Concurrent Validity of the Stanford-Binet: Fourth Edition and Kaufman Assessment Battery for Children with Learning-Disabled Students.

ERIC Educational Resources Information Center

Knight, B. Caleb; And Others

1990-01-01

Examined the concurrent validity of the composite and area scores of the Stanford-Binet Intelligence Scale: Fourth Edition (SBIV) and the Mental Processing Composite and global scale scores of the Kaufman Assessment Battery for Children in Black, learning-disabled elementary school students (N=30). Findings demonstrated adequate concurrent…

[From Binet and Wundt to neuropsychological measurements and behavior scales].

PubMed

Lehmann, H E

1983-01-01

Experimental psychology was the first form of scientific psychology and saw its beginnings in Wundt's laboratory toward the end of the 19th century. Psychometric measures of cognitive functions were introduced, at about the same time, by Binet, while Galton was pioneering in studies of personality profiles. Most of the systematic work, both in the theory and practice of psychology, was focused on standardization of norms, or types and measures of normal mental functions. With the establishment of psychopharmacology as a new discipline with an important role in clinical psychiatry, there emerged an urgent need for scales that indicate the presence and measure the extent and severity of psychopathology. The AMDP scales, created in the context of the European tradition in psychopathology, are some of the most prominent and promising scales of this type.

The advanced-stage therapy group.

PubMed

Berman, A; Weinberg, H

1998-10-01

Many authors describe a stage of maturity in the development of groups, but each highlights a different dimension. This article describes the characteristics of the advanced stage and the main axes along which it develops (internalization and containment, symbolization, self and self-other development, differentiation and individuation). It also offers a conceptual explanation for these developments and attempts to identify the conditions necessary for the emergence of this stage of maturity. An understanding of this stage and the conditions required for its development can be used by the group leader as a compass to help him or her navigate the group toward this objective.

Item Fairness of the Nonverbal Subtests of the Stanford-Binet Intelligence Test, Fifth Edition, in a Latina/o Sample

ERIC Educational Resources Information Center

Harlow, Simone C.

2011-01-01

Every widely used psychological assessment instrument is under scrutiny in terms of cultural fairness. The expectation of the reduced-language (Nonverbal) section of the Stanford-Binet Intelligence Scales, Fifth Edition (SB5; Roid, 2003) is that language ought not to be a modifying factor in terms of final score. The purpose of the present study…

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

From the Binet-Simon to the Wechsler-Bellevue: tracing the history of intelligence testing.

PubMed

Boake, Corwin

2002-05-01

The history of David Wechsler's intelligence scales is reviewed by tracing the origins of the subtests in the 1939 Wechsler-Bellevue Intelligence Scale. The subtests originated from tests developed between 1880 and World War I, and was based on approaches to mental testing including anthropometrics, association psychology, the Binet-Simon scales, language-free performance testing of immigrants and school children, and group testing of military recruits. Wechsler's subtest selection can be understood partly from his clinical experiences during World War I. The structure of the Wechsler-Bellevue Scale, which introduced major innovations in intelligence testing, has remained almost unchanged through later revisions.

Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

PubMed

Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

2016-10-01

Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction.

Assessing Giftedness in Children: Comparing the Accuracy of Three Shortened Measures of Intelligence to the Stanford-Binet Intelligence Scales, Fifth Edition

ERIC Educational Resources Information Center

Newton, Jocelyn H.; McIntosh, David E.; Dixon, Felicia; Williams, Tasha; Youman, Elizabeth

2008-01-01

This study examined the accuracy of three shortened measures of intelligence: the Woodcock-Johnson Tests of Cognitive Ability, Third Edition Brief Intellectual Ability (WJ III COG BIA) score; the Stanford-Binet Intelligence Scale, Fifth Edition Abbreviated IQ (SB5 ABIQ); and the Kaufman Brief Intelligence Test IQ Composite (K-BIT) in predicting…

THE IMPORTANCE OF INSTRUMENT MAKERS FOR THE DEVELOPMENT OF EXPERIMENTAL PSYCHOLOGY: THE CASE OF ALFRED BINET AT THE SORBONNE LABORATORY.

PubMed

Nicolas, Serge

2016-07-01

The importance of instrument firms in the development of psychology, and science in general, should not be underestimated since it would not have been possible for various leading psychologists at the turn of the twentieth century to conduct certain experiments without the assistance of instrument makers, as is often the case today. To illustrate the historical perspective introduced here, the example of Alfred Binet is taken, as he is an interesting case of a psychologist working in close collaboration with various French instrument designers of the time. The objective of this article is twofold: (1) to show the considerable activity carried out by early psychologists to finalize new laboratory instruments in order to develop their research projects; (2) to reassess the work of a major figure in French psychology through his activity as a designer of precision instruments. The development of these new instruments would certainly have been difficult without the presence in Paris of numerous precision instrument manufacturers such as Charles Verdin, Otto Lund, Henri Collin, and Lucien Korsten, on whom Binet successively called in order to develop his projects in the field of experimental psychology. © 2016 Wiley Periodicals, Inc.

Effect of hydronephrosis on survival in advanced stage cervical cancer.

PubMed

Goklu, Mehmet Rıfat; Seckin, Kerem Doga; Togrul, Cihan; Goklu, Yasemin; Tahaoglu, Ali Emre; Oz, Murat; Ertas, Ibrahim Egemen

2015-01-01

Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (p<0.05). There was no significant survival difference between patients with unilateral and bilateral hydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (p<0.05). Hydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be

Comparison of the Leiter International Performance Scale-Revised and the Stanford-Binet Intelligence Scales, 5th Edition, in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Grondhuis, Sabrina Nicole; Mulick, James A.

2013-01-01

A review of hospital records was conducted for children evaluated for autism spectrum disorders who completed both the Leiter International Performance Scale-Revised (Leiter-R) and Stanford-Binet Intelligence Scales, 5th Edition (SB5). Participants were between 3 and 12 years of age. Diagnoses were autistic disorder (n = 26, 55%) and pervasive…

Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages.

PubMed

Chapiro, Elise; Leporrier, Nathalie; Radford-Weiss, Isabelle; Bastard, Christian; Mossafa, Hossein; Leroux, Dominique; Tigaud, Isabelle; De Braekeleer, Marc; Terré, Christine; Brizard, Françoise; Callet-Bauchu, Evelyne; Struski, Stéphanie; Veronese, Lauren; Fert-Ferrer, Sandra; Taviaux, Sylvie; Lesty, Claude; Davi, Frédéric; Merle-Béral, Hélène; Bernard, Olivier A; Sutton, Laurent; Raynaud, Sophie D; Nguyen-Khac, Florence

2010-01-01

Using array-based CGH, we identified 2p gain in 22/78 (28%) untreated Binet stages B/C CLL, which was the second most frequent copy number change after 13q deletion. It never occurred as a sole abnormality and was associated with other changes (6q deletion; 1p gain). The region of 2p gain frequently included two oncogenes, REL and MYCN. All patients with gain of REL were unmutated for IGHV (p=0.03). Gain of MYCN was associated with increased mRNA expression (p=0.005), suggesting a pathogenic role for MYCN. Gain of 2p appears to be a marker of progression and may contribute to the poor prognosis. 2009 Elsevier Ltd. All rights reserved.

Tumor angiogenesis in advanced stage ovarian carcinoma.

PubMed

Hollingsworth, H C; Kohn, E C; Steinberg, S M; Rothenberg, M L; Merino, M J

1995-07-01

Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.

Alfred Binet and the Concept of Heterogeneous Orders†

PubMed Central

Michell, Joel

2012-01-01

In a comment, hitherto unremarked upon, Alfred Binet, well known for constructing the first intelligence scale, claimed that his scale did not measure intelligence, but only enabled classification with respect to a hierarchy of intellectual qualities. Attempting to understand the reasoning behind this comment leads to an historical excursion, beginning with the ancient mathematician, Euclid and ending with the modern French philosopher, Henri Bergson. As Euclid explained (Heath, 1908), magnitudes constituting a given quantitative attribute are all of the same kind (i.e., homogeneous), but his criterion covered only extensive magnitudes. Duns Scotus (Cross, 1998) included intensive magnitudes by considering differences, which raised the possibility (later considered by Sutherland, 2004) of ordered attributes with heterogeneous differences between degrees (“heterogeneous orders”). Of necessity, such attributes are non-measurable. Subsequently, this became a basis for the “quantity objection” to psychological measurement, as developed first by Tannery (1875a,b) and then by Bergson (1889). It follows that for attributes investigated in science, there are three structural possibilities: (1) classificatory attributes (with heterogeneous differences between categories); (2) heterogeneous orders (with heterogeneous differences between degrees); and (3) quantitative attributes (with thoroughly homogeneous differences between magnitudes). Measurement is possible only with attributes of kind (3) and, as far as we know, psychological attributes are exclusively of kinds (1) or (2). However, contrary to the known facts, psychometricians, for their own special reasons insist that test scores provide measurements. PMID:22912619

Alfred binet and the concept of heterogeneous orders.

PubMed

Michell, Joel

2012-01-01

In a comment, hitherto unremarked upon, Alfred Binet, well known for constructing the first intelligence scale, claimed that his scale did not measure intelligence, but only enabled classification with respect to a hierarchy of intellectual qualities. Attempting to understand the reasoning behind this comment leads to an historical excursion, beginning with the ancient mathematician, Euclid and ending with the modern French philosopher, Henri Bergson. As Euclid explained (Heath, 1908), magnitudes constituting a given quantitative attribute are all of the same kind (i.e., homogeneous), but his criterion covered only extensive magnitudes. Duns Scotus (Cross, 1998) included intensive magnitudes by considering differences, which raised the possibility (later considered by Sutherland, 2004) of ordered attributes with heterogeneous differences between degrees ("heterogeneous orders"). Of necessity, such attributes are non-measurable. Subsequently, this became a basis for the "quantity objection" to psychological measurement, as developed first by Tannery (1875a,b) and then by Bergson (1889). It follows that for attributes investigated in science, there are three structural possibilities: (1) classificatory attributes (with heterogeneous differences between categories); (2) heterogeneous orders (with heterogeneous differences between degrees); and (3) quantitative attributes (with thoroughly homogeneous differences between magnitudes). Measurement is possible only with attributes of kind (3) and, as far as we know, psychological attributes are exclusively of kinds (1) or (2). However, contrary to the known facts, psychometricians, for their own special reasons insist that test scores provide measurements.

Staging laparoscopy improves treatment decision-making for advanced gastric cancer.

PubMed

Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

2016-02-07

To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy.

Advanced Hepatocellular Carcinoma: Which Staging Systems Best Predict Prognosis?

PubMed Central

Huitzil-Melendez, Fidel-David; Capanu, Marinela; O'Reilly, Eileen M.; Duffy, Austin; Gansukh, Bolorsukh; Saltz, Leonard L.; Abou-Alfa, Ghassan K.

2010-01-01

Purpose The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival. Patients and Methods Patients with advanced HCC treated over a 5-year period at Memorial Sloan-Kettering Cancer Center were identified from an electronic medical record database. Patients with sufficient data for utilization in all staging systems were included. TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH) systems were ranked on the basis of their accuracy at predicting survival by using concordance index (c-index). Other independent prognostic variables were also identified. Results Overall, 187 eligible patients were identified and were staged by using the seven staging systems. CLIP, CUPI, and GETCH were the three top-ranking staging systems. BCLC and TNM sixth edition lacked any meaningful prognostic discrimination. Performance status, AST, abdominal pain, and esophageal varices improved the discriminatory ability of CLIP. Conclusion In our selected patient population, CLIP, CUPI, and GETCH were the most informative staging systems in predicting survival in patients with advanced HCC. Prospective validation is required to determine if they can be accurately used to stratify patients in clinical trials and to direct the appropriate need for systemic therapy versus best supportive care. BCLC and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. PMID:20458042

A French description of German psychology laboratories in 1893 by Victor Henri, a collaborator of Binet.

PubMed

Nicolas, Serge; Barnes, Marissa E; Murray, David J

2015-05-01

There is a rich tradition of writings about the foundation of psychology laboratories, particularly in the United States but also in France. Various documents exist concerning former German laboratories in American and French literature. But the most interesting French paper was certainly written by a young psychologist named Victor Henri (1872-1940) who was a close collaborator of Alfred Binet (1857-1911) in the 1890s. Visiting various psychology laboratories, he wrote, in 1893, a clear description of the laboratories of Wundt, G. E. Müller, Martius and Ebbinghaus. An English translation is given of Henri's paper and the historical importance of his contribution is here expounded by contrasting the German and French psychologies of the time.

[Prognostic factors of advanced stage non-small-cell lung cancer].

PubMed

Kwas, H; Guermazi, E; Khattab, A; Hrizi, C; Zendah, I; Ghédira, H

2017-09-01

Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years. To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages. A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013. The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment. The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Joint Confirmatory Factor Analysis of the Woodcock-Johnson Tests of Cognitive Abilities, Third Edition, and the Stanford-Binet Intelligence Scales, Fifth Edition, with a Preschool Population

ERIC Educational Resources Information Center

Chang, Mei; Paulson, Sharon E.; Finch, W. Holmes; Mcintosh, David E.; Rothlisberg, Barbara A.

2014-01-01

This study examined the underlying constructs measured by the Woodcock-Johnson Tests of Cognitive Abilities, Third Edition (WJ-III COG) and the Stanford-Binet Intelligence Scales, Fifth Edition (SB5), based on the Cattell-Horn-Carrol (CHC) theory of cognitive abilities. This study reports the results of the first joint confirmatory factor analysis…

[Staging gastritis with the OLGA system: prevalence of advanced stages of gastric atrophy in Mexican patients].

PubMed

Ramírez-Mendoza, P; Ruiz-Castillo, S A; Maroun-Marun, C; Trujillo-Benavides, O; Baltazar-Montúfar, P; Méndez del Monte, R; Angeles-Garay, U

2011-01-01

Gastric adenocarcinoma of intestinal type is preceded by inflammation, which produces mucosal atrophy and intestinal metaplasia, progressing eventually to dysplasia and invasive cancer. Recently an international group, the Operative Link on Gastritis Assessment (OLGA) proponed a staging system for gastric biopsies. To recognize the distribution of advanced stages of gastric mucosal atrophy in Mexican patients with dyspepsia according to the OLGA system. We apply the OLGA system for cancer risk (Stages 0 to IV) to 322 gastric biopsies from consecutive patients with dyspepsia. Using the Sydney protocol, we recorded the presence of atrophy, dysplasia and the relationship with ulcer disease. We report the stage of atrophy for each region and the Helicobacter pylori infection status. We documented 72 (22.4%) cases with atrophy, 50 of them (69.4%) were metaplastic-type. Overall, nine biopsies (2.78%) were stage III (all of them with metaplastic-type atrophy) and there was not stage IV cases. We did not find high-grade dysplasia or intramucosal carcinoma. In 8 of subjects with stage III, we observed low-grade dysplasia. We documented gastric ulcer in 5 patients with stage II, 60% of them with associated low-grade dysplasia. Five patients with duodenal ulcer were found in stages 0 and I. We found low prevalence of advanced stages of mucosal gastric atrophy among patients with dyspepsia. However we recognized 9 patients with stage III according to OLGA system worthy of follow-up because the high risk for developing gastric cancer.

Rectosigmoidian Involvement in Advanced-stage Ovarian Cancer - Intraoperative Decisions.

PubMed

Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona

2017-01-01

Ovarian cancer remains one of the most commonly encountered malignancies affecting women worldwide, that is unfortunately commonly diagnosed in advanced stages of the disease. In these stages, the tumoral process usually involves the surrounding viscera throughout contiguity or induces the apparition of distant metastases via peritoneal, lymphatic or hematogenous spread, multiple resections being needed in order to achieve a good control of the disease. In the present study, we present a case series of 12 patients in whom various surgical procedures on the rectosigmoidian loop were performed in order to achieve debulking surgery to no residual disease. Digestive tract resections consisted of rectosigmoidian resection with left colostomy in three cases, low rectosigmoidian resections with anastomosis in eight cases and a stripping procedure of the peritoneal layer in one case. Due to the close proximity of the digestive and gynecological tract, advanced-stage ovarian tumors frequently involve the rectosigmoidian loop, imposing association of digestive tract surgical procedures. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Racial/Ethnic, socioeconomic, and geographic disparities of cervical cancer advanced-stage diagnosis in Texas.

PubMed

Zhan, F Benjamin; Lin, Yan

2014-01-01

Advanced-stage diagnosis is among the primary causes of mortality among cervical cancer patients. With the wide use of Pap smear screening, cervical cancer advanced-stage diagnosis rates have decreased. However, disparities of advanced-stage diagnosis persist among different population groups. A challenging task in cervical cancer disparity reduction is to identify where underserved population groups are. Based on cervical cancer incidence data between 1995 and 2008, this study investigated advanced-stage cervical cancer disparities in Texas from three social domains: Race/ethnicity, socioeconomic status (SES), and geographic location. Effects of individual and contextual factors, including age, tumor grade, race/ethnicity, as well as contextual SES, spatial access to health care, sociocultural factors, percentage of African Americans, and insurance expenditures, on these disparities were examined using multilevel logistic regressions. Significant variations by race/ethnicity and SES were found in cervical cancer advanced-stage diagnosis. We also found a decline in racial/ethnic disparities of advanced cervical cancer diagnosis rate from 1995 to 2008. However, the progress was slower among African Americans than Hispanics. Geographic disparities could be explained by age, race/ethnicity, SES, and the percentage of African Americans in a census tract. Our findings have important implications for developing effective cervical cancer screening and control programs. We identified the location of underserved populations who need the most assistance with cervical cancer screening. Cervical cancer intervention programs should target Hispanics and African Americans, as well as individuals from communities with lower SES in geographic areas where higher advanced-stage diagnosis rates were identified in this study. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Rectosigmoidian Involvement in Advanced-stage Ovarian Cancer – Intraoperative Decisions

PubMed Central

BACALBASA, NICOLAE; BALESCU, IRINA; DIMA, SIMONA

2017-01-01

Background/Aim: Ovarian cancer remains one of the most commonly encountered malignancies affecting women worldwide, that is unfortunately commonly diagnosed in advanced stages of the disease. In these stages, the tumoral process usually involves the surrounding viscera throughout contiguity or induces the apparition of distant metastases via peritoneal, lymphatic or hematogenous spread, multiple resections being needed in order to achieve a good control of the disease. Patients and Methods: In the present study, we present a case series of 12 patients in whom various surgical procedures on the rectosigmoidian loop were performed in order to achieve debulking surgery to no residual disease. Results: Digestive tract resections consisted of rectosigmoidian resection with left colostomy in three cases, low rectosigmoidian resections with anastomosis in eight cases and a stripping procedure of the peritoneal layer in one case. Conclusion: Due to the close proximity of the digestive and gynecological tract, advanced-stage ovarian tumors frequently involve the rectosigmoidian loop, imposing association of digestive tract surgical procedures. PMID:28882968

Normal serum protein electrophoresis and mutated IGHV genes detect very slowly evolving chronic lymphocytic leukemia patients.

PubMed

Chauzeix, Jasmine; Laforêt, Marie-Pierre; Deveza, Mélanie; Crowther, Liam; Marcellaud, Elodie; Derouault, Paco; Lia, Anne-Sophie; Boyer, François; Bargues, Nicolas; Olombel, Guillaume; Jaccard, Arnaud; Feuillard, Jean; Gachard, Nathalie; Rizzo, David

2018-05-09

More than 35 years after the Binet classification, there is still a need for simple prognostic markers in chronic lymphocytic leukemia (CLL). Here, we studied the treatment-free survival (TFS) impact of normal serum protein electrophoresis (SPE) at diagnosis. One hundred twelve patients with CLL were analyzed. The main prognostic factors (Binet stage; lymphocytosis; IGHV mutation status; TP53, SF3B1, NOTCH1, and BIRC3 mutations; and cytogenetic abnormalities) were studied. The frequencies of IGHV mutation status, cytogenetic abnormalities, and TP53, SF3B1, NOTCH1, and BIRC3 mutations were not significantly different between normal and abnormal SPE. Normal SPE was associated with Binet stage A, nonprogressive disease for 6 months, lymphocytosis below 30 G/L, and the absence of the IGHV3-21 gene rearrangement which is associated with poor prognosis. The TFS of patients with normal SPE was significantly longer than that of patients with abnormal SPE (log-rank test: P = 0.0015, with 51% untreated patients at 5.6 years and a perfect plateau afterward vs. a median TFS at 2.64 years for abnormal SPE with no plateau). Multivariate analysis using two different Cox models and bootstrapping showed that normal SPE was an independent good prognostic marker for either Binet stage, lymphocytosis, or IGHV mutation status. TFS was further increased when both normal SPE and mutated IGHV were present (log-rank test: P = 0.008, median not reached, plateau at 5.6 years and 66% untreated patients). A comparison with other prognostic markers suggested that normal SPE could reflect slowly advancing CLL disease. Altogether, our results show that a combination of normal SPE and mutated IGHV genes defines a subgroup of patients with CLL who evolve very slowly and who might never need treatment. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

PubMed

Hansen, Eric; Panwala, Kathryn; Holland, John

2002-11-01

Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report.

PubMed

Ghalleb, Montassar; Bouzaiene, Hatem; Slim, Skander; Hadiji, Achraf; Hechiche, Monia; Ben Hassouna, Jamel; Rahal, Khaled

2017-12-17

Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor. Fertility preservation is an important issue because malignant ovarian germ cell tumor commonly affects young women. Although conservation is the standard for early stage, it becomes more debatable as the disease progresses to more advanced stages. Report the case of a patient with an International Federation of Gynecology and Obstetrics Stage IIIc malignant ovarian germ cell tumor, who had conservative surgery and chemotherapy with a good fertility outcome. A 23-year-old North African woman with a left malignant ovarian germ cell tumor stage IIIc was treated by left adnexectomy and omentectomy followed by chemotherapy. A 15-year follow-up showed no signs of relapse, and she completed three full-term natural pregnancies. Malignant ovarian germ cell tumor is a rare ovarian tumor with a good prognosis. It is usually associated with a good fertility outcome in early stages. However, due to the rarity of the disease in advanced stages, the fertility outcome for this group of patients is not clear. This lack of data surrounding advanced stages points to the need for a meta-analysis of all published cases.

Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

PubMed

Grob, Charles S; Danforth, Alicia L; Chopra, Gurpreet S; Hagerty, Marycie; McKay, Charles R; Halberstadt, Adam L; Greer, George R

2011-01-01

Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. A clinical research unit within a large public sector academic medical center. Twelve adults with advanced-stage cancer and anxiety. In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. clinicaltrials.gov Identifier: NCT00302744.

Advanced Low-Noise Research Fan Stage Design

NASA Technical Reports Server (NTRS)

Neubert, Robert; Bock, Larry; Malmborg, Eric; Owen-Peer, William

1997-01-01

This report describes the design of the Advanced Low-Noise Research Fan stage. The fan is a variable pitch design, which is designed at the cruise pitch condition. Relative to the cruise setting, the blade is closed at takeoff and opened for reverse thrust operation. The fan stage is a split flow design with fan exit guide vanes (FEGVs) and core stators. The fan stage design is combined with a nacelle and engine core duct to form a powered fan/nacelle subscale model. This model is intended for use in combined aerodynamic, acoustic, and structural testing in a wind tunnel. The fan has an outer diameter of 22 in. and a hub-to-tip of 0.426 in., which allows the use of existing NASA fan and cowl force balance and rig drive systems. The design parameters were selected to permit valid acoustic and aerodynamic comparisons with the Pratt & Whitney (P&W) 17- and 22-in. rigs previously tested under NASA contract. The fan stage design is described in detail. The results of the design axisymmetric and Navier-Stokes aerodynamic analysis are presented at the critical design conditions. The structural analysis of the fan rotor and attachment is included. The blade and attachment are predicted to have adequate low-cycle fatigue life and an acceptable operating range without resonant stress or flutter. The stage was acoustically designed with airfoil counts in the FEGV and core stator to minimize noise. A fan/FEGV tone analysis developed separately under NASA contract was used to determine the optimum airfoil counts. The fan stage was matched to the existing nacelle, designed under the previous P&W low-noise contract, to form a fan/nacelle model for wind tunnel testing. It is an axisymmetric nacelle for convenience in testing and analysis. Previous testing confirmed that the nacelle performed as required at various aircraft operating conditions.

Clinical and Cost Implications of Universal Versus Locally Advanced-Stage and Advanced-Stage-Only Molecular Testing for Epidermal Growth Factor Receptor Mutations and Anaplastic Lymphoma Kinase Rearrangements in Non-Small Cell Lung Carcinoma: A Tertiary Academic Institution Experience.

PubMed

Sauter, Jennifer L; Butnor, Kelly J

2016-04-01

Although epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-directed therapies are not approved for patients with early-stage non-small cell lung carcinoma (NSCLC), many institutions perform EGFR and ALK testing for all patients with NSCLC at the time of initial diagnosis. Current consensus guidelines recommend EGFR testing and suggest ALK testing at the time of initial diagnosis for patients with advanced disease. To examine the cost and clinical impact of EGFR and ALK testing of patients with early-stage NSCLC. Records from all patients with a diagnosis of NSCLC made on a nonresection specimen at our institution during a single calendar year (2012) were reviewed, and a cost analysis was performed. Of 133 total patients, 47 (35%) had early-stage (stage I or II) disease and 86 (65%) had locally advanced (stage III) or advanced (stage IV) disease at presentation. Eight of 47 patients with early-stage disease (17%) had progression/recurrence during 18 to 30 months of follow-up, 6 of 8 (75%) of whom had pathologic confirmation of progression/recurrence. The estimated additional cost of EGFR and ALK testing for all newly diagnosed patients with NSCLC at our institution is $75,200 per year, compared to testing only patients with locally advanced and advanced-stage disease. The cost of universal molecular testing of NSCLC is substantial. EGFR and ALK testing of patients with early-stage disease appears to have negligible clinical impact, as most patients do not have disease recurrence/progression. Those whose disease recurs/progresses typically undergo rebiopsy. Our findings do not support the practice of universal EGFR and ALK testing in NSCLC at the time of initial diagnosis.

Prediction of Bayley and Stanford-Binet scores with a group of very low birthweight children.

PubMed

Dezoete, J A; MacArthur, B A; Tuck, B

2003-09-01

To study the prediction of cognitive development with a group of very low birthweight infants (<1500 g) at 18 months and at 4 years of age. Bayley Scales of Infant Development-II Mental Development Indexes (MDI), and Stanford-Binet Intelligence Scale (S-B) Composite Scores were studied in a population of 334 children with birthweights <1500 g. Independent variables measured were gestational age, birthweight, gender and parental socio-economic status (SES). Longer gestation (28 weeks and over) and higher birthweight (1000-1500 g) proved to be advantageous for cognitive ability at both 18 months and 4 years. Other significant advantages were associated with female and higher SES. High correlations were found between MDI and the S-B Composite Score (r = 0.62), and between birthweight and gestation (r = 0.72). When information available at birth was included in forward stepwise regression analyses to predict the S-B Composite at 4 years, the best predictors were MDI at 18 months and SES. With the measures employed and this population, prediction of cognitive development from early childhood to preschool was possible. This may enable reliable identification of those children at risk for delayed cognitive development who require intervention before starting school.

Nomogram for suboptimal cytoreduction at primary surgery for advanced stage ovarian cancer.

PubMed

Gerestein, Cornelis G; Eijkemans, Marinus J; Bakker, Jeanette; Elgersma, Otto E; van der Burg, Maria E L; Kooi, Geertruida S; Burger, Curt W

2011-11-01

Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve counseling. The objective of this study was to identify predictive computed tomographic (CT) scan and clinical parameters for suboptimal cytoreduction at primary cytoreductive surgery for advanced stage EOC and to generate a nomogram with the identified parameters, which would be easy to use in daily clinical practice. Between October 2005 and December 2008, all patients with primary surgery for suspected advanced stage EOC at six participating teaching hospitals in the South Western part of the Netherlands entered the study protocol. To investigate independent predictors of suboptimal cytoreduction, a Cox proportional hazard model with backward stepwise elimination was utilized. One hundred and fifteen patients with FIGO stage III/IV EOC entered the study protocol. Optimal cytoreduction was achieved in 52 (45%) patients. A suboptimal cytoreduction was predicted by preoperative blood platelet count (p=0.1990; odds ratio (OR)=1.002), diffuse peritoneal thickening (DPT) (p=0.0074; OR=3.021), and presence of ascites on at least two thirds of CT scan slices (p=0.0385; OR=2.294) with a for-optimism corrected c-statistic of 0.67. Suboptimal cytoreduction was predicted by preoperative platelet count, DPT and presence of ascites. The generated nomogram can, after external validation, be used to estimate surgical outcome and to identify those patients, who might benefit from alternative treatment approaches.

Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

PubMed

Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

2015-02-01

Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

PubMed

Nieuwenhuyzen-de Boer, G M; Gerestein, C G; Eijkemans, M J C; Burger, C W; Kooi, G S

2016-01-01

Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment. Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk. 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups. Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

SPIRIT advance care planning intervention in early stage dementias: An NIH stage I behavioral intervention development trial.

PubMed

Song, Mi-Kyung; Ward, Sandra E; Hepburn, Kenneth; Paul, Sudeshna; Shah, Raj C; Morhardt, Darby J

2018-06-02

People in the early stages of Alzheimer's disease and related dementias (ADRD) are encouraged to engage in advance care planning (ACP) while they are still competent to appoint a surrogate decision maker and meaningfully participate in ACP discussions with the surrogate. In this NIH Stage I behavioral intervention development trial, we will adapt and test an efficacious ACP intervention, SPIRIT (Sharing Patient's Illness Representation to Increase Trust), with people with mild dementia and their surrogates to promote open, honest discussions while such discussions about end-of-life care are possible. We will first adapt SPIRIT (in person) to target people with mild dementia and their surrogates through a process of modification-pretesting-refinement using stakeholders (persons with mild dementia, family caregivers, and clinicians) and experts, including adapting the delivery mode to interactive web-based videoconference format (SPIRIT-remote). Then in a 3-group RCT with 120 patient-surrogate dyads, we will evaluate the feasibility and acceptability of SPIRIT in-person and SPIRIT remote, and preliminary efficacy of SPIRIT compared to usual care on preparedness outcomes for end-of-life decision making (dyad congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence) shortly after the intervention. This Stage I research of SPIRIT will generate valuable insights regarding how to improve ACP for people with mild dementia who will progress to an advanced stage of the disease in the foreseeable future. ClinicalTrials.gov NCT03311711, Registered 10/12/2017. Copyright © 2018. Published by Elsevier Inc.

Utility of an abbreviated version of the stanford-binet intelligence scales (5th ed.) in estimating 'full scale' IQ for young children with autism spectrum disorder.

PubMed

Twomey, Conal; O'Connell, Helen; Lillis, Mary; Tarpey, Sarah Louise; O'Reilly, Gary

2018-03-01

The fifth edition of the Stanford-Binet Intelligence scales allows 'full scale' IQ (FSIQ) to be estimated using an abridged version of the test-the abbreviated battery IQ (ABIQ). Set within a public early intervention team service, the current cross-sectional study investigated the utility of the ABIQ in estimating FSIQ for 40 children with autism spectrum disorder (ASD) aged 3-5 years. A strong ABIQ-FSIQ association was yielded (r = 0.89; r 2  = 0.808) and the ABIQ did not over-estimate mean FSIQ above a clinically-relevant threshold; however, clinically significant over-estimation occurred in 17.5% of individual cases. While the findings provide support for the utility of the ABIQ in estimating FSIQ for young children with ASD, caution relating to the over-estimation of FSIQ is warranted. Careful clinical judgment-ideally based on examination of previous cognitive assessment results (if available), thorough interactional observations, and close multi-disciplinary consultation-is necessary to determine the applicability of the ABIQ to individual cases. Autism Res 2018, 11: 503-508. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We investigated the utility of a shortened version of the Stanford-Binet Intelligence Scales in estimating IQ for 40 young children with autism spectrum disorder (ASD). The findings provide qualified support for the instrument: acceptably accurate IQ estimation was achieved for most cases; but not so for a sizeable minority (17.5%). Careful clinical judgment is necessary to determine the applicability of the ABIQ to individual cases. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

PubMed

Gambichler, T; Rooms, I; Scholl, L; Stockfleth, E; Stücker, M; Sand, M

2016-11-01

Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. We aimed to investigate Bim protein expression in cutaneous melanoma (CM). Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target. © 2016 European Academy of Dermatology and Venereology.

[Chronic lymphocytic leukemia].

PubMed

Maurer, C; Hallek, M

2013-10-01

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that accounts for approximately 30 % of adult leukemias and 25 % of Non-Hodgkin lymphomas (NHL). It is the most common form of leukemia in the western world (incidence 3-5/100 000). Elderly people are mainly affected, median age at diagnosis is around 70 years and there is a slight predominance in men. The etiology of the disease is unknown. The initial symptoms are nonspecific. Cervical lymphadenopathy and splenomegaly followed by general fatigue are seen most commonly. Other possible symptoms include night sweats, fever, loss of weight (so-called B symptoms) and frequent infections. Several patients develop autoimmune complications as autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia (ITP). To confirm the diagnosis more than 5000 B-lymphocytes/µl need to be present. The expression of the typical surface markers CD5, CD19, and CD23 has to be confirmed by flow cytometry. Imaging studies as X-ray of the chest, ultrasound of the abdomen, or CT scan are used to assess the degree of lymphadenopathy or organomegaly. A bone marrow biopsy is not mandatory for the diagnosis. According to the European Binet staging system, CLL is divided into 3 stages (A, B and C). Patients in Binet stage A have 0 to 2 areas of node or organ enlargement with normal levels of hemoglobin and platelets. Binet stage B patients have 3 to 5 areas of node or organ enlargement and normal or slightly decreased levels of hemoglobin and platelets. Binet stage C patients have anemia (hemoglobin < 10 g/dl) and/or thrombocytopenia (platelet counts < 100 000/µl), with or without lymphadenopathy or organomegaly. As there is no survival benefit associated with early intervention, asymptomatic patients with early stage CLL (Binet stage A and B) are usually not treated but are followed on a "watch and wait" principle. Treatment indications include stage Binet C or signs of an active disease as rapidly progressive

Variation in advanced stage at diagnosis of lung and female breast cancer in an English region 2006-2009.

