, Eleanora; Aprikian, Armen

    2012-12-01

    We evaluated the value of the 'alternative slices mirror image method' used in prostate tissue banking in terms of predicting the sampling of cancerous tissue while preserving the pathological prognostic information. The concordance of diagnosis between banked sections and their mirror image paraffin- sections was studied using 50 cases corresponding to 400 H&E sections taken from 400 banked frozen blocks (two presumed benign and two presumed cancer for each case). The mean number of paraffin blocks in each case was 21. On average 29% of the prostate gland was banked and banked tissue contained cancer in 47 cases (94%). There was no difference between the concordant and discordant groups in terms of the final Gleason score, pathological stage, prostate size, number of banked blocks and the percentage of the prostate submitted for banking. However, concordant cases had larger foci of cancer in the mirror image paraffin block (P = 0.0088). In addition, the surgical margins sections which are not banked using this method provided important information about the pathological stage, surgical margins status and the final Gleason score in 2.6, 2.6, and 1.3% of cases, respectively. The 'alternative slices mirror image method' is a straightforward method that is highly efficient in banking prostatic cancerous tissue. Overall, tumor volume and especially size of tumor foci in the image paraffin block are the most important factors in dictating the success rate of banking frozen cancerous tissue. Including 'surgical margins' sections for histology provides additional important prognostic information in a minority of cases. PMID:22200970

  19. 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.

  20. Reassessing Domain Architecture Evolution of Metazoan Proteins: Major Impact of Gene Prediction Errors

    PubMed Central

    Nagy, Alinda; Szláma, György; Szarka, Eszter; Trexler, Mária; Bányai, László; Patthy, László

    2011-01-01

    In view of the fact that appearance of novel protein domain architectures (DA) is closely associated with biological innovations, there is a growing interest in the genome-scale reconstruction of the evolutionary history of the domain architectures of multidomain proteins. In such analyses, however, it is usually ignored that a significant proportion of Metazoan sequences analyzed is mispredicted and that this may seriously affect the validity of the conclusions. To estimate the contribution of errors in gene prediction to differences in DA of predicted proteins, we have used the high quality manually curated UniProtKB/Swiss-Prot database as a reference. For genome-scale analysis of domain architectures of predicted proteins we focused on RefSeq, EnsEMBL and NCBI's GNOMON predicted sequences of Metazoan species with completely sequenced genomes. Comparison of the DA of UniProtKB/Swiss-Prot sequences of worm, fly, zebrafish, frog, chick, mouse, rat and orangutan with those of human Swiss-Prot entries have identified relatively few cases where orthologs had different DA, although the percentage with different DA increased with evolutionary distance. In contrast with this, comparison of the DA of human, orangutan, rat, mouse, chicken, frog, zebrafish, worm and fly RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences with those of the corresponding/orthologous human Swiss-Prot entries identified a significantly higher proportion of domain architecture differences than in the case of the comparison of Swiss-Prot entries. Analysis of RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences with DAs different from those of their Swiss-Prot orthologs confirmed that the higher rate of domain architecture differences is due to errors in gene prediction, the majority of which could be corrected with our FixPred protocol. We have also demonstrated that contamination of databases with incomplete, abnormal or mispredicted sequences introduces a bias in DA

  1. Reassessing domain architecture evolution of metazoan proteins: major impact of gene prediction errors.

    PubMed

    Nagy, Alinda; Szláma, György; Szarka, Eszter; Trexler, Mária; Bányai, László; Patthy, László

    2011-01-01

    In view of the fact that appearance of novel protein domain architectures (DA) is closely associated with biological innovations, there is a growing interest in the genome-scale reconstruction of the evolutionary history of the domain architectures of multidomain proteins. In such analyses, however, it is usually ignored that a significant proportion of Metazoan sequences analyzed is mispredicted and that this may seriously affect the validity of the conclusions. To estimate the contribution of errors in gene prediction to differences in DA of predicted proteins, we have used the high quality manually curated UniProtKB/Swiss-Prot database as a reference. For genome-scale analysis of domain architectures of predicted proteins we focused on RefSeq, EnsEMBL and NCBI's GNOMON predicted sequences of Metazoan species with completely sequenced genomes. Comparison of the DA of UniProtKB/Swiss-Prot sequences of worm, fly, zebrafish, frog, chick, mouse, rat and orangutan with those of human Swiss-Prot entries have identified relatively few cases where orthologs had different DA, although the percentage with different DA increased with evolutionary distance. In contrast with this, comparison of the DA of human, orangutan, rat, mouse, chicken, frog, zebrafish, worm and fly RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences with those of the corresponding/orthologous human Swiss-Prot entries identified a significantly higher proportion of domain architecture differences than in the case of the comparison of Swiss-Prot entries. Analysis of RefSeq, EnsEMBL and NCBI's GNOMON predicted protein sequences with DAs different from those of their Swiss-Prot orthologs confirmed that the higher rate of domain architecture differences is due to errors in gene prediction, the majority of which could be corrected with our FixPred protocol. We have also demonstrated that contamination of databases with incomplete, abnormal or mispredicted sequences introduces a bias in DA

  2. Update on emissions and environmental impacts from the international fleet of ships. The contribution from major ship types and ports

    NASA Astrophysics Data System (ADS)

    Dalsøren, S. B.; Eide, M. S.; Endresen, Ø.; Mjelde, A.; Gravir, G.; Isaksen, I. S. A.