PubMed

Lyratzopoulos, G; Abel, G A; Barbiere, J M; Brown, C H; Rous, B A; Greenberg, D C

2012-03-13

Understanding variation in stage at diagnosis can inform interventions to improve the timeliness of diagnosis for patients with different cancers and characteristics. We analysed population-based data on 17,836 and 13,286 East of England residents diagnosed with (female) breast and lung cancer during 2006-2009, with stage information on 16,460 (92%) and 10,435 (79%) patients, respectively. Odds ratios (ORs) of advanced stage at diagnosis adjusted for patient and tumour characteristics were derived using logistic regression. We present adjusted ORs of diagnosis in stages III/IV compared with diagnosis in stages I/II. For breast cancer, the frequency of advanced stage at diagnosis increased stepwise among old women (ORs: 1.21, 1.46, 1.68 and 1.78 for women aged 70-74, 75-79, 80-84 and ≥85, respectively, compared with those aged 65-69 , P<0.001). In contrast, for lung cancer advanced stage at diagnosis was less frequent in old patients (ORs: 0.82, 0.74, 0.73 and 0.66, P<0.001). Advanced stage at diagnosis was more frequent in more deprived women with breast cancer (OR: 1.23 for most compared with least deprived, P=0.002), and in men with lung cancer (OR: 1.14, P=0.011). The observed patterns were robust to sensitivity analyses approaches for handling missing stage data under different assumptions. Interventions to help improve the timeliness of diagnosis of different cancers should be targeted at specific age groups.

Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

PubMed Central

2013-01-01

Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

Expression signatures of early-stage and advanced medaka melanomas.

PubMed

Klotz, Barbara; Kneitz, Susanne; Regensburger, Martina; Hahn, Lena; Dannemann, Michael; Kelso, Janet; Nickel, Birgit; Lu, Yuan; Boswell, William; Postlethwait, John; Warren, Wesley; Kunz, Manfred; Walter, Ronald B; Schartl, Manfred

2018-06-01

Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

Retinopathy of prematurity: mutations in the Norrie disease gene and the risk of progression to advanced stages.

PubMed

Haider, M Z; Devarajan, L V; Al-Essa, M; Srivastva, B S; Kumar, H; Azad, R; Rashwan, N

2001-04-01

Retinopathy of prematurity (ROP) is a retinal vascular disease that occurs in infants with short gestational age and low birth weight and may lead to retinal detachment and blindness. Missense mutations in the Norrie disease (ND) gene have been associated with the risk of progression to advanced stages in cases of ROP from the US and also in clinically similar ND and familial exudative vitreoretinopathy. We have screened two ND gene mutations, namely A105T and Val60Glu, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR methods, respectively, in 210 Kuwaiti premature newborns to replicate these findings in a different ethnic group. In the Kuwaiti premature newborn cohort, 115 of 210 babies had no eye problems and served as controls, while 95 were cases of ROP. In 71 of 95 ROP cases, the disease regressed spontaneously on or before stage 3, while in 24 of 95 ROP cases the disease progressed to advanced stages 4 and 5. In case of missense mutation (A105T), the AA genotype was detected in 96% of controls compared with 87% of ROP cases (NS); similarly no significant difference was found between spontaneously regressed ROP cases and those who progressed to advanced stages. For the Val60Glu mutation, no significant association was detected between the genotype and progression of ROP to advanced stages. Unlike data from the US, our findings from a Kuwaiti cohort of ROP cases and controls suggest a lack of association between the two ND gene mutations (A105T and Val60Glu) and ROP and the risk of progression of the disease to advanced stages.

Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

PubMed

Albrecht, Tara A; Taylor, Ann Gill

2012-06-01

The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives.

Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

PubMed Central

Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

2014-01-01

Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

Two-stage, low noise advanced technology fan. 5: Acoustic final report

NASA Technical Reports Server (NTRS)

Sofrin, T. G.; Riloff, N., Jr.

1975-01-01

The NASA Q2S(quiet two-stage) fan is a 0.836m (32.9 in.) diameter model of the STF 433 engine fan, selected in a 1972 study for an Advanced Technology Transport (ATT) airplane. Noise-control features include: low tip speed, moderate stage pressure rise, large blade-vane spacings, no inlet guide vanes, and optimum blade and vane numbers. Tests were run on the baseline Q2S fan with standard inlet and discharge ducts. Further tests were made of a translating centerbody sonic inlet device and treated discharge ducts. Results were scaled to JT8D and JT3D engine fan size for comparison with current two-stage fans, and were also scaled to STF 433 fan size to compare calculated ATT flyover noise with FAR 36 limits. Baseline Q2S results scaled to JT8D and JT3D engine fan sizes showed substantial noise reductions. Calculated unsuppressed baseline ATT flyovers averaged about 2.5 EPNdB below FAR 36 limits. Using measured sonic inlet results, scaled baseline Q2S fan results, and calculated attenuations for a 1975 technology duct liner, projected flyover noise calculations for the ATT averaged about FAR 36 limits minus 10 EPNdB. Advances in suppression technology required to meet the 1985 goal of FAR 36 limits minus 20 EPNdB are discussed.

The experience of living with advanced-stage cancer: a thematic synthesis of the literature.

PubMed

García-Rueda, N; Carvajal Valcárcel, A; Saracíbar-Razquin, M; Arantzamendi Solabarrieta, M

2016-07-01

The aim of the study was to understand the experience of people living with advanced-stage cancer through literature. The search included The Cochrane Library, PubMed, PsycInfo, CINAHL and Cuiden. Thirteen studies were included. A qualitative meta-synthesis was conducted. One thread emerged from the thematic synthesis: the desire to live as normally as possible, despite being aware of the proximity of death. Three themes also emerged: "a process that is unique" with its four sub-themes; "support network" and "health context," each of them having two sub-themes. This study concludes that living with advanced-stage cancer is a unique and complex process which has both positive and negative aspects. The review provides a comprehensive view of the experience, which considers the importance of the support network and the health context in which the person lives. In this study, "normalcy" is the adjustment to the new reality and living as closely as possible to the way one lived before the disease, while developing a new relationship with being finite and death. A better understanding of the experience of living with advanced-stage cancer will help health professionals to identify the needs of the patients in order to plan individual, high-quality care. © 2016 John Wiley & Sons Ltd.

Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL.

PubMed

Blanco, Gonzalo; Vardi, Anna; Puiggros, Anna; Gómez-Llonín, Andrea; Muro, Manuel; Rodríguez-Rivera, María; Stalika, Evangelia; Abella, Eugenia; Gimeno, Eva; López-Sánchez, Manuela; Senín, Alicia; Calvo, Xavier; Abrisqueta, Pau; Bosch, Francesc; Ferrer, Ana; Stamatopoulos, Kostas; Espinet, Blanca

2018-01-01

Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 + and CD8 + T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 + T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

Combined treatment of advanced stages of recurrent skin cancer of the head.

PubMed

Pompucci, Angelo; Rea, Giancarla; Farallo, Eugenio; Salgarello, Marzia; Campanella, Antonino; Fernandez, Eduardo

2004-04-01

The authors investigated whether skull base resection and primary free-flap reconstruction in a single-stage surgery is oncologically effective for treating advanced stages of recurrent skin cancer (RSC) of the head. Eighteen consecutive patients were surgically treated. Twelve of them underwent an anterolateral skull base resection, which was performed using a pterional craniotomy combined with an orbitozygomatic osteotomy. Six patients underwent a posterolateral skull base resection, which was performed using an asterional craniotomy combined with a retrolabyrinthine petrosectomy. The wide postoperative defects were covered with muscular or myocutaneous free flaps. The main factor influencing survival was the extent of the resection: patients with no or minimal residual disease showed a statistically significant longer survival time than those with consistent residual disease. Basal cell carcinoma had a better prognosis than squamous cell carcinoma. A trend toward improved survival was observed in patients classified as T4M0 with negative lymph nodes (N0), but this trend was not statistically significant. Adjuvant radiotherapy significantly influenced both survival time and the rate of local recurrence. The surgical morbidity rate was 27.8%; there were two transient cerebrospinal fluid leaks and three seventh cranial nerve injuries. Late complications included radionecrosis in one patient and skin erosion requiring a second surgery in another patient. No deaths occurred during a 30-day postoperative period. Advances in skull base surgery and free-flap reconstruction allowed the authors to treat patients with advanced-stage RSC of the head in a rather satisfactory manner. Only when it is impossible to achieve no or minimal residual disease should aggressive treatment be considered.

Impact of paranasal sinus invasion on advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: the validity of advanced T stage of AJCC/UICC eighth edition staging system.

PubMed

Wang, Ying; Zhao, Jie; Zhao, Yajie; Yang, Zhen; Lei, Mingjun; Li, Zhanzhan; Wei, Rui; Chen, Dengming; He, Yuxiang; Shen, Liangfang

2018-05-01

The aim of this study was to clarify the prognostic role of paranasal sinus invasion in advanced NPC patients. Data of patients (n = 295) with advanced NPC (T3/T4N0-3 M0) treated with intensity-modulated radiation therapy were retrospectively analyzed. Staging was according to the AJCC/UICC eighth edition staging system. Overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were calculated, and differences were compared between patients with and without paranasal sinus invasion. Multivariate analysis was used to identify the independent predictors of different survival parameters. Paranasal sinus invasion was present in 126 of 295 (42.7%) patients. Sphenoid, ethmoid, maxillary, and frontal sinus involvements were present in 123 of 295 (41.7%), 95 of 295 (32.2%), 45 of 295 (15.3%), and 0 of 295 (0%), respectively. All survival parameters were significantly better in patients without paranasal sinus invasion. When paranasal sinus invasion was reclassified as T4 instead of T3, all survival rates, other than LRFS (P = 0.156), were significantly better in the new T3 patients, and differences in all survival parameters remained nonsignificant between T3 with paranasal sinus invasion and T4 without paranasal sinus invasion patients (all P > 0.05). In multivariate analysis, paranasal sinus invasion was found to be an independent negative prognostic factor for OS, DFS, and DMFS (P = 0.016, P = 0.004, and P = 0.006, respectively), but not for LRFS (P = 0.068). Paranasal sinus invasion has prognostic value in advanced NPC. It may be reasonable to classify paranasal sinus invasion as T4 stage. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Novel Therapeutic Modality for Advanced Stage Prostate Cancer Treatment

DTIC Science & Technology

2017-10-01

Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of...PrCa are non-selective and provide only limited response rate Thus, novel treatment modalities are needed to treat advanced stage PrCa. In this...of ORM on MTA1 protein. Considering effective therapeutic index of ORM, we are also making more potent analogues of ORM. These findings suggest that

Is uniportal thoracoscopic surgery a feasible approach for advanced stages of non-small cell lung cancer?

PubMed Central

Fieira, Eva; Delgado, Maria; Mendez, Lucía; Fernandez, Ricardo; de la Torre, Mercedes

2014-01-01

Objectives Conventional video-assisted thoracoscopic (VATS) lobectomy for advanced lung cancer is a feasible and safe surgery in experienced centers. The aim of this study is to assess the feasibility of uniportal VATS approach in the treatment of advanced non-small cell lung cancer (NSCLC) and compare the perioperative outcomes and survival with those in early-stage tumors operated through the uniportal approach. Methods From June 2010 to December 2012, we performed 163 uniportal VATS major pulmonary resections. Only NSCLC cases were included in this study (130 cases). Patients were divided into two groups: (A) early stage and (B) advanced cases (>5 cm, T3 or T4, or tumors requiring neoadjuvant treatment). A descriptive and retrospective study was performed, comparing perioperative outcomes and survival obtained in both groups. A survival analysis was performed with Kaplan-Meier curves and the log-rank test was used to compare survival between patients with early and advanced stages. Results A total of 130 cases were included in the study: 87 (A) vs. 43 (B) patients (conversion rate 1.1 vs. 6.5%, P=0.119). Mean global age was 64.9 years and 73.8% were men. The patient demographic data was similar in both groups. Upper lobectomies (A, 52 vs. B, 21 patients) and anatomic segmentectomies (A, 4 vs. B, 0) were more frequent in group A while pneumonectomy was more frequent in B (A, 1 vs. B, 6 patients). Surgical time was longer (144.9±41.3 vs. 183.2±48.9, P<0.001), and median number of lymph nodes (14 vs. 16, P=0.004) were statistically higher in advanced cases. Median number of nodal stations (5 vs. 5, P=0.165), days of chest tube (2 vs. 2, P=0.098), HOS (3 vs. 3, P=0.072), and rate of complications (17.2% vs. 14%, P=0.075) were similar in both groups. One patient died on the 58th postoperative day. The 30-month survival rate was 90% for the early stage group and 74% for advanced cases Conclusions Uniportal VATS lobectomy for advanced cases of NSCLC is a safe and

Advanced two-stage compressor program design of inlet stage

NASA Technical Reports Server (NTRS)

Bryce, C. A.; Paine, C. J.; Mccutcheon, A. R. S.; Tu, R. K.; Perrone, G. L.

1973-01-01

The aerodynamic design of an inlet stage for a two-stage, 10/1 pressure ratio, 2 lb/sec flow rate compressor is discussed. Initially a performance comparison was conducted for an axial, mixed flow and centrifugal second stage. A modified mixed flow configuration with tandem rotors and tandem stators was selected for the inlet stage. The term conical flow compressor was coined to describe a particular type of mixed flow compressor configuration which utilizes axial flow type blading and an increase in radius to increase the work input potential. Design details of the conical flow compressor are described.

Experiences of family of patient with newly diagnosed advanced terminal stage hepatocellular cancer.

PubMed

Shih, Whei-Mei Jean; Hsiao, Ping-Ju; Chen, Min-Li; Lin, Mei-Hsiang

2013-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide due to its generally poor prognosis. Caregiver burden for liver cancer cases is higher than with other cancer and needs especial attention. To explore the experiences of families of patients with newly diagnosed advanced terminal stage hepatocellular cancer by interview. Nine participants were recruited in this study. Content analysis of the interviews revealed four themes: blaming oneself, disrupting the pace of life, searching all possible regimens, and not letting go. This study provides new insight into the needs and support of family members especially when they are facing loved ones with newly diagnosed advanced terminal stage HCC. These results will inform future supportive care service development and intervention research aimed at providing assistance in reducing unmet supportive care needs and psychological distress of these family members.

Racial disparities in advanced stage colorectal cancer survival

PubMed Central

Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

2013-01-01

Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

Para-aortic lymphadenectomy in advanced stage cervical cancer, a protocol for comparing safety, feasibility and diagnostic accuracy of surgical staging versus PET-CT; PALDISC trial.

PubMed

Tax, Casper; Abbink, Karin; Rovers, Maroeska M; Bekkers, Ruud L M; Zusterzeel, Petra L M

2018-01-01

Currently, a PET-CT is used to assess the need for extended field radiotherapy of para-aortic lymph nodes (PALN) in International Federation of Gynaecology and Obstetrics (FIGO) stage IB2, IIA2-IVA (locally advanced stage) cervical cancer. A small study established a sensitivity and specificity estimate for PALN metastases of 50% (95% CI; 7-93%) and 83% (95% CI; 52-98%), respectively. Surgical staging of PALN may lead to a higher diagnostic accuracy. However, surgical staging of para-aortic lymph nodes in locally advanced stage cervical cancer is not common practice. Therefore, a phase 2 randomised controlled trial is needed to assess its safety and feasibility. In addition to standard imaging (MRI or CT scan) with PET-CT, 30 adult women with FIGO stage IB2, IIA2-IVA cervical cancer will be randomised to receive either surgical staging or usual PET-CT staging. Administering extended field radiotherapy will be based on lymphadenectomy results for the intervention group and on the PET-CT results for the control group. Follow-up visits at 0, 3, 6, 9 and 12 months will assess health-related quality of life and progression-free survival.Primary safety and feasibility outcomes of surgical staging will be assessed by calculating means with 95% confidence intervals for duration of surgery, number of complications, blood loss, nodal yield after para-aortic lymphadenectomy and treatment delay due to surgical staging. Secondary patient-centred outcomes on quality of life and first year survival will be documented and compared between the two groups. Estimates of sensitivity, specificity and negative and positive predictive values of MRI, PET-CT and surgical staging will be presented with 95% CI.. All analysis will be performed according to the intention to treat principle. This study will assess safety and feasibility, expressed as the number and severity of complications, effect on quality of life and the treatment delay due to surgically staging para-aortic lymph nodes in

Racial disparities in advanced-stage colorectal cancer survival.

PubMed

Wallace, Kristin; Hill, Elizabeth G; Lewin, David N; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E; Wargovich, Michael J; Berger, Franklin G; Bolick, Susan W; Thomas, Melanie B; Alberg, Anthony J

2013-03-01

African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival. The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI. We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06-1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01-1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82-1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years. Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

PubMed

Brenkman, H J F; Gertsen, E C; Vegt, E; van Hillegersberg, R; van Berge Henegouwen, M I; Gisbertz, S S; Luyer, M D P; Nieuwenhuijzen, G A P; van Lanschot, J J B; Lagarde, S M; de Steur, W O; Hartgrink, H H; Stoot, J H M B; Hulsewe, K W E; Spillenaar Bilgen, E J; van Det, M J; Kouwenhoven, E A; van der Peet, D L; Daams, F; van Sandick, J W; van Grieken, N C T; Heisterkamp, J; van Etten, B; Haveman, J W; Pierie, J P; Jonker, F; Thijssen, A Y; Belt, E J T; van Duijvendijk, P; Wassenaar, E; van Laarhoven, H W M; Wessels, F J; Haj Mohammad, N; van Stel, H F; Frederix, G W J; Siersema, P D; Ruurda, J P

2018-04-20

Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. NCT03208621 . This trial was registered prospectively on June 30, 2017.

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

PubMed

Dervisis, Nikolaos G; Dominguez, Pedro A; Newman, Rebecca G; Cadile, Casey D; Kitchell, Barbara E

2011-01-01

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

PubMed Central

Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

2015-01-01

Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

Liquid biopsy: A potential and promising diagnostic tool for advanced stage non-small cell lung cancer patients.

PubMed

Doval, D C; Deshpande, R; Dhabhar, B; Babu, K G; Prabhash, K; Chopra, R; Sripada, P V; Deshmukh, C; Suryavanshi, M

2017-12-01

More than 50% of non-small cell lung cancer (NSCLC) cases harbor an actionable mutation, and molecular testing at different intervals can help in personalized and targeted treatment. Core tissue biopsy and needle biopsy done at the time of diagnosis/disease progression are interventional, time-consuming and can affect the patients adversely. Noninterventional biomarker testing by liquid biopsy promises to revolutionize advanced stage cancer screening. The present report was formulated based on an expert panel meeting of renowned oncologists who gave their opinions for minimally invasive liquid biopsy to detect targetable molecular biomarkers in advanced NSCLC cases. An exhaustive literature search was done to support their recommendations. Clinical utility of minimally invasive liquid biopsy, for detection of molecular biomarkers in advanced stage NSCLC patients, was broadly discussed by the key opinion leaders.

Experimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions

NASA Technical Reports Server (NTRS)

Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

2015-01-01

NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency of large gas turbine engines. Under ERA the task for a High Pressure Ratio Core Technology program calls for a higher overall pressure ratio of 60 to 70. This mean that the HPC would have to almost double in pressure ratio and keep its high level of efficiency. The challenge is how to match the corrected mass flow rate of the front two supersonic high reaction and high corrected tip speed stages with a total pressure ratio of 3.5. NASA and GE teamed to address this challenge by using the initial geometry of an advanced GE compressor design to meet the requirements of the first 2 stages of the very high pressure ratio core compressor. The rig was configured to run as a 2 stage machine, with Strut and IGV, Rotor 1 and Stator 1 run as independent tests which were then followed by adding the second stage. The goal is to fully understand the stage performances under isolated and multi-stage conditions and fully understand any differences and provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to isolate fluid dynamics loss source mechanisms due to interaction and endwalls. The paper will present the description of the compressor test article, its predicted performance and operability, and the experimental results for both the single stage and two stage configurations. We focus the detailed measurements on 97 and 100 of design speed at 3 vane setting angles.

Exprimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions.

NASA Technical Reports Server (NTRS)

Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

2015-01-01

NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency for large gas turbine engines. Under ERA, the highly loaded core compressor technology program attempts to realize the fuel burn reduction goal by increasing overall pressure ratio of the compressor to increase thermal efficiency of the engine. Study engines with overall pressure ratio of 60 to 70 are now being investigated. This means that the high pressure compressor would have to almost double in pressure ratio while keeping a high level of efficiency. NASA and GE teamed to address this challenge by testing the first two stages of an advanced GE compressor designed to meet the requirements of a very high pressure ratio core compressor. Previous test experience of a compressor which included these front two stages indicated a performance deficit relative to design intent. Therefore, the current rig was designed to run in 1-stage and 2-stage configurations in two separate tests to assess whether the bow shock of the second rotor interacting with the upstream stage contributed to the unpredicted performance deficit, or if the culprit was due to interaction of rotor 1 and stator 1. Thus, the goal was to fully understand the stage 1 performance under isolated and multi-stage conditions, and additionally to provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to understand fluid dynamics loss source mechanisms due to rotor shock interaction and endwall losses. This paper will present the description of the compressor test article and its measured performance and operability, for both the single stage and two stage configurations. We focus the paper on measurements at 97% corrected speed with design intent vane setting angles.

Management of untreated advanced stage follicular lymphoma: Role of patient discernment.

PubMed

Umakanthan, Jayadev Manikkam; Lunning, Mathew A

2018-03-01

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount. Copyright © 2017 Elsevier Ltd. All rights reserved.

Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care.

PubMed

Diehl-Schmid, J; Richard-Devantoy, S; Grimmer, T; Förstl, H; Jox, R

2017-08-01

The aim of the present study was to gain insight into the living and care situation in advanced behavioral variant frontotemporal dementia (bvFTD), to describe symptoms and findings in advanced bvFTD, and to evaluate somatic comorbidities and circumstances of death. Standardized interviews were conducted with family caregivers of 83 patients with bvFTD. Forty-four percent of the patients were already deceased at the time of the interview. At the time of the interview or death, respectively, 47% of the patients lived in a nursing home. The median time between symptom onset and nursing home admission was 5.0 ± 5.5 years. In moderate and severe dementia stages almost all patients suffered from severe disabilities including impairment of language, gait, swallowing, and of the ability to care for themselves. Sixteen percent of the patients had got enteral tube feeding. Comorbid somatic diseases were diagnosed in 46% of the patients. Twenty-three percent of the deceased patients had been admitted into a hospital before death. Cardiovascular disease and respiratory disease, mostly pneumonia, were the most frequent causes of death. Advanced bvFTD is characterized by severe cognitive impairment and physical disabilities. BvFTD leads to a premature death. Our findings stress the importance of strategies that maximize patient comfort in advanced disease stages and allow for a peaceful death. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

FcγRIIb expression in early stage chronic lymphocytic leukemia.

PubMed

Bosch, Rosa; Mora, Alba; Vicente, Eva Puy; Ferrer, Gerardo; Jansà, Sonia; Damle, Rajendra; Gorlatov, Sergey; Rai, Kanti; Montserrat, Emili; Nomdedeu, Josep; Pratcorona, Marta; Blanco, Laura; Saavedra, Silvana; Garrido, Ana; Esquirol, Albert; Garcia, Irene; Granell, Miquel; Martino, Rodrigo; Delgado, Julio; Sierra, Jorge; Chiorazzi, Nicholas; Moreno, Carol

2017-11-01

In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d. Moreover, patients with low FcγRIIb expression (69/155, 44.5%) required therapy earlier than those with high FcγRIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=.071). These results encourage further investigation on the role of FcγRIIb in CLL biology and prognostic significance in larger series of patients.

Resting energy expenditure and body composition in bedridden institutionalized elderly women with advanced-stage pressure sores.

PubMed

Sergi, Giuseppe; Coin, Alessandra; Mulone, Silvana; Castegnaro, Eugenio; Giantin, Valter; Manzato, Enzo; Busetto, Luca; Inelmen, Emine Meral; Marin, Sara; Enzi, Giuliano

2007-03-01

Our study investigated nutritional status, body composition, and resting energy expenditure (REE) in elderly patients with advanced-stage pressure sores (PS), in addition to researching any hypermetabolic condition and its relationship with PS size. The study involved 52 institutionalized bedridden elderly women (aged 83.7 +/- 6.3 years), divided into two groups: 23 with advanced-stage (stage 3 and 4) PS and 29 without PS. Albumin, prealbumin, and retinol-binding protein were measured in all patients, and fat-free mass (FFM) and fat mass (FM) were obtained by dual-energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry and predicted with the Harris-Benedict formula. PS area and volume were also measured. The elderly women with and without PS were comparable in age, FFM, and FM. Mean albumin, prealbumin, and retinol-binding protein values were lower in cases with PS. Unadjusted mean REE was significantly higher in patients with PS (1212.3 +/- 236.7 vs 1085.5 +/- 161.3 kcal/d; p <.05), even after adjusting for FFM or expressed per kilogram of body weight (25.8 +/- 6.7 vs 21.1 +/- 4.0 kcal/d/kg; p <.01). Hypermetabolism, i.e., a measured REE > 110% of the predicted REE, was seen in 74% of patients with PS and 38% of controls. The difference between measured and predicted REE (DeltaREE) correlated with PS volume (r = 0.58; p <.01), but not with area. Advanced-stage PS in elderly women are associated with a hypermetabolic state that is influenced by the volume of the PS.

Prediction of 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

PubMed

Gerestein, C G; Nieuwenhuyzen-de Boer, G M; Eijkemans, M J; Kooi, G S; Burger, C W

2010-01-01

Treatment in advanced stage epithelial ovarian cancer (EOC) is based on primary cytoreductive surgery followed by platinum-based chemotherapy. Successful cytoreduction to minimal residual tumour burden is the most important determinant of prognosis. However, extensive surgical procedures to achieve maximal debulking are inevitably associated with postoperative morbidity and mortality. The objective of this study is to determine predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC. All patients in the South Western part of the Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007 were identified from the Rotterdam Cancer Registry database. All peri- and postoperative complications within 30 days after surgery were registered and classified according to the definitions of the National Surgical Quality Improvement Programme (NSQIP). To investigate independent predictors of 30-day morbidity, a Cox proportional hazards model with backward stepwise elimination was utilised. The identified predictors were entered into a nomogram. Two hundred and ninety-three patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. 30-day morbidity was seen in 99 (34%) patients. Postoperative morbidity could be predicted by age (P=0.007; odds ratio [OR] 1.034), WHO performance status (P=0.046; OR 1.757), extent of surgery (P=0.1308; OR=2.101), and operative time (P=0.017; OR 1.007) with an optimism corrected c-statistic of 0.68. 30-day morbidity could be predicted by age, WHO performance status, operative time and extent of surgery. The generated nomogram could be valuable for predicting operative risk in the individual patient.

HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma.

PubMed

Sorigué, Marc; García, Olga; Tapia, Gustavo; Baptista, Maria-Joao; Moreno, Miriam; Mate, José-Luis; Sancho, Juan M; Feliu, Evarist; Ribera, Josep-Maria; Navarro, José-Tomás

2017-06-19

Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients. We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD. A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival (DFS) [10-year DFS probability (95% CI) 70% (41-99%) vs. 74% (57-91%)], P = 0.907 and overall survival (OS) [10-year OS probability (95% CI) 73% (52-94%) vs. 68% (51-85%)], P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS. Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

Risk factors for competing noncancer mortality after definitive treatment for advanced-stage head and neck cancer.

PubMed

Kim, Yong Han; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-05-27

Patients with head and neck cancer (HNC) can die of index tumor progression and second tumor or noncancer causes. Here, we investigated the risk factors for competing noncancer mortality (NCM) in a prospective cohort of patients with advanced-stage HNC. A prospective observational study was conducted with 604 patients who underwent definitive treatment for advanced-stage HNC between 2010 and 2015. Main outcomes were NCM and cancer mortality (CM) defined as death from noncancer causes and HNC or second cancers, respectively. Cumulative incidence and cause-specific hazard functions were used to analyze the risk factors of NCM and CM. Age, smoking, Charlson comorbidity index (CCI), performance status, body mass index, rural residence, education and hemoglobin level at diagnosis, and chemotherapy were significantly associated with NCM (all P<0.05). Multivariate analyses showed that age, CCI, and hemoglobin were independent factors of NCM. Age (≥65 years), CCI (≥2), and hemoglobin (<11 g/dL) were related to 4.5-, 3.2-, and 2.7-fold increased adjusted risk of NCM, respectively. Old age, comorbidity, and hemoglobin at diagnosis were independent predictors of NCM. The risk factors could be used to predict noncancer death after definitive treatment for advanced-stage HNC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anterior Urethral Advancement as a Single-Stage Technique for Repair of Anterior Hypospadias: Our Experience.

PubMed

Gite, Venkat A; Nikose, Jayant V; Bote, Sachin M; Patil, Saurabh R

2017-07-02

Many techniques have been described to correct anterior hypospadias with variable results. Anterior urethral advancement as one stage technique was first described by Ti Chang Shing in 1984. It was also used for the repair of strictures and urethrocutaneous fistulae involving distal urethra. We report our experience of using this technique with some modification for the repair of anterior hypospadias. In the period between 2013-2015, 20 cases with anterior hypospadias including 2 cases of glanular, 3 cases of coronal, 12 cases of subcoronal and 3 cases of distal penile hypospadias were treated with anterior urethral advancement technique. Patients' age groups ranged from 18 months to 10 years. Postoperatively, patients were passing urine from tip of neomeatus with satisfactory stream during follow up period of 6 months to 2 years. There were no major complications in any of our patients except in one patient who developed meatal stenosis which was treated by periodic dilatation. Three fold urethral mobilization was sufficient in all cases. Anterior urethral advancement technique is a single-stage procedure with good cosmetic results and least complications for anterior hypospadias repair in properly selected cases.

Perioperative BRAF inhibitors in locally advanced stage III melanoma.

PubMed

Zippel, Douglas; Markel, Gal; Shapira-Frommer, Roni; Ben-Betzalel, Guy; Goitein, David; Ben-Ami, Eytan; Nissan, Aviram; Schachter, Jacob; Schneebaum, Schlomo

2017-12-01

Stage III malignant melanoma is a heterogeneous disease where those cases deemed marginally resectable or irresecatble are frequently incurable by surgery alone. Targeted therapy takes advantage of the high incidence of BRAF mutations in melanomas, most notably the V600E mutation. These agents have rarely been used in a neoadjuvant setting prior to surgery. Thirteen consecutive patients with confirmed BRAF V600E regionally advanced melanoma deemed marginally resectable or irrresectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The primary outcome measures were a successful resection and pathological response. Disease-free survival was a secondary outcome measure. Overall, 12/13 patients showed a marked clinical responsiveness to medical treatment, enabling a macroscopically successful resection in all cases. Four patients had a complete pathological response with no viable tumor evident in the resected specimens and eight patients showed evidence of minimally residual tumor with extensive tumoral necrosis and fibrosis. One patient progressed and died before surgery. At a median follow up of 20 months, 10 patients remain free of disease. Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival. © 2017 Wiley Periodicals, Inc.

Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients

PubMed Central

Zhou, Ting; Wang, Bangyan; Liu, Huiquan; Yang, Kaixiang; Thapa, Sudip; Zhang, Haowen; Li, Lu

2018-01-01

Abstract Background Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. Methods Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC‐F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non‐cachexia, pre‐cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. Results Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non‐cachexia (n = 69), pre‐cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well‐being), and shorter survival times (P < 0.001). Conclusions The CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials. PMID:29372594

Preoperative tumour staging with multidisciplinary team assessment improves the outcome in locally advanced primary rectal cancer.

PubMed

Palmer, G; Martling, A; Cedermark, B; Holm, T

2011-12-01

Multidisciplinary team meetings have been introduced as a result of developments in preoperative radiological tumour staging and neoadjuvant treatment. Multidisciplinary team recommendations will influence treatment decisions but their effect on patient outcome is unknown. The aim of this study was to assess outcome in relation to preoperative local and distant staging, with or without multidisciplinary team assessment. A population-based registry of all patients with rectal cancer, treated in the Stockholm region from 1995 to 2004, identified 303 patients with locally advanced primary rectal cancer. The patients were classified into three groups: group 1, preoperative local and distant radiological tumour staging with discussion at a multidisciplinary team meeting; group 2, preoperative staging but no multidisciplinary team assessment; and group 3, no proper preoperative radiological staging. Neoadjuvant treatment was more prevalent in groups 1 and 2 than in group 3. The incidence of R0 resection differed significantly between the groups (52% in group 1, 43% in group 2 and 21% in group 3; P < 0.001). Local tumour control was achieved in 57%, 36%, and 19% of patients in groups 1, 2 and 3, respectively (P < 0.001). The estimated overall 5-year survival of patients was 30%, 28% and 12% in groups 1, 2 and 3, respectively. Preoperative radiological tumour staging in patients with locally advanced primary rectal cancer and discussion at a multidisciplinary team meeting increases the proportion of patients receiving neoadjuvant treatment and cancer-specific end-points. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Drivers of advanced stage at breast cancer diagnosis in the multicountry African breast cancer – disparities in outcomes (ABC‐DO) study

PubMed Central

Zietsman, Annelle; Galukande, Moses; Anele, Angelica; Adisa, Charles; Parham, Groesbeck; Pinder, Leeya; Cubasch, Herbert; Joffe, Maureen; Kidaaga, Frederick; Lukande, Robert; Offiah, Awa U.; Egejuru, Ralph O.; Shibemba, Aaron; Schuz, Joachim; Anderson, Benjamin O.; dos Santos Silva, Isabel; McCormack, Valerie

2017-01-01

Breast cancer (BC) survival rates in sub‐Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting‐specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer–Disparities in Outcomes (ABC‐DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman‐level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended stage BC in SSA is largely attributed to modifiable factors and strategies to improve BC education and awareness in women and the health system should be intensified. PMID:29197068

Advances in single- and multi-stage Stirling-type pulse tube cryocoolers for space applications in NLIP/SITP/CAS

NASA Astrophysics Data System (ADS)

Dang, Haizheng; Tan, Jun; Zha, Rui; Li, Jiaqi; Zhang, Lei; Zhao, Yibo; Gao, Zhiqian; Bao, Dingli; Li, Ning; Zhang, Tao; Zhao, Yongjiang; Zhao, Bangjian

2017-12-01

This paper presents a review of recent advances in single- and multi-stage Stirling-type pulse tube cryocoolers (SPTCs) for space applications developed at the National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences (NLIP/SITP/CAS). A variety of single-stage SPTCs operating at 25-150 K have been developed, including several mid-sized ones operating at 80-110 K. Significant progress has been achieved in coolers operating at 30-40 K which use common stainless steel meshes as regenerator matrices. Another important advance is the micro SPTCs with an overall mass of 300-800 g operating at high frequencies varying from 100 Hz to 400 Hz. The main purpose of developing two-stage SPTCs is to simultaneously acquire cooling capacities at both stages, obviating the need for auxiliary precooling in various applications. The three-stage SPTCs are developed mainly for applications at around 10 K, which are also used for precooling the J-T coolers to achieve further lower temperatures. The four-stage SPTCs are developed to directly achieve the liquid helium temperature for cooling space low-Tc superconducting devices and for the deep space exploration as well. Several typical development programs are described and an overview of the cooler performances is presented.

Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

NASA Technical Reports Server (NTRS)

Seiler, James; Brasfield, Fred; Cannon, Scott

2008-01-01

Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling.

PubMed

Sachdeva, Meenakshi; Sharma, Aman; Arora, Sunil K

2015-01-01

Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs). The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART). Phenotypic and functional characteristics of circulating myeloid DCs (mDCs) in 56 ART-naive patients (23 in early and 33 in advanced stage of disease), 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs) were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS)-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR. The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase (SHP)-1 and a reduced expression of positive regulators like Janus kinase (JAK)2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells. Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease, needs

An Effective Technique for Endoscopic Resection of Advanced Stage Angiofibroma

PubMed Central

Mohammadi Ardehali, Mojtaba; Samimi, Seyyed Hadi; Bakhshaee, Mehdi

2014-01-01

Introduction: In recent years, the surgical management of angiofibroma has been greatly influenced by the use of endoscopic techniques. However, large tumors that extend into difficult anatomic sites present major challenges for management by either endoscopy or an open-surgery approach which needs new technique for the complete en block resection. Materials and Methods: In a prospective observational study we developed an endoscopic transnasal technique for the resection of angiofibroma via pushing and pulling the mass with 1/100000 soaked adrenalin tampons. Thirty two patients were treated using this endoscopic technique over 7 years. The mean follow-up period was 36 months. The main outcomes measured were tumor staging, average blood loss, complications, length of hospitalization, and residual and/or recurrence rate of the tumor. Results: According to the Radkowski staging, 23,5, and 4 patients were at stage IIC, IIIA, and IIIB, respectively. Twenty five patients were operated on exclusively via transnasal endoscopy while 7 patients were managed using endoscopy-assisted open-surgery techniques. Mean blood loss in patients was 1261± 893 cc. The recurrence rate was 21.88% (7 cases) at two years following surgery. Mean hospitalization time was 3.56 ± 0.6 days. Conclusion: Using this effective technique, endoscopic removal of more highly advanced angiofibroma is possible. Better visualization, less intraoperative blood loss, lower rates of complication and recurrence, and shorter hospitalization time are some of the advantages. PMID:24505571

Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma.

PubMed

Jardim, J F; Francisco, A L N; Gondak, R; Damascena, A; Kowalski, L P

2015-01-01

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.

PubMed

Galluzzi, Paolo; Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro

2015-02-01

This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. © The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.

Health-related quality-of-life outcomes: a reflexology trial with patients with advanced-stage breast cancer.

PubMed

Wyatt, Gwen; Sikorskii, Alla; Rahbar, Mohammad Hossein; Victorson, David; You, Mei

2012-11-01

To evaluate the safety and efficacy of reflexology, a complementary therapy that applies pressure to specific areas of the feet. Longitudinal, randomized clinical trial. Thirteen community-based medical oncology clinics across the midwestern United States. A convenience sample of 385 predominantly Caucasian women with advanced-stage breast cancer receiving chemotherapy and/or hormonal therapy. Following the baseline interview, women were randomized into three primary groups: reflexology (n = 95), lay foot manipulation (LFM) (n = 95), or conventional care (n = 96). Two preliminary reflexology (n = 51) and LFM (n = 48) test groups were used to establish the protocols. Participants were interviewed again postintervention at study weeks 5 and 11. Breast cancer-specific health-related quality of life (HRQOL), physical functioning, and symptoms. No adverse events were reported. A longitudinal comparison revealed significant improvements in physical functioning for the reflexology group compared to the control group (p = 0.04). Severity of dyspnea was reduced in the reflexology group compared to the control group (p < 0.01) and the LFM group (p = 0.02). No differences were found on breast cancer-specific HRQOL, depressive symptomatology, state anxiety, pain, and nausea. Reflexology may be added to existing evidence-based supportive care to improve HRQOL for patients with advanced-stage breast cancer during chemotherapy and/or hormonal therapy. Reflexology can be recommended for safety and usefulness in relieving dyspnea and enhancing functional status among women with advanced-stage breast cancer.

Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population.

PubMed

Ezzat, A A; Ibrahim, E M; Raja, M A; Al-Sobhi, S; Rostom, A; Stuart, R K

1999-07-01

In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age +/- SD was 46 +/- 11.6 years which is distinctly different from the 60-65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage IIIA and Stage III B. Patients received multimodality treatment, including surgery, adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95% CI, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% CI, 14.2 to 113 months). Cox proportional hazard model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III

Sub-classification of Advanced-Stage Hepatocellular Carcinoma: A Cohort Study Including 612 Patients Treated with Sorafenib.

PubMed

Yoo, Jeong-Ju; Chung, Goh Eun; Lee, Jeong-Hoon; Nam, Joon Yeul; Chang, Young; Lee, Jeong Min; Lee, Dong Ho; Kim, Hwi Young; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

2018-04-01

Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C. This retrospective study included consecutive patientswho received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea. A Cox proportional hazard model was used to develop a scoring system, and internal validationwas performed by a 5-fold cross-validation. The performance of the model in predicting risk was assessed by the area under the curve and the Hosmer-Lemeshow test. A total of 612 BCLC stage C HCC patients were sub- classified into strata depending on their performance status. Five independent prognostic factors (Child-Pugh score, α-fetoprotein, tumor type, extrahepatic metastasis, and portal vein invasion) were identified and used in the prognostic scoring system. This scoring system showed good discrimination (area under the receiver operating characteristic curve, 0.734 to 0.818) and calibration functions (both p < 0.05 by the Hosmer-Lemeshow test at 1 month and 12 months, respectively). The differences in survival among the different risk groups classified by the total score were significant (p < 0.001 by the log-rank test in both the Eastern Cooperative Oncology Group 0 and 1 strata). The heterogeneity of patientswith BCLC stage C HCC requires sub-classification of advanced HCC. A prognostic scoring system with five independent factors is useful in predicting the survival of patients with BCLC stage C HCC.

Airway reconstruction: review of an approach to the advanced-stage laryngotracheal stenosis.

PubMed

Bitar, Mohamad Ahmad; Al Barazi, Randa; Barakeh, Rana

The management of laryngotracheal stenosis is complex and is influenced by multiple factors that can affect the ultimate outcome. Advanced lesions represent a special challenge to the treating surgeon to find the best remedying technique. To review the efficacy of our surgical reconstructive approach in managing advanced-stage laryngotracheal stenosis treated at a tertiary medical center. A retrospective review of all patients that underwent open laryngotracheal repair/reconstruction by the senior author between 2002 and 2014. Patients with mild/moderate stenosis (e.g. stage 1 or 2), or those who had an open reconstructive procedure prior to referral, were excluded. Patients who had only endoscopic treatment (e.g. laser, balloon dilatation) and were not subjected to an open reconstructive procedure at our institution, were not included in this study. Variables studied included patient demographics, clinical presentation, etiology of the laryngotracheal pathology, the location of stenosis, the stage of stenosis, the type of corrective or reconstructive procedure performed with the type of graft used (where applicable), the type and duration of stent used, the post-reconstruction complications, and the duration of follow-up. Outcome measures included decannulation rate, total number of reconstructive surgeries needed to achieve decannulation, and the number of post-operative endoscopies needed to reach a safe patent airway. Twenty five patients were included, aged 0.5 months to 45 years (mean 13.5 years, median 15 years) with 16 males and 9 females. Seventeen patients (68%) were younger than 18 years. Most patients presented with stridor, failure of decannulation, or respiratory distress. Majority had acquired etiology for their stenosis with only 24% having a congenital pathology. Thirty-two reconstructive procedures were performed resulting in decannulating 24 patients (96%), with 15/17 (88%) pediatric patients and 5/8 (62.5%) adult patients requiring only a single

Dual-Fuel Propulsion in Single-Stage Advanced Manned Launch System Vehicle

NASA Technical Reports Server (NTRS)

Lepsch, Roger A., Jr.; Stanley, Douglas O.; Unal, Resit

1995-01-01

As part of the United States Advanced Manned Launch System study to determine a follow-on, or complement, to the Space Shuttle, a reusable single-stage-to-orbit concept utilizing dual-fuel rocket propulsion has been examined. Several dual-fuel propulsion concepts were investigated. These include: a separate-engine concept combining Russian RD-170 kerosene-fueled engines with space shuttle main engine-derivative engines: the kerosene- and hydrogen-fueled Russian RD-701 engine; and a dual-fuel, dual-expander engine. Analysis to determine vehicle weight and size characteristics was performed using conceptual-level design techniques. A response-surface methodology for multidisciplinary design was utilized to optimize the dual-fuel vehicles with respect to several important propulsion-system and vehicle design parameters, in order to achieve minimum empty weight. The tools and methods employed in the analysis process are also summarized. In comparison with a reference hydrogen- fueled single-stage vehicle, results showed that the dual-fuel vehicles were from 10 to 30% lower in empty weight for the same payload capability, with the dual-expander engine types showing the greatest potential.

Health-Related Quality-of-Life Outcomes: A Reflexology Trial With Patients With Advanced-Stage Breast Cancer

PubMed Central

Wyatt, Gwen; Sikorskii, Alla; Rahbar, Mohammad Hossein; Victorson, David; You, Mei

2013-01-01

Purpose/Objectives To evaluate the safety and efficacy of reflexology, a complementary therapy that applies pressure to specific areas of the feet. Design Longitudinal, randomized clinical trial. Setting Thirteen community-based medical oncology clinics across the midwestern United States. Sample A convenience sample of 385 predominantly Caucasian women with advanced-stage breast cancer receiving chemotherapy and/or hormonal therapy. Methods Following the baseline interview, women were randomized into three primary groups: reflexology (n = 95), lay foot manipulation (LFM) (n = 95), or conventional care (n = 96). Two preliminary reflexology (n = 51) and LFM (n = 48) test groups were used to establish the protocols. Participants were interviewed again postintervention at study weeks 5 and 11. Main Research Variables Breast cancer–specific health-related quality of life (HRQOL), physical functioning, and symptoms. Findings No adverse events were reported. A longitudinal comparison revealed significant improvements in physical functioning for the reflexology group compared to the control group (p = 0.04). Severity of dyspnea was reduced in the reflexology group compared to the control group (p < 0.01) and the LFM group (p = 0.02). No differences were found on breast cancer–specific HRQOL, depressive symptomatology, state anxiety, pain, and nausea. Conclusions Reflexology may be added to existing evidence-based supportive care to improve HRQOL for patients with advanced-stage breast cancer during chemotherapy and/or hormonal therapy. Implications for Nursing Reflexology can be recommended for safety and usefulness in relieving dyspnea and enhancing functional status among women with advanced-stage breast cancer. PMID:23107851

A high proportion of cells carrying trisomy 12 is associated with a worse outcome in patients with chronic lymphocytic leukemia.

PubMed

González-Gascón Y Marín, Isabel; Hernández-Sánchez, María; Rodríguez-Vicente, Ana-Eugenia; Sanzo, Carmen; Aventín, Anna; Puiggros, Anna; Collado, Rosa; Heras, Cecilia; Muñoz, Carolina; Delgado, Julio; Ortega, Margarita; González, María-Teresa; Marugán, Isabel; de la Fuente, Ignacio; Recio, Isabel; Bosch, Francesc; Espinet, Blanca; González, Marcos; Hernández-Rivas, Jesús-María; Hernández, José-Ángel

2016-06-01

The prognosis of chronic lymphocytic leukemia (CLL) patients displaying trisomy 12 (+12) remains unclear. In this study, we analyzed the influence of the proportion of cells with +12, and other clinical and biologic factors, in time to first therapy (TTFT) and overall survival (OS), in 289 patients diagnosed with CLL carrying +12. Median OS was 129 months. One hundred seventy-four patients (60.2%) presented +12 in <60% of cells. TTFT and OS for this subgroup were longer than for the subgroup with +12 in ≥60% of cells, with a median TTFT of 49 months (CI95%, 39-58) vs 30 months (CI95%, 22-38) (P = 0.001); and a median OS of 159 months (CI95%, 119-182), vs 96 months (CI95%, 58-134) (P = 0.015). Other factors associated with a shorter TTFT were: Binet stage, B symptoms, lymphadenopathy, splenomegaly, high lymphocyte count, 11q-, high β2 microglobulin, and high LDH. In the multivariate analysis, clinical stage, +12 in ≥60% of cells, high lymphocyte count, B symptoms, and 11q- in addition, resulted of significance in predicting shorter TTFT. Significant variables for OS were: Binet stage, lymphadenopathy, splenomegaly, high LDH, high β2 microglobulin, 11q-, and CD38. In the multivariate analysis, only Binet stage, 11q-, and high β2microglobulin significantly predicted shorter OS. CLL with +12 entails a heterogeneous group with intermediate prognosis. However, a high proportion of cells carrying +12 separates a subgroup of patients with poor outcome. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Optimized ex-ovo culturing of chick embryos to advanced stages of development.

PubMed

Cloney, Kellie; Franz-Odendaal, Tamara Anne

2015-01-24

Research in anatomy, embryology, and developmental biology has largely relied on the use of model organisms. In order to study development in live embryos model organisms, such as the chicken, are often used. The chicken is an excellent model organism due to its low cost and minimal maintenance, however they present observational challenges because they are enclosed in an opaque eggshell. In order to properly view the embryo as it develops, the shell must be windowed or removed. Both windowing and ex ovo techniques have been developed to assist researchers in the study of embryonic development. However, each of the methods has limitations and challenges. Here, we present a simple, optimized ex ovo culture technique for chicken embryos that enables the observation of embryonic development from stage HH 19 into late stages of development (HH 40), when many organs have developed. This technique is easy to adopt in both undergraduate classes and more advanced research laboratories where embryo manipulations are conducted.

The ideas about advanced life support and affecting factors at the end-stage of life in a hospital in Turkey.

PubMed

Albayrak, Turgay; Şencan, İrfan; Akça, Ömer; Koç, Esra Meltem; Aksoy, Hilal; Ünsal, Selim; Bülbül, İskender; Bahadır, Adem; Kasım, İsmail; Kahveci, Rabia; Özkara, Adem

2017-01-01

The participation of the people in health decisions may be structured in various levels. One of these is participation in decisions for the treatment. "Advanced directives" is one of the examples for the participation in decisions for the treatment. We wanted to determine the decisions on advanced life support at the end-stage of life in case of a life-threatening illness for the people themselves and their first degree relatives and the factors effecting these decisions. The cross-sectional study was conducted with volunteers among patients and patient relatives who applied to all polyclinics of the Ankara Numune Training and Research Hospital except the emergency, oncology and psychiatry polyclinics between 15.12.2012 and 15.03.2013. A questionnaire, the Hospital Anxiety Depression (HAD) scale, and Templer's Death Anxiety Scale (TDA) were applied to all individuals. SPSS for Win. Ver. 17.0 and MS-Excel 2010 Starter software bundles were used for all statistical analysis and calculations. The participants want both themselves and their first degree relatives included in end-stage decision-making process. Therefore, the patients and their families should be informed adequately during decision making process and quality communication must be provided. Participants who have given their end-stage decisions previously want to be treated according to these decisions. This desire can just be possible by advanced directives.When moral and material loads of end-stage process are taken into consideration, countries, in which advanced directives are practiced, should be examined well and participants' desire should be evaluated in terms of practicability.

Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre.

PubMed

Livraghi, Tito; Ceriani, R; Palmisano, A; Pedicini, V; Pich, M G; Tommasini, M A; Torzilli, G

2011-02-01

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.

Evaluation of pelvic posterior exenteration in the management of advanced-stage ovarian cancer.

PubMed

Tixier, Hervé; Fraisse, Jean; Chauffert, Bruno; Mayer, Françoise; Causeret, Sylvain; Loustalot, Catherine; Deville, Coralie; Bonnetain, Franck; Sagot, Paul; Douvier, Serge; Cuisenier, Jean

2010-03-01

The main aim of this study was to show the interest of pelvic posterior exenteration to obtain complete resection of the tumor in case of invasion of the rectum by contiguity in advanced-stage ovarian cancer. The secondary aim was to determine the morbidity of this surgery. It is a multicentric, retrospective study of a series of 41 patients, who underwent posterior pelvectomy for advanced-stage ovarian cancer, over a period of 18 years, from July 1989 to July 2007. The surgery resulted in macroscopically complete resection in 19 patients (46.34%), a residual tumor <2 cm in 19 patients (46.34%) and >2 cm in 3 patients (7.32%). In 34 patients (34/41), digestive continuity with satisfactory anal sphincter function was restored immediately or in the short term. The mean delay to the start of complementary treatment was 36 days. Median overall survival was 33 months. The main aim of surgery for ovarian peritoneal carcinomatosis is to obtain a complete resection. In the case of direct invasion of the rectum by contiguity, when there is no cleavage plane between the uterus and the rectum, pelvic posterior exenteration is an effective method to achieve this objective. Morbidity is relatively high, but acceptable given the poor prognosis of this disease, the improved survival after surgery, and improvements in post-operative quality of life and functions.

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

PubMed

Specht, Lena

2016-01-01

Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

The ideas about advanced life support and affecting factors at the end-stage of life in a hospital in Turkey

PubMed Central

Albayrak, Turgay; Şencan, İrfan; Akça, Ömer; Aksoy, Hilal; Ünsal, Selim; Bülbül, İskender; Bahadır, Adem; Kasım, İsmail; Kahveci, Rabia; Özkara, Adem

2017-01-01

Background The participation of the people in health decisions may be structured in various levels. One of these is participation in decisions for the treatment. “Advanced directives” is one of the examples for the participation in decisions for the treatment. Aim We wanted to determine the decisions on advanced life support at the end-stage of life in case of a life-threatening illness for the people themselves and their first degree relatives and the factors effecting these decisions. Design and setting The cross-sectional study was conducted with volunteers among patients and patient relatives who applied to all polyclinics of the Ankara Numune Training and Research Hospital except the emergency, oncology and psychiatry polyclinics between 15.12.2012 and 15.03.2013. Method A questionnaire, the Hospital Anxiety Depression (HAD) scale, and Templer’s Death Anxiety Scale (TDA) were applied to all individuals. SPSS for Win. Ver. 17.0 and MS-Excel 2010 Starter software bundles were used for all statistical analysis and calculations. Results The participants want both themselves and their first degree relatives included in end-stage decision-making process. Therefore, the patients and their families should be informed adequately during decision making process and quality communication must be provided. Conclusion Participants who have given their end-stage decisions previously want to be treated according to these decisions. This desire can just be possible by advanced directives.When moral and material loads of end-stage process are taken into consideration, countries, in which advanced directives are practiced, should be examined well and participants’ desire should be evaluated in terms of practicability. PMID:28732071

Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

PubMed

Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

2013-03-01

To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

Urinary Tract Resections in Advanced-stage Cervical Cancer - A Series of Eight Cases.

PubMed

Oprescu, Dana Nuti; Bacalbasa, Nicolae; Balescu, Irina; Filipescu, Alexandru

2017-06-01

Cervical cancer is one of the most frequent malignancies in women worldwide and is unfortunately diagnosed in advanced stages of the disease. Whenever local invasion is present, neoadjuvant therapy might be needed in order to limit the degree of local invasion. However, in certain cases local invasion persists even after completing the neoadjuvant radiochemotherapy; in these patients more extensive resections might be needed in order to achieve a radical resection. We present a case series of eight patients in whom segmental ureteral or uretero-vesical resections were performed as part of the radical resections for locally advanced cervical tumors. The continuity of the urinary tract was re-established by performing ureteral reimplantation via uretero-neocystostomy, augmentation cystoplasties with ureteral reimplantations. In a single case ureteral reimplantation was not feasible, a definitive cutaneous ureterostomy being performed. The postoperative course was uneventful in seven cases while in a single case urinary leak occurred, necessitating the exteriorization of the ureter in terminal cutaneous ureterostomy. Ureteral resections can be safely performed in patients with locally advanced cervical cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Content of Advance Directives for Individuals with Advanced Dementia

PubMed Central

Black, Betty S.; Phillips, Hilary; Fahrendorf, Sarah Richardson; Schwartz, Jack; Angelino, Andrew F.; Anderson, Danielle; Rabins, Peter V.

2010-01-01

Objectives To examine how people with end-stage dementia have conveyed their wishes for end-of-life care in advance directives. Methods The documents of 123 residents of three Maryland nursing homes, all with end-stage dementia, were reviewed. Results More years of education and White race were significantly associated with having an advance directive. With the exceptions of comfort care and pain treatment, advance directives were used primarily to restrict, not request, many forms of care at the end-of-life. Decisions about care for end-stage conditions such as Alzheimer's dementia are less often addressed in these documents than for terminal conditions and persistent vegetative state. Discussion In order for advance directives to better reflect a person's wishes, discussions with individuals and families about advance directives should include a range of care issues in the settings of terminal illness, persistent vegetative state or end-stage illness. These documents should be reviewed periodically to make certain they convey accurately the person's treatment preferences. PMID:18625761

Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer.

PubMed

Boysen, Anders Kindberg; Wettergren, Yvonne; Sorensen, Boe Sandahl; Taflin, Helena; Gustavson, Bengt; Spindler, Karen-Lise Garm

2017-11-01

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

Smooth Transition for Advancement to Graduate Education (STAGE) for Underrepresented Groups in the Mathematical Sciences Pilot Project: Broadening Participation through Mentoring

ERIC Educational Resources Information Center

Eubanks-Turner, Christina; Beaulieu, Patricia; Pal, Nabendu

2018-01-01

The Smooth Transition for Advancement to Graduate Education (STAGE) project was a three-year pilot project designed to mentor undergraduate students primarily from under-represented groups in the mathematical sciences. The STAGE pilot project focused on mentoring students as they transitioned from undergraduate education to either graduate school…

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers

PubMed Central

Blakely, Collin M.; Watkins, Thomas B.K.; Wu, Wei; Gini, Beatrice; Chabon, Jacob J.; McCoach, Caroline E.; McGranahan, Nicholas; Wilson, Gareth A.; Birkbak, Nicolai J.; Olivas, Victor R.; Rotow, Julia; Maynard, Ashley; Wang, Victoria; Gubens, Matthew A.; Banks, Kimberly C.; Lanman, Richard B.; Caulin, Aleah F.; John, John St.; Cordero, Anibal R.; Giannikopoulos, Petros; Simmons, Andrew D.; Mack, Philip C.; Gandara, David R.; Husain, Hatim; Doebele, Robert C.; Riess, Jonathan W.; Diehn, Maximilian; Swanton, Charles; Bivona, Trever G.

2017-01-01

A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant protein product (e.g. EGFR inhibitor treatment in EGFR-mutant lung cancers). However, genetically-driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1122 EGFR-mutant lung cancer cell-free DNA samples and whole exome analysis of seven longitudinally collected tumor samples from an EGFR-mutant lung cancer patient, we identify critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. We define new pathways limiting EGFR inhibitor response, including WNT/β-catenin and cell cycle gene (e.g. CDK4, CDK6) alterations. Tumor genomic complexity increases with EGFR inhibitor treatment and co-occurring alterations in CTNNB1, and PIK3CA exhibit non-redundant functions that cooperatively promote tumor metastasis or limit EGFR inhibitor response. This study challenges the prevailing single-gene driver oncogene view and links clinical outcomes to co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancer patients. PMID:29106415

The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

PubMed

Gerestein, C G; Eijkemans, M J C; de Jong, D; van der Burg, M E L; Dykgraaf, R H M; Kooi, G S; Baalbergen, A; Burger, C W; Ansink, A C

2009-02-01

Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease <1 cm (P = 0.004) predicted PFS with a optimism corrected c-statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease <1 cm (P = 0.028) with a optimism corrected c-statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

Low-Noise Potential of Advanced Fan Stage Stator Vane Designs Verified in NASA Lewis Wind Tunnel Test

NASA Technical Reports Server (NTRS)

Hughes, Christopher E.

1999-01-01

With the advent of new, more stringent noise regulations in the next century, aircraft engine manufacturers are investigating new technologies to make the current generation of aircraft engines as well as the next generation of advanced engines quieter without sacrificing operating performance. A current NASA initiative called the Advanced Subsonic Technology (AST) Program has set as a goal a 6-EPNdB (effective perceived noise) reduction in aircraft engine noise relative to 1992 technology levels by the year 2000. As part of this noise program, and in cooperation with the Allison Engine Company, an advanced, low-noise, high-bypass-ratio fan stage design and several advanced technology stator vane designs were recently tested in NASA Lewis Research Center's 9- by 15-Foot Low-Speed Wind Tunnel (an anechoic facility). The project was called the NASA/Allison Low Noise Fan.

Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages.

PubMed

Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

2014-12-28

To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages

PubMed Central

Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

2014-01-01

AIM: To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. METHODS: Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. RESULTS: The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. CONCLUSION: High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC. PMID:25561807

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PubMed Central

Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

2015-01-01

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.

PubMed

Scarisbrick, Julia J; Prince, H Miles; Vermeer, Maarten H; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L; Rodríguez-Peralto, Jose L; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T; Duvic, Madeleine; Whittaker, Sean J; Kim, Youn H

2015-11-10

Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value

An update on the role of advanced diagnostic bronchoscopy in the evaluation and staging of lung cancer

PubMed Central

Belanger, Adam R.; Akulian, Jason A.

2017-01-01

Lung cancer remains a common and deadly disease. Many modalities are available to the bronchoscopist to evaluate and stage lung cancer. We review the role of bronchoscopy in the staging of the mediastinum with convex endobronchial ultrasound (EBUS) and discuss emerging role of esophageal ultrasonography as a complementary modality. In addition, we discuss advances in scope technology and elastography. We review the bronchoscopic methods available for the diagnosis of peripheral lung nodules including radial EBUS and navigational bronchoscopy (NB) with a consideration of the basic methodologies and diagnostic accuracies. We conclude with a discussion of the comparison of the various methodologies. PMID:28470104

Six-minute walk test and heart rate variability: lack of association in advanced stages of heart failure.

PubMed

Woo, M A; Moser, D K; Stevenson, L W; Stevenson, W G

1997-09-01

The 6-minute walk and heart rate variability have been used to assess mortality risk in patients with heart failure, but their relationship to each other and their usefulness for predicting mortality at 1 year are unknown. To assess the relationships between the 6-minute walk test, heart rate variability, and 1-year mortality. A sample of 113 patients in advanced stages of heart failure (New York Heart Association Functional Class III-IV, left ventricular ejection < 0.25) were studied. All 6-minute walks took place in an enclosed, level, measured corridor and were supervised by the same nurse. Heart rate variability was measured by using (1) a standard-deviation method and (2) Poincaré plots. Data on RR intervals obtained by using 24-hour Holter monitoring were analyzed. Survival was determined at 1 year after the Holter recording. The results showed no significant associations between the results of the 6-minute walk and the two measures of heart rate variability. The results of the walk were related to 1-year mortality but not to the risk of sudden death. Both measures of heart rate variability had significant associations with 1-year mortality and with sudden death. However, only heart rate variability measured by using Poincaré plots was a predictor of total mortality and risk of sudden death, independent of left ventricular ejection fraction, serum levels of sodium, results of the 6-minute walk test, and the standard-deviation measure of heart rate variability. Results of the 6-minute walk have poor association with mortality and the two measures of heart rate variability in patients with advanced-stage heart failure and a low ejection fraction. Further studies are needed to determine the optimal clinical usefulness of the 6-minute walk and heart rate variability in patients with advanced-stage heart failure.

Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

PubMed

Prescott, J S; Andrews, P A; Baker, R W; Bogdanffy, M S; Fields, F O; Keller, D A; Lapadula, D M; Mahoney, N M; Paul, D E; Platz, S J; Reese, D M; Stoch, S A; DeGeorge, J J

2017-08-01

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

PubMed

Reese, Adam C; Wessel, Sean R; Fisher, Susan G; Mydlo, Jack H

2016-08-01

The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Determining the satisfaction levels of the family members of patients with advanced-stage cancer.

PubMed

Ozcelik, Hanife; Cakmak, Deniz Ezgi; Fadiloglu, Cicek; Yildirim, Yasemin; Uslu, Ruchan

2015-06-01

The objective of our study was to determine the satisfaction levels of family members of patients with advanced-stage cancer. This descriptive study was conducted in the palliative care and medical oncology clinics of a university hospital in the province of Izmir between April of 2011 and January of 2012. The study sample consisted of a total of 145 family members, who were selected from among the family members of patients with advanced-stage cancer receiving palliative treatment. The study data were obtained using the Patient Description Form and Family Satisfaction Scale during face-to-face interviews with patients. Some 67% of patients were female and 33% male, 70% were married, 35% were high school graduates, and 34.5% were housewives. The average total family satisfaction score was 76.87 ± 1.14, and the average scores for the component variables were as follows: information giving 74.37 ± 1.28, availability of care 78.40 ± 1.17, physical care 78.99 ± 1.09, and psychosocial care 74.52 ± 1.30. We found a relationship between the level of satisfaction of family members and (1) gender, (2) occupation, (3) presence of someone supporting the care, and (4) possession of sufficient information about the patient (p < 0.05). Satisfaction levels of participants were determined to be high. We found that family member satisfaction levels were affected by gender and occupation, the existence of someone supporting the care, and possession of sufficient information about the patient.

Irreversible electroporation of stage 3 locally advanced pancreatic cancer: optimal technique and outcomes

PubMed Central

2015-01-01

Objective Irreversible electroporation (IRE) of stage 3 pancreatic adenocarcinoma has been used to provide quality of life time in patients who have undergone appropriate induction therapy. The optimal technique has been reported within the literature, but not in video form. IRE of locally advanced pancreatic cancer is technically demanding requiring precision ultrasound use for continuous imaging in multiple needle placements and during IRE energy delivery. Methods Appropriate patients with locally advanced pancreatic cancer should have undergone appropriate induction chemotherapy for a reasonable duration. The safe and effective technique for irreversible electroporation is preformed through an open approach with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open irreversible electroporation of the pancreas involves bracketing the target tumor with IRE probes and any and all invaded vital structures including the celiac axis, superior mesenteric artery (SMA), superior mesenteric-portal vein, and bile duct with continuous intraoperative ultrasound imaging through a caudal to cranial approach. Optimal IRE delivery requires a change in amperage of at least 12 amps from baseline tissue conductivity in order to achieve technical success. Multiple pull-backs are necessary since the IRE ablation probe lengths are 1 cm and thus needed to achieve technical success along the caudal to cranial plane. Conclusions Irreversible electroporation in combination with multi-modality therapy for locally advanced pancreatic carcinoma is feasible for appropriate patients with locally advanced cancer. Technical demands are high and require the highest quality ultrasound for precise spacing measurements and optimal delivery to ensure adequate change in tissue resistance. PMID:29075594

A heartrending burden of gynaecological cancers in advance stage at nuclear institute of medicine and radiotherapy Jamshoro Sindh

PubMed Central

Bibi, Seema; Ashfaque, Sanober; Laghari, Naeem Ahmed

2016-01-01

Objectives: In Pakistan gynaecological cancers are among the leading causes of women’s morbidity and mortality posing huge financial burden on families, communities and state. Due to lack of national cancer registry exact facts and figures are unknown therefore this study was planned to find out prevalence, age, site and stage of presentation of gynaecological cancers at Nuclear Institute of Medicine and Radiotherapy (NIMRA), Jamshoro. Methods: A retrospective, cross sectional study was conducted from 1st January 2011 to 31st December 2011 at NIMRA Jamshoro. All cases of genital tract cancers were evaluated, required data was entered on predesigned performa and results were analyzed manually. Results: Out of 2401 total registered cancer cases, 231 (9.6%) patients were suffering from gynaecological cancer making it third most common cancer. Ovary was commonest site followed by cervix and uterus. More than 60% cases presented in advanced stage, mostly during 4th and 5th decade of life. Conclusion: Gynecological cancer was among top three cancers at one of the busiest public sector cancer institute in Sindh province and significant number presented in advance stage making treatment difficult and expensive. There is urgent need for development and implementation of an effective health policy regarding cancer prevention and treatment. PMID:27022358

ranibizumab in the management of advanced Coats disease Stages 3B and 4: long-term outcomes.

PubMed

Gaillard, Marie-Claire; Mataftsi, Assimina; Balmer, Aubin; Houghton, Susan; Munier, Francis L

2014-11-01

Laser photocoagulation and cryotherapy to completely destroy telangiectatic vessels and ischemic retina in Coats disease is barely applicable in advanced cases with total retinal detachment, and globe survival is notoriously poor in Stages 3B and 4. Anti-vascular endothelial growth factor intravitreal injections may offer new prospects for these patients. This study is a retrospective review of all consecutive patients with Coats disease treated with neoadjuvant or adjuvant intravitreal ranibizumab plus conventional and amblyopia treatment as appropriate. Nine patients (median age, 13 months) presenting Coats Stages 3B and 4 (5 and 4 eyes, respectively) were included. Iris neovascularization resolved within 2 weeks and retinal reapplication within 4 months in all patients. At last follow-up, globe survival was 100% with anatomical success in 8 of the 9 eyes. With a median follow-up of 50 months, fibrotic vitreoretinopathy was developed in 5 of the 9 cases, one leading to tractional retinal detachment and ultimately phthisis bulbi. The remaining 4 of the 9 eyes achieved some vision (range, 0.02-0.063). To the best of the authors' knowledge, this is the largest reported series of late-stage Coats undergoing anti-vascular endothelial growth factor therapy, a homogenous cohort of patients treated with a single agent and with the longest follow-up. This study supports the role of ranibizumab in advanced disease by transient restoration of the hemato-retinal barrier and suppression of neovascularization to facilitate classic treatment. At the last follow-up, the authors report unprecedented anatomical success and functional outcome.

Staging of breast cancer and the advanced applications of digital mammogram: what the physician needs to know?

PubMed

Helal, Maha H; Mansour, Sahar M; Zaglol, Mai; Salaleldin, Lamia A; Nada, Omniya M; Haggag, Marwa A

2017-03-01

To study the role of advanced applications of digital mammogram, whether contrast-enhanced spectral mammography (CESM) or digital breast tomosynthesis (DBT), in the "T" staging of histologically proven breast cancer before planning for treatment management. In this prospective analysis, we evaluated 98 proved malignant breast masses regarding their size, multiplicity and the presence of associated clusters of microcalcifications. Evaluation methods included digital mammography (DM), 3D tomosynthesis and CESM. Traditional DM was first performed then in a period of 10-14-day interval; breast tomosynthesis and contrast-based mammography were performed for the involved breast only. Views at tomosynthesis were acquired in a "step-and-shoot" tube motion mode to produce multiple (11-15), low-dose images and in contrast-enhanced study, low-energy (22-33 kVp) and high-energy (44-49 kVp) exposures were taken after the i.v. injection of the contrast agent. Operative data were the gold standard reference. Breast tomosynthesis showed the highest accuracy in size assessment (n = 69, 70.4%) than contrast-enhanced (n = 49, 50%) and regular mammography (n = 59, 60.2%). Contrast-enhanced mammography presented the least performance in assessing calcifications, yet it was most sensitive in the detection of multiplicity (92.3%), followed by tomosynthesis (77%) and regular mammography (53.8%). The combined analysis of the three modalities provided an accuracy of 74% in the "T" staging of breast cancer. The combined application of tomosynthesis and contrast-enhanced digital mammogram enhanced the performance of the traditional DM and presented an informative method in the staging of breast cancer. Advances in knowledge: Staging and management planning of breast cancer can divert according to tumour size, multiplicity and the presence of microcalcifications. DBT shows sharp outlines of the tumour with no overlap tissue and spots microcalcifications. Contrast

Staging of breast cancer and the advanced applications of digital mammogram: what the physician needs to know?