    2008-10-01

    globally. In certain coastal regions the contributions may be in the range 15 50%. In general we find that ship emissions have a large impact on acidic deposition and surface ozone in western North America, Scandinavia, western Europe, western North Africa and Malaysia/Indonesia. For most of these regions container traffic, the largest emitter by ship type, has the largest impact. This is the case especially for the Pacific and the related container trade routes between Asia and North America. However, the contributions from bulk ships and tank vessels are also significant in the above mentioned impact regions. Though the total ship impact at low latitudes is lower, the tank vessels have a quite large contribution at low latitudes and near the Gulf of Mexico and Middle East. The bulk ships are characterized by large impact in Oceania compared to other ship types. In Scandinavia and north-western Europe, one of the major ship impact regions, the three largest ship types have rather small relative contributions. The impact in this region is probably dominated by smaller ships operating closer to the coast. For emissions in ports impacts on NO2 and SO2 seem to be of significance. For most ports the contribution to the two components is in the range 0.5 5%, for a few ports it exceeds 10%. The approach presented provides an improvement in characterizing fleet operational patterns, and thereby ship emissions and impacts. Furthermore, the study shows where emission reductions can be applied to most effectively minimize the impacts by different ship types.

  3. Update on emissions and environmental impacts from the international fleet of ships: the contribution from major ship types and ports

    NASA Astrophysics Data System (ADS)

    Dalsøren, S. B.; Eide, M. S.; Endresen, Ø.; Mjelde, A.; Gravir, G.; Isaksen, I. S. A.

    2009-03-01

    globally. In certain coastal regions the contributions may be in the range 15-50%. In general we find that ship emissions have a large impact on acidic deposition and surface ozone in Western North America, Scandinavia, Western Europe, western North Africa and Malaysia/Indonesia. For most of these regions container traffic, the largest emitter by ship type, has the largest impact. This is the case especially for the Pacific and the related container trade routes between Asia and North America. However, the contributions from bulk ships and tank vessels are also significant in the above mentioned impact regions. Though the total ship impact at low latitudes is lower, the tank vessels have a quite large contribution at low latitudes and near the Gulf of Mexico and Middle East. The bulk ships are characterized by large impact in Oceania compared to other ship types. In Scandinavia and north-Western Europe, one of the major ship impact regions, the three largest ship types have rather small relative contributions. The impact in this region is probably dominated by smaller ships operating closer to the coast. For emissions in ports impacts on NO2 and SO2 seem to be of significance. For most ports the contribution to the two components is in the range 0.5-5%, for a few ports it exceeds 10%. The approach presented provides an improvement in characterizing fleet operational patterns, and thereby ship emissions and impacts. Furthermore, the study shows where emission reductions can be applied to most effectively minimize the impacts by different ship types.

  4. Human health and wellbeing in environmental impact assessment in New South Wales, Australia: Auditing health impacts within environmental assessments of major projects

    SciTech Connect

    Harris, Patrick J.; Harris, Elizabeth; Thompson, Susan; Harris-Roxas, Ben; Kemp, Lynn

    2009-09-15

    Internationally the inclusion of health within environmental impact assessment (EIA) has been shown to be limited. While Australian EIA documentation has not been studied empirically to date, deficiencies in practice have been documented. This research developed an audit tool to undertake a qualitative descriptive analysis of 22 Major Project EAs in New South Wales, Australia. Results showed that health and wellbeing impacts were not considered explicitly. They were, however, included indirectly in the identification of traditional public health exposures associated with the physical environment and to a lesser extent the inclusion of social and economic impacts. However, no health data was used to inform any of the assessments, there was no reference to causal pathways between exposures or determinants and physical or mental health effects, and there was no inclusion of the differential distribution of exposures or health impacts on different populations. The results add conceptually and practically to the long standing integration debate, showing that health is in a position to add value to the EIA process as an explicit part of standard environmental, social and economic considerations. However, to overcome the consistently documented barriers to integrating health in EIA, capacity must be developed amongst EIA professionals, led by the health sector, to progress health related knowledge and tools.

  5. External biliary drainage following major liver resection for perihilar cholangiocarcinoma: impact on development of liver failure and biliary leakage

    PubMed Central

    Olthof, Pim B.; Coelen, Robert J.S.; Wiggers, Jimme K.; Besselink, Marc G.H.; Busch, Olivier R.C.; van Gulik, Thomas M.