PubMed Central

Helal, Maha H; Zaglol, Mai; Salaleldin, Lamia A; Nada, Omniya M; Haggag, Marwa A

2017-01-01

Objective: To study the role of advanced applications of digital mammogram, whether contrast-enhanced spectral mammography (CESM) or digital breast tomosynthesis (DBT), in the “T” staging of histologically proven breast cancer before planning for treatment management. Methods: In this prospective analysis, we evaluated 98 proved malignant breast masses regarding their size, multiplicity and the presence of associated clusters of microcalcifications. Evaluation methods included digital mammography (DM), 3D tomosynthesis and CESM. Traditional DM was first performed then in a period of 10–14-day interval; breast tomosynthesis and contrast-based mammography were performed for the involved breast only. Views at tomosynthesis were acquired in a “step-and-shoot” tube motion mode to produce multiple (11–15), low-dose images and in contrast-enhanced study, low-energy (22–33 kVp) and high-energy (44–49 kVp) exposures were taken after the i.v. injection of the contrast agent. Operative data were the gold standard reference. Results: Breast tomosynthesis showed the highest accuracy in size assessment (n = 69, 70.4%) than contrast-enhanced (n = 49, 50%) and regular mammography (n = 59, 60.2%). Contrast-enhanced mammography presented the least performance in assessing calcifications, yet it was most sensitive in the detection of multiplicity (92.3%), followed by tomosynthesis (77%) and regular mammography (53.8%). The combined analysis of the three modalities provided an accuracy of 74% in the “T” staging of breast cancer. Conclusion: The combined application of tomosynthesis and contrast-enhanced digital mammogram enhanced the performance of the traditional DM and presented an informative method in the staging of breast cancer. Advances in knowledge: Staging and management planning of breast cancer can divert according to tumour size, multiplicity and the presence of microcalcifications. DBT shows sharp outlines of the tumour with no overlap

Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

PubMed

He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

2017-12-01

This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

PubMed

Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

2014-11-01

The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease.

Interferon after surgery for women with advanced (Stage II-IV) epithelial ovarian cancer.

PubMed

Lawal, Aramide O; Musekiwa, Alfred; Grobler, Liesl

2013-06-06

Epithelial ovarian cancer (EOC) is a life-threatening disease. Most often women become symptomatic only in the advanced stages of the disease, increasing the difficulty of treatment. Whilst the disease responds well to surgery and chemotherapy, the relapse rate is high. New treatments to prevent disease recurrence or progression, prolong survival, and increase the quality of life are needed. To assess the effectiveness and safety of interferon after surgery in the treatment of advanced (stage II-IV) EOC. The Cochrane Gynaecological Cancer Review Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2012, MEDLINE and EMBASE were searched to January 2012. Handsearching of conference proceedings was also undertaken. Reference lists of reviews and included trials were screened and experts in the field were contacted for additional trials. Clinical trials registers were searched for ongoing trials. Randomised controlled trials (RCTs) involving participants with advanced EOC that compared post-operative chemotherapy alone with post-operative interferon therapy in combination with chemotherapy or post-operative chemotherapy followed by interferon or observation alone Two review authors (AL and AM) independently screened the search results for relevant trials and extracted pre-specified information from each included trial. Data were managed using Review Manager 5.1. Hazard ratios (HR) were calculated for time-to-event outcomes and risk ratios (RR) for dichotomous outcomes, with corresponding 95% confidence intervals (CI). Five trials, including 1476 participants, were included in the review. Two trials compared interferon with observation alone and three trials compared interferon plus chemotherapy with chemotherapy alone. A meta-analysis of two trials involving 370 participants found no significant difference in both overall survival (HR 1.14, 95% CI 0.84 to 1.55) and progression free survival (HR 0.99, 95% CI 0.79 to 1.24) between

Single stage, low noise, advanced technology fan. Volume 1: Aerodynamic design

NASA Technical Reports Server (NTRS)

Sullivan, T. J.; Younghans, J. L.; Little, D. R.

1976-01-01

The aerodynamic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec 11,650 ft/sec). The fan and booster components are designed in a scale model flow size convenient for testing with existing facility and vehicle hardware. The design corrected flow per unit annulus area at the fan face is 215 kg/sec sq m (44.0 lb m/sec sq ft) with a hub-tip ratio of 0.38 at the leading edge of the fan rotor. This results in an inlet corrected airflow of 117.9 kg/sec (259.9 lb m/sec) for the selected rotor tip diameter if 90.37 cm (35.58 in.). The variable geometry inlet is designed utilizing a combination of high throat Mach number and acoustic treatment in the inlet diffuser for noise suppression (hybrid inlet). A variable fan exhaust nozzle was assumed in conjunction with the variable inlet throat area to limit the required area change of the inlet throat at approach and hence limit the overall diffusion and inlet length. The fan exit duct design was primarily influenced by acoustic requirements, including length of suppressor wall treatment; length, thickness and position on a duct splitter for additional suppressor treatment; and duct surface Mach numbers.

Mechanical design of a precision linear flexural stage for 3D x-ray diffraction microscope at the Advanced Photon Source

NASA Astrophysics Data System (ADS)

Shu, D.; Liu, W.; Kearney, S.; Anton, J.; Tischler, J. Z.

2015-09-01

The 3-D X-ray diffraction microscope is a new nondestructive tool for the three-dimensional characterization of mesoscopic materials structure. A flexural-pivot-based precision linear stage has been designed to perform a wire scan as a differential aperture for the 3-D diffraction microscope at the Advanced Photon Source, Argonne National Laboratory. The mechanical design and finite element analyses of the flexural stage, as well as its initial mechanical test results with laser interferometer are described in this paper.

Design and overall performance of four highly loaded, high speed inlet stages for an advanced high-pressure-ratio core compressor

NASA Technical Reports Server (NTRS)

Reid, L.; Moore, R. D.

1978-01-01

The detailed design and overall performances of four inlet stages for an advanced core compressor are presented. These four stages represent two levels of design total pressure ratio (1.82 and 2.05), two levels of rotor aspect ratio (1.19 and 1.63), and two levels of stator aspect ratio (1.26 and 1.78). The individual stages were tested over the stable operating flow range at 70, 90, and 100 percent of design speeds. The performances of the low aspect ratio configurations were substantially better than those of the high aspect ratio configurations. The two low aspect ratio configurations achieved peak efficiencies of 0.876 and 0.872 and corresponding stage efficiencies of 0.845 and 0.840. The high aspect ratio configurations achieved peak ratio efficiencies of 0.851 and 0.849 and corresponding stage efficiencies of 0.821 and 0.831.

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report.

PubMed

Suwannarurk, Komsun; Thaweekul, Yudthadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Tangtiang, Kaan; Piyawang, Wichet; Bhamarapravatana, Kornkarn

2015-04-01

Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer. A case of an advanced stage epithelial ovarian cancer (EOC) receiving a combination of bevacizumab, carboplatin andpaclitaxel chemotherapy was reported. A 44-year-old woman was presented with abdominal discomfort and distention for 4 months. Bilateral 12 cm diameter ovarian tumors were diagnosed as FIGO stage IIIc after surgical staging operation. Histopathology report showed the mixed type of serous and endometriod adenocarcinoma. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery every 3 weeks. Bevacizumab (7.5 mg/ m2) was concurrently administered with chemotherapy every 3 weeks startingfrom the 2nd cycle. A complete remission was achieved after the end of the chemotherapy treatment. Bevacizumab was continued for one year after the completion of the standard chemotherapy. Bone marrow suppression, hypertension and proteinuria were not found during Bevacizumab treatment. At bevacizumab treatment completion, a platinum-sensitive recurrent ovarian cancer was diagnosed at the two weeks postprogram routine check-up. The patient was counseled to start second line chemotherapy treatment and has yet to come back with her decision. Combination of bevacizumab, carboplatin and paclitaxelfor first line chemotherapy in advanced EOC in this case had no serious side effects and need further study.

High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

PubMed

Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

2014-02-01

To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013

Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

PubMed

Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

2017-07-24

This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

Brief cognitive assessment of Alzheimer's disease in advanced stages: Proposal for a Brazilian version of the Short Battery for Severe Impairment (SIB-8).

PubMed

Wajman, José Roberto; Bertolucci, Paulo Henrique Ferreira

2013-01-01

The measurement of cognitive abilities of patients with severe dementia can serve a wide range of methodological and clinical needs. To validate a proposed severe impairment battery SIB-8 for a Brazilian population sample as part of the neuropsychological assessment of patients with Alzheimer's disease (AD) in advanced stages. After a systematic process of translation and back-translation, the SIB-8 was applied to 95 patients with AD at different stages; moderate, moderately severe and severe according to FAST subdivisions (5, 6 and 7), with scores on the Mini-Mental State Examination (MMSE) of between 5 and 15 and followed by the Division of Behavioral Neurology and the Center for Aging Brain of the Federal University of São Paulo - UNIFESP. Inferential data revealed that the SIB-8 instrument behaved differently at each stage of the disease with a statistical value of sensitivity p<0.001, gradually reflecting the expected course of the dementia, inherent with the decline of cognitive functions. Findings indicated that the SIB-8 is a useful tool for the evaluation and prospective comparison of AD patients in advanced stages, retaining its original characteristics in our population.

[Comparative analysis of TACE alone or plus RFA in the treatment of 167 cases of intermediate and advanced staged primary hepatocellular carcinoma].

PubMed

Zhao, Ming; Wang, Jian-peng; Wu, Pei-hong; Zhang, Fu-jun; Huang, Zi-lin; Li, Wang; Zhang, Liang; Pan, Chang-chuan; Li, Chuan-xing; Jiang, Yong

2010-11-09

To evaluate the clinical efficacy and survival rate of transarterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in patients with intermediate or advanced stage primary hepatocellular carcinoma (HCC). In this retrospective study, 467 cases received RFA or TACE plus RFA. Among them, 167 cases with strict clinical procedure (TACE alone or plus RFA) and complete follow-up data were included. Eighty-seven cases received TACE and 80 cases had TACE plus RFA between January 2000 and December 2006. Hierarchical analyses were performed using log-rank tests and survival curve was estimated by Kaplan-Meier method. A total of 167 patients received TACE alone or plus RFA for a follow-up period of 1 to 89 months. In the TACE alone group, the time-to-progression (TTP) was an average of 3.6 months. The median survival was 13 months, one-year survival rate 52.9%, three-year survival rate 11.5% and five-year survival rate 4.6%. In the TACE plus RFA group, the TTP time was an average of 10.8 months. The median survival time was 30 months, one-year survival rate 85.0%, three-year survival rate 45.0% and five-year survival rate 11.3%. In the TACE alone group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3% and five-year survival rate 4.4%; In the TACE plus RFA group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 90.1%, three-year survival rate 52.9% and five-year survival rate 13.7%. All differences of two groups has statistical significance (P < 0.05). In intermediate stage HCC, the median survival of TACE alone group was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3%, five-year survival rate 4.4% versus 32 months, 90.1%, 52.9%, 13.7% in the TACE plus RFA group respectively. For the advanced stage HCC, the median survival time was 12 months, one-year survival rate 35%, three-year survival rate 7.1% and five-year survival rate

Upper stage technology evaluation studies

NASA Technical Reports Server (NTRS)

1972-01-01

Studies to evaluate advanced technology relative to chemical upper stages and orbit-to-orbit stages are reported. The work described includes: development of LH2/LOX stage data, development of data to indicate stage sensitivity to engine tolerance, modified thermal routines to accommodate storable propellants, added stage geometries to computer program for monopropellant configurations, determination of the relative gain obtainable through improvement of stage mass fraction, future propulsion concepts, effect of ultrahigh chamber-pressure increases, and relative gains obtainable through improved mass fraction.

Single stage, low noise, advanced technology fan. Volume 5: Fan acoustics. Section 1: Results and analysis

NASA Technical Reports Server (NTRS)

Jutras, R. R.

1976-01-01

The acoustic tests and data analysis for a 0.508-scale fan vehicle of a 111,300 newton (25,000 pound) thrust, full-size engine, which would have application on an advanced transport aircraft, is described. The single-stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec (1,650 ft/sec) to achieve the desired pressure ratio in a single-stage fan with low radius ratio (0.38), and to maintain adequate stall margin. The fan has 44 tip-shrouded rotor blades and 90 outlet guide vanes. The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise was accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels (20 EPNdB) below current Federal Air Regulation noise standards for a full-scale fan at the takeoff, cutback, and approach conditions. The suppression goal of FAR 36-20 was not reached, but improvements in the technology of both front and aft fan-noise suppression were realized. The suppressed fan noise was shown to be consistent with the proposed federal regulation on aircraft noise.

"EXHALE": exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients.

PubMed

Quist, Morten; Langer, Seppo W; Rørth, Mikael; Christensen, Karl Bang; Adamsen, Lis

2013-10-14

Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb-IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO₂peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. http://ClinicalTrials.gov, NCT01881906.

Laparoscopic common hepatic artery ligation and staging followed by distal pancreatectomy with en bloc resection of celiac artery for advanced pancreatic cancer.

PubMed

Raut, V; Takaori, K; Kawaguchi, Y; Mizumoto, M; Kawaguchi, M; Koizumi, M; Kodama, S; Kida, A; Uemoto, S

2011-11-01

Adeno-carcinomas of pancreatic body are usually asymptomatic and progress to advanced stage with involvement of major arteries. Resection of advanced cancer along with en bloc resection of a common hepatic artery and celiac trunk enables a "curative" resections and only possible treatment. However, the celiac axis resection always has a risk of compromising blood supply to liver, resulting in the hepatic insufficiency. We evaluated practicability of a two-stage procedure for the advanced pancreases body cancer, laparoscopic clamping of a common hepatic artery followed by open distal pancreatectomy with en bloc celiac arterial resection to prevent the hepatic insufficiency. Seventy-five-year-old woman diagnosed with a 50-mm pancreatic body mass, invading splenic artery, common hepatic artery, splenic vein, and portal vein at the confluence. STAGE-1: At laparoscopy, after confirming absence of the peritoneal, superficial liver metastases and negative peritoneal cytology; we approached the common hepatic artery through the lesser sac and ligated. STAGE-2: Her liver function tests were normal after 2 weeks, and CT angiography showed complete blockage of the common hepatic artery with sufficient collateral circulation to the liver through inferior pancreatico-duodenal artery and gastro-duodenal artery. We performed an open distal pancreatectomy with en bloc resection of celiac artery. Histopathology examination confirmed R0 resection. The celiac axis resection with distal pancreatectomy improves the chance of R0 resection and potentially, survival of the patient. Preoperative laparoscopic ligation of the common hepatic artery is a safe, effective, and in-expensive technique to prevent postoperative hepatic insufficiency and improves the safety of en bloc celiac artery resection with a distal pancreatectomy. Also these patients have high risk of peritoneal dissemination. Diagnostic laparoscopy is useful to detect occult metastasis, which are missed by per-operative CT

Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated with Delay in Diagnosis and Advanced Stage at Presentation.

PubMed

Swords, Douglas S; Mone, Mary C; Zhang, Chong; Presson, Angela P; Mulvihill, Sean J; Scaife, Courtney L

2015-10-01

Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown. This study is a retrospective review (2000-2010) from a University-based cancer center of new diagnoses of proximal PDAC. Of 313 patients, 98 (31.3 %) had an initial misdiagnosis. Misdiagnosed patients were younger, 62.8 ± 12.6 vs. 68.0 ± 10.1 (p < 0.001). The most common initial misdiagnoses were: gallbladder disease, gastroesophageal reflux disease, and peptic ulcer disease. After excluding patients with prior cholecystectomy, 14.2 % were misdiagnosed with gallbladder disease and underwent cholecystectomy before PDAC diagnosis. Misdiagnosed patients had higher rates of abdominal pain (p < 0.001), weight loss (p = 0.04), and acute pancreatitis (p < 0.001) and lower rate of jaundice (p < 0.001). Median time between symptoms to PDAC diagnosis was longer in misdiagnosed: 4.2 months vs. 1.4 (p < 0.001). Median time from contact with medical provider to axial imaging was longer in misdiagnosed (p < 0.001). Rate of stages III-IV disease at diagnosis was higher in misdiagnosed: 61.2 vs. 43.7 % (p = 0.004), with a 1.4 (95 % confidence interval (CI), 1.12-1.74) higher risk of stages III-IV disease at diagnosis; however, there was no difference in median overall survival in misdiagnosed patients (9.6 months in misdiagnosed vs. 10.3 months in correctly diagnosed, p = 0.69). Initial misdiagnosis of patients with proximal PDAC is associated with delay in diagnosis and higher risk of locally advanced or advanced disease at time of PDAC diagnosis.

Optimal debulking targets in women with advanced stage ovarian cancer: a retrospective study of immediate versus interval debulking surgery.

PubMed

Altman, Alon D; Nelson, Gregg; Chu, Pamela; Nation, Jill; Ghatage, Prafull

2012-06-01

The objective of this study was to examine both overall and disease-free survival of patients with advanced stage ovarian cancer after immediate or interval debulking surgery based on residual disease. We performed a retrospective chart review at the Tom Baker Cancer Centre in Calgary, Alberta of patients with pathologically confirmed stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer between 2003 and 2007. We collected data on the dates of diagnosis, recurrence, and death; cancer stage and grade, patients' age, surgery performed, and residual disease. One hundred ninety-two patients were included in the final analysis. The optimal debulking rate with immediate surgery was 64.8%, and with interval surgery it was 85.9%. There were improved overall and disease-free survival rates for optimally debulked disease (< 1 cm) with both immediate and interval surgery (P < 0.001) compared to suboptimally debulked disease. Overall survival rates for optimally debulked disease were not significantly different in patients having immediate and interval surgery (P = 0.25). In the immediate surgery group, patients with microscopic residual disease had better disease-free survival (P = 0.015) and overall survival (P = 0.005) than patients with < 1 cm residual disease. In patients who had interval surgery, those who had microscopic residual disease had more improved disease-free survival than those with < 1 cm disease (P = 0.05), but they did not have more improved overall survival (P = 0.42). Patients with microscopic residual disease who had immediate surgery had a significantly better overall survival rate than those who had interval surgery (P = 0.034). In women with advanced stage ovarian cancer, the goal of surgery should be resection of disease to microscopic residual at the initial procedure. This results in improved overall survival than lesser degrees of resection. Further studies are required to determine optimal surgical management.

Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting

PubMed Central

Suneja, Gita; Tapela, Neo; Mapes, Abigail; Pusoentsi, Malebogo; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Musimar, Zola; Ramogola-Masire, Doreen; Grover, Surbhi; Nsingo-Bvochora, Memory; Kayembe, Mukendi; Efstathiou, Jason; Lockman, Shahin; Dryden-Peterson, Scott

2016-01-01

Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0–185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59–653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79–1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09–1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30–1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05–1.75), male sex (aOR 1.45, 95% CI 1.12–1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03–1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. Implications for Practice: The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to

Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting.

PubMed

Brown, Carolyn A; Suneja, Gita; Tapela, Neo; Mapes, Abigail; Pusoentsi, Malebogo; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Musimar, Zola; Ramogola-Masire, Doreen; Grover, Surbhi; Nsingo-Bvochora, Memory; Kayembe, Mukendi; Efstathiou, Jason; Lockman, Shahin; Dryden-Peterson, Scott

2016-06-01

Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to specialized oncology care was 13 months. For HIV-infected patients (51% of total

Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

PubMed

Omran, Dalia; Yosry, Ayman; Darweesh, Samar K; Nabeel, Mohammed M; El-Beshlawey, Mohammed; Saif, Sameh; Fared, Azza; Hassany, Mohamed; Zayed, Rania A

2018-02-01

Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL) - detected by spectral karyotyping (SKY).

PubMed

Stark, Batia; Jeison, Marta; Glaser-Gabay, Leticia; Bar-Am, Irit; Mardoukh, Jacques; Ash, Shifra; Atias, Dina; Stein, Jerry; Zaizov, Rina; Yaniv, Isaac

2003-07-18

Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer.

PubMed

Yalcin, Suayib; Oksuzoglu, Berna; Tekuzman, Gülten; Engin, Hüseyin; Celik, Ismail; Turker, Alev; Barista, Ibrahim; Gullu, Ibrahim; Guler, Nilufer; Altundag, Kadri; Ozisik, Yavuz; Kars, Ayse

2003-11-01

In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.

Stage-directed individualized therapy in esophageal cancer.

PubMed

Goense, Lucas; van Rossum, Peter S N; Kandioler, Daniela; Ruurda, Jelle P; Goh, Khean-Lee; Luyer, Misha D; Krasna, Mark J; van Hillegersberg, Richard

2016-10-01

Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Advanced Launch Vehicle Upper Stages Using Liquid Propulsion and Metallized Propellants

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan A.

1990-01-01

Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum (Al) particles are the metal additive. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellant for volume-and mass-constrained upper stages can deliver modest increases in performance for low earth orbit to geosynchronous earth orbit (LEO-GEO) and other earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage (IUS) are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System (STS) and Space Transportation System-Cargo (STS-C) launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle.

PubMed

Gutman, Haim; Ben-Ami, Eytan; Shapira-Frommer, Roni; Schachter, Jacob

2012-08-01

Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this

Association of code status discussion with invasive procedures among advanced-stage cancer and noncancer patients.

PubMed

Sasaki, Akinori; Hiraoka, Eiji; Homma, Yosuke; Takahashi, Osamu; Norisue, Yasuhiro; Kawai, Koji; Fujitani, Shigeki

2017-01-01

Code status discussion is associated with a decrease in invasive procedures among terminally ill cancer patients. We investigated the association between code status discussion on admission and incidence of invasive procedures, cardiopulmonary resuscitation (CPR), and opioid use among inpatients with advanced stages of cancer and noncancer diseases. We performed a retrospective cohort study in a single center, Ito Municipal Hospital, Japan. Participants were patients who were admitted to the Department of Internal Medicine between October 1, 2013 and August 30, 2015, with advanced-stage cancer and noncancer. We collected demographic data and inquired the presence or absence of code status discussion within 24 hours of admission and whether invasive procedures, including central venous catheter placement, intubation with mechanical ventilation, and CPR for cardiac arrest, and opioid treatment were performed. We investigated the factors associated with CPR events by using multivariate logistic regression analysis. Among the total 232 patients, code status was discussed with 115 patients on admission, of which 114 (99.1%) patients had do-not-resuscitate (DNR) orders. The code status was not discussed with the remaining 117 patients on admission, of which 69 (59%) patients had subsequent code status discussion with resultant DNR orders. Code status discussion on admission decreased the incidence of central venous catheter placement, intubation with mechanical ventilation, and CPR in both cancer and noncancer patients. It tended to increase the rate of opioid use. Code status discussion on admission was the only factor associated with the decreased use of CPR ( P <0.001, odds ratio =0.03, 95% CI =0.004-0.21), which was found by using multivariate logistic regression analysis. Code status discussion on admission is associated with a decrease in invasive procedures and CPR in cancer and noncancer patients. Physicians should be educated about code status discussion to

Method and apparatus for advanced staged combustion utilizing forced internal recirculation

DOEpatents

Rabovitser, Iosif K.; Knight, Richard A.; Cygan, David F.; Nester, Serguei; Abbasi, Hamid A.

2003-12-16

A method and apparatus for combustion of a fuel in which a first-stage fuel and a first-stage oxidant are introduced into a combustion chamber and ignited, forming a primary combustion zone. At least about 5% of the total heat output produced by combustion of the first-stage fuel and the first-stage oxidant is removed from the primary combustion zone, forming cooled first-stage combustion products. A portion of the cooled first-stage combustion products from a downstream region of the primary combustion zone is recirculated to an upstream region of primary combustion zone. A second-stage fuel is introduced into the combustion chamber downstream of the primary combustion zone and ignited, forming a secondary combustion zone. At least about 5% of the heat from the secondary combustion zone is removed. In accordance with one embodiment, a third-stage oxidant is introduced into the combustion chamber downstream of the secondary combustion zone, forming a tertiary combustion zone.

The Impact of a Multidimensional Exercise Intervention on Physical and Functional Capacity, Anxiety, and Depression in Patients With Advanced-Stage Lung Cancer Undergoing Chemotherapy.

PubMed

Quist, Morten; Adamsen, Lis; Rørth, Mikael; Laursen, Jørgen H; Christensen, Karl B; Langer, Seppo W

2015-07-01

Patients with advanced-stage lung cancer face poor survival and experience co-occurring chronic physical and psychosocial symptoms. Despite several years of research in exercise oncology, few exercise studies have targeted advanced lung cancer patients undergoing chemotherapy. The aim of the present study was to investigate the benefits of a 6-week supervised group exercise intervention and to outline the effect on aerobic capacity, strength, health-related quality of life (HRQoL), anxiety, and depression. VO2peak was assessed using an incremental exercise test. Muscle strength was measured with one repetition maximum test (1RM). HRQoL, anxiety, and depression were assessed using Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale (HADS). One hundred and forthteen patients with advanced stage lung cancer were recruited. Forty-three patients dropped out. No serious adverse events were reported. Exercise adherence in the group training was 68%. Improvements in VO2peak (P < .001) and 6-minute walk distance (P < .001) and muscle strength measurements (P < .05) were seen. There was a reduction in anxiety level (P = .0007) and improvement in the emotional well-being parameter (FACT-L) but no statistically significant changes in HRQoL were observed. The results of the present study show that during a 6-week hospital-based supervised, structured, and group-based exercise program, patients with advanced-stage lung cancer (NSCLC IIIb-IV, ED-SCLC) improve their physical capacity (VO2peak, 1RM), functional capacity, anxiety level, and emotional well-being, but not their overall HRQoL. A randomized controlled trial testing the intervention including 216 patients is currently being carried out. © The Author(s) 2015.

SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

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

Qu, H; Xia, P; Yu, N

Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less

Barriers to Advance Care Planning in End-Stage Renal Disease: Who is to Blame, and What Can be Done?

PubMed

Kelley, Alan Taylor; Turner, Jeffrey; Doolittle, Benjamin

2018-07-01

Patients with end-stage renal disease experience significant mortality and morbidity, including cognitive decline. Advance care planning has been emphasized as a responsibility and priority of physicians caring for patients with chronic kidney disease in order to align with patient values before decision-making capacity is lost and to avoid suffering. This emphasis has proven ineffective, as illustrated in the case of a patient treated in our hospital. Is this ineffectiveness a consequence of failure in the courtroom or the clinic? Through our own experience we affirm what has been written before: that legal precedent favors intensive treatment in virtually all cases without 'clear and convincing evidence' of a patient's previously declared wishes to the contrary. Equally clear is that more than 20 years of support in the clinical literature suggesting advance care planning early in the course of disease can address challenges in the legal system for those lacking capacity. However, many physicians fail to recognize the need for advance care planning in a timely manner and lack the necessary training to provide it. The need for more training and new tools to recognize opportunities for advance care planning in daily practice remains unmet.

Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma.

PubMed

Cheng, Nai-Ming; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Huang, Chung-Guei; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Lin, Chien-Yu; Liao, Chun-Ta; Yen, Tzu-Chen

2013-10-01

Previous studies have shown that total lesion glycolysis (TLG) may serve as a prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether the textural features of pretreatment (18)F-FDG PET/CT images can provide any additional prognostic information over TLG and clinical staging in patients with advanced T-stage OPSCC. We retrospectively analyzed the pretreatment (18)F-FDG PET/CT images of 70 patients with advanced T-stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or radiotherapy with curative intent. All of the patients had data on human papillomavirus (HPV) infection and were followed up for at least 24 mo or until death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor boundary. The textural features of pretreatment (18)F-FDG PET/CT images were extracted from histogram analysis (SUV variance and SUV entropy), normalized gray-level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast, homogeneity, inverse different moment, and correlation), and neighborhood gray-tone difference matrix (coarseness, contrast, busyness, complexity, and strength). Receiver-operating-characteristic curves were used to identify the optimal cutoff values for the textural features and TLG. Thirteen patients were HPV-positive. Multivariate Cox regression analysis showed that age, tumor TLG, and uniformity were independently associated with progression-free survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV positivity were significantly associated with overall survival (OS). A prognostic scoring system based on TLG and uniformity was derived. Patients who presented with TLG > 121.9 g and uniformity ≤ 0.138 experienced significantly worse PFS, DSS, and OS rates than those without (P < 0.001, < 0.001, and 0.002, respectively). Patients with TLG > 121.9 g or uniformity ≤ 0.138 were further divided according to age, and different PFS and DSS were observed

Assessment of capabilities in persons with advanced stage of dementia: Validation of The Montessori Assessment System (MAS).

PubMed

Erkes, Jérôme; Camp, Cameron J; Raffard, Stéphane; Gély-Nargeot And, Marie-Christine; Bayard, Sophie

2017-01-01

This study evaluated the validity and reliability of the Montessori Assessment System. The Montessori Assessment System assesses preserved abilities in persons with moderate to severe dementia. In this respect, this instrument provides crucial information for the development of effective person-centered care plans. A total of 196 persons with a diagnosis of dementia in the moderate to severe stages of dementia were recruited in 10 long-term care facilities in France. All participants completed the Montessori Assessment System, the Clinical Dementia Rating Scale and/or the Mini Mental State Examination and the Severe Impairment Battery-short form. The internal consistency and temporal stability of the Montessori Assessment System were high. Additionally, good construct and divergent validity were demonstrated. Factor analysis showed a one-factor structure. The Montessori Assessment System demonstrated satisfactory psychometric properties while being a useful instrument to assess capabilities in persons with advanced stages of dementia and hence to develop person-centered plans of care.

ADVANCED MANUFACTURING TEAM

NASA Image and Video Library

2014-01-16

ZACK JONES AND JIM LYDON OF MSFC’S ADVANCED MANUFACTURING TEAM, WITH MSFC’S M2 SELECTIVE LASER MELTING SYSTEM. THE M2 IS CURRENTLY DEDICATED TO ADVANCED COPPER MATERIAL DEVELOPMENT FOR THE LOW COST UPPER STAGE PROGRAM.

Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

PubMed

Samrao, Damanzoopinder; Wang, Dan; Ough, Faith; Lin, Yvonne G; Liu, Song; Menesses, Teodulo; Yessaian, Annie; Turner, Nicole; Pejovic, Tanja; Mhawech-Fauceglia, Paulette

2012-12-01

The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.

ADVANCED MANUFACTURING TEAM

NASA Image and Video Library

2014-01-16

QUINCY BEAN, JIM LYDON, AND ZACK JONES OF MSFC’S ADVANCED MANUFACTURING TEAM, WITH MSFC’S M2 SELECTIVE LASER MELTING SYSTEM. THE M2 IS CURRENTLY DEDICATED TO ADVANCED COPPER MATERIAL DEVELOPMENT FOR THE LOW COST UPPER STAGE PROGRAM.

Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

PubMed

Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

2016-01-01

Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

Two stage launch vehicle

NASA Technical Reports Server (NTRS)

1987-01-01

The Advanced Space Design project for 1986-87 was the design of a two stage launch vehicle, representing a second generation space transportation system (STS) which will be needed to support the space station. The first stage is an unmanned winged booster which is fully reusable with a fly back capability. It has jet engines so that it can fly back to the landing site. This adds safety as well as the flexibility to choose alternate landing sites. There are two different second stages. One of the second stages is a manned advanced space shuttle called Space Shuttle II. Space Shuttle II has a payload capability of delivering 40,000 pounds to the space station in low Earth orbit (LEO), and returning 40,000 pounds to Earth. Servicing the space station makes the ability to return a heavy payload to Earth as important as being able to launch a heavy payload. The other second stage is an unmanned heavy lift cargo vehicle with ability to deliver 150,000 pounds of payload to LEO. This vehicle will not return to Earth; however, the engines and electronics can be removed and returned to Earth in the Space Shuttle II. The rest of the vehicle can then be used on orbit for storage or raw materials, supplies, and space manufactured items awaiting transport back to Earth.

A Model to Predict the Use of Surgical Resection for Advanced-Stage Non-Small Cell Lung Cancer Patients.

PubMed

David, Elizabeth A; Andersen, Stina W; Beckett, Laurel A; Melnikow, Joy; Kelly, Karen; Cooke, David T; Brown, Lisa M; Canter, Robert J

2017-11-01

For advanced-stage non-small cell lung cancer, chemotherapy and chemoradiotherapy are the primary treatments. Although surgical intervention in these patients is associated with improved survival, the effect of selection bias is poorly defined. Our objective was to characterize selection bias and identify potential surgical candidates by constructing a Surgical Selection Score (SSS). Patients with clinical stage IIIA, IIIB, or IV non-small cell lung cancer were identified in the National Cancer Data Base from 1998 to 2012. Logistic regression was used to develop the SSS based on clinical characteristics. Estimated area under the receiver operating characteristic curve was used to assess discrimination performance of the SSS. Kaplan-Meier analysis was used to compare patients with similar SSSs. We identified 300,572 patients with stage IIIA, IIIB, or IV non-small cell lung cancer without missing data; 6% (18,701) underwent surgical intervention. The surgical cohort was 57% stage IIIA (n = 10,650), 19% stage IIIB (n = 3,483), and 24% stage IV (n = 4,568). The areas under the receiver operating characteristic curve from the best-fit logistic regression model in the training and validation sets were not significantly different, at 0.83 (95% confidence interval, 0.82 to 0.83) and 0.83 (95% confidence interval, 0.82 to 0.83). The range of SSS is 43 to 1,141. As expected, SSS was a good predictor of survival. Within each quartile of SSS, patients in the surgical group had significantly longer survival than nonsurgical patients (p < 0.001). A prediction model for selection of patients for surgical intervention was created. Once validated and prospectively tested, this model may be used to identify patients who may benefit from surgical intervention. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Dilemmas in Lung Cancer Staging.

PubMed

Vlahos, Ioannis

2018-05-01

The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Design options for advanced manned launch systems

NASA Astrophysics Data System (ADS)

Freeman, Delma C.; Talay, Theodore A.; Stanley, Douglas O.; Lepsch, Roger A.; Wilhite, Alan W.

1995-03-01

Various concepts for advanced manned launch systems are examined for delivery missions to space station and polar orbit. Included are single-and two-stage winged systems with rocket and/or air-breathing propulsion systems. For near-term technologies, two-stage reusable rocket systems are favored over single-stage rocket or two-stage air-breathing/rocket systems. Advanced technologies enable viable single-stage-to-orbit (SSTO) concepts. Although two-stage rocket systems continue to be lighter in dry weight than SSTO vehicles, advantages in simpler operations may make SSTO vehicles more cost-effective over the life cycle. Generally, rocket systems maintain a dry-weight advantage over air-breathing systems at the advanced technology levels, but to a lesser degree than when near-term technologies are used. More detailed understanding of vehicle systems and associated ground and flight operations requirements and procedures is essential in determining quantitative discrimination between these latter concepts.

Guidelines on Chemotherapy in Advanced Stage Gynecological Malignancies: An Evaluation of 224 Professional Societies and Organizations

PubMed Central

Polyzos, Nikolaos P.; Mauri, Davide; Ioannidis, John P. A.

2011-01-01

Background Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. Methods We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. Results Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. Conclusions Clinical practice guidelines are provided by the minority of professional societies and organizations. Available

Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy

PubMed Central

Yamashita, Keishi; Ema, Akira; Hosoda, Kei; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Watanabe, Masahiko

2017-01-01

AIM To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer. PMID:28451064

Advanced stages of embryonic development and cotylocidial morphogenesis in the intrauterine eggs of Aspidogaster limacoides Diesing, 1835 (Aspidogastrea), with comments on their phylogenetic implications.

PubMed

Świderski, Zdzisław; Poddubnaya, Larisa G; Gibson, David I; Młocicki, Daniel

2012-06-01

Ultrastructural aspects of the advanced embryonic development and cotylocidial morphogenesis of the aspidogastrean Aspidogaster limacoides are described. The posterior or distal regions of the uterus are filled with eggs containing larvae at advanced stages of morphogenesis and fully-formed cotylocidia. Various stages and organs of this larva are described in detail, including the aspects of the developing and fully-differentiated cotylocidium, the body wall (tegument and musculature), glandular regions and the protonephridial excretory system. Blastomere multiplication by means of mitotic divisions takes place simultaneously with the degeneration or apoptosis of some micromeres; this frequently observed characteristic is compared and discussed in relation to corresponding reports for other neodermatans. During the advanced stages of the embryonic development of A. limacoides, the vitelline syncytium disappears and the size of the embryo increases rapidly. Evident polarization of the differentiating larva was observed; towards one pole of the egg, cytodifferentiation of the mouth, surrounded by the oral sucker and cephalic glands, takes place, whereas, towards the opposite pole, differentiation of the posterior sucker (incipient ventral disc) occurs. The oral and posterior suckers are formed from numerous embryonic cells which have differentiated into myocytes. The central part of the oral sucker undergoes invagination and forms the future pharynx and intestine. Fully-developed cotylocidia of A. limacoides have a neodermatan type of tegument, flame cells and two types of glandular structures. These results suggest a sister relationship between the Aspidogastrea and the Digenea, although the systematic position of aspidogastreans in relation to other platyhelminth taxa remains somewhat equivocal.

Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

PubMed

Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

2016-04-01

Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.

Reduced Empathy Scores in Patients with Parkinson's Disease: A Non-Motor Symptom Associated with Advanced Disease Stages.

PubMed

Schmidt, Nele; Paschen, Laura; Deuschl, Günther; Witt, Karsten

2017-01-01

Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease (PD). To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients. Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery. PD patients had a significant lower global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn & Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables. PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced.

The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

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

Orman, Amber; Koru-Sengul, Tulay; Miao, Feng

2014-12-01

Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT inmore » 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.« less

Two-stage, low noise advanced technology fan. 4: Aerodynamic final report

NASA Technical Reports Server (NTRS)

Harley, K. G.; Keenan, M. J.

1975-01-01

A two-stage research fan was tested to provide technology for designing a turbofan engine for an advanced, long range commercial transport having a cruise Mach number of 0.85 -0.9 and a noise level 20 EPNdB below current requirements. The fan design tip speed was 365.8m/sec (1200ft/sec);the hub/tip ratio was 0.4; the design pressure ratio was 1.9; and the design specific flow was 209.2 kg/sec/sq m(42.85lbm/sec/sq ft). Two fan-versions were tested: a baseline configuration, and an acoustically treated configuration with a sonic inlet device. The baseline version was tested with uniform inlet flow and with tip-radial and hub-radial inlet flow distortions. The baseline fan with uniform inlet flow attained an efficiency of 86.4% at design speed, but the stall margin was low. Tip-radial distortion increased stall margin 4 percentage points at design speed and reduced peak efficiency one percentage point. Hub-radial distortion decreased stall margin 4 percentage points at all speeds and reduced peak efficiency at design speed 8 percentage points. At design speed, the sonic inlet in the cruise position reduced stall margin one percentage point and efficiency 1.5 to 4.5 percentage points. The sonic inlet in the approach position reduced stall margin 2 percentage points.

Weekly docetaxel is safe and effective in the treatment of advanced-stage acquired immunodeficiency syndrome-related Kaposi sarcoma.

PubMed

Lim, Soon Thye; Tupule, Anil; Espina, Byron M; Levine, Alexandra M

2005-01-15

Intravenous paclitaxel, 100 mg/m(2), given over 3 hours every 2 weeks is associated with a response rate of 59% in patients with recurrent or refractory acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS). However, this regimen is associated with significant myelosuppression, and the inconvenience of a 3-hour infusion. Moreover, no effective therapies have been defined for use after treatment failure with this agent. A Phase II trial was conducted with weekly docetaxel in patients with advanced-stage KS to assess safety and antitumor activity. Docetaxel was administered at a dose of 25 mg/m(2) intravenously over 15-30 minutes weekly for 8 weeks. Thereafter, if the patient experienced stable disease or better response, treatment doses were given every other week until complete disease remission, disease progression, or unacceptable toxicity occurred. Twelve patients were accrued-9 had > 25 mucocutaneous lesions, 1 had lymphedema, and 2 had visceral involvement. Ten patients (83%) had previous systemic chemotherapy, including 4 who received previous paclitaxel. Treatment was well tolerated, with no Grade 4 toxicity of any type. Grade 3 neutropenia occurred in 33% of patients but no patient had neutropenic fever. Five patients (42%) achieved a partial response, including 1 who had previously failed to respond to paclitaxel. The median time to disease progression was 26 months (range, 5-53 months). With a median follow-up period of 45 months, the median survival point had not been reached. Weekly docetaxel is safe, with reasonable antitumor activity in patients with advanced-stage, recurrent, or refractory AIDS-related KS. (c) 2004 American Cancer Society.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

PubMed

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Single stage, low noise, advanced technology fan. Volume 5: Fan acoustics. Section 2: One-third octave data tabulations and selected narrowband traces

NASA Technical Reports Server (NTRS)

Jutras, R. R.

1976-01-01

The raw-acoustic data corrected to standard day, from acoustic tests performed on a 0.508-scale fan vehicle of a 111,300 newton thrust, full-size engine, which has application on an advanced transport aircraft, are presented. The single-stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec to achieve the desired pressure ratio in a single-stage fan with low radius ratio, and to maintain adequate stall margin. The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise was accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels. The suppression goal of FAR 36-20 was not reached, but improvements in the technology of both front and aft fan-noise suppression were realized.

Treatment of localized-stage follicular lymphoma.

PubMed

Sorigue, Marc; Tuset, Victòria; Sancho, Juan-Manuel

2018-05-12

Follicular lymphoma (FL) is the most common indolent lymphoma and it most frequently presents in an advanced-stage. Therapeutic considerations for advanced-stage are different from those of localized-stage FL, in which radiotherapy (RT) is generally recommended. However, the available evidence suffers from shortcomings that are relatively specific to this clinical entity due to its rarity and long survival with all available treatment modalities, including that most of the existing evidence originated at a time when diagnostic classifications, staging procedures and radiotherapeutic standards were different from those available today and when anti-CD20 monoclonal antibodies were not available. Available treatment modalities include observation, systemic therapy only, RT only and RT in combination with systemic therapy. We review the evidence available with each of them and the data from present day clinical practice studies as well as briefly discuss what diagnostic and therapeutic developments may take place in the next few years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Automatic age-related macular degeneration detection and staging

NASA Astrophysics Data System (ADS)

van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

2013-03-01

Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

Autologous transplantation in CLL patients with B and C Binet stages: final results of the prospective randomized GOELAMS LLC 98 trial.

PubMed

Brion, A; Mahé, B; Kolb, B; Audhuy, B; Colombat, P; Maisonneuve, H; Foussard, C; Bureau, A; Ferrand, C; Lesesve, J F; Béné, M C; Feugier, P

2012-04-01

The relevance of high-dose chemotherapy followed by auto-SCT in CLL remains to be defined. The aim of the prospective, randomized, GOELAMS LLC 98 trial was to compare two strategies in previously untreated CLL patients aged <60 years. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP followed by six CHOP courses in every 3 months in those achieving a complete or PR. Arm A was compared with high-dose therapy with auto-SCT (Arm B), used as consolidation after three CHOP courses in case of CR or very good PR. A total of 86 patients were enrolled, of which 39 and 43 patients were evaluable in arm A and arm B, respectively. The primary endpoint was PFS. On an intent-to-treat basis and with a median follow-up time of 77.1 (range 1-135.5) months, the median PFS was 22 months in Arm A and 53 months in Arm B (P<0.0001). Median survival time was 104.7 months in arm A and 107.4 months in arm B. This trial demonstrates that frontline high-dose therapy with auto-SCT prolongs PFS but does not translate into a survival advantage in advanced CLL patients in the pre-rituximab era.

Body weight, hemoglobin, and absolute neutrophil count in patients with advanced-stage epithelial ovarian cancer who received chemotherapy: A single-center study

NASA Astrophysics Data System (ADS)

Gunawan, Y.; Winarto, H.

2017-08-01

The side effects of chemotherapy, a treatment modality of ovarian cancer, can disrupt overall treatment. To date, the clinical and laboratory profiles of ovarian cancer patients during chemotherapy have not been investigated. This study aimed to elucidate the clinical and laboratory profiles of patients with advanced-stage epithelial ovarian cancer who received chemotherapy in Dr. Cipto Mangunkusumo Hospital, including body mass index (BMI), hemoglobin (Hb), and absolute neutrophil count (ANC). To generate these clinical and laboratory profiles, we collected secondary data from the medical records of advanced-stage epithelial ovarian cancer patients who received six cycles of carboplatin and paclitaxel chemotherapy. We enrolled 23 patients with advanced-stage epithelial ovarian cancer patients who received six cycles of chemotherapy. Mean patient BMI before and after chemotherapy was 22.86 kg/m2 and 21.78 kg/m2, respectively. Hb levels before chemotherapy were 8-13 g/dl, with Hb < 10 g/dl in one patient (4.35%) and Hb ≥ 10 g/dl in 22 patients (95.65%). Mean ANC was 5845.6 ± 3325.0. An average of 24.65% of patients experienced anemia after each cycle of chemotherapy. Mean ANC before chemotherapy was 3.5582 ± 3.3250. An average of 26.81% of patients had ANC <1500 after each cycle of chemotherapy; no patients had ANC <1500 before chemotherapy initiation. After six cycles of chemotherapy, three patients (13.04%) had mild neutropenia, four patients (17.39%) had moderate neutropenia, and one patient (4.35%) had severe neutropenia. Of the 22 patients with Hb ≥ 10 g/dl before chemotherapy, 16 (72.72%) experienced a decrease in ANC during chemotherapy. Of the 20 patients (60.87%) with normal BMI or higher, 14 experienced a decrease in ANC during chemotherapy. The mean patient body weight decreased after six cycles of chemotherapy. Hb and ANC were persistently decreased in approximately a quarter of the 23 subjects. The decrease in ANC was not influenced by initial Hb

[Factors associated with advanced thyroid cancer in pediatric patients in a high specialty medical unit in Northeast Mexico].

PubMed

García-Castillo, Lizbeth Ariana; Bahena-García, Ana Laura; Sánchez-Sánchez, Luz María; del Carmen Palacios-Saucedo, Gerardo

2015-01-01

Thyroid cancer represents 2% of all childhood malignances. Its incidence rises 1.1% per year. In comparison with adults, childhood thyroid cancer is detected in a more advanced stage, but with a survival rate above 95%. The objective of this study was to evaluate whether there are factors associated with advanced stages of thyroid cancer in pediatric patients. Nineteen patients were included, 13 (68.4%) were female and six male, all between 7-15 years, with a median of 11 years. Fifteen in advanced and four in early stage. The median age of patients in advanced stage at time of diagnosis was 10.6 years (7-15) and 13.2 (12-14) were in early stage (p=0.075). There was a delay of nine months to get a diagnosis in advanced stage, and 7.2 in early stage (p=0.931). Three of the patients with advanced stage and two with early stage were from Nuevo León (Mexico) and the rest were foreign (p=0.567). In the group with advanced stage, two had thyroid cancer familiar history, and none in the early stage group (p=0.452). Nine patients in advanced stage and three in early stage presented thyroid nodule as the first sign of illness. Six patients in advanced stage and one in early stage presented goiter (p=0.590). None of the studied patients had radiation history. Six patients in advanced stage and one in early stage suffered from Hashimoto's Thyroiditis (p=0.590). Eleven in advanced stage and one in early stage had papillary histologic variety. Four in advanced stage and three in early stage had papillary histologic variety with a follicular patter (p=0.083). Eight patients presented lung metastasis at time of diagnosis (p=0.061). There are no factors associated with advanced stage thyroid cancer in pediatric populations. Although half of studied patients presented lung metastasis, treatment response and survival is satisfactory.

Predictive markers of chemoresistance in advanced stages epithelial ovarian carcinoma.

PubMed

Bonneau, Claire; Rouzier, Roman; Geyl, Caroline; Cortez, Annie; Castela, Mathieu; Lis, Raphael; Daraï, Emile; Touboul, Cyril

2015-01-01

DNA repair mechanisms, environment-mediated drug resistance and cancer initiating cells (CIC) are three major research concepts that can explain the chemoresistance of epithelial ovarian cancer (EOC). The objective was to test if changes in the expression of potential markers associated with drug resistance before and after chemotherapy would correlate with platinum resistance, defined as a recurrence within the first year after chemotherapy cessation, and with survival, in advanced EOC. We included 32 patients with stage IIIC-IV EOC who underwent laparoscopy to evaluate the extent of carcinomatosis, neoadjuvant chemotherapy (carboplatin/taxol) and interval surgery. Biopsies taken during the initial laparoscopies and interval surgeries were evaluated using immunohistochemistry for the expression of 7 proteins: CD117, CD44 and ALDH1 to evaluate CIC; IL-6, IL-8 and BMP2 to evaluate environment-mediated drug resistance; and ERCC1 to evaluate DNA repair. Expression measurements were correlated with platin resistance and survival. The markers' relevance was confirmed in vitro using chemoresistance tests and flow cytometric measurements of the proportion of CD44+ cells. 17 patients were chemoresistant and 15 patients were chemosensitive. We observed increases in CD44, IL-6 and ERCC1 expression and stable ALDH1, CD117, IL-8, and BMP2 expression. Reduced expression of cancer initiating cell markers and increased expression of environment-mediated drug resistance markers were associated with poor prognosis. We also demonstrated that CD44+ cells had survival advantages in vitro. Changes in CD44 and IL-8 expression on tumor cells appeared to correlate with overall survival and should be further tested as predictors of chemoresistance using larger cohort. Copyright © 2014 Elsevier Inc. All rights reserved.

Catching Galactic open clusters in advanced stages of dynamical evolution

NASA Astrophysics Data System (ADS)

Angelo, M. S.; Piatti, A. E.; Dias, W. S.; Maia, F. F. S.

2018-04-01

During their dynamical evolution, Galactic open clusters (OCs) gradually lose their stellar content mainly because of internal relaxation and tidal forces. In this context, the study of dynamically evolved OCs is necessary to properly understand such processes. We present a comprehensive Washington CT1 photometric analysis of six sparse OCs, namely: ESO 518-3, Ruprecht 121, ESO 134-12, NGC 6573, ESO 260-7 and ESO 065-7. We employed Markov chain Monte-Carlo simulations to robustly determine the central coordinates and the structural parameters and T1 × (C - T1) colour-magnitude diagrams (CMDs) cleaned from field contamination were used to derive the fundamental parameters. ESO 518-03, Ruprecht 121, ESO 134-12 and NGC 6573 resulted to be of nearly the same young age (8.2 ≤log(t yr-1) ≤ 8.3); ESO 260-7 and ESO065-7 are of intermediate age (9.2 ≤log(t yr-1) ≤ 9.4). All studied OCs are located at similar Galactocentric distances (RG ˜ 6 - 6.9 kpc), considering uncertainties, except for ESO 260-7 (RG = 8.9 kpc). These OCs are in a tidally filled regime and are dynamically evolved, since they are much older than their half-mass relaxation times (t/trh ≳ 30) and present signals of low-mass star depletion. We distinguished two groups: those dynamically evolving towards final disruptions and those in an advanced dynamical evolutionary stage. Although we do not rule out that the Milky Way potential could have made differentially faster their dynamical evolutions, we speculate here with the possibility that they have been mainly driven by initial formation conditions.

Catching Galactic open clusters in advanced stages of dynamical evolution

NASA Astrophysics Data System (ADS)

Angelo, M. S.; Piatti, A. E.; Dias, W. S.; Maia, F. F. S.

2018-07-01

During their dynamical evolution, Galactic open clusters (OCs) gradually lose their stellar content mainly because of internal relaxation and tidal forces. In this context, the study of dynamically evolved OCs is necessary to properly understand such processes. We present a comprehensive Washington CT1 photometric analysis of six sparse OCs, namely ESO 518-3, Ruprecht 121, ESO 134-12, NGC 6573, ESO 260-7, and ESO 065-7. We employed Markov chain Monte Carlo simulations to robustly determine the central coordinates and the structural parameters and T1 × (C - T1) colour-magnitude diagrams cleaned from field contamination were used to derive the fundamental parameters. ESO 518-03, Ruprecht 121, ESO 134-12, and NGC 6573 resulted to be of nearly the same young age [8.2 ≤log(t yr-1) ≤ 8.3]; ESO 260-7 and ESO065-7 are of intermediate age [9.2 ≤log(t yr-1) ≤ 9.4]. All studied OCs are located at similar Galactocentric distances (RG ˜6-6.9 kpc), considering uncertainties, except for ESO 260-7 (RG = 8.9 kpc). These OCs are in a tidally filled regime and are dynamically evolved, since they are much older than their half-mass relaxation times (t/trh ≳ 30) and present signals of low-mass star depletion. We distinguished two groups: those dynamically evolving towards final disruptions and those in an advanced dynamical evolutionary stage. Although we do not rule out that the Milky Way potential could have made differentially faster their dynamical evolutions, we speculate here with the possibility that they have been mainly driven by initial formation conditions.

Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree.

PubMed

Gelibter, Alain; Malaguti, Paola; Di Cosimo, Serena; Bria, Emilio; Ruggeri, Enzo Maria; Carlini, Paolo; Carboni, Fabio; Ettorre, Giuseppe Maria; Pellicciotta, Mario; Giannarelli, Diana; Terzoli, Edmondo; Cognetti, Francesco; Milella, Michele

2005-09-15

Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy. Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR). The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%). FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC. Copyright 2005 American Cancer Society.

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PubMed

Zinzani, Pier Luigi; Broccoli, Alessandro; Gioia, Daniela Maria; Castagnoli, Antonio; Ciccone, Giovannino; Evangelista, Andrea; Santoro, Armando; Ricardi, Umberto; Bonfichi, Maurizio; Brusamolino, Ercole; Rossi, Giuseppe; Anastasia, Antonella; Zaja, Francesco; Vitolo, Umberto; Pavone, Vincenzo; Pulsoni, Alessandro; Rigacci, Luigi; Gaidano, Gianluca; Stelitano, Caterina; Salvi, Flavia; Rusconi, Chiara; Tani, Monica; Freilone, Roberto; Pregno, Patrizia; Borsatti, Eugenio; Sacchetti, Gian Mauro; Argnani, Lisa; Levis, Alessandro

2016-04-20

The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology.

The Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Broadway, Jeramie W.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Borowski, Stanley K.; Scott, John

2014-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progres made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

The influence of suggestibility on memory.

PubMed

Nicolas, Serge; Collins, Thérèse; Gounden, Yannick; Roediger, Henry L

2011-06-01

We provide a translation of Binet and Henri's pioneering 1894 paper on the influence of suggestibility on memory. Alfred Binet (1857-1911) is famous as the author who created the IQ test that bears his name, but he is almost unknown as the psychological investigator who generated numerous original experiments and fascinating results in the study of memory. His experiments published in 1894 manipulated suggestibility in several ways to determine effects on remembering. Three particular modes of suggestion were employed to induce false recognitions: (1) indirect suggestion by a preconceived idea; (2) direct suggestion; and (3) collective suggestion. In the commentary we suggest that Binet and Henri's (1894) paper written over 115 years ago is still highly relevant even today. In particular, Binet's legacy lives on in modern research on misinformation effects in memory, in studies of conformity, and in experiments on the social contagion of memory. Copyright © 2010 Elsevier Inc. All rights reserved.

Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

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

Lin, Chien-Yu; Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

2010-11-15

Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-yearmore » overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.« less

Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

PubMed

Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

2014-10-01

The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer

PubMed Central

Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

2014-01-01

Background and Purpose The psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. Experimental Approach To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. Key Results CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. Conclusions and Implications O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. PMID:24910342

Treatment complexity: a description of chemotherapy and supportive care treatment visits in patients with advanced-stage cancer diagnoses.

PubMed

Sumpio, Catherine; Knobf, M Tish; Jeon, Sangchoon

2016-01-01

Modern chemotherapy regimens are growing increasingly complex, involving lengthy outpatient infusions, and additional visits for supportive care. The treatment of advanced-stage patients is uniquely one of unremitting therapy and varying complexity. The study's purpose was to describe and quantify the dimensions of treatment complexity in terms of chemotherapy (CT) and supportive care (SC) visits. Electronic medical records for 121 subjects with stages III and IV cancer were reviewed. Visits were classified as SC and CT types, and actual hours and visit numbers were calculated for a 3-month treatment period. Analysis included descriptive and generalized linear modeling statistics. Subjects ≥65 years spent fewer total hours (M = 18.17 h, SD = 10.17 h, p = 0.04), but experienced more total visits (M = 10.96 visits, SD = 4.65 visits, p = 0.02) than younger subjects. More than 71% of younger patients spent two or more hours per chemotherapy visit, compared to 41.7% of older patients (p = 0.001). Older subjects were more likely to have a SC visit (p = 0.03), but did not differ from younger subjects in SC visit numbers (p = 0.3) or hours (p = 0.6). Females averaged 3.81 more total hours (M = 22. 61 h, SD = 11.06 h, p = 0.055) and had more total visits (M = 10.80 visits, SD = 3.71, p = 0.02) than males. By visit type, women spent twice the hours undergoing SC than males (M = 3.3 vs. 1.5 h, p = 0.051), but genders did not differ in CT visit hours or average length. By diagnosis, colon/esophageal subjects spent more hours in CT visits (M = 21.90 h, SD = 8.60 h, p < 0.01), and lung subjects trended toward spending more hours in SC visits (M = 4.80 h, SD = 8.23 h, p < 0.06). Advanced-stage cancer patients differed in visit types, hours, and treatment length undergoing CT and SC visits. Age, gender, and diagnosis explained the differences, and this study adds new understanding to

Note on the Construct Validity of the ITPA

ERIC Educational Resources Information Center

Silverstein, A. B.

1978-01-01

Correlations with Binet IQ in the ITPA normative sample were corrected for restricted intelligence range. The corrected correlation for the Psycholinguistic Quotient is as high as that between the WISC and the Binet, a finding that raises a serious question about the construct validity of the ITPA. (Author)

Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non-small-cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage.

PubMed

Kim, Tae-Jung; Park, Chan Kwon; Yeo, Chang Dong; Park, Kihoon; Rhee, Chin Kook; Kim, Jusang; Kim, Seung Joon; Lee, Sang Haak; Lee, Kyo-Young; Yoon, Hyoung-Kyu

2014-09-01

Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized. We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner. Of 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10-15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (>15% ALK FISH split) than <10% ALK FISH split group. Simultaneous panel genotyping revealed more prevalent ALK rearrangements than reported in previous studies and their strong association with advanced stage irrespective of sex or smoking history. ALK rearrangement seems to be a marker for aggressive tumor biology and should be assessed in advanced disease. © 2014 Wiley Periodicals, Inc.

Advanced Beamline Design for Fermilab's Advanced Superconducting Test Accelerator

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

Prokop, Christopher

2014-01-01

The Advanced Superconducting Test Accelerator (ASTA) at Fermilab is a new electron accelerator currently in the commissioning stage. In addition to testing superconducting accelerating cavities for future accelerators, it is foreseen to support a variety of Advanced Accelerator R&D (AARD) experiments. Producing the required electron bunches with the expected flexibility is challenging. The goal of this dissertation is to explore via numerical simulations new accelerator beamlines that can enable the advanced manipulation of electron bunches. The work especially includes the design of a low-energy bunch compressor and a study of transverse-to-longitudinal phase space exchangers.

Serum antioxidant levels and nutritional status in early and advanced stage lung cancer patients.

PubMed

Klarod, Kultida; Hongsprabhas, Pranithi; Khampitak, Tueanjit; Wirasorn, Kosin; Kiertiburanakul, Sasisopin; Tangrassameeprasert, Roongpet; Daduang, Jureerut; Yongvanit, Puangrat; Boonsiri, Patcharee

2011-01-01

Malnutrition frequently occurs in lung cancer patients. We aimed to determine nutritional status and antioxidant and mineral levels in Thai patients with lung cancer. A prospective study with matched case-control was conducted. Nutritional status was assessed by body mass index (BMI) and subjective global assessment (SGA). Eastern Cooperative Oncology Group (ECOG) performance status was used to assess the performance. The serum antioxidant and mineral levels were determined. Forty-nine patients with a mean age of 58.8 (range, 35-82) who were first diagnosed with lung cancer were enrolled. They were compared with 60 healthy controls, and levels of retinol, α-tocopherol, β-carotene, lycopene, β-cryptoxanthin, selenium, and zinc were lower (P < 0.05). However, peroxidase activity was higher (P = 0.002) in patients. Selenium levels were higher in early stage compared to advanced stage patients (P = 0.041). Overweight patients had higher selenium levels (0.04 mg/L) than normal BMI patients (β = 0.04, P = 0.035). Patients with SGA class C had lower selenium levels (0.03 mg/L) than those with class A (β = -0.03, P = 0.035). The poorer ECOG performance patients had significantly lower β-carotene (β = -0.192, P = 0.003) and selenium (β = -0.031, P = 0.011) levels compared with those with good ECOG performance status. Significantly lower levels of antioxidants and selenium were found in lung cancer patients compared to healthy controls. Levels of some antioxidants and minerals differed among categories of BMI, SGA categories, or ECOG performance status. These findings may be helpful for further studies, such as the effect of nutritional supplementation on clinical outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia

PubMed Central

Herriott, Ashleigh; Tudhope, Susan J.; Junge, Gesa; Rodrigues, Natalie; Patterson, Miranda J.; Woodhouse, Laura; Lunec, John; Hunter, Jill E.; Mulligan, Evan A.; Cole, Michael; Allinson, Lisa M.; Wallis, Jonathan P.; Marshall, Scott; Wang, Evelyn; Curtin, Nicola J.; Willmore, Elaine

2015-01-01

In chronic lymphocytic leukemia (CLL), mutation and loss of p53 and ATM abrogate DNA damage signalling and predict poorer response and shorter survival. We hypothesised that poly (ADP-ribose) polymerase (PARP) activity, which is crucial for repair of DNA breaks induced by oxidative stress or chemotherapy, may be an additional predictive biomarker and a target for therapy with PARP inhibitors. We measured PARP activity in 109 patient-derived CLL samples, which varied widely (192 – 190052 pmol PAR/106 cells) compared to that seen in healthy volunteer lymphocytes (2451 – 7519 pmol PAR/106 cells). PARP activity was associated with PARP1 protein expression and endogenous PAR levels. PARP activity was not associated with p53 or ATM loss, Binet stage, IGHV mutational status or survival, but correlated with Bcl-2 and Rel A (an NF-kB subunit). Levels of 8-hydroxy-2′-deoxyguanosine in DNA (a marker of oxidative damage) were not associated with PAR levels or PARP activity. The potent PARP inhibitor, talazoparib (BMN 673), inhibited CD40L-stimulated proliferation of CLL cells at nM concentrations, independently of Binet stage or p53/ATM function. PARP activity is highly variable in CLL and correlates with stress-induced proteins. Proliferating CLL cells (including those with p53 or ATM loss) are highly sensitive to the PARP inhibitor talazoparib. PMID:26539646

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. | Office of Cancer Genomics

Cancer.gov

A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers.

[Perimetric changes in advanced glaucoma].

PubMed

Feraru, Crenguta Ioana; Pantalon, Anca

2011-01-01

The evaluation of various perimetric aspects in advanced glaucoma stages correlated to morpho-functional changes. MATHERIAL AND METHOD: Retrospective clinical trial over a 10 months time period that included patients with advanced glaucoma stages, for which there have been recorded several computerised visual field tests (central 24-2 strategy, 10-2 strategy with either III or V--Goldman stimulus spot size) along with other morpho-funtional ocular paramaters: VA, lOP optic disk analysis. We included in our study 56 eyes from 45 patients. In most cases 89% it was an open angle glaucoma (either primary or secondary) Mean visual acuity was 0.45 +/- 0.28. Regarding the perimetric deficit 83% had advanced deficit, 9% moderate and 8% early visual changes. As perimetric type of defect we found a majority with general reduction of sensitivity (33 eyes) + ring shape scotoma. In 6 eyes (10.7%) having left only a central isle of vision we performed the central 10-2 strategy with III or V Goldmann stimulus spot size. Statistic analysis showed scarce correlation between the visual acuity and the quantitative perimetric parameters (MD and PSD), and variance analysis found present a multiple correlation parameter p = 0.07 that proves there is no liniary correspondence between the morpho-functional parameters: VA-MD(PSD) and C/D ratio. In advanced glaucoma stages, the perimetric changes are mostly severe. Perimetric evaluation is essential in these stages and needs to be individualised.

International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review.

PubMed

Kushner, B H; Cheung, N K; LaQuaglia, M P; Ambros, P F; Ambros, I M; Bonilla, M A; Ladanyi, M; Gerald, W L

1996-07-01

To gain insight into the management of non-metastatic neuroblastoma by examining clinical and biologic features of International Neuroblastoma Staging System (INSS) stage 1 tumors. Patients were staged by both the INSS and the Evans staging system and were evaluated for biologic prognostic factors. Patients with INSS stage 1 received no cytotoxic therapy. The literature was reviewed for clinical and biologic data about INSS stage 1. We evaluated 10 consecutive patients (median age, 17.5 months) with INSS stage 1; all remain disease-free (median follow-up duration, > 5 years). Tumors were in the abdomen (n = 6), chest (n = 3), or pelvis (n = 1). Neuroblastoma involved margins of resection in six tumors. Poor-prognostic biologic findings included tumor-cell diploidy (n = 2) and unfavorable Shimada histopathology (n = 2). Two patients were to receive chemotherapy for, respectively, a tumor deemed unresectable and a tumor classified as Evans stage III; second opinions resulted in surgical management alone in each case. Published reports confirm that some INSS stage 1 patients (1) are at risk for overtreatment, and (2) have poor-prognostic biologic findings yet do well. Surgery alone suffices for INSS stage 1 neuroblastoma, even if biologic prognostic factors are unfavorable, microscopic disease remains after surgery, and tumor size is suggestive of "advanced-stage" status in other staging systems. Attempts to resect regionally confined neuroblastomas should take precedence over immediate use of cytotoxic therapy; otherwise, some patients may receive chemotherapy or radiotherapy unnecessarily.

Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma.

PubMed

Aman, Murasaki; Ohishi, Yoshihiro; Imamura, Hiroko; Shinozaki, Tomoko; Yasutake, Nobuko; Kato, Kiyoko; Oda, Yoshinao

2017-06-01

Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress up-regulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of ovarian endometrioid carcinoma (OEC) were also examined. No significant differences in the expression of cyclooxygenase-2 and inducible nitric oxide synthase were observed between OCCC and OEC. Sixty-two percent of the OCCC cases showed high 8-hydroxydeoxyguanosine expression, whereas all of the OEC cases showed almost negative immunoreactivities. The presence of endometriosis did not affect the expression of these oxidative stress markers or prognosis. High PAR-2 expression was observed in 20% (14/71) of the early International Federation of Gynecology and Obstetrics (FIGO) stage cases and 58% (14/24) of the advanced FIGO stage cases. High PAR-2 expression was significantly correlated with advanced FIGO stage and shorter overall survival. We found no correlations between PAR-2 expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an important role in the progression of OCCC. The expression of 8-hydroxydeoxyguanosine is a characteristic finding of OCCC, indicating that the injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Implementation status and explanatory analysis of early advance care planning for Stage IV non-small cell lung cancer patients.

PubMed

Tokito, Takaaki; Murakami, Haruyasu; Mori, Keita; Osaka, Iwao; Takahashi, Toshiaki

2015-03-01

The American Society of Clinical Oncology published the goals of individualized care including advance care planning for advanced cancer patients in 2011. However, no data are available on the implementation status of advance care planning. We retrospectively reviewed the electronic medical records and informed consent forms of consecutive Stage IV non-small cell lung cancer patients treated with chemotherapy between January 2010 and December 2012 at our institution. Two outcomes were defined to investigate the advance care planning implementation status: C-D, the duration from the last day of chemotherapy to death and D-D, that from the day of confirmed do-not-attempt-resuscitation order to death. The study included 136 eligible patients. The advance care planning implementation status in participating patients was as follows: 96 (70%) patients received information on 'incurable disease before first-line chemotherapy', 69 (50%) were informed about 'supportive care before first-line chemotherapy', whereas 43 (32%) learned about their prognosis. The do-not-attempt-resuscitation decision was reflected in 29 patients' will (21%). The median C-D was 64 days. Receipt of ≤2 chemotherapy regimens and provision of prognosis information to patients were significantly associated with long C-D in multivariate analysis. The median D-D was 25 days. Provision of information on supportive care before first-line chemotherapy and provision of prognosis information to patients were significantly associated with long D-D in multivariate analysis. Our results suggest that there is possible benefit from providing information on supportive care before first-line chemotherapy and informing patients about their prognosis in prolonging the duration of supportive care. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypofractionated Image-guided Radiation Therapy (3Gy/fraction) in Patients Affected by Inoperable Advanced-stage Non-small Cell Lung Cancer After Long-term Follow-up.