    2016-01-01

    Background Preoperative biliary drainage is considered essential in perihilar cholangiocarcinoma (PHC) requiring major hepatectomy with biliary-enteric reconstruction. However, evidence for postoperative biliary drainage as to protect the anastomosis is currently lacking. This study investigated the impact of postoperative external biliary drainage on the development of post-hepatectomy biliary leakage and liver failure (PHLF). Methods All patients who underwent major liver resection for suspected PHC between 2000 and 2015 were retrospectively analyzed. Biliary leakage and PHLF was defined as grade B or higher according to the International Study Group of Liver Surgery (ISGLS) criteria. Results Eighty-nine out of 125 (71%) patients had postoperative external biliary drainage. PHLF was more prevalent in the drain group (29% versus 6%; P = 0.004). There was no difference in the incidence of biliary leakage (32% versus 36%). On multivariable analysis, postoperative external biliary drainage was identified as an independent risk factor for PHLF (Odds-ratio 10.3, 95% confidence interval 2.1–50.4; P = 0.004). Conclusions External biliary drainage following major hepatectomy for PHC was associated with an increased incidence of PHLF. It is therefore not recommended to routinely use postoperative external biliary drainage, especially as there is no evidence that this decreases the risk of biliary anastomotic leakage. PMID:27037204

  6. Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma

    PubMed Central

    Lu, Yi-Jhu; Liang, Shu-Man; Liu, Chia-Chia; Chen, Shyh-Chang; Wang, John; Shyue, Song-Kun; Liou, Jun-Yang

    2015-01-01

    14-3-3ε is overexpressed in hepatocellular carcinoma (HCC) and its expression significantly associates with a poor prognostic outcome. To uncover how 14-3-3ε contributes to the tumor progression of HCC, we investigated the potential downstream targets regulated by 14-3-3ε. We found that 14-3-3ε increases expression and nuclear translocation of β-catenin and that 14-3-3ε-induced cell proliferation is attenuated by β-catenin silencing in HCC cells. Moreover, 14-3-3ε induces aldo-keto reductase family 1 member B10 (AKR1B10) expression through the activation of β-catenin signaling. Knockdown of AKR1B10 by siRNAs abolished 14-3-3ε-induced in vitro cell proliferation, anchorage-independent growth as well as in vivo tumor growth. Furthermore, AKR1B10 silencing increased retinoic acid (RA) levels in the serum of tumor-bearing mice and RA treatment attenuated 14-3-3ε-induced HCC cell proliferation. We further examined 14-3-3ε and AKR1B10 expression and clinicopathological characteristics of HCC tumors. Although the expression of AKR1B10 was significantly correlated with 14-3-3ε, an increase of AKR1B10 expression in 14-3-3ε positive patients paradoxically had better overall survival and disease-free survival rates as well as lower metastatic incidence than those without an AKR1B10 increase. Finally, we found a loss of AKR1B10 expression in cells exhibiting a high capacity of invasiveness. Silencing of AKR1B10 resulted in inducing snail and vimentin expression in HCC cells. These results indicate that AKR1B10 may play a dual role during HCC tumor progression. Our results also indicate that 14-3-3ε regulates AKR1B10 expression by activating β-catenin signaling. A combination of 14-3-3ε with AKR1B10 is a potential therapeutic target and novel prognostic biomarker of HCC. PMID:26516929

  7. Prognostic impact of initial maximum standardized uptake value of 18F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib

    PubMed Central

    Kus, Tulay; Aktas, Gokmen; Sevinc, Alper; Kalender, Mehmet Emin; Yilmaz, Mustafa; Kul, Seval; Oztuzcu, Serdar; Oktay, Cemil; Camci, Celaletdin

    2015-01-01

    Purpose To investigate whether the initial maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has a prognostic significance in metastatic lung adenocarcinoma. Patients and methods Sixty patients (24 females, mean age: 57.9±12 years) with metastatic stage lung adenocarcinoma who used erlotinib and underwent 18F-FDG PET/CT at the time of diagnosis between May 2010 and May 2014 were enrolled in this retrospective study. The patients were stratified according to the median SUVmax value, which was found as 11. Progression-free survival (PFS) rates for 3, 6, and 12 months were examined for SUVmax values and epidermal growth factor receptor (EGFR) mutation status. Results The number of EGFR-sensitizing mutation positive/negative/unknown was 26/17/17, respectively, and the number of patients using erlotinib at first-line, second-line, and third-line therapy was 15, 31, and 14 consecutively. The PFS rates of EGFR mutation positive, negative, and unknown patients for 3 months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45–13.26), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6 months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82–6.96), respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12 months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42–5.26), respectively. Thirty-one of 60 patients had SUVmax values ≤11. The PFS rates for 3, 6, and 12 months were 70.5%/28% (P=0.001, OR=9.0; 95% CI: 2.79–29.04), 61.7%/8% (P<0.001, OR=28.35; 95% CI: 5.5–143), and 52.9%/8% (P<0.001, OR=18.69; 95% CI: 3.76–92.9) for low SUVmax (≤11) group/high SUVmax (>11) group, respectively. Conclusion Initial SUVmax value on 18F-FDG PET/CT is found to be a prognostic factor anticipating the response to erlotinib for 3, 6, and 12-month rates of PFS in both EGFR

  8. The impact of pitch counts and days of rest on performance among major-league baseball pitchers.

    PubMed

    Bradbury, John C; Forman, Sean L

    2012-05-01

    Although the belief that overuse can harm pitchers is widespread, there exists little evidence to show that the number of pitches thrown and the days of rest affect future performance and injury among adults. The purpose of this study is to quantify the effects of pitches thrown and the days of rest on pitcher performance. We examined performances of major-league baseball starting pitchers from 1988 to 2009 using fractional polynomial multiple regression to estimate the immediate and cumulative impact of pitches thrown and the days of rest on performance, while controlling for other factors that likely affect pitcher effectiveness. Estimates indicate each pitch thrown in the preceding game increased earned run average (ERA) by 0.007 in the following game. Each pitch averaged in the preceding 5 and 10 games increased the ERA by 0.014 and 0.022, respectively. Older pitchers were more sensitive to cumulative pitching loads than younger pitchers were, but they were less affected by pitches thrown in the preceding game. Rest days were weakly associated with performance. In summary, we found that there is a negative relationship between past pitches thrown and future performance that is virtually linear. The impact of the cumulative pitching load is larger than the impact of a single game. Rest days do not appear to have a large impact on performance. This study supports the popular notion that high pitching loads can dampen future performance; however, because the effect is small, pitch-count benchmarks have limited use for maintaining performance and possibly preventing injury. PMID:22344048

  9. 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.

  10. The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics

    PubMed Central

    How, J; Sykes, J; Minden, M D; Gupta, V; Yee, K W L; Schimmer, A D; Schuh, A C; Kamel-Reid, S; Brandwein, J M

    2013-01-01

    Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AML who received a uniform reinduction regimen, with respect to FLT3-ITD and NPM1 mutation status and first complete remission (CR1) duration. CR1 duration, but not molecular status, was significantly correlated with CR2 rate. On univariate analysis, patients with mutated FLT3-ITD (FLT3+) had significantly worse overall survival (OS) compared with those with neither an NPM1 nor FLT3-ITD mutation (NPM1-/FLT3-). On multivariate analysis, shorter CR1 duration was significantly correlated with inferior OS at relapse (P<0.0001), while FLT3 and NPM1 mutation status and age were not significantly correlated with OS. Patients who subsequently underwent allogeneic stem cell transplant (alloSCT) had a superior OS regardless of CR1 duration, but outcomes were better in patients with CR1 duration>12 months. In intermediate-risk karyotype AML patients receiving reinduction, CR1 duration remains the most important predictor of OS at relapse; FLT3-ITD and NPM1 status are not independent predictors of survival. PMID:23708641

  11. The prognostic impact of FLT3-ITD and NPM1 mutations in patients with relapsed acute myeloid leukemia and intermediate-risk cytogenetics.

    PubMed

    How, J; Sykes, J; Minden, M D; Gupta, V; Yee, K W L; Schimmer, A D; Schuh, A C; Kamel-Reid, S; Brandwein, J M

    2013-01-01

    Internal tandem duplication of the fms-like tyrosine kinase-3 gene (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations have prognostic importance in acute myeloid leukemia (AML) patients with intermediate-risk karyotype at diagnosis, but less is known about their utility to predict outcomes at relapse. We retrospectively analysed outcomes of 70 patients with relapsed, intermediate-risk karyotype AML who received a uniform reinduction regimen, with respect to FLT3-ITD and NPM1 mutation status and first complete remission (CR1) duration. CR1 duration, but not molecular status, was significantly correlated with CR2 rate. On univariate analysis, patients with mutated FLT3-ITD (FLT3+) had significantly worse overall survival (OS) compared with those with neither an NPM1 nor FLT3-ITD mutation (NPM1-/FLT3-). On multivariate analysis, shorter CR1 duration was significantly correlated with inferior OS at relapse (P<0.0001), while FLT3 and NPM1 mutation status and age were not significantly correlated with OS. Patients who subsequently underwent allogeneic stem cell transplant (alloSCT) had a superior OS regardless of CR1 duration, but outcomes were better in patients with CR1 duration>12 months. In intermediate-risk karyotype AML patients receiving reinduction, CR1 duration remains the most important predictor of OS at relapse; FLT3-ITD and NPM1 status are not independent predictors of survival. PMID:23708641

  12. Usefulness of Geriatric Nutritional Risk Index for Assessing Nutritional Status and Its Prognostic Impact in Patients Aged ≥65 Years With Acute Heart Failure.

    PubMed

    Honda, Yasuyuki; Nagai, Toshiyuki; Iwakami, Naotsugu; Sugano, Yasuo; Honda, Satoshi; Okada, Atsushi; Asaumi, Yasuhide; Aiba, Takeshi; Noguchi, Teruo; Kusano, Kengo; Ogawa, Hisao; Yasuda, Satoshi; Anzai, Toshihisa

    2016-08-15

    Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (HR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged ≥65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification. PMID:27324158

  13. Prognostic impact of KRAS mutant type and MET amplification in metastatic and recurrent gastric cancer patients treated with first-line S-1 plus cisplatin chemotherapy

    PubMed Central

    Matsusaka, Satoshi; Kobunai, Takashi; Yamamoto, Noriko; Chin, Keisho; Ogura, Mariko; Tanaka, Gotaro; Matsuoka, Kazuaki; Ishikawa, Yuichi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