PubMed

Agolli, Linda; Valeriani, Maurizio; Bracci, Stefano; Nicosia, Luca; DE Sanctis, Vitaliana; Enrici, Riccardo Maurizi; Osti, Mattia Falchetto

2015-10-01

We conducted long-term follow-up analysis of the outcomes for patients affected by advanced-stage non-small cell lung cancer (NSCLC) treated with hypofractionated radiotherapy (RT). Sixty patients with advanced-stage NSCLC (IIIA-IV) treated with hypofractionated radiotherapy (60Gy/20 fractions) were analyzed. Radiation was delivered using an image-guided RT technique to verify the correct position. Toxicities were graded according to the Common Toxicity Criteria for Adverse Effects v4.0 scale. Overall, six patients achieved a complete response and 46 patients had a partial response (tumor response rate 86%). After a median follow-up of 30 months, locoregional progression occurred in 23 patients and distant progression occurred in 38. The 1-year and 2-years overall survival were 57% and 40%, respectively. The 1-year and 2-years progression-free survival (PFS) were 47.1% and 33.5%, respectively. The median duration of OS and PFS was 13 months and 12 months, respectively. The 2-year local PFS and metastases-free survival (MFS) were 53% and 40.3%, respectively. On univariate analysis, the T-size (≥5 cm), and type of response to RT (non-response/progressive disease) were significantly associated with worse OS. Type of response was identified as significant prognostic factors for PFS (p<0.01) local PFS (p=0.015) and MFS (p<0.01). Acute grade 3 esophagitis and pneumonitis occurred in three patients (5%) and four patients (6%), respectively. Late grade 3 esophagitis and pneumonitis occurred in 2% (one patient) and 3% (two patients), respectively. No patient experienced grade 4 acute or late RT-related toxicities. Hypofractionated RT offers good disease control for patients with advanced-stage NSCLC with acceptable toxicity rates. Phase III randomized trials are necessary to compare hypofractionated RT with conventional RT. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Advanced Theory of Mind in patients at early stage of Parkinson's disease.

PubMed

Yu, Rwei-Ling; Wu, Ruey-Meei; Chiu, Ming-Jang; Tai, Chun-Hwei; Lin, Chin-Hsien; Hua, Mau-Sun

2012-01-01

Advanced Theory of Mind (ToM) refers to the sophisticated ability to infer other people's thoughts, intentions, or emotions in social situations. With appropriate advanced ToM, one can behave well in social interactions and can understand the intention of others' behavior. Prefrontal cortex plays a vital role in this ability, as shown in functional brain imaging and lesion studies. Considering the primary neuropathology of Parkinson's disease (PD) involving the frontal lobe system, patients with PD are expected to exhibit deficits in advanced ToM. However, few studies on this issue have been explored, and whether advanced ToM is independent of executive functions remains uncertain. Thirty-nine early non-demented PD patients and 40 normal control subjects were included. Both groups were matched in age, level of education, and verbal intelligence quotient. Each participant received advanced ToM, executive functions, and verbal intelligence quotient tests. We discovered that the performance of the PD patients on the Cartoon ToM task was significantly poorer than that of their normal counterparts. Correlation analysis revealed that performance scores of advanced ToM in PD patients were significantly associated with their executive functions scores; however, this is not the case for normal controls. We conclude that dysfunction of advanced ToM develops in early PD patients, who require more cognitive abilities than their normal counterparts to generate advanced ToM. Our findings might be helpful in developing educational and medical care programs for PD patients in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

2017-04-26

Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

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

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less

Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria.

PubMed

Gunn, Andrew J; Sheth, Rahul A; Luber, Brandon; Huynh, Minh-Huy; Rachamreddy, Niranjan R; Kalva, Sanjeeva P

2017-01-01

The purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC). Hospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which, if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP). 75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6-24.8) and 9.8 months (95 % CI 7.1-21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51-0.58 in the univariate model; range: 0.54-0.58 in the multivariate model) or TTP (C-statistic range: 0.55-0.59 in the univariate model; range: 0.57-0.61 in the multivariate model). Current response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.

[Advances in the management of cervical lymphadenopathies of unknown primary: advances in diagnostic imaging and surgical modalities and new international staging system].

PubMed

Troussier, Idriss; Klausner, Guillaume; Morinière, Sylvain; Blais, Eivind; Jean-Christophe Faivre; Champion, Ambroise; Geoffrois, Lionnel; Pflumio, Carole; Babin, Emmanuel; Maingon, Philippe; Thariat, Juliette

2018-02-01

Cervical lymphadenopathies of unknown primary represent 3 % of head and neck cancers. Their diagnostic work up has largely changed in recent years. This review provides an update on diagnostic developments and their potential therapeutic impact. This is a systematic review of the literature. In recent years, changes in epidemiology-based prognostic factors such as human papilloma virus (HPV) cancers, advances in imaging and minimally invasive surgery have been integrated in the management of cervical lymphadenopathies of unknown primary. In particular, systematic use of PET scanner and increasing practice of robotic or laser surgery have contributed to increasing detection rate of primary cancers. These allow more adapted and personalized treatments. The impact of changes in the eighth TNM staging system is discussed. The management of cervical lymphadenopathies of unknown primary cancer has changed significantly in the last 10 years. On the other hand, practice changes will have to be assessed. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

TEN-YEAR FOLLOW UP OF A PHASE II STUDY OF DOSE-INTENSE PACLITAXEL WITH CISPLATIN AND CYCLOPHOSPHAMIDE AS INITIAL THERAPY FOR POOR-PROGNOSIS ADVANCED-STAGE EPITHELIAL OVARIAN CANCER

PubMed Central

Sarosy, Gisele A.; Hussain, Mahrukh M.; Seiden, Michael V.; Fuller, A.F.; Nikrui, N.; Goodman, Annekathryn; Minasian, Lori; Reed, Eddie; Steinberg, Seth M.; Kohn, Elise C.

2009-01-01

SUMMARY Background To assess activity and toxicity in newly diagnosed advanced stage epithelial ovarian cancer (EOC) patients receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. Methods Patients with Stage III/IV EOC received cyclophosphamide 750 mg/m2, followed by 24 hr infusion of paclitaxel 250 mg/m2, and cisplatin 75 mg/m2 on day 2. Filgrastim began on day 3 at 10 μg/kg/d × 9d. Patients received six cycles of all drugs. Those with pathologic complete response or microscopic residual disease at the conclusion of six cycles of therapy received an additional cycles two to four cycles of paclitaxel with cyclophosphamide. Patients with objective response continued cyclophosphamide and paclitaxel. Results 62 patients were enrolled. Thirty-two of these 62 patients had stage IIIC disease, and 26 of 62 had stage IV disease. Using an intent to treat analysis, 55 (89%) experienced clinical complete remission (CCR). With a median potential follow-up of 11.4 years, the median progression free survival is 18.9 months and median survival is 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with decrease or cessation of paclitaxel. Conclusions This regimen yielded a high response rate and encouraging overall survival. These data and those of the Japanese Gynecologic Oncology Group suggest that further study of dose dense or intense paclitaxel regimens in women with newly diagnosed advanced stage EOC is warranted. PMID:20091841

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

PubMed

Shankar, Ananth G; Roques, Gaelle; Kirkwood, Amy A; Lambilliotte, Anne; Freund, Katja; Leblanc, Thierry; Hayward, Janis; Abbou, Samuel; Ramsay, Alan D; Schmitt, Claudine; Gorde-Grosjean, Stephanie; Pacquement, Hélène; Haouy, Stephanie; Boudjemaa, Sabah; Aladjidi, Nathalie; Hall, Georgina W; Landman-Parker, Judith

2017-04-01

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. © 2017 John Wiley & Sons Ltd.

Laparoscopic staging for apparent stage I epithelial ovarian cancer.

PubMed

Melamed, Alexander; Keating, Nancy L; Clemmer, Joel T; Bregar, Amy J; Wright, Jason D; Boruta, David M; Schorge, John O; Del Carmen, Marcela G; Rauh-Hain, J Alejandro

2017-01-01

Whereas advances in minimally invasive surgery have made laparoscopic staging technically feasible in stage I epithelial ovarian cancer, the practice remains controversial because of an absence of randomized trials and lack of high-quality observational studies demonstrating equivalent outcomes. This study seeks to evaluate the association of laparoscopic staging with survival among women with clinical stage I epithelial ovarian cancer. We used the National Cancer Data Base to identify all women who underwent surgical staging for clinical stage I epithelial ovarian cancer diagnosed from 2010 through 2012. The exposure of interest was planned surgical approach (laparoscopy vs laparotomy), and the primary outcome was overall survival. The primary analysis was based on an intention to treat: all women whose procedures were initiated laparoscopically were categorized as having had a planned laparoscopic procedure, regardless of subsequent conversion to laparotomy. We used propensity methods to match patients who underwent planned laparoscopic staging with similar patients who underwent planned laparotomy based on observed characteristics. We compared survival among the matched cohorts using the Kaplan-Meier method and Cox regression. We compared the extent of lymphadenectomy using the Wilcoxon rank-sum test. Among 4798 eligible patients, 1112 (23.2%) underwent procedures that were initiated laparoscopically, of which 190 (17%) were converted to laparotomy. Women who underwent planned laparoscopy were more frequently white, privately insured, from wealthier ZIP codes, received care in community cancer centers, and had smaller tumors that were more frequently of serous and less often of mucinous histology than those who underwent staging via planned laparotomy. After propensity score matching, time to death did not differ between patients undergoing planned laparoscopic vs open staging (hazard ratio, 0.77, 95% confidence interval, 0.54-1.09; P = .13). Planned

[The initial (I and II) and advanced (III and IV) stages of juvenile patellar chondromalacia. Its diagnosis by magnetic resonance using a 1.5-T magnet with FLASH sequences].

PubMed

Macarini, L; Rizzo, A; Martino, F; Zaccheo, N; Angelelli, G; Rotondo, A

1998-06-01

Juvenile patellar chondromalacia is a common orthopedic disorder which can mimic other conditions; early diagnosis is mandatory to prevent its evolution into osteoarthrosis. In the early stages of patellar chondromalacia (I and II), the lesions originate in the deep cartilage layer and the joint surface is not affected. Arthroscopy can demonstrate joint surface changes only and give indirect information about deeper lesions. We investigated the yield of 2D FLASH MRI with 30 degrees flip angle and a dedicated coil in the diagnosis of patellar chondromalacia, especially in its early stages. Eighteen patients (mean age: 21 years) with clinically suspected patellar chondromalacia were examined with MRI; 13 of them were also submitted to arthroscopy. A 1.5 T unit with a transmit-and-receive extremity coil was used. We acquired T1 SE sequences (TR/TE: 500-700/15/20) and 2D T2* FLASH sequence (TR/TE/FA: 500-800/18/30 degrees). The field of view was 160-180 mm and the matrix 192 x 256, with 2-3 NEX. The images were obtained on the axial plane. The lesions were classified in 4 stages according to Shahriaree classification. Agreement between MR and arthroscopic findings was good in both early and advanced lesions in 12/13 cases. Early lesions appeared as hyperintense focal thickening of the hyaline cartilage (stage I) or as small cystic lesions within the cartilage and no articular surface involvement (stage II). The medial patellar facet was the most frequent site. Advanced lesions appeared as articular surface ulcerations, thinning and cartilage hypointensity (stage III); stage IV lesions presented as complete erosions of the hyaline cartilage and hypointense underlying bone. 2D FLASH MRI with 30 degrees flip angle can show the differences in water content in the cartilage and thus permit to detect early chondromalacia lesions in the deep cartilage.

No advanced retinopathy of prematurity stages 4 or 5 in a large high-risk German cohort.

PubMed

Muether, Philipp S; Kribs, Angela; Hahn, Moritz; Schumacher, Jasmin; Eifinger, Frank; Kirchhof, Bernd; Roth, Bernhard; Fauser, Sascha

2012-03-01

Retinopathy of prematurity (ROP) remains a major cause of juvenile blindness. As screening recommendations are refined, decreasing gestational age (GA) and birth weight (BW) constitute an increasing risk for ROP. This retrospective case series reviews the screening results of a very immature cohort in Germany. We conducted ROP screening according to the German guidelines of 1999: all preterm infants with a GA of < 32 weeks and/or a BW of < 1501 g, or with GA ≥ 32 weeks and postnatal oxygen treatment for > 3 days, were assigned for screening. Dense laser coagulation was performed according to the current treatment criteria. All 767 consecutive inborn (patients born at the Department of Neonatology, University Hospital of Cologne, Germany) preterm infants of a tertiary medical centre of maximum care underwent complete screening from 2001 to 2009. The treatment incidence was 7.0%. No preterm infant developed stage 4/5 ROP. Mean GA and BW of untreated/treated preterm infants were 28.4/24.6 weeks and 1109/635 g, respectively. Increasing treatment incidence was associated with lower GA, but not with lower BW in logistic regression analysis. In this very immature high-risk cohort, advanced stages 4 and 5 were avoided throughout 9 years of screening. We suggest three factors that contributed to this outcome: (1) strict adherence to current ROP screening and treatment guidelines; (2) prompt and very dense laser coagulation if necessary; and (3) a specialised neonatal intensive care unit with experience of very immature babies.

Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

PubMed Central

Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

2010-01-01

Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

Juvenile nasopharyngeal angiofibroma staging: An overview.

PubMed

Alshaikh, Nada Ali; Eleftheriadou, Anna

2015-06-01

Staging of tumors is very important in treatment and surgical decision making, as well as in predicting disease recurrence and prognosis. This review focuses on the different available classifications of juvenile nasopharyngeal angiofibroma (JNA) and their impact on the evaluation, management, and prognosis of JNA. The literature was reviewed, and publications on JNA staging were examined. Our MEDLINE search of the entire English-language literature found no review article on the current available staging systems for JNA. In this article, we review the common JNA classification systems that have been published, and we discuss some of their advantages and disadvantages. The most commonly used staging systems for JNA are the Radkowski and the Andrews-Fisch staging systems. However, some newer staging systems that are based on advances in technology and surgical approaches-the Onerci, INCan, and UPMC systems-have shown promising utility, and they will probably gain popularity in the future.

Evolution in Stage-Structured Populations

PubMed Central

Barfield, Michael; Holt, Robert D.; Gomulkiewicz, Richard

2016-01-01

For many organisms, stage is a better predictor of demographic rates than age. Yet no general theoretical framework exists for understanding or predicting evolution in stage-structured populations. Here, we provide a general modeling approach that can be used to predict evolution and demography of stage-structured populations. This advances our ability to understand evolution in stage-structured populations to a level previously available only for populations structured by age. We use this framework to provide the first rigorous proof that Lande’s theorem, which relates adaptive evolution to population growth, applies to stage-classified populations, assuming only normality and that evolution is slow relative to population dynamics. We extend this theorem to allow for different means or variances among stages. Our next major result is the formulation of Price’s theorem, a fundamental law of evolution, for stage-structured populations. In addition, we use data from Trillium grandiflorum to demonstrate how our models can be applied to a real-world population and thereby show their practical potential to generate accurate projections of evolutionary and population dynamics. Finally, we use our framework to compare rates of evolution in age- versus stage-structured populations, which shows how our methods can yield biological insights about evolution in stage-structured populations. PMID:21460563

[Advances in studies on multi-stage countercurrent extraction technology in traditional Chinese medicine].

PubMed

Xie, Zhi-Peng; Liu, Xue-Song; Chen, Yong; Cai, Ming; Qu, Hai-Bin; Cheng, Yi-Yu

2007-05-01

Multi-stage countercurrent extraction technology, integrating solvent extraction, repercolation with dynamic and countercurrent extraction, is a novel extraction technology for the traditional Chinese medicine. This solvent-saving, energy-saving and high-extraction-efficiency technology can at the most drive active compounds to diffuse from the herbal materials into the solvent stage by stage by creating concentration differences between the herbal materials and the solvents. This paper reviewed the basic principle, the influence factors and the research progress and trends of the equipments and the application of the multi-stage countercurrent extraction.

Endometrial cancer: socioeconomic status and racial/ethnic differences in stage at diagnosis, treatment, and survival.

PubMed

Madison, Terri; Schottenfeld, David; James, Sherman A; Schwartz, Ann G; Gruber, Stephen B

2004-12-01

We evaluated the association between socioeconomic status and racial/ ethnic differences in endometrial cancer stage at diagnosis, treatment, and survival. We conducted a population-based study among 3656 women. Multivariate analyses showed that either race/ethnicity or income, but not both, was associated with advanced-stage disease. Age, stage at diagnosis, and income were independent predictors of hysterectomy. African American ethnicity, increased age, aggressive histology, poor tumor grade, and advanced-stage disease were associated with increased risk for death; higher income and hysterectomy were associated with decreased risk for death. Lower income was associated with advanced-stage disease, lower likelihood of receiving a hysterectomy, and lower rates of survival. Earlier diagnosis and removal of barriers to optimal treatment among lower-socioeconomic status women will diminish racial/ethnic differences in endometrial cancer survival.

Disability in Activities of Daily Living and Severity of Dyskinesias Determine the Handicap of Parkinson's Disease Patients in Advanced Stage Selected to DBS.

PubMed

Coelho, Miguel; Abreu, Daisy; Correia-Guedes, Leonor; Lobo, Patricia Pita; Fabbri, Margherita; Godinho, Catarina; Domingos, Josefa; Albuquerque, Luisa; Freitas, Vanda; Pereira, João Miguel; Cattoni, Begona; Carvalho, Herculano; Reimão, Sofia; Rosa, Mário M; Ferreira, António Gonalves; Ferreira, Joaquim J

2017-01-01

There is scarce data on the level of handicap in Parkinson's disease (PD) and none in advanced stage PD. To assess the handicap in advanced stage PD patients with disabling levodopa-induced motor complications selected to deep brain stimulation (DBS). Data was prospectively recorded during routine evaluation for DBS. Handicap was measured using London Handicap Scale (LHS) (0 = maximal handicap; 1 = no handicap). Disease severity was evaluated using the Hoehn & Yahr scale and the UPDRS/MDS-UPDRS, during off and on after a supra-maximal dose of levodopa. Schwab and England Scale (S&E) was scored in off and on. Dyskinesias were scored using the modified Abnormal Involuntary Movement Scale (mAIMS). Results concern cross-sectional assessment before DBS. 100 PD patients (mean age 61 (±7.6); mean disease duration 12.20 (±4.6) years) were included. Median score of motor MDS-UPDRS was 54 in off and 25 in on. Mean total LHS score was 0.56 (±0.14). Patients were handicapped in several domains with a wide range of severity. Physical Independence and Social Integration were the most affected domains. Determinants of total LHS score were MDS-UPDRS part II off (β= -0.271; p = 0.020), S&E on (β= 0.264; p = 0.005) and off (β= 0.226; p = 0.020), and mAIMS on (β= -0.183; p = 0.042) scores (R2  = 29.6%). We were able to use handicap to measure overall health condition in advanced stage PD. Patients were moderately to highly handicapped and this was strongly determined by disability in ADL and dyskinesias. Change in handicap may be a good patient-centred outcome to assess efficiency of DBS.

A Matched Cohort Study of Patients With End-Stage Heart Failure from Anthracycline-Induced Cardiomyopathy Requiring Advanced Cardiac Support.

PubMed

Thomas, Garry R; McDonald, Michael A; Day, Jennifer; Ross, Heather J; Delgado, Diego H; Billia, Filio; Butany, Jagdish W; Rao, Vivek; Amir, Eitan; Bedard, Philippe L; Thavendiranathan, Paaladinesh

2016-11-15

Anthracycline-induced cardiomyopathy (AIC) may progress to end-stage heart failure requiring mechanical circulatory support or orthotopic heart transplantation (OHT). Previous studies have described important clinical differences between AIC and nonischemic cardiomyopathy (NIC) cohorts requiring these advanced interventions. Therefore, we sought to extend this literature by comparing echocardiographic parameters, treatment strategies, and the prognosis between matched patients from these cohorts. This is a retrospective matched cohort study. All patients who received a ventricular assist device or OHT at a large Canadian center were reviewed (n = 421; 1988 to 2015) and subjects with clinical and pathologic evidence of AIC were included (n = 17, 4.0%). A comparison cohort with idiopathic NIC from the same database, matched 3:1 for age, gender, ethnicity, and year of heart failure onset was selected. The Mann-Whitney rank-sum and Fisher's exact tests were used for comparisons. Patients with AIC were predominantly women (70.6%) with heart failure diagnosed at age 40.2 ± 15.8 and 8.3 ± 8.9 years after anthracycline treatment. Compared with NIC, no differences were seen in co-morbidities, echocardiographic measures, the proportion of patients receiving a defibrillator, ventricular assist device, or OHT, the incidence of graft failure, and all-cause mortality. In contrast to other studies, AIC was not associated with a higher incidence of right ventricular dysfunction. A greater proportion of patients with AIC developed cancer (recurrence or new primary) post-OHT (21.4% vs 2.3%, p = 0.042). In conclusion, we demonstrate that when matched cohorts of patients with end-stage heart failure secondary to AIC and idiopathic NIC are compared, they are similar with respect to co-morbidities, degree of ventricular dysfunction, and advanced therapeutics used. The prognosis with OHT is also similar. Copyright © 2016 Elsevier Inc. All rights reserved.

Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria

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

Gunn, Andrew J., E-mail: agunn@uabmc.edu; Sheth, Rahul A.; Luber, Brandon

2017-01-15

PurposeThe purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC).Materials and methodsHospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which,more » if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP).Results75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6–24.8) and 9.8 months (95 % CI 7.1–21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51–0.58 in the univariate model; range: 0.54–0.58 in the multivariate model) or TTP (C-statistic range: 0.55–0.59 in the univariate model; range: 0.57–0.61 in the multivariate model).ConclusionCurrent response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE.« less

The Unique Dorsal Brood Pouch of Thermosbaenacea (Crustacea, Malacostraca) and Description of an Advanced Developmental Stage of Tulumella unidens from the Yucatan Peninsula (Mexico), with a Discussion of Mouth Part Homologies to Other Malacostraca

PubMed Central

Olesen, Jørgen; Boesgaard, Tom; Iliffe, Thomas M.

2015-01-01

The Thermosbaenacea, a small taxon of crustaceans inhabiting subterranean waters, are unique among malacostracans as they brood their offspring dorsally under the carapace. This habit is of evolutionary interest but the last detailed report on thermosbaenacean development is more than 40 years old. Here we provide new observations on an ovigerous female of Tulumella unidens with advanced developmental stages in its brood chamber collected from an anchialine cave at the Yucatan Peninsula, which is only the third report on developmental stages of Thermosbaenacea and the first for the genus Tulumella. Significant in a wider crustacean context, we report and discuss hitherto unexplored lobate structures inside the brood chamber of the female originating at the first (maxilliped) and second thoracic segments, which are most likely modified epipods, perhaps serving as gills. At the posterior margin of carapace of the female are rows of large spines preventing the developing stages from falling out. The external morphology of the advanced developmental stages is described in much detail, providing information on e.g., carapace formation and early limb morphology. Among the hitherto unknown structures in the advanced developmental stages provided by this study are the presence of an embryonic dorsal organ and rudimentary ‘naupliar processes’ of the second antennae. Since most hypotheses on crustacean (and malacostracan and peracaridan) relationship rest on external limb morphology, we use early limb bud morphology of Tulumella to better establish thermosbaenacean limb homologies to those of other crustaceans, which is a necessary basis for future morphology based phylogenetic considerations. PMID:25901753

The Unique Dorsal Brood Pouch of Thermosbaenacea (Crustacea, Malacostraca) and Description of an Advanced Developmental Stage of Tulumella unidens from the Yucatan Peninsula (Mexico), with a Discussion of Mouth Part Homologies to Other Malacostraca.

PubMed

Olesen, Jørgen; Boesgaard, Tom; Iliffe, Thomas M

2015-01-01

The Thermosbaenacea, a small taxon of crustaceans inhabiting subterranean waters, are unique among malacostracans as they brood their offspring dorsally under the carapace. This habit is of evolutionary interest but the last detailed report on thermosbaenacean development is more than 40 years old. Here we provide new observations on an ovigerous female of Tulumella unidens with advanced developmental stages in its brood chamber collected from an anchialine cave at the Yucatan Peninsula, which is only the third report on developmental stages of Thermosbaenacea and the first for the genus Tulumella. Significant in a wider crustacean context, we report and discuss hitherto unexplored lobate structures inside the brood chamber of the female originating at the first (maxilliped) and second thoracic segments, which are most likely modified epipods, perhaps serving as gills. At the posterior margin of carapace of the female are rows of large spines preventing the developing stages from falling out. The external morphology of the advanced developmental stages is described in much detail, providing information on e.g., carapace formation and early limb morphology. Among the hitherto unknown structures in the advanced developmental stages provided by this study are the presence of an embryonic dorsal organ and rudimentary 'naupliar processes' of the second antennae. Since most hypotheses on crustacean (and malacostracan and peracaridan) relationship rest on external limb morphology, we use early limb bud morphology of Tulumella to better establish thermosbaenacean limb homologies to those of other crustaceans, which is a necessary basis for future morphology based phylogenetic considerations.

Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: discordance between stage and biology.

PubMed

Jung, Hyun Ae; Park, Yeon Hee; Kim, Moonjin; Kim, Sungmin; Chang, Won Jin; Choi, Moon Ki; Hong, Jung Yong; Kim, Seok Won; Kil, Won Ho; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck

2015-02-01

Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I-III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4%) patients were stage I, and 682 (59.6%) were stage II or III. In addition, 701 (61.2%) patients were HR positive, 239 (20.9%) were HER2 positive, and 205 (20.9%) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0-25%) was 99%. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83%, respectively (P value = <0.001). In multivariate analysis, advanced stage (II/III) and unfavorable biology (HER2 positive or triple negative) retained their statistical significance as predictors of decreased RFS and OS. Patients with advanced-stage disease (II or III) but favorable tumor biology (HR positive and HER2 negative and low Ki 67) had better clinical outcomes than those with stage I disease and unfavorable tumor biology in terms of RFS (99 versus 92%, P value = 0.011) and OS (99 versus 96%, P value = 0.03) at 5 years. The current results showed that intrinsic subtype has a greater prognostic impact in predicting clinical outcomes in subpopulations of patients with stage I-III breast cancer who show

Results of Two-Stage Light-Gas Gun Development Efforts and Hypervelocity Impact Tests of Advanced Thermal Protection Materials

NASA Technical Reports Server (NTRS)

Cornelison, C. J.; Watts, Eric T.

1998-01-01

Gun development efforts to increase the launching capabilities of the NASA Ames 0.5-inch two-stage light-gas gun have been investigated. A gun performance simulation code was used to guide initial parametric variations and hardware modifications, in order to increase the projectile impact velocity capability to 8 km/s, while maintaining acceptable levels of gun barrel erosion and gun component stresses. Concurrent with this facility development effort, a hypervelocity impact testing series in support of the X-33/RLV program was performed in collaboration with Rockwell International. Specifically, advanced thermal protection system materials were impacted with aluminum spheres to simulate impacts with on-orbit space debris. Materials tested included AETB-8, AETB-12, AETB-20, and SIRCA-25 tiles, tailorable advanced blanket insulation (TABI), and high temperature AFRSI (HTA). The ballistic limit for several Thermal Protection System (TPS) configurations was investigated to determine particle sizes which cause threshold TPS/structure penetration. Crater depth in tiles was measured as a function of impact particle size. The relationship between coating type and crater morphology was also explored. Data obtained during this test series was used to perform a preliminary analysis of the risks to a typical orbital vehicle from the meteoroid and space debris environment.

Endometrial Cancer: Socioeconomic Status and Racial/Ethnic Differences in Stage at Diagnosis, Treatment, and Survival

PubMed Central

Madison, Terri; Schottenfeld, David; James, Sherman A.; Schwartz, Ann G.; Gruber, Stephen B.

2004-01-01

Objective. We evaluated the association between socioeconomic status and racial/ ethnic differences in endometrial cancer stage at diagnosis, treatment, and survival. Methods. We conducted a population-based study among 3656 women. Results. Multivariate analyses showed that either race/ethnicity or income, but not both, was associated with advanced-stage disease. Age, stage at diagnosis, and income were independent predictors of hysterectomy. African American ethnicity, increased age, aggressive histology, poor tumor grade, and advanced-stage disease were associated with increased risk for death; higher income and hysterectomy were associated with decreased risk for death. Conclusions. Lower income was associated with advanced-stage disease, lower likelihood of receiving a hysterectomy, and lower rates of survival. Earlier diagnosis and removal of barriers to optimal treatment among lower-socioeconomic status women will diminish racial/ethnic differences in endometrial cancer survival. PMID:15569961

Stage acoustics for musicians: A multidimensional approach using 3D ambisonic technology

NASA Astrophysics Data System (ADS)

Guthrie, Anne

In this research, a method was outlined and tested for the use of 3D Ambisonic technology to inform stage acoustics research and design. Stage acoustics for musicians as a field has yet to benefit from recent advancements in auralization and spatial acoustic analysis. This research attempts to address common issues in stage acoustics: subjective requirements for performers in relation to feelings of support, quality of sound, and ease of ensemble playing in relation to measurable, objective characteristics that can be used to design better stage enclosures. While these issues have been addressed in previous work, this research attempts to use technological advancements to improve the resolution and realism of the testing and analysis procedures. Advancements include measurement of spatial impulse responses using a spherical microphone array, higher-order ambisonic encoding and playback for real-time performer auralization, high-resolution spatial beamforming for analysis of onstage impulse responses, and multidimensional scaling procedures to determine subjective musician preferences. The methodology for implementing these technologies into stage acoustics research is outlined in this document and initial observations regarding implications for stage enclosure design are proposed. This research provides a robust method for measuring and analyzing performer experiences on multiple stages without the costly and time-intensive process of physically surveying orchestras on different stages, with increased repeatability while maintaining a high level of immersive realism and spatial resolution. Along with implications for physical design, this method provides possibilities for virtual teaching and rehearsal, parametric modeling and co-located performance.

Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

PubMed

Wong, Kwong-Kwok; Lu, Karen H; Malpica, Anais; Bodurka, Diane C; Shvartsman, Hyun S; Schmandt, Rosemarie E; Thornton, Angela D; Deavers, Michael T; Silva, Elvio G; Gershenson, David M

2007-10-01

A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

Cascaded interactions between Raman induced solitons and dispersive waves in photonic crystal fibers at the advanced stage of supercontinuum generation.

PubMed

Driben, Rodislav; Mitschke, Fedor; Zhavoronkov, Nickolai

2010-12-06

The complex mechanism of multiple interactions between solitary and dispersive waves at the advanced stage of supercontinuum generation in photonic crystal fiber is studied in experiment and numerical simulations. Injection of high power negatively chirped pulses near zero dispersion frequency results in an effective soliton fission process with multiple interactions between red shifted Raman solitons and dispersive waves. These interactions may result in relative acceleration of solitons with further collisions between them of quasi-elastic or quasi-plastic kinds. In the spectral domain these processes result in enhancement of certain wavelength regions within the spectrum or development of a new significant band at the long wavelength side of the spectrum.

New advances in focal therapy for early stage prostate cancer.

PubMed

Tay, Kae Jack; Schulman, Ariel A; Sze, Christina; Tsivian, Efrat; Polascik, Thomas J

2017-08-01

Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

The Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Broadway, Jeramie W.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Borowski, Stanley K.; Scott, John

2014-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP). Nuclear propulsion can be affordable and viable compared to other propulsion systems and must overcome a biased public fear due to hyper-environmentalism and a false perception of radiation and explosion risk.

Cancer Stage at Diagnosis in HIV-infected People and Transplant Recipients

PubMed Central

Shiels, Meredith S.; Copeland, Glenn; Goodman, Marc T.; Harrell, Janna; Lynch, Charles F.; Pawlish, Karen; Pfeiffer, Ruth M.; Engels, Eric A.

2015-01-01

Background It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. As cancer stage is influenced both by tumor biology and medical surveillance, we assessed cancer stage in HIV-infected individuals and solid organ transplant recipients, two immunosuppressed groups with differences in healthcare utilization. Methods We used data on all cases of 15 cancer types, diagnosed during 1996–2010 in two studies that linked U.S. cancer registries to HIV and transplant registries. Odds ratios (ORs) for advanced (vs. local) disease were estimated comparing HIV and transplant populations to immunocompetent people in polytomous logistic regression models, adjusted for age, sex, race, registry and year. Results A total of 8,411 of 4.5 million cancer cases occurred in HIV-infected people, and 7,322 of 6.4 million cancer cases occurred in transplant recipients. Compared to immunocompetent people with cancer, HIV-infected people were more likely to be diagnosed with distant stage lung (OR=1.13), female breast (OR=1.99), and prostate cancers (OR=1.57), while transplant recipients had fewer distant stage lung (OR=0.54), female breast (OR=0.75) and prostate cancers (OR=0.72). Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs: HIV=1.97; transplant=1.82) and bladder cancer (ORs: HIV=1.42; transplant=1.54). Conclusions Bladder cancer and melanoma were more likely to be diagnosed at non-local stage in both HIV-infected people and transplant recipients, suggesting a role of immunosuppression in their progression. Additionally, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, consistent with differential access to medical care or surveillance. PMID:25739496

Nuclear Cryogenic Propulsion Stage for Mars Exploration

NASA Technical Reports Server (NTRS)

Houts, M. G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

Challenges of advanced hepatocellular carcinoma

PubMed Central

Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

2016-01-01

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

Long-term/strategic scenario for reusable booster stages

NASA Astrophysics Data System (ADS)

Sippel, Martin; Manfletti, Chiara; Burkhardt, Holger

2006-02-01

This paper describes the final design status of a partially reusable space transportation system which has been under study for five years within the German future launcher technology research program ASTRA. It consists of dual booster stages, which are attached to an advanced expendable core. The design of the reference liquid fly-back boosters (LFBB) is focused on LOX/LH2 propellant and a future advanced gas-generator cycle rocket motor. The preliminary design study was performed in close cooperation between DLR and the German space industry. The paper's first part describes recent progress in the design of this reusable booster stage. The second part of the paper assesses a long-term, strategic scenario of the reusable stage's operation. The general idea is the gradual evolution of the above mentioned basic fly-back booster vehicle into three space transportation systems performing different tasks: Reusable First Stage for a small launcher application, successive development to a fully reusable TSTO, and booster for a super-heavy-lift rocket to support an ambitious space flight program like manned Mars missions. The assessment addresses questions of technical sanity, preliminary sizing and performance issues and, where applicable, examines alternative options.