    2016-01-01

    Receptor tyrosine kinase (RTK)-related genes, including HER2, EGFR, MET, FGFR2 and KRAS, are target molecules that are clinically beneficial in gastric cancer (GC). We investigated the correlation between RTK-related genes and the curative effect of first-line S-1 plus cisplatin (SP) combination chemotherapy in metastatic and recurrent GC. We enrolled 150 patients with histopathologically confirmed metastatic and recurrent GC treated with SP. KRAS mutation was detected using direct sequencing. DNA copy number was measured by real-time PCR. Formalin-fixed paraffin-embedded specimens were examined immunohistochemically for HER2, EGFR, FGFR2 and MET. Among 144 patients, KRAS mutation was detected in five (3.5%) at codon 12 and one (0.7%) at codon 13. FGFR2, EGFR, HER2, MET and KRAS gene amplification was suggested in 4.4%, 5.9%, 9%, 3.7% and 10.3% of patients, respectively. KRAS mutation, but not KRAS amplification, was associated with significantly shorter overall and progression-free survival. MET membranous overexpression was associated with a significantly higher tumor response. MET amplification was associated with significantly shorter overall survival. We show for the first time that KRAS mutation and MET amplification are promising predictive markers in metastatic and recurrent GC patients treated with SP. KRAS status may be a useful prognostic marker in patients treated with SP. PMID:27014419

  14. Air pollution and early deaths in the United States. Part I: Quantifying the impact of major sectors in 2005

    NASA Astrophysics Data System (ADS)

    Caiazzo, Fabio; Ashok, Akshay; Waitz, Ian A.; Yim, Steve H. L.; Barrett, Steven R. H.

    2013-11-01

    Combustion emissions adversely impact air quality and human health. A multiscale air quality model is applied to assess the health impacts of major emissions sectors in United States. Emissions are classified according to six different sources: electric power generation, industry, commercial and residential sources, road transportation, marine transportation and rail transportation. Epidemiological evidence is used to relate long-term population exposure to sector-induced changes in the concentrations of PM2.5 and ozone to incidences of premature death. Total combustion emissions in the U.S. account for about 200,000 (90% CI: 90,000-362,000) premature deaths per year in the U.S. due to changes in PM2.5 concentrations, and about 10,000 (90% CI: -1000 to 21,000) deaths due to changes in ozone concentrations. The largest contributors for both pollutant-related mortalities are road transportation, causing ∼53,000 (90% CI: 24,000-95,000) PM2.5-related deaths and ∼5000 (90% CI: -900 to 11,000) ozone-related early deaths per year, and power generation, causing ∼52,000 (90% CI: 23,000-94,000) PM2.5-related and ∼2000 (90% CI: -300 to 4000) ozone-related premature mortalities per year. Industrial emissions contribute to ∼41,000 (90% CI: 18,000-74,000) early deaths from PM2.5 and ∼2000 (90% CI: 0-4000) early deaths from ozone. The results are indicative of the extent to which policy measures could be undertaken in order to mitigate the impact of specific emissions from different sectors - in particular black carbon emissions from road transportation and sulfur dioxide emissions from power generation.

  15. Prognostic impact of serum and tissue MMP-9 in non-small cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Zou, Jianding; Chen, Jianqiang; Chen, Liangyu; Chen, Yun; Ni, Chao; Yuan, Hongjun

    2016-01-01

    Matrix metalloproteinases-9 (MMP-9) was one of the most important enzyme to breakdown extracellular matrix, aim to clarify the prognostic value of MMP-9 in non-small cell lung cancer (NSCLC), we investigated the serum MMP-9 of NSCLC patients and performed a meta-analysis of the published literature. The expression and activity of serum MMP-9 were assessed by ELISA and gelatin zymography in 163 NSCLC patients. Moreover, 26 studies were included in meta-analysis by searching Medline and ISI Web of Knowledge. Our own data revealed high activity but not expression of MMP-9 significantly correlated with advanced T category and positive metastasis. In contrast, the meta-analysis revealed that increased MMP-9 level indicate high T category (RR = 0.83, 95% CI: 0.73-0.94), tumor stage (RR = 0.72, 95% CI: 0.63-0.82) and poor OS (5-year overall survival, RR = 1.32, 95% CI: 1.19-1.48). Moreover, stratified analysis based on sample types found that high MMP-9 expression in tissue specimen but not serum was significant correlated with advanced T category (RR = 0.81, 95% CI: 0.72-0.92), tumor stage (RR = 0.69, 95% CI: 0.60-0.80) and poor 5-year OS (1.33, 95% CI: 1.18-1.50). In conclusion, the activity of MMP-9 was positively correlated with advanced T category and distant metastasis. Moreover, the meta-analysis revealed that overexpression of MMP-9 in tissue but not in serum was a risk factor of advanced T category, tumor stage and poor outcome. PMID:26918342

  16. 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.

  17. Phenotypic characterization and prognostic impact of circulating γδ and αβ T-cells in metastatic malignant melanoma.

    PubMed

    Wistuba-Hamprecht, Kilian; Di Benedetto, Svetlana; Schilling, Bastian; Sucker, Antje; Schadendorf, Dirk; Garbe, Claus; Weide, Benjamin; Pawelec, Graham

    2016-02-01

    Human T cells carrying γδ T-cell receptors (TCRs) represent a minor population relative to those with αβ TCRs. There has been much interest recently in the possibility of using these γδ T-cells in cancer therapy because they can kill tumor cells in vitro in an MHC-unrestricted manner, and possess potential regulatory capability and antigen-presenting capacity. The presence of γδ T-cells in late-stage melanoma patients and their relationship with survival has not been extensively explored, although relatively lower percentages of total γδ T-cells and Vδ2+ cells have been reported. Here, we present a detailed analysis of associations of γδ T-cell subsets and differentiation stages with survival in Stage IV patients, compared with CD4+ and CD8+ αβ T-cells. We found an increased Vδ1:Vδ2-ratio and a decreased CD4:CD8-ratio in patients compared to healthy controls, on the basis both of relative frequencies and absolute cell counts per μL blood. Nonetheless, Kaplan-Meier analyses showed that a higher than median frequency of Vδ1+ cells was negatively associated with survival, whereas there were no positive or negative associations with frequencies of Vδ2+ cells. Correlations of cell differentiation status with survival revealed a negative association of early-differentiated Vδ1+ T cells with survival, both on the basis of relative frequencies and absolute counts. There was also a positive correlation between the frequencies of early-differentiated CD8+ αβ T-cells and survival. Our findings suggest peripheral blood frequencies of Vδ1+ T-cells as a potential prognostic marker in melanoma. The mechanisms by which higher abundance of Vδ1+ cells are associated with poorer survival require determination. PMID:26383054

  18. 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

  19. Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy.

    PubMed

    Shien, Kazuhiko; Toyooka, Shinichi; Ichimura, Kouichi; Soh, Junichi; Furukawa, Masashi; Maki, Yuho; Muraoka, Takayuki; Tanaka, Norimitsu; Ueno, Tsuyoshi; Asano, Hiroaki; Tsukuda, Kazunori; Yamane, Masaomi; Oto, Takahiro; Kiura, Katsuyuki; Miyoshi, Shinichiro

    2012-07-01

    The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P = 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P = 0.047) and cN2-3 single station metastasis (P = 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy. PMID:22387005

  20. 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

  1. 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.

  2. Impact of Major Depression and Subsyndromal Symptoms on Quality of Life and Attitudes toward Aging in an International Sample of Older Adults

    ERIC Educational Resources Information Center

    Chachamovich, Eduardo; Fleck, Marcelo; Laidlaw, Ken; Power, Mick

    2008-01-01

    Purpose: The impact of major depression on quality of life (QOL) and aging experiences in older adults has been reported. Studies have demonstrated that the clinical diagnosis of major depression is the strongest predictor for QOL. We postulate that some findings are biased because of the use of inadequate instruments. Although subsyndromal…

  3. Modeled Sea Level Rise Impacts on Coastal Ecosystems at Six Major Estuaries on Florida's Gulf Coast: Implications for Adaptation Planning.

    PubMed

    Geselbracht, Laura L; Freeman, Kathleen; Birch, Anne P; Brenner, Jorge; Gordon, Doria R

    2015-01-01

    The Sea Level Affecting Marshes Model (SLAMM) was applied at six major estuaries along Florida's Gulf Coast (Pensacola Bay, St. Andrews/Choctawhatchee Bays, Apalachicola Bay, Southern Big Bend, Tampa Bay and Charlotte Harbor) to provide quantitative and spatial information on how coastal ecosystems may change with sea level rise (SLR) and to identify how this information can be used to inform adaption planning. High resolution LiDAR-derived elevation data was utilized under three SLR scenarios: 0.7 m, 1 m and 2 m through the year 2100 and uncertainty analyses were conducted on selected input parameters at three sites. Results indicate that the extent, spatial orientation and relative composition of coastal ecosystems at the study areas may substantially change with SLR. Under the 1 m SLR scenario, total predicted impacts for all study areas indicate that coastal forest (-69,308 ha; -18%), undeveloped dry land (-28,444 ha; -2%) and tidal flat (-25,556 ha; -47%) will likely face the greatest loss in cover by the year 2100. The largest potential gains in cover were predicted for saltmarsh (+32,922 ha; +88%), transitional saltmarsh (+23,645 ha; na) and mangrove forest (+12,583 ha; +40%). The Charlotte Harbor and Tampa Bay study areas were predicted to experience the greatest net loss in coastal wetlands The uncertainty analyses revealed low to moderate changes in results when some numerical SLAMM input parameters were varied highlighting the value of collecting long-term sedimentation, accretion and erosion data to improve SLAMM precision. The changes predicted by SLAMM will affect exposure of adjacent human communities to coastal hazards and ecosystem functions potentially resulting in impacts to property values, infrastructure investment and insurance rates. The results and process presented here can be used as a guide for communities vulnerable to SLR to identify and prioritize adaptation strategies that slow and/or accommodate the changes underway. PMID:26207914

  4. Empirical evidence of direct impact of extreme temperatures on wheat yield in major wheat growing region of India.

    NASA Astrophysics Data System (ADS)

    Murari, K. K.; Mahato, S.; Jayaraman, T.