Clinical diagnosis and staging of cholangiocarcinoma

PubMed Central

Blechacz, Boris; Komuta, Mina; Roskams, Tania; Gores, Gregory J.

2012-01-01

Cholangiocarcinoma is the most frequent biliary malignancy. It is difficult to diagnose owing to its anatomic location, growth patterns and lack of definite diagnostic criteria. Currently, cholangiocarcinoma is classified into the following types according to its anatomic location along the biliary tree: intrahepatic, perihilar or distal extrahepatic cholangiocarcinoma. These cholangiocarcinoma types differ in their biological behavior and management. The appropriate stratification of patients with regard to the anatomic location and stage of cholangiocarcinoma is a key determinate in their management. Staging systems can guide this stratification and provide prognostic information. In addition, staging systems are essential in order to compare and contrast the outcomes of different therapeutic approaches. A number of staging systems exist for cholangiocarcinoma—several early ones have been updated, and new ones are being developed. We discuss the emerging diagnostic criteria as well as the different staging systems for cholangiocarcinoma, and provide a critical appraisal regarding these advances in biliary tract malignancies. PMID:21808282

Composites for Exploration Upper Stage

NASA Technical Reports Server (NTRS)

Fikes, J. C.; Jackson, J. R.; Richardson, S. W.; Thomas, A. D.; Mann, T. O.; Miller, S. G.

2016-01-01

The Composites for Exploration Upper Stage (CEUS) was a 3-year, level III project within the Technology Demonstration Missions program of the NASA Space Technology Mission Directorate. Studies have shown that composites provide important programmatic enhancements, including reduced weight to increase capability and accelerated expansion of exploration and science mission objectives. The CEUS project was focused on technologies that best advanced innovation, infusion, and broad applications for the inclusion of composites on future large human-rated launch vehicles and spacecraft. The benefits included near- and far-term opportunities for infusion (NASA, industry/commercial, Department of Defense), demonstrated critical technologies and technically implementable evolvable innovations, and sustained Agency experience. The initial scope of the project was to advance technologies for large composite structures applicable to the Space Launch System (SLS) Exploration Upper Stage (EUS) by focusing on the affordability and technical performance of the EUS forward and aft skirts. The project was tasked to develop and demonstrate critical composite technologies with a focus on full-scale materials, design, manufacturing, and test using NASA in-house capabilities. This would have demonstrated a major advancement in confidence and matured the large-scale composite technology to a Technology Readiness Level 6. This project would, therefore, have bridged the gap for providing composite application to SLS upgrades, enabling future exploration missions.

Quality analysis of population-based information on cancer stage at diagnosis across Europe, with presentation of stage-specific cancer survival estimates: A EUROCARE-5 study.

PubMed

Minicozzi, Pamela; Innos, Kaire; Sánchez, Maria-José; Trama, Annalisa; Walsh, Paul M; Marcos-Gragera, Rafael; Dimitrova, Nadya; Botta, Laura; Visser, Otto; Rossi, Silvia; Tavilla, Andrea; Sant, Milena

2017-10-01

Cancer registries (CRs) are fundamental for estimating cancer burden, evaluating screening and monitoring health service performance. Stage at diagnosis-an essential information item collected by CRs-has been made available, for the first time, by CRs participating in EUROCARE-5. We analysed the quality of this information and estimated stage-specific survival across Europe for CRs with good data quality. Sixty-two CRs sent stage (as TNM, condensed TNM or extent of disease) for 15 cancers diagnosed in 2000-2007. We assessed the quality, partly by comparing stage according to the three systems. We also developed procedures to reconstruct stage (categories: local, regional, metastatic and unknown) using information from all three systems, thus minimising the amount of missing information. Moderate-to-excellent stage concordance was found for practically all 24 CRs, for which it was possible to compare at least two staging systems. However, since stage was often incorrectly assigned, and information on the presence/absence of metastases was often lacking, data on only 7/15 cancers from 34/62 CRs (15 countries) were of sufficient quality for further analysis. Cases diagnosed ≥70 years had more advanced (or lacking) stage- and worse stage-specific survival than those <70 years. Many European CRs collect and record reasonably accurate stage information. Others have difficulties. Both the completeness of primary data and the accuracy of stage coding need to be improved in order for CRs to fulfil their expanding roles in cancer control. We propose our stage reconstruction/checking procedures as a means of fully exploiting the stage information provided by EUROCARE CRs. More advanced (or lacking) stage at diagnosis plus poorer stage-specific survival in the elderly are worrying. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sorafenib Tosylate and Pembrolizumab in Treating Patients With Advanced or Metastatic Liver Cancer

ClinicalTrials.gov

2018-06-04

Advanced Adult Hepatocellular Carcinoma; Child-Pugh Class A; Stage III Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

Changes in inflorescence protein during advanced stages of floret development in Buchloe dactyloides (Poaceae).

PubMed

Zhou, Y-J; Xue, J-G; Wang, X-G; Zhang, X-Q

2012-11-12

Buffalograss, Buchloe dactyloides, is a dioecious species native to the Great Plains of North America. The florets at the early stages of development possess both gynoecium and androecium organ primordia but later become unisexual. Very little is known about the proteomic changes that occur when the florets change from hermaphroditism to unisexuality. We compared the protein composition of florets at the hermaphroditic stage with that at the unisexual stage. The development stage of the floret was determined by stereomicroscopic observation. Two-dimensional gel electrophoresis was used to separate the proteins extracted from female and male inflorescences. Stage- specific protein maps, with an average of about 400 spots per map, were analyzed with the protein analysis software. Eighteen spots were found to be differentially expressed between the hermaphrodite and unisexual stages. Of these, 12 were present at both stages but with a different expression value. Four specific spots appeared at the hermaphrodite stage and disappeared at the unisexual stage. Two specific protein spots were associated with female and male floret differentiation. One appears to be associated with contabescence in the female floret and the final protein appears to lead to the abortion of gynoecium in the male floret. The MALDI TOF/TOF technique was used for peptide mass fingerprinting of the differentially expressed proteins and the MASCOT software was used to search the protein database. However, only two protein spots were identified from the database. These were aldolase1 and Os05g0574400 (similar to malate dehydrogenase). This type of proteomic study can help to identify novel protein products and determine the mechanisms involved in the floral sex differentiation process in buffalo grass.

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Glacier advance during Marine Isotope Stage 11 in the McMurdo Dry Valleys of Antarctica

PubMed Central

Swanger, Kate M.; Lamp, Jennifer L.; Winckler, Gisela; Schaefer, Joerg M.; Marchant, David R.

2017-01-01

We mapped six distinct glacial moraines alongside Stocking Glacier in the McMurdo Dry Valleys, Antarctica. Stocking Glacier is one of several alpine glaciers in the Dry Valleys fringed by multiple cold-based drop moraines. To determine the age of the outermost moraine, we collected 10 boulders of Ferrar Dolerite along the crest of the moraine and analyzed mineral separates of pyroxene for cosmogenic 3He. On the basis of these measurements, the exposure age for the outermost moraine is 391 ± 35 ka. This represents the first documented advance of alpine glacier ice in the Dry Valleys during Marine Isotope Stage (MIS) 11. At this time, Stocking Glacier was ~20–30% larger than today. The cause of ice expansion is uncertain, but most likely it is related to increased atmospheric temperature and precipitation, associated with reduced ice extent in the nearby Ross Embayment. The data suggest complex local environmental response to warm climates in Antarctica and have implications for glacial response to Holocene warming. The study also demonstrates the potential for using alpine glacier chronologies in the Transantarctic Mountains as proxies for retreat of grounded glacier ice in the Ross Embayment. PMID:28139676

Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

ClinicalTrials.gov

2018-05-07

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

Endoscopic ultrasound for the characterization and staging of rectal cancer. Current state of the method. Technological advances and perspectives.

PubMed

Gersak, Mariana M; Badea, Radu; Graur, Florin; Hajja, Nadim Al; Furcea, Luminita; Dudea, Sorin M

2015-06-01

Endoscopic ultrasound is the most accurate type of examination for the assessment of rectal tumors. Over the years, the method has advanced from gray-scale examination to intravenous contrast media administration and to different types of elastography. The multimodal approach of tumors (transrectal, transvaginal) is adapted to each case. 3D ultrasound is useful for spatial representation and precise measurement of tumor formations, using CT/MR image reconstruction; color elastography is useful for tumor characterization and staging; endoscopic ultrasound using intravenous contrast agents can help study the amount of contrast agent targeted at the level of the tumor formations and contrast wash-in/wash-out time, based on the curves displayed on the device. The transvaginal approach often allows better visualization of the tumor than the transrectal approach. Performing the procedure with the rectal ampulla distended with contrast agent may be seen as an optimization of the examination methodology. All these aspects are additional methods for gray-scale endoscopic ultrasound, capable of increasing diagnostic accuracy. This paper aims at reviewing the progress of transrectal and transvaginal ultrasound, generically called endoscopic ultrasound, for rectal tumor diagnosis and staging, with emphasis on the current state of the method and its development trends.

Hepatocellular carcinoma: early-stage management challenges

PubMed Central

Erstad, Derek J; Tanabe, Kenneth K

2017-01-01

Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349

Affordable Development of a Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, M. G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. The foundation provided by development and utilization of a NCPS could enable development of extremely high performance systems. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

CD44v6 expression in patients with stage II or stage III sporadic colorectal cancer is superior to CD44 expression for predicting progression

PubMed Central

Zhao, LH; Lin, QL; Wei, J; Huai, YL; Wang, KJ; Yan, HY

2015-01-01

Background: Currently, it is difficult to predict the prognosis of patients exhibiting stage II or stage III colorectal cancer (CRC) and to identify those patients most likely to benefit from aggressive treatment. The current study was performed to examine the clinicopathological significance of CD44 and CD44v6 protein expression in these patients. Study design: We retrospectively investigated 187 consecutive patients who underwent surgery with curative intent for stage II to III CRC from 2007 to 2013 in the Beijing Civil Aviation Hospital. CD44 and CD44v6 protein expression levels were determined using immunohistochemistry and compared to the clinicopathological data. Results: Using immunohistochemical detection, CD44 expression was observed in 108 (57.75%) of the CRC patients; and its detection was significantly associated with greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological tumor-lymph node-metastasis (TNM) stage. CD44v6 expression was observed in 135 (72.19%) of the CRC patients; and its expression was significantly associated with a poorly differentiated histology, greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological TNM stage. Expression of CD44v6 was higher than that of CD44 in stage II and stage III sporadic CRC. Conclusion: CD44v6 is a more useful marker for predicting a poor prognosis in stage II and stage III sporadic CRC as compared to CD44. PMID:25755763

Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients.

PubMed

Cao, Yabing; Xiao, Guangli; Qiu, Xibin; Ye, Sheng; Lin, Tongyu

2014-01-01

We report the efficacy and safety of crizotinib treatment among Chinese patients with advanced-stage NSCLC. We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. The primary goal was to evaluate the efficacy of crizotinib in patients who were previously treated patients or who had poor ECOG performance status (PS). Forty patients were evaluable for safety and efficacy. Median age was 43 years, 100% had adenocarcinoma and stage IV disease, and 42.5% were female. Six patients received frontline treatment with crizotinib, 17 patients had 1 prior treatment, and 17 patients had more than 2 lines of prior treatment. Patients received a median of 5 cycles of treatment (range 1-15 cycles). After the first cycle, 92.5% (37/40) patients archived partial remission (PR). At the end of the follow-up period, the overall PR rate was 70% (28/40), and progression of disease (PD) occurred in 30% of patients (12/40). The median PFS was 28 weeks (95% CI 15.4 to 40.5 weeks), and median OS was 40 weeks (95% CI 38.6 to 49.3 weeks). The most frequent treatment-related AEs were vomiting (47.5%), vision disorder (27.5%) and increased ALT/AST (42%); most toxicities were Grade 1/2. Observed treatment-related Grade 3/4 AEs included increased ALT/AST (10%) and vomiting (5%). The EML4-ALK fusion rate and number of prior chemotherapy cycles did not appear to significantly affect the efficacy of crizotinib. However, PS 0-2 patients had improved PFS (50 weeks vs. 24 weeks, p = 0.015). Crizotinib was safe, well-tolerated, and effective in Chinese patients with pre-treated ALK-rearranged NSCLC. QOL was improved and PS appears to have an effect on the efficacy of crizotinib, but prior treatment and ALK fusion rate do not.

Magnetic Resonance Imaging Features of the Nigrostriatal System: Biomarkers of Parkinson’s Disease Stages?

PubMed Central

Hopes, Lucie; Grolez, Guillaume; Moreau, Caroline; Lopes, Renaud; Ryckewaert, Gilles; Carrière, Nicolas; Auger, Florent; Laloux, Charlotte; Petrault, Maud; Devedjian, Jean-Christophe; Bordet, Regis; Defebvre, Luc; Jissendi, Patrice; Delmaire, Christine; Devos, David

2016-01-01

Introduction Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson’s disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Methods Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. Results The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Conclusion Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease. PMID:27035571

Study of blade aspect ratio on a compressor front stage

NASA Technical Reports Server (NTRS)

Behlke, R. F.; Brooky, J. D.; Canal, E., Jr.

1980-01-01

A single stage, low aspect ratio, compressor with a 442.0 m/sec (1450 ft/sec) tip speed and a 0.597 hub/tip ratio typical of an advanced core compressor front stage was tested. The test stage incorporated an inlet duct which was representative of an engine transition duct between fan and high pressure compressors. At design speed, the rotor stator stage achieved a peak adiabatic efficiency of 86.6 percent at a flow of 44.35 kg/sec (97.8 lbm/sec) and a pressure ratio of 1.8. Surge margin was 12.5 percent from the peak stage efficiency point.

Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs.

PubMed

Hinrichsen, Inga; Kemp, Matthias; Peveling-Oberhag, Jan; Passmann, Sandra; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

2014-01-01

Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC) specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV). However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR) genes and thereby enhanced progression of hepatocarcinogenesis has been the subject of controversial discussion. We investigated promoter methylation pattern of the MMR genes MLH1, MSH2 and PMS2 as well as the cyclin-dependent kinase inhibitor 2A gene (p16) in 61 well characterized patients with HCCs associated with HCV, Hepatitis B virus infection or alcoholic liver disease. DNA was isolated from formalin-fixed, paraffin-embedded tumour and non-tumour adjacent tissue and analysed by methylation-specific PCR. Moreover, microsatellite analysis was performed in tissues showing methylation in MMR gene promoters. Our data demonstrated that promoter methylation of MLH1, MSH2, PMS2 and p16 is present among all considered HCCs. Hereby, promoter silencing was detectable more frequently in advanced-stage HCCs than in low-stage ones. However, there was no significant correlation between aberrant DNA methylation of MMR genes or p16 and HCV infection in related HCC specimens. In summary, we show that promoter methylation of essential MMR genes and p16 is detectable in HCCs most dominantly in pT3 stage tumour cases. Since loss of MMR proteins was previously described to be not only responsible for tumour development but also for chemotherapy resistance, the knowledge of mechanisms jointly responsible for HCC progression might enable significant improvement of individual HCC therapy in the future.

Neural networks predict tomato maturity stage

NASA Astrophysics Data System (ADS)

Hahn, Federico

1999-03-01

Almost 40% of the total horticultural produce exported from Mexico the USA is tomato, and quality is fundamental for maintaining the market. Many fruits packed at the green-mature stage do not mature towards a red color as they were harvested before achieving its physiological maturity. Tomato gassed for advancing maturation does not respond on those fruits, and repacking is necessary at terminal markets, causing losses to the producer. Tomato spectral signatures are different on each maturity stage and tomato size was poorly correlated against peak wavelengths. A back-propagation neural network was used to predict tomato maturity using reflectance ratios as inputs. Higher success rates were achieved on tomato maturity stage recognition with neural networks than with discriminant analysis.

High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification.

PubMed Central

Hailat, N; Keim, D R; Melhem, R F; Zhu, X X; Eckerskorn, C; Brodeur, G M; Reynolds, C P; Seeger, R C; Lottspeich, F; Strahler, J R

1991-01-01

The gene encoding a novel protein designated nm23-H1, which was recently identified as identical to the A subunit of nucleotide diphosphate kinase from human erythrocytes, has been proposed to play a role in tumor metastasis suppression. We report that untreated neuroblastoma tumors contain a cellular polypeptide (Mr = 19,000) designated p19, identified in two-dimensional electrophoretic gels, which occurs at significantly higher levels (P = 0.0001) in primary tumors containing amplified N-myc gene. The partial amino acid sequence obtained for p19 is identical to the sequence of the human nm23-H1 protein. An antibody to the A subunit of erythrocyte nucleotide diphosphate kinase reacted exclusively with p19. In this study, significantly higher levels of p19/nm23 occurred in primary neuroblastoma tumors from patients with advanced stages (III and IV) relative to tumors from patients with limited stages (I and II) of the disease. Even among patients with a single copy of the N-myc gene, tumors from patients with stages III and IV had statistically significantly higher levels of p19/nm23 than tumors from patients with stages I and II. Our findings indicate that, in contrast to a proposed role for nm23-H1 as a tumor metastasis suppressor, increased p19/nm23 protein in neuroblastoma is correlated with features of the disease that are associated with aggressive tumors. Therefore, nm23-H1 may have distinct if not opposite roles in different tumors. Images PMID:2056128

Optimism, Symptom Distress, Illness Appraisal, and Coping in Patients With Advanced-Stage Cancer Diagnoses Undergoing Chemotherapy Treatment.

PubMed

Sumpio, Catherine; Jeon, Sangchoon; Northouse, Laurel L; Knobf, M Tish

2017-05-01

To explore the relationships between optimism, self-efficacy, symptom distress, treatment complexity, illness appraisal, coping, and mood disturbance in patients with advanced-stage cancer.
. Cross-sectional study.
. Smilow Cancer Hospital at Yale New Haven in Connecticut, an outpatient comprehensive cancer center.
. A convenience sample of 121 adult patients with stages III-IV cancer undergoing active chemotherapy.
. Participants completed common self-report questionnaires to measure variables. Treatment hours and visits were calculated from data retrieved from medical record review. Mediation and path analysis were conducted to identify direct and indirect pathways from the significant antecedent variables to mood disturbance.
. Dispositional optimism, self-efficacy, social support, treatment complexity, symptom distress, illness appraisal, coping, and mood disturbance.
. Greater optimism and self-efficacy were associated with less negative illness appraisal, less avoidant coping, and decreased mood disturbance. Conversely, greater symptom distress was associated with greater negative illness appraisal, greater avoidant coping, and greater mood disturbance. In the final model, optimism and symptom distress had direct and indirect effects on mood disturbance. Indirect effects were partially mediated by illness appraisal.
. Mood disturbance resulted from an interaction of disease stressors, personal resources, and cognitive appraisal of illness. Avoidant coping was associated with greater disturbed mood, but neither avoidant nor active coping had a significant effect on mood in the multivariate model. 
. Illness appraisal, coping style, and symptom distress are important targets for intervention. Optimism is a beneficial trait and should be included, along with coping style, in comprehensive nursing assessments of patients with cancer.

Successful treatment by pembrolizumab in a patient with end-stage renal disease with advanced non-small cell lung cancer and high PD-L1 expression.

PubMed

Ishizuka, Shiho; Sakata, Shinya; Yoshida, Chieko; Takaki, Akira; Saeki, Sho; Nakamura, Kazuyoshi; Fujii, Kazuhiko

2018-05-10

We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation. Therefore, pembrolizumab can be administered for patients with ESRD and advanced NSCLC, who harbor high PD-L1 expression, during preparation for hemodialysis. Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Differences in colorectal carcinoma stage and survival by race and ethnicity.

PubMed

Chien, Chloe; Morimoto, Libby M; Tom, Jamie; Li, Christopher I

2005-08-01

In the United States, blacks with colorectal carcinoma (CRC) presented with more advanced-stage disease and had higher mortality rates compared with non-Hispanic whites. Data regarding other races/ethnicities were limited, especially for Asian/Pacific Islander and Hispanic white subgroups. Using data from 11 population-based cancer registries that participate in the Surveillance, Epidemiology and End Results program, the authors evaluated the relation among 18 different races/ethnicities and disease stage and mortality rates among 154,103 subjects diagnosed with CRC from 1988 to 2000. Compared with non-Hispanic whites, blacks, American Indians, Chinese, Filipinos, Koreans, Hawaiians, Mexicans, South/Central Americans, and Puerto Ricans were 10-60% more likely to be diagnosed with Stage III or IV CRC. Alternatively, Japanese had a 20% lower risk of advanced-stage CRC. With respect to mortality rates, blacks, American Indians, Hawaiians, and Mexicans had a 20-30% greater risk of mortality, whereas Chinese, Japanese, and Indians/Pakistanis had a 10-40 % lower risk. The authors observed numerous racial/ethnic disparities in the risks of advanced-stage cancer and mortality among patients with CRC, and there was considerable variation in these risks across Asian/Pacific Islander and Hispanic white subgroups. Although the etiology of these disparities was multifactorial, developing screening and treatment programs that target racial/ethnic populations with elevated risks of poor CRC outcomes may be an important means of reducing these disparities. (c) 2005 American Cancer Society.

Contemporary surgical management of advanced end stage emphysema: an evidence based review.

PubMed

Sachithanandan, Anand; Badmanaban, Balaji

2012-06-01

Emphysema is a progressive unrelenting component of chronic obstructive pulmonary disease and a major source of mortality and morbidity globally. The prevalence of moderate to severe emphysema is approximately 5% in Malaysia and likely to increase in the future. Hence advanced emphysema will emerge as a leading cause of hospital admission and a major consumer of healthcare resources in this country in the future. Patients with advanced disease have a poor quality of life and reduced survival. Medical therapy has been largely ineffective for many patients however certain subgroups have disease amenable to surgical palliation. Effective surgical therapies include lung volume reduction surgery, lung transplantation and bullectomy. This article is a comprehensive evidence based review of the literature evaluating the rationale, efficacy, safety and limitations of surgery for advanced emphysema highlighting the importance of meticulous patient selection and local factors relevant to Malaysia.

Initial Stage Reference Search : Behavioral Economics and Transportation

DOT National Transportation Integrated Search

2015-04-01

The initial stage investigation is the beginning step in the Exploratory Advanced Research (EAR) Program process for exploring ideas across traditional and nontraditional fields of research and stimulating new approaches to problem solving. The proce...

Computer-assisted preoperative simulation for positioning and fixation of plate in 2-stage procedure combining maxillary advancement by distraction technique and mandibular setback surgery.

PubMed

Suenaga, Hideyuki; Taniguchi, Asako; Yonenaga, Kazumichi; Hoshi, Kazuto; Takato, Tsuyoshi

2016-01-01

Computer-assisted preoperative simulation surgery is employed to plan and interact with the 3D images during the orthognathic procedure. It is useful for positioning and fixation of maxilla by a plate. We report a case of maxillary retrusion by a bilateral cleft lip and palate, in which a 2-stage orthognathic procedure (maxillary advancement by distraction technique and mandibular setback surgery) was performed following a computer-assisted preoperative simulation planning to achieve the positioning and fixation of the plate. A high accuracy was achieved in the present case. A 21-year-old male patient presented to our department with a complaint of maxillary retrusion following bilateral cleft lip and palate. Computer-assisted preoperative simulation with 2-stage orthognathic procedure using distraction technique and mandibular setback surgery was planned. The preoperative planning of the procedure resulted in good aesthetic outcomes. The error of the maxillary position was less than 1mm. The implementation of the computer-assisted preoperative simulation for the positioning and fixation of plate in 2-stage orthognathic procedure using distraction technique and mandibular setback surgery yielded good results. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Management of end-stage heart failure: a perspective on the Arab Gulf states

PubMed Central

Al Habeeb, Waleed; Stewart, Garrick C.; Mudge, Gilbert H.

2009-01-01

The ever expanding epidemic of end-stage heart failure represents one of the greatest challenges of modern cardiovascular medicine. With medical treatments hampered by significant limitations, physicians caring for patients with advanced heart disease have turned to cardiac transplantation and durable mechanical circulatory assist devices as definitive therapies. These advanced therapeutic modalities are not widely available outside the United States and Europe, but nevertheless offer enormous potential for patients in the Arab Gulf suffering from end-stage heart failure. This review will discuss the management of end-stage heart failure in the Gulf States, with an emphasis on therapies best utilized within a framework of regional cooperation and coordination. PMID:19847084

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

PubMed

Kim, Yong-Hyub; Ahn, Sung-Ja; Kim, Young-Chul; Kim, Kyu-Sik; Oh, In-Jae; Ban, Hee-Jung; Chung, Woong-Ki; Nam, Taek-Keun; Yoon, Mee Sun; Jeong, Jae-Uk; Song, Ju-Young

2016-02-01

Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The cost of unresectable stage III or stage IV melanoma in Italy

PubMed Central

2012-01-01

Background In recent decades, melanoma incidence has been increasing in European countries; in 2006, there were approximately 60,000 cases leading to 13,000 deaths. Within Europe there is some geographical variation in the incidence of melanoma, with the highest rates reported in Scandinavia (15 cases per 100,000 inhabitants per year) and the lowest in the Mediterranean countries (5 to 7 cases per 100,000 inhabitants per year). Methods The present article is based on the information collected in the MELODY study (MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal survey). In that study, the medical charts of patients were reviewed to document current treatment patterns and to analyse information on patients, disease characteristics and healthcare resource utilization related to the treatment of advanced melanoma regarding patients who presented with a diagnosis of malignant melanoma (stage I to IV) at participating sites between 01 July, 2005 and 30 June, 2006. Results Summarizing, though the length of the follow-up period varies among sample patients, an amount of the yearly cost per patient can be estimated, dividing the average per patient total cost (€ 5.040) by the average follow-up duration (17.5 months) and reporting to one year; on these grounds, unresectable stage III or stage IV melanoma in Italy would cost € 3,456 per patient per year. PMID:23116062

Wearable Sensors in Transportation - Exploratory Advanced Research Program Initial Stage Investigation

DOT National Transportation Integrated Search

2016-03-01

This report summarizes an initial stage investigation into wearable sensors for transportation research : applications. The Federal Highway Administration (FHWA) has observed significant activity in this area and : seeks to obtain an understanding of...

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

2016-11-01

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

2017-01-01

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

[Clinical analysis of 25 patients with aggressive peripheral T-cell lymphoma in advanced stage treated with autologous stem cell transplantation].

PubMed

Zou, Dehui; Huang, Wenyang; Liu, Hong; Fu, Mingwei; Li, Zengjun; Sui, Weiwei; Qi, Junyuan; Zhao, Yaozhong; Ru, Kun; Han, Mingzhe; Qiu, Lugui

2015-06-01

To investigate the outcomes of autologous stem cell transplantation (ASCT) for patients with aggressive peripheral T-cell lymphoma (PTCLs) in advanced stage. The clinical data of 25 patients in complete remission (CR) with aggressive PTCLs received ASCT from May 1997 to June 2013 were retrospectively analyzed. ① Of the 25 cases, 16 were unspecified PTCL (PTCL-U), 4 with angioimmunoblastic T cell lymphoma (AITL), 3 with anaplastic large cell lymphoma (ALCL) and 2 with hepatosplenic T cell lymphoma (HSTL), with a median age of 30(12-54) years old. Ratio of male to female is 16∶9. The distribution of stages was 8 cases with stage Ⅲ and 17 patients with stage Ⅳ. Nine patients presented with bone marrow involvement. Before ASCT, 18 patients were in CR1 and 7 patients were in CR2. ②Two patients with HSTL in stage ⅣB and IPI score 4/5 in CR1 relapsed and died within 12 months after ASCT. At a median follow-up of 38 (range 14-110) months, the estimated 3-year probability of PFS and OS for the other 23 patients was (63.1 ± 10.5)% and (71.8 ± 9.9)%, respectively. The patients in first CR had a better survival than the patients in second CR. The 3-year probability of PFS were (74.9 ± 11.0)% vs (33.3 ± 19.2)% (P=0.092) and OS were (80.2 ± 10.4)% vs (50.0 ± 20.4)% (P=0.043), respectively. The 3-year probability of PFS and OS were (40.0 ± 17.4)% and (53.3 ± 17.3)% in bone marrow involvement patients and the corresponding figure were (77.9 ± 11.3)% and (84.4 ± 10.2)% in non- bone marrow involvement patients. ASCT could improve the survival of aggressive PTCLs. Non CR1 status and bone marrow involvement had negative influence on OS in patients with aggressive PTCLs treated by ASCT. The prognosis was very poor in patients with HSTL and satisfactory regimens should be investigated.

Efficacy of Rotigotine at Different Stages of Parkinson's Disease Symptom Severity and Disability: A Post Hoc Analysis According to Baseline Hoehn and Yahr Stage.

PubMed

Giladi, Nir; Nicholas, Anthony P; Asgharnejad, Mahnaz; Dohin, Elisabeth; Woltering, Franz; Bauer, Lars; Poewe, Werner

2016-10-19

The efficacy of rotigotine has been demonstrated in studies of patients with early (i.e. not receiving levodopa) and advanced (i.e. not adequately controlled on levodopa; average 2.5 h/day in 'off' state) Parkinson's disease (PD). To further investigate the efficacy of rotigotine transdermal patch across different stages of PD symptom severity and functional disability, according to baseline Hoehn and Yahr (HY) staging. Post hoc analysis of six placebo-controlled studies of rotigotine in patients with early PD (SP506, SP512, SP513; rotigotine ≤8 mg/24 h) or advanced-PD (CLEOPATRA-PD, PREFER, SP921; rotigotine ≤16 mg/24 h). Data were pooled and analyzed according to baseline HY stage (1, 2, 3 or 4) for change from baseline to end of maintenance in Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living), UPDRS III (motor) and UPDRS II+III; statistical tests are exploratory. Data were available for 2057 patients (HY 1 : 262; HY 2 : 1230; HY 3 : 524; HY 4 : 41). Patients at higher HY stages were older, had a longer time since PD diagnosis and higher baseline UPDRS II+III scores vs patients at lower HY stages. Rotigotine improved UPDRS II+III versus placebo for each individual HY stage (p < 0.05 for each HY stage), with treatment differences increasing with increasing HY stages. Similar results were observed for UPDRS II and UPDRS III. This post hoc analysis suggests that rotigotine may be efficacious across a broad range of progressive stages of PD symptom severity and functional disability (HY stages 1-4).

Assessing Behavioral Stages From Social Media Data.

PubMed

Liu, Jason; Weitzman, Elissa R; Chunara, Rumi

2017-01-01

Important work rooted in psychological theory posits that health behavior change occurs through a series of discrete stages. Our work builds on the field of social computing by identifying how social media data can be used to resolve behavior stages at high resolution (e.g. hourly/daily) for key population subgroups and times. In essence this approach opens new opportunities to advance psychological theories and better understand how our health is shaped based on the real, dynamic, and rapid actions we make every day. To do so, we bring together domain knowledge and machine learning methods to form a hierarchical classification of Twitter data that resolves different stages of behavior. We identify and examine temporal patterns of the identified stages, with alcohol as a use case (planning or looking to drink, currently drinking, and reflecting on drinking). Known seasonal trends are compared with findings from our methods. We discuss the potential health policy implications of detecting high frequency behavior stages.

Stage progression of congenital cholesteatoma in children.

PubMed

Kim, Young Ho; Yoo, Jae Chul; Lee, Jun Ho; Oh, Seung-Ha; Chang, Sun O; Koo, Ja-Won; Kim, Chong Sun

2012-03-01

This study aimed to investigate the most prevalent stage in each age-group of children with congenital cholesteatoma (CC) and verify the correlation between the stage and the age of the patients for the type of CC ("closed" keratotic cyst and "open" infiltrative types). Patients diagnosed with CC between 2004 and 2009 (n = 156; 116 boys and 40 girls; mean age, 5 years and 5 months; range, 12 months-16 years and 7 months) were enrolled retrospectively. Assessment of stage and type of CC was performed with preoperative high-resolution temporal bone computed tomography and intraoperative findings. The stage of CC was determined using Potsic's staging system classified into four stages according to ossicular involvement and mastoid extension. The patients consisted of groups divided on the basis of a 2-year interval. The prevalence of stage I began to decline from the age-group of 1-2 years. In contrast, the prevalence of stages III increased from the age-group of 3-4 years and that of stage IV from the age-group 5-6 years. The prevalence of "open" infiltrative type CC increased from approximately the age of 7 years, thus showing some correlation with age but not with stage. The prevalence of CC with the advanced stage increased since the age of 2 years. Therefore, the importance of early diagnosis and treatment of CC should be more emphasized.

Cognitive benefits of memantine in Alzheimer's 5XFAD model mice decline during advanced disease stages.

PubMed

Devi, Latha; Ohno, Masuo

2016-05-01

Memantine, a noncompetitive NMDA receptor antagonist with neuroprotective properties, has been used for the treatment of Alzheimer's disease (AD). Administration of memantine to various transgenic AD mice has been reported to improve cognitive deficits, very often completely back to normal wild-type control levels. However, such great benefits of memantine in preclinical studies do not translate into clinical results of this drug, showing only marginal and transient efficacy in moderate to severe AD. To further address in vivo efficacy, we compared the effects of memantine at different disease stages in 5XFAD mice, one of the rapid-onset and most aggressive amyloid models. Specifically, we administered memantine once daily for 30 days to 5XFAD mice, which showed moderate (6-7 months of age) and robust (12-15 months) β-amyloid (Aβ) accumulation. Treatments with memantine (10mg/kg, i.p.) reversed memory impairments in the younger 5XFAD mice, as tested by the contextual fear conditioning and spontaneous alternation Y-maze paradigms. Memantine had no effects on soluble Aβ oligomer or total Aβ42 levels in 5XFAD mouse brains. In contrast, subchronic treatments with memantine showed no behavioral benefits in the older 5XFAD group, which exhibited more profound memory deficits concomitant with highly increased concentrations of Aβ as compared with those of the younger 5XFAD group. Since subchronic memantine at the higher dose (30 mg/kg) impaired memory performances in wild-type controls, we further tested acute administration of 50mg/kg memantine, which was reported to enhance hippocampal adult neurogenesis and memory function. However, this treatment also failed to rescue memory deficits in 12-15-month-old 5XFAD mice. Collectively, our results demonstrate that cognitive benefits of memantine independent of Aβ reductions were no longer observed in the 5XFAD Alzheimer mouse model during advanced stages, which may be reflective of the limited efficacy of memantine in

Discriminating ability of Cirrus and RTVue optical coherence tomography in different stages of glaucoma.

PubMed

Mittal, Deepti; Dubey, Suneeta; Gandhi, Monica; Pegu, Julie; Bhoot, Madhu; Gupta, Yadunandan Prasad

2018-05-01

The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma.