    2014-12-01

    Exposure to extreme temperatures during the grain filling stage of winter wheat may lead to reduction in the yield. Over the last decade, there has been an increasing trend of exposure to extreme temperature conditions, particularly during crop growing season. The Indo Gangetic plain (IGP) is a particular concern since an optimal temperature for wheat production already exists in the region. This is also a major concern for global wheat production since the region accounts for about 15% of the global wheat production. Previous studies conducted in this region have found a strong impact of extreme temperatures causing an early occurrence of senescence, defined as the last developmental stage of the plant. The early occurrence of senescence period induces shortening of growing season length, which is a critical grain filling stage. However, the direct effect of extreme temperatures on the yield data has not yet been looked at, which reflects the impact of extreme temperature at different growth stages including anthesis (flowering) and the grain-filling stage. Here in this study, we explore the relationship of extreme heat conditions on the yield using fixed-effect panel data model for the districts in the IGP region. The first result indicates approximately 16% reduction in wheat yield with 1˚C rise in mean growing season temperature. There is a significant negative trend between the yield and the fourth quartile of extreme temperature (>34˚C) days. Furthermore, we establish a scope of existence of a nonlinear relationship between temperature and yield, which needs to be further examined.

  5. The impact of a major earthquake on the evacuation of the emergency planning zone of a nuclear power plant.

    PubMed

    Cohen, Rebecca; Weinisch, Kevin

    2015-01-01

    United States regulations require nuclear power plants (NPPs) to estimate the time needed to evacuate the emergency planning zone (EPZ, a circle with an approximate 10-mile radius centered at the NPP). These evacuation time estimate (ETE) studies are to be used by emergency personnel in the event of a radiological emergency. ETE studies are typically done using traffic simulation and evacuation models, based on traffic engineering algorithms that reflect congestion and delay. ETE studies are typically conducted assuming all evacuation routes are traversable. As witnessed in the Great East Japan Earthquake in March 2011, an earthquake and the ensuing tsunami can cause an incident at a NPP that requires an evacuation of the public. The earthquake and tsunami can also damage many of the available bridges and roadways and, therefore, impede evacuation and put people at risk of radiation exposure. This article presents a procedure, using traffic simulation and evacuation models, to estimate the impact on ETE due to bridge and roadway damage caused by a major earthquake, or similar hazardous event. The results of this analysis are used by emergency personnel to make protective action decisions that will minimize the exposure of radiation to the public. Additionally, the results allow emergency planners to ensure proper equipment and personnel are available for these types of events. Emergency plans are revised to ensure prompt response and recovery action during critical times. PMID:25902296

  6. The Impacts of Migraine among Outpatients with Major Depressive Disorder at a Two-Year Follow-Up

    PubMed Central

    Hung, Ching-I; Liu, Chia-Yih; Yang, Ching-Hui; Wang, Shuu-Jiun

    2015-01-01

    Background No study has investigated the impacts of migraine on depression, anxiety, and somatic symptoms and remission at the two-year follow-up point among patients with major depressive disorder (MDD). This study aimed to investigate the above issues. Methods Psychiatric outpatients with MDD recruited at baseline were investigated at a two-year follow-up (N = 106). The Hamilton Depression Rating Scale, Hospital Anxiety and Depression Scale, and Depression and Somatic Symptoms Scale were used. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. The patients were divided into no migraine, inactive migraine, and active migraine subgroups. Multiple logistic regressions were used to investigate the significant factors related to full remission of depression. Results Among patients without pharmacotherapy at the follow-up, patients with active migraine had significantly greater severities of anxiety and somatic symptoms as compared with patients without migraine; moreover, patients with active migraine had the lowest improvement percentage and full remission rate. There were no significant differences in depression, anxiety, and somatic symptoms between patients with inactive migraine and those without migraine. Active headache at follow-up was a significant factor related to a lower full remission rate. Conclusions Active headache at follow-up was associated with a lower rate of full remission and more residual anxiety and somatic symptoms at follow-up among patients with migraine. Physicians should integrate a treatment plan for depression and migraine for the treatment of patients with MDD. PMID:26000962

  7. Impacts of silver nanoparticles on bacterial species B. subtilis and E. coli and the major crop plant Z. mays

    NASA Astrophysics Data System (ADS)

    Doody, Michael A.

    This thesis examines the impacts of citrate-coated silver nanoparticles (c-AgNPs) on two species of bacteria (Bacillus subtilis and Escherichia coli), the major crop plant Zea mays, and the beneficial plant-microbe relationship between Z. mays and B. subtilis. AgNPs are an increasing component of antimicrobial consumer, industrial, and military products. This has led to widespread scientific concern for the ecological safety outside their intended use. An overview of their history, use, and toxicity was used to inform the design of experiments and resulting data. Growth inhibition and sub-lethal toxic effects were used to assess the effects of c-AgNP exposure to bacteria. Similar analytical methods were used to quantify the response of Z. mays to c-AgNP exposure. Results showed that exposure to c-AgNP significantly reduced the growth of bacterial populations and alters their growth kinetics. Z. mays experienced significant sub-lethal effects due to exposure, including reduced root length and biomass, and hyper-accumulated Ag in root tissues. Beneficial interactions between B. subtilis and Z. mays were reduced as both species suffered sub-lethal effects of exposure to c-AgNPs.

  8. Amino acid motifs in both the major and minor capsid proteins of HPV51 impact antigenicity and infectivity.

    PubMed

    Godi, Anna; Epifano, Ilaria; Bissett, Sara L; Dell'Anna, Tiziana; Piana, Andrea; Cocuzza, Clementina; Beddows, Simon

    2015-07-01

    Persistent infection with oncogenic human papillomavirus (HPV) is a prerequisite for cervical disease development, yet data regarding the host immune response to infection at the genotype level are quite limited. We created pseudoviruses bearing the major (L1) and minor (L2) capsid proteins and L1 virus-like particles representing the reference sequence and a consensus of 34 European sequences of HPV51. Despite the formation of similarly sized particles, motifs in the reference L1 and L2 genes had a profound impact on the immunogenicity, antigenicity and infectivity of these antigens. The antibody status of women exhibiting low-grade disease was similar between HPV16 and the consensus HPV51, but both demonstrated discrepancies between binding and neutralizing antibody responses. These data support the use of pseudoviruses as the preferred target antigen in studies of natural HPV infection and the need to consider variation in both the L1 and L2 proteins for the appropriate presentation of antibody epitopes. PMID:25770119

  9. Making the animal model for AIDS research more precise: the impact of major histocompatibility complex (MHC) genes on pathogenesis and disease progression in SIV-infected monkeys.

    PubMed

    Sauermann, U

    2001-09-01

    Experimentally infected rhesus monkeys serve as an indispensable animal model to assess the pathogenesis, to validate therapy approaches and to develop vaccination strategies against viral diseases such as AIDS threatening the human population. Upon infection with simian immunodeficiency virus (SIV), a retrovirus closely related to the human immunodeficiency virus (HIV), macaques develop clinical manifestations similar to those of HIV-infected humans. As in humans, the disease course is variable. Polymorphic genes of the major histocompatibility complex (MHC) are required for the initiation and regulation of a specific immune response and represent a major host factor accounting for the differential outcome of infection. During the last few years, our understanding of the structure and function of the rhesus macaque MHC has increased substantially. Functional studies have led to the identification of specific SIV and HIV peptide epitopes presented by rhesus macaque MHC molecules. The subsequent development of MHC class I tetramers has allowed further insight into the cellular immune response following SIV-infection. Detailed studies demonstrated that viral escape mutants are generated during the acute and chronic phase of infection and explain why control of viral replication ultimately fails. Furthermore, particular MHC haplotypes which influence disease progression have been discovered. Thus, MHC-typing can have a prognostic potential. The further elucidation of the rhesus macaque MHC and the search for other relevant genes will remain an important task for future research and will stimulate all immunologically-related investigations in macaques. PMID:11899095

  10. Prognostic impact of KI67, p53, human epithelial growth factor receptor 2, topoisomerase IIalpha, epidermal growth factor receptor, and nm23 expression of ovarian carcinomas and disseminated tumor cells in the bone marrow.

    PubMed

    Schindlbeck, C; Hantschmann, P; Zerzer, M; Jahns, B; Rjosk, D; Janni, W; Rack, B; Sommer, H; Friese, K

    2007-01-01

    Examination of tumor biological factors for prognostic and predictive indicators is not part of routine testing in ovarian cancer. As in other tumors, the detection of hematogenous tumor spread could help to estimate the risk of metastatic disease. We examined the expression of p53, KI67, topoisomerase IIalpha (Top IIa), epidermal growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2) and nm23 in tumor tissues from 90 patients with ovarian cancer. All underwent bone marrow (BM) aspiration and screening for disseminated tumor cells in the bone marrow (DTC-BM) at primary diagnosis. BM aspiration, cytospin preparation, and immunocytochemical staining with the anticytokeratin antibody (A45-B/B3) were done following a standardized protocol. The expression of p53, KI67, Top IIa, EGFR, HER2, and nm23 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells or immunoreactive score (IRS). The prognostic impact of the individual factors together with standard histologic parameters was calculated by univariate and multivariate analyses. Expression rates for HER2 (2+/3+: 34.5%), KI67 (median 30%), p53 (median IRS 5), and Top IIa (median IRS 4) were relatively high, whereas nm23 (median IRS 2) and EGFR (IRS 0: 61%) showed weak staining. In 21/90 patients (23.3%), DTC-BM (>/=1/2 x 10(6) cells) could be detected. The presence of DTC-BM was inversely related to nodal status (P = .015) but not to the other factors examined. Tumor stage (P = .02), lymph node involvement (P = .003), grade (P = .046), postoperative tumor residue (P < .001), peritoneal seeding (P = .02), and KI67 (P = .046) significantly correlated with overall survival (OS) after a median observation time of 28 months (2-105). The finding of ascites was borderline significant (P = .050). The presence of DTC-BM (P = .04) and KI67 positivity (P = .02) predicted reduced distant disease-free survival. By multivariate analysis