The staging of testicular tumors.

PubMed

Sandeman, T F; Matthews, J P

1979-06-01

Sufficient information was recorded in the majority of a series of 531 germinal malignancies of the testis, to stage them retrospectively according to the T.N.M. staging system recommended by the U.I.C.C. and compare this with a locally devised scheme. By separately analyzing the commonest pathological types (differentiated seminoma, malignant teratoma intermediate and undifferentiated malignant teratoma) the histological influence on prognosis was minimized in this comparison. The predictive ability and greater simplicity of the Peter MacCallum Hospital system appears to be superior and it is put forward as an advance in staging for consideration when this comes up for review. It is pointed out that reporting results according to a more rigorous staging system can give the impression that survival figures are better than those obtained at another center using less stringent criteria, when in fact the overall results are the same and nothing has been done for the individual patient. This must be allowed for when considering different methods of treatment. Because of the importance of biochemical markers their inclusion in any staging system is essential; however, they are difficult if not impossible to incorporate under the anatomical sections. A separate category is proposed.

Underlying Motivations of Volunteering Across Life Stages.

PubMed

Yamashita, Takashi; Keene, Jennifer R; Lu, Chi-Jung; Carr, Dawn C

2017-03-01

Volunteering is beneficial not only for individuals' well-being but also for society's well-being; yet only a fraction of U.S. citizens regularly engage in volunteer activities. This study examined how underlying motivations are associated with interest in volunteering for individuals in three major life phases: early, middle, and later adulthood. Data were collected from 1,046 adults who volunteered through nonprofit organizations in Nevada (USA). Exploratory factor analysis revealed that community service, career advancement, and well-being were common underlying motivations for individuals across life stages. However, generativity among the later adulthood group, and social networking among the early and middle adulthood groups were unique motivations for volunteering. Regression analysis showed that the community service motivation was significantly associated with individuals' interest in volunteering among all life stages. Simultaneously, generativity for the later adulthood group, and career advancement for the early adulthood group were unique motivations linked to their actual interest in volunteering.

Advanced expander test bed engine

NASA Technical Reports Server (NTRS)

Mitchell, J. P.

1992-01-01

The Advanced Expander Test Bed (AETB) is a key element in NASA's Space Chemical Engine Technology Program for development and demonstration of expander cycle oxygen/hydrogen engine and advanced component technologies applicable to space engines as well as launch vehicle upper stage engines. The AETB will be used to validate the high pressure expander cycle concept, study system interactions, and conduct studies of advanced mission focused components and new health monitoring techniques in an engine system environment. The split expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust.

Advanced Melanoma Facebook Live Event

Cancer.gov

In case you missed it, watch this recent Facebook Live event about the current state of research and treatment for advanced stage melanoma. To learn more, see our evidence-based information about skin cancer, including melanoma.

An incidence model of the cost of advanced prostate cancer in Spain.

PubMed

Hart, W M; Nazir, J; Baskin-Bey, E

2014-02-01

Prostate cancer (PCa) is the second leading cancer diagnosed among men. In Spain the incidence of PCa was 70.75 cases per 100,000 males. Advanced PCa has spread outside of the prostate capsule and may involve other parts of the body. The aim of this study was to estimate the lifetime costs of a cohort of advanced PCa patients diagnosed in Spain in 2012. A partitioned economic model was developed in EXCEL incorporating Spanish incidence, mortality, and cost data supplemented with data from the international literature. Progression from Stage III to Stage IV was permitted. Costs were discounted at the standard rate of 3%. Lifetime costs were presented on an individual basis and for the entire cohort of newly diagnosed Stage III and Stage IV PCa patients. Lifetime costs for advanced PCa were ∼€19,961 per patient (mean survival of 8.4 years). Using the projected incident cases for 2012 (3047), the total cost for the incident cohort of patients in 2012 would amount to €61 million. These results were more sensitive to changes in the ongoing costs (post-initial 12 months) of Stage III PCa, the rate of progression from Stage III to Stage IV, and the discount rate applied to costs. This study provides an estimate of the lifetime costs of advanced PCa in Spain and a framework for further research. The study is limited by the availability of long-term Spanish data and the need to make inferences from international studies. However, until long-term prospective or observational data do become available in Spain, based on the assumptions, the current results indicate that the burden of advanced PCa in Spain is substantial. Any treatments that could potentially reduce the economic burden of the disease should be of interest to healthcare decision makers.

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients

PubMed Central

Hoogendam, Jacob P.; Zweemer, Ronald P.; Verkooijen, Helena M.; de Jong, Pim A.; van den Bosch, Maurice A. A. J.; Verheijen, René H. M.; Veldhuis, Wouter B.

2015-01-01

Aim Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. Methods All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 – September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Results Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman – with advanced pre-radiograph stage (IVA) disease – showed findings consistent with pulmonary metastases. Radiographs of 7 other women – 4 early, 3 advanced stage disease – were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Conclusion Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID:26135733

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

PubMed

Hoogendam, Jacob P; Zweemer, Ronald P; Verkooijen, Helena M; de Jong, Pim A; van den Bosch, Maurice A A J; Verheijen, René H M; Veldhuis, Wouter B

2015-01-01

Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.

Relationship of the length of the first stage of labor to the length of the second stage.

PubMed

Nelson, David B; McIntire, Donald D; Leveno, Kenneth J

2013-07-01

To evaluate the relationship between the lengths of the first and second stages of labor. In this observational study of women delivering at our hospital, the onset of the first stage of labor was defined as admission at 3-cm to 4-cm dilatation in the presence of uterine contractions with or without rupture of membranes. This study was limited to nulliparous women with a singleton, cephalic live birth at 37 0/7 weeks of gestation or more. Women presenting with more advanced cervical dilatation (greater than 4 cm), prior cesarean delivery, diabetes, hypertension, and placental accidents were excluded. Each woman was analyzed based on her specific lengths of first and second stages of labor, that is, paired observations for each woman. Between January 1, 2001, and June 30, 2012, a total of 172,522 women were delivered and 12,523 (7.3%) met the inclusion criteria. The 95 percentile was 15.6 and 2.9 hours for the first and second stages, respectively. Women with first stages greater than the 95 percentile had a 16.3% rate of a second-stage length greater than the 95 percentile compared with 4.5% (P<.001) in women with first stages less than the 95 percentile. This relationship persisted when analyzed for variables influencing labor to include neonate birth weight, epidural analgesia, or maternal size. Overall, the length of the second stage significantly increased concomitantly with increasing length of the first stage (P<.001). II.

A discussion of serum albumin level in advanced-stage hepatocellular carcinoma: a medical oncologist's perspective.

PubMed

Tanriverdi, Ozgur

2014-11-01

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and it is particularly prevalent in East and Southeast Asia. With surgical and/or local interventional treatment methods, survival rates for early-stage hepatocellular cancers have increased. However, it is not yet clear which staging systems are more applicable in hepatocellular carcinoma. Serum albumin level is already being used as a criterion in most staging systems. Albumin is an important serum protein in human bodily functions, but only 5 % of the daily amount needed is synthesized by the liver. The serum albumin level is affected by multifactorial situations, including capillary permeability, drugs, liver insufficiency, inflammation and/or infections, dehydration or overhydration, protein loosing disorders, and decreased nutrition intake in anorexia-malnutrition syndrome and cancer cachexia. Because of this complex situation, serum albumin level may affect many staging systems for hepatocellular carcinoma by leading to false-negative results. In this paper, the statuses of current staging systems are reviewed, and possible negative events regarding the serum albumin levels found in these staging systems are discussed.

Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

PubMed

Eng, Kevin H; Morrell, Kayla; Starbuck, Kristen; Spring-Robinson, Chandra; Khan, Aalia; Cleason, Dana; Akman, Levent; Zsiros, Emese; Odunsi, Kunle; Szender, J Brian

2017-07-01

The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436). Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002). Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging

PubMed Central

Harlow, Siobán D.; Gass, Margery; Hall, Janet E.; Lobo, Roger; Maki, Pauline; Rebar, Robert W.; Sherman, Sherry; Sluss, Patrick M.; de Villiers, Tobie J.

2012-01-01

Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage –3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage–1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. PMID:22343510

Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

PubMed

Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

2017-12-01

Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

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

Blackstock, A. William; Farmer, Michael R.; Lovato, James

2006-02-01

Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligiblemore » because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival.« less

Raytheon advanced pulse-tube cryocoolers

NASA Astrophysics Data System (ADS)

Conrad, Ted; Yates, Ryan; Kuo, Daniel; Schaefer, Brian; Arnoult, Matt

2016-05-01

Since the 1970s, Raytheon has developed, built, tested and integrated high performance cryocoolers. Our versatile designs for single and multi-stage cryocoolers provide reliable operation for temperatures from 10 to 200 Kelvin with power levels ranging from 50 W to nearly 600 W. These cryocoolers incorporate clearance seals, flexure suspensions, hermetic housings and dynamic balancing to provide long service life and reliable operation in all relevant environments. Recently, Raytheon has developed an advanced regenerator technology capable of operating efficiently at high frequencies and outperforming traditional screen regenerators. The Raytheon Advanced Miniature (RAM-100) cryocooler, a flight packaged, high frequency, single stage pulse tube cooler with an integrated surge volume and inertance tube, has been designed for use with this regenerator. Design details and experimentally measured performance of two iterations of the RAM cryocooler are presented in this paper.

Proposal of a novel system for the staging of thymic epithelial tumors.

PubMed

Bedini, Amedeo Vittorio; Andreani, Stefano Michele; Tavecchio, Luca; Fabbri, Alessandra; Giardini, Roberto; Camerini, Tiziana; Bufalino, Rosaria; Morabito, Alberto; Rosai, Juan

2005-12-01

We designed and assessed a new TNM staging system (herein called the INT [Istituto Nazionale Tumori] system) for thymic epithelial tumors in order to overcome the perceived drawbacks of Masaoka's system, which represents the current standard. In all, 123 cases were evaluated. The histologic types according to the World Health Organization (WHO) classification were as follows: subtype A: 5 cases; AB: 40; B1: 16; B2: 29; B3: 16; and C: 17 cases. There were 45 Masaoka's stage I, 33 stage II, 26 stage III, and 19 stage IV cases. A total of 11 INT definitions were grouped into three stages: locally restricted disease (75 cases), which included Masaoka's stage I and selected stage II cases (no pleural invasion); locally advanced disease (37 cases), which included Masaoka's stage III cases plus those staged II owing to pleural invasion and those staged IV owing to intrathoracic nodal or limited pleuropericardial involvement; and systemic disease (11 cases), which included the remaining Masaoka's stage IV cases. Completeness of resection, WHO types, and both staging systems were significant prognostic factors (p < 0.0001) on univariate analysis. The 95-month progression-free survival rates according to Masaoka's system were stage I: 100%; II: 93.6%; III: 46.3%; and IV: 23.2%. The INT system corresponding figures were as follows: locally restricted disease: 98.6%; locally advanced disease: 46.9%; and systemic disease: 11.7%. The INT system was the prognostic factor with the greatest impact (p = 0.0218) on multivariate analysis (Masaoka's system: p = 0.2012; completeness of resection: p = 0.6855; histology: p = 0.9386). The INT system allows finer disease descriptions than Masaoka's system, resulting in a stage grouping with higher prognostic distinctiveness.

Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease.

PubMed

Ueno, Hiroki; Koyama, Hidenori; Fukumoto, Shinya; Tanaka, Shinji; Shoji, Takuhito; Shoji, Tetsuo; Emoto, Masanori; Tahara, Hideki; Inaba, Masaaki; Kakiya, Ryusuke; Tabata, Tsutomu; Miyata, Toshio; Nishizawa, Yoshiki

2011-04-01

Numbers of endothelial progenitor cells (EPCs) have been shown to be decreased in subjects with end-stage renal disease (ESRD), the mechanism of which remained poorly understood. In this study, mutual association among circulating EPC levels, carotid atherosclerosis, serum pentosidine, and skin autofluorescence, a recently established noninvasive measure of advanced glycation end products accumulation, was examined in 212 ESRD subjects undergoing hemodialysis. Numbers of circulating EPCs were measured as CD34+ CD133+ CD45(low) VEGFR2+ cells and progenitor cells as CD34+ CD133+ CD45(low) fraction by flow cytometry. Skin autofluorescence was assessed by the autofluorescence reader; and serum pentosidine, by enzyme-linked immunosorbent assay. Carotid atherosclerosis was determined as intimal-medial thickness (IMT) measured by ultrasound. Circulating EPCs were significantly and inversely correlated with skin autofluorescence in ESRD subjects (R = -0.216, P = .002), but not with serum pentosidine (R = -0.079, P = .25). Circulating EPCs tended to be inversely associated with IMT (R = -0.125, P = .069). Intimal-medial thickness was also tended to be correlated positively with skin autofluorescence (R = 0.133, P = .054) and significantly with serum pentosidine (R = 0.159, P = .019). Stepwise multiple regression analyses reveal that skin autofluorescence, but not serum pentosidine and IMT, was independently associated with low circulating EPCs. Of note, skin autofluorescence was also inversely and independently associated with circulating progenitor cells. Thus, tissue accumulated, but not circulating, advanced glycation end products may be a determinant of a decrease in circulating EPCs in ESRD subjects. Copyright © 2011 Elsevier Inc. All rights reserved.

Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.

PubMed

Horn, L-C; Hommel, N; Roschlau, U; Bilek, K; Hentschel, B; Einenkel, J

2012-07-01

Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX). 131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF. 66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p=0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome. Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

ClinicalTrials.gov

2018-05-15

Advanced Malignant Solid Neoplasm; Recurrent Melanoma; Refractory Malignant Solid Neoplasm; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Discriminating ability of Cirrus and RTVue optical coherence tomography in different stages of glaucoma

PubMed Central

Mittal, Deepti; Dubey, Suneeta; Gandhi, Monica; Pegu, Julie; Bhoot, Madhu; Gupta, Yadunandan Prasad

2018-01-01

Purpose: The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. Methods: One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Results: Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Conclusion: Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma. PMID:29676314

Improvement in intelligence test scores from 6 to 10 years in children of teenage mothers.

PubMed

Cornelius, Marie D; Goldschmidt, Lidush; De Genna, Natacha M; Richardson, Gale A; Leech, Sharon L; Day, Richard

2010-06-01

This study investigates change in IQ scores among 290 children born to teenage mothers and identifies social, economic, and environmental variables that may be associated with change in intelligence test performance. The children of 290 teenage mothers (72% African-American and 28% European American) were assessed with the Stanford-Binet Intelligence Scale-4th Edition at ages 6 and 10. The mean composite score at age 6 was 84.8 and 91.2 at age 10, an improvement of 6.4 points. Significant cross-sectional predictors at both ages 6 and 10 of higher Stanford-Binet Intelligence Scale scores were maternal cognitive ability, school grade, white ethnicity, and caregiver education. Having more children in the household significantly predicted lower Stanford-Binet Intelligence Scale scores at age 6. Higher satisfaction with maternal social support predicted higher Stanford-Binet Intelligence Scale scores at age 10. Change in IQ scores was not related to maternal socioeconomic status, social support, home environment, ethnicity, or family interactions. Custodial stability was associated with an improvement in IQ scores, whereas increase in caregiver depression was related to decline in IQ scores. Our findings suggest that improvement in IQ scores of offspring of teenage mothers may be related to stability of maternal custody. More research is needed to determine the impact of the maturation of adolescent mothers' parenting and the role of early education on improvement in cognitive abilities.

Applications of the Magnetocaloric Effect in Single-Stage, Multi-Stage and Continuous Adiabatic Demagnetization Refrigerators

NASA Technical Reports Server (NTRS)

Shirron, Peter J.

2014-01-01

Adiabatic demagnetization refrigerators (ADR), based on the magnetocaloric effect, are solid-state coolers that were the first to achieve cooling well into the sub-kelvin regime. Although supplanted by more powerful dilution refrigerators in the 1960s, ADRs have experienced a revival due to the needs of the space community for cooling astronomical instruments and detectors to temperatures below 100 mK. The earliest of these were single-stage refrigerators using superfluid helium as a heat sink. Their modest cooling power (<1 µW at 60 mK[1]) was sufficient for the small (6x6) detector arrays[2], but recent advances in arraying and multiplexing technologies[3] are generating a need for higher cooling power (5-10 µW), and lower temperature (<30 mK). Single-stage ADRs have both practical and fundamental limits to their operating range, as mass grows very rapidly as the operating range is expanded. This has led to the development of new architectures that introduce multi-staging as a way to improve operating range, efficiency and cooling power. Multi-staging also enables ADRs to be configured for continuous operation, which greatly improves cooling power per unit mass. This paper reviews the current field of adiabatic demagnetization refrigeration, beginning with a description of the magnetocaloric effect and its application in single-stage systems, and then describing the challenges and capabilities of multi-stage and continuous ADRs.

Efficacy of Rotigotine at Different Stages of Parkinson’s Disease Symptom Severity and Disability: A Post Hoc Analysis According to Baseline Hoehn and Yahr Stage

PubMed Central

Giladi, Nir; Nicholas, Anthony P.; Asgharnejad, Mahnaz; Dohin, Elisabeth; Woltering, Franz; Bauer, Lars; Poewe, Werner

2016-01-01

Background: The efficacy of rotigotine has been demonstrated in studies of patients with early (i.e. not receiving levodopa) and advanced (i.e. not adequately controlled on levodopa; average 2.5 h/day in ‘off’ state) Parkinson’s disease (PD). Objective: To further investigate the efficacy of rotigotine transdermal patch across different stages of PD symptom severity and functional disability, according to baseline Hoehn and Yahr (HY) staging. Methods: Post hoc analysis of six placebo-controlled studies of rotigotine in patients with early PD (SP506, SP512, SP513; rotigotine ≤8 mg/24 h) or advanced-PD (CLEOPATRA-PD, PREFER, SP921; rotigotine ≤16 mg/24 h). Data were pooled and analyzed according to baseline HY stage (1, 2, 3 or 4) for change from baseline to end of maintenance in Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living), UPDRS III (motor) and UPDRS II+III; statistical tests are exploratory. Results: Data were available for 2057 patients (HY 1 : 262; HY 2 : 1230; HY 3 : 524; HY 4 : 41). Patients at higher HY stages were older, had a longer time since PD diagnosis and higher baseline UPDRS II+III scores vs patients at lower HY stages. Rotigotine improved UPDRS II+III versus placebo for each individual HY stage (p < 0.05 for each HY stage), with treatment differences increasing with increasing HY stages. Similar results were observed for UPDRS II and UPDRS III. Conclusions: This post hoc analysis suggests that rotigotine may be efficacious across a broad range of progressive stages of PD symptom severity and functional disability (HY stages 1–4). PMID:27567886

PET staging of amyloidosis using striatum.

PubMed

Hanseeuw, Bernard J; Betensky, Rebecca A; Mormino, Elizabeth C; Schultz, Aaron P; Sepulcre, Jorge; Becker, John A; Jacobs, Heidi I L; Buckley, Rachel F; LaPoint, Molly R; Vanini, Patrizia; Donovan, Nancy J; Chhatwal, Jasmeer P; Marshall, Gad A; Papp, Kathryn V; Amariglio, Rebecca E; Rentz, Dorene M; Sperling, Reisa A; Johnson, Keith A

2018-05-21

Amyloid PET data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid. PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research. Copyright © 2018. Published by Elsevier Inc.

Research on advanced transportation systems

NASA Astrophysics Data System (ADS)

Nagai, Hirokazu; Hashimoto, Ryouhei; Nosaka, Masataka; Koyari, Yukio; Yamada, Yoshio; Noda, Keiichirou; Shinohara, Suetsugu; Itou, Tetsuichi; Etou, Takao; Kaneko, Yutaka

1992-08-01

An overview of the researches on advanced space transportation systems is presented. Conceptual study is conducted on fly back boosters with expendable upper stage rocket systems assuming a launch capacity of 30 tons and returning to the launch site by the boosters, and prospect of their feasibility is obtained. Reviews are conducted on subjects as follows: (1) trial production of 10 tons sub scale engines for the purpose of acquiring hardware data and picking up technical problems for full scale 100 tons thrust engines using hydrocarbon fuels; (2) development techniques for advanced liquid propulsion systems from the aspects of development schedule, cost; (3) review of conventional technologies, and common use of component; (4) oxidant switching propulsion systems focusing on feasibility of Liquefied Air Cycle Engine (LACE) and Compressed Air Cycle Engine (CACE); (5) present status of slosh hydrogen manufacturing, storage, and handling; (6) construction of small high speed dynamometer for promoting research on mini pump development; (7) hybrid solid boosters under research all over the world as low-cost and clean propulsion systems; and (8) high performance solid propellant for upper stage and lower stage propulsion systems.

Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study.

PubMed

Cuneo, Antonio; Follows, George; Rigolin, Gian Matteo; Piciocchi, Alfonso; Tedeschi, Alessandra; Trentin, Livio; Medina Perez, Angeles; Coscia, Marta; Laurenti, Luca; Musuraca, Gerardo; Farina, Lucia; Rivas Delgado, Alfredo; Orlandi, Ester Maria; Galieni, Piero; Mauro, Francesca Romana; Visco, Carlo; Amendola, Angela; Billio, Atto; Marasca, Roberto; Chiarenza, Annalisa; Meneghini, Vittorio; Ilariucci, Fiorella; Marchetti, Monia; Molica, Stefano; Re, Francesca; Gaidano, Gianluca; Gonzalez, Marcos; Forconi, Francesco; Ciolli, Stefania; Cortelezzi, Agostino; Montillo, Marco; Smolej, Lukas; Schuh, Anna; Eyre, Toby A; Kennedy, Ben; Bowles, Kris M; Vignetti, Marco; de la Serna, Javier; Moreno, Carol; Foà, Robin; Ghia, Paolo

2018-04-19

We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival was 74.5 months. Advanced Binet stage (i.e. III-IV or C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within named patient programs in the United Kingdom and in Italy was carried out with overall survival as objective endpoint. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, the overall survival did not differ between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in chronic lymphocytic leukemia in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of overall survival when used as first salvage treatment in patients without 17p deletion. ClinicalTrials.gov identifier: NCT02491398. Copyright © 2018, Ferrata Storti Foundation.

Modeling and Test Data Analysis of a Tank Rapid Chill and Fill System for the Advanced Shuttle Upper Stage (ASUS) Concept

NASA Technical Reports Server (NTRS)

Flachbart, Robin; Hedayat, Ali; Holt, Kimberly A.; Cruit, Wendy (Technical Monitor)

2001-01-01

The Advanced Shuttle Upper Stage (ASUS) concept addresses safety concerns associated .with cryogenic stages by launching empty, and filling on ascent. The ASUS employs a rapid chill and fill concept. A spray bar is used to completely chill the tank before fill, allowing the vent valve to be closed during the fill process. The first tests of this concept, using a flight size (not flight weight) tank. were conducted at Marshall Space Flight Center (MSFC) during the summer of 2000. The objectives of the testing were to: 1) demonstrate that a flight size tank could be filled in roughly 5 minutes to accommodate the shuttle ascent window, and 2) demonstrate a no-vent fill of the tank. A total of 12 tests were conducted. Models of the test facility fill and vent systems, as well as the tank, were constructed. The objective of achieving tank fill in 5 minutes was met during the test series. However, liquid began to accumulate in the tank before it was chilled. Since the tank was not chilled until the end of each test, vent valve closure during fill was not possible. Even though the chill and fill process did not occur as expected, reasonable model correlation with the test data was achieved.

Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.

PubMed

Baeta-Corral, Raquel; Defrin, Ruti; Pick, Chagi G; Giménez-Llort, Lydia

2015-07-23

Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

After accounting for competing causes of death and more advanced stage, do Aboriginal and Torres Strait Islander peoples with cancer still have worse survival? A population-based cohort study in New South Wales.

PubMed

Tervonen, Hanna E; Walton, Richard; You, Hui; Baker, Deborah; Roder, David; Currow, David; Aranda, Sanchia

2017-06-02

Aboriginal and Torres Strait Islander peoples in Australia have been found to have poorer cancer survival than non-Aboriginal people. However, use of conventional relative survival analyses is limited due to a lack of life tables. This cohort study examined whether poorer survival persist after accounting for competing risks of death from other causes and disparities in cancer stage at diagnosis, for all cancers collectively and by cancer site. People diagnosed in 2000-2008 were extracted from the population-based New South Wales Cancer Registry. Aboriginal status was multiply imputed for people with missing information (12.9%). Logistic regression models were used to compute odds ratios (ORs) with 95% confidence intervals (CIs) for 'advanced stage' at diagnosis (separately for distant and distant/regional stage). Survival was examined using competing risk regression to compute subhazard ratios (SHRs) with 95%CIs. Of the 301,356 cases, 2517 (0.84%) identified as Aboriginal (0.94% after imputation). After adjusting for age, sex, year of diagnosis, socio-economic status, remoteness, and cancer site Aboriginal peoples were more likely to be diagnosed with distant (OR 1.30, 95%CI 1.17-1.44) or distant/regional stage (OR 1.29, 95%CI 1.18-1.40) for all cancers collectively. This applied to cancers of the female breast, uterus, prostate, kidney, others (those not included in other categories) and cervix (when analyses were restricted to cases with known stages/known Aboriginal status). Aboriginal peoples had a higher hazard of death than non-Aboriginal people after accounting for competing risks from other causes of death, socio-demographic factors, stage and cancer site (SHR 1.40, 95%CI 1.31-1.50 for all cancers collectively). Consistent results applied to colorectal, lung, breast, prostate and other cancers. Aboriginal peoples with cancer have an elevated hazard of cancer death compared with non-Aboriginal people, after accounting for more advanced stage and competing

Nuclear electric propulsion stage requirements and description

NASA Technical Reports Server (NTRS)

Mondt, J. F.; Peelgren, M. L.; Nakashima, A. M.; Nsieh, T. M.; Phillips, W. M.; Kikin, G. M.

1974-01-01

The application of a nuclear electric propulsion (NEP) stage in the exploration of near-earth, cometary, and planetary space was discussed. The NEP stage is powered by a liquid-metal-cooled, fast spectrum thermionic reactor capable of providing 120 kWe for 20,000 hours. This power is used to drive a number of mercury ion bombardment thrusters with specific impulse in the range of 4000-5000 seconds. The NEP description, characteristics, and functional requirements are discussed. These requirements are based on a set of five coordinate missions, which are described in detail. These five missions are a representative part of a larger set of missions used as a basic for an advanced propulsion comparison study. Additionally, the NEP stage development plan and test program is outlined and a schedule presented.

[Device-aided therapies in advanced Parkinson's disease].

PubMed

Timofeeva, A A

Advanced stages of Parkinson's disease (PD) is a consequence of the severe neurodegenerative process and are characterized by the development of motor fluctuations and dyskinesia, aggravation of non-motor symptoms. Treatment with peroral and transdermal drugs can't provide an adequate control of PD symptoms and quality-of-life of the patients at this stage of disease. Currently, three device-aided therapies: deep brain stimulation (DBS), intrajejunal infusion of duodopa, subcutaneous infusion of apomorphine can be used in treatment of patients with advanced stages of PD. Timely administration of device-aided therapies and right choice of the method determine, to a large extent, the efficacy and safety of their use. Despite the high efficacy of all three methods with respect to the fluctuation of separate symptoms, each method has its own peculiarities. The authors reviewed the data on the expediency of using each method according to the severity of motor and non-motor symptoms, patient's age, PD duration, concomitant pathology and social support of the patients.

Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

PubMed Central

Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

2013-01-01

Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

Advanced Glycation End-Products Are Associated With the Presence and Severity of Paratonia in Early Stage Alzheimer Disease.

PubMed

Drenth, Hans; Zuidema, Sytse U; Krijnen, Wim P; Bautmans, Ivan; van der Schans, Cees; Hobbelen, Hans

2017-07-01

Paratonia, a distinctive form of hypertonia in patients with dementia, causes loss of functional mobility in early stage dementia to severe contractures and pain in the late stages. The pathogenesis of paratonia is not well understood. Patients in early stage dementia with diabetes mellitus showed a significantly higher risk for the development of paratonia. Both Alzheimer disease and diabetes mellitus are related to higher concentrations of advanced glycation end-products (AGEs). The purpose of this study is to explore the association of AGEs with the prevalence and severity of paratonia in patients with Alzheimer disease. Observational longitudinal, 1-year follow-up cohort study with 3 assessments. Day care centers for patients with dementia. A total of 144 community-dwelling patients with early stage Alzheimer or Alzheimer/vascular disease were recruited from 24 dementia day care centers in The Netherlands. The presence of paratonia (Paratonia Assessment Instrument), the severity of paratonia (Modified Ashworth Scale for paratonia), and AGE levels (AGE-reader). From the 144 participants (56.3% female and 43.7% male, with a mean [standard deviation] age of 80.7 [7.7] years), 118 participants were available for final follow-up. A significant association between AGE levels and the presence of paratonia (odds ratio 3.47, 95% confidence interval [CI] 1.87-6.44, P < .001) and paratonia severity (β = 0.17, 95% CI 0.11-0.23, P < .001) was determined. In participants who developed paratonia and those with persistent paratonia throughout the study the AGE levels (95% CI -0.38 to -0.13, P < .001 and 95% CI -0.46 to -0.06, P = .012, respectively) and the severity of paratonia (95% CI -0.60 to -0.35, P < .001 and 95% CI -0.38 to -0.12, P < .001, respectively) significantly increased, whereas the AGE levels remained stable in those participants without paratonia. Notwithstanding, change in AGE levels was not significantly (P = .062) related to change

A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment

DTIC Science & Technology

2015-10-01

as an oral contraceptive [6, 7]. Recently, its anti-cancer activity has been reported against advanced breast cancer [8] and head and neck squamous...profile of Centchroman--a new post-coital contraceptive . Indian J Exp Biol, 1977. 15(12): p. 1144-50. 7. Misra, N.C., et al., Centchroman--a non-steroidal... contraceptive and for the management of hormone-related clinical disorders. Med Res Rev, 2001. 21(4): p. 302-47. 11. Jaggi, M., et al., Bryostatin 1 modulates

[Comparison of treatments in patients with inoperable stage IV advanced esophageal cancer].

PubMed

Lee, Gyu Jin; Park, Moo In; Gwoo, Sangeon; Jung, Hyun Joo; Kim, Joo Hoon; Park, Seun Ja; Moon, Won; Kim, Hyung Hun; Kim, Yang Soo; Park, Sung Dal; Jeong, Tae Sig

2012-04-01

The aim of this study was to compare palliative treatments such as chemotherapy, chemoradiotherapy or radiotherapy with best supportive care in patients with inoperable advanced esophageal cancer. A total of 67 patients with inoperable advanced esophageal cancer visiting Kosin University Gospel Hospital between January 2000 and July 2010 were included in a retrospective analysis. Patients were categorized as having palliative treatment or best supportive care to compare their prognosis. The median survival was 6.4 months in 67 patients. There was significant difference in median survival between the palliative and best supportive treatment (9.8 months vs. 4.5 months, p=0.01). The patients who underwent palliative treatment had superior 1-year and 3-year overall survival rate than those with best supportive treatment (27%, 10% vs. 5%, 5%, respectively). The 1-year and 3-year overall survival rate of palliative treatment was 18% (1-year overall survival rate) in chemotherapy, 33% (1-year overall survival rate) in radiotherapy, 45% and 9% in concurrent chemoradiotherapy, and 20% and 20% in sequential chemoradiotherapy, respectively. These results may suggest that palliative treatments are more effective than best supportive care. Further prospective studies are still needed to elucidate beneficial effect of palliative treatments on inoperable advanced esophageal cancer.

Aerodynamic Design Study of Advanced Multistage Axial Compressor

NASA Technical Reports Server (NTRS)

Larosiliere, Louis M.; Wood, Jerry R.; Hathaway, Michael D.; Medd, Adam J.; Dang, Thong Q.

2002-01-01

As a direct response to the need for further performance gains from current multistage axial compressors, an investigation of advanced aerodynamic design concepts that will lead to compact, high-efficiency, and wide-operability configurations is being pursued. Part I of this report describes the projected level of technical advancement relative to the state of the art and quantifies it in terms of basic aerodynamic technology elements of current design systems. A rational enhancement of these elements is shown to lead to a substantial expansion of the design and operability space. Aerodynamic design considerations for a four-stage core compressor intended to serve as a vehicle to develop, integrate, and demonstrate aerotechnology advancements are discussed. This design is biased toward high efficiency at high loading. Three-dimensional blading and spanwise tailoring of vector diagrams guided by computational fluid dynamics (CFD) are used to manage the aerodynamics of the high-loaded endwall regions. Certain deleterious flow features, such as leakage-vortex-dominated endwall flow and strong shock-boundary-layer interactions, were identified and targeted for improvement. However, the preliminary results were encouraging and the front two stages were extracted for further aerodynamic trimming using a three-dimensional inverse design method described in part II of this report. The benefits of the inverse design method are illustrated by developing an appropriate pressure-loading strategy for transonic blading and applying it to reblade the rotors in the front two stages of the four-stage configuration. Multistage CFD simulations based on the average passage formulation indicated an overall efficiency potential far exceeding current practice for the front two stages. Results of the CFD simulation at the aerodynamic design point are interrogated to identify areas requiring additional development. In spite of the significantly higher aerodynamic loadings, advanced CFD

Advanced LIGO status

NASA Astrophysics Data System (ADS)

Dwyer, S.; LIGO Scientific Collaboration

2015-05-01

Advanced LIGO is currently in the final stages of installation and early commissioning. In the design of Advanced LIGO a key goal was the ability to detect gravitational waves from compact object binary inspirals, as these are thought to be the most likely candidates for early detections with ground based interferometers. Special emphasis has been placed on improving the low frequency sensitivity relative to the first generations of LIGO, in addition to improving the high frequency sensitivity by increasing the laser power. The interferometer in Livingston Louisiana has been locked (continuously held within the linear operating range) and noise investigations have begun, and the major installation activities for the interferometer at Hanford, Washington are completed.

Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?

PubMed

Park, Geumju; Lee, Sang-Wook; Kim, Sang Yoon; Nam, Soon Yuhl; Choi, Seung-Ho; Kim, Sung-Bae; Roh, Jong-Lyel; Yoon, Dok Hyun; Kim, Su Ssan; Park, Jin-Hong; Kim, Young Seok; Yoon, Sang Min; Song, Si Yeol; Kim, Jong Hoon; Choi, Eun Kyung; DO Ahn, Seung

2013-03-01

To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications. The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group. There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups. CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.

Two stage turbine for rockets

NASA Technical Reports Server (NTRS)

Veres, Joseph P.

1993-01-01

The aerodynamic design and rig test evaluation of a small counter-rotating turbine system is described. The advanced turbine airfoils were designed and tested by Pratt & Whitney. The technology represented by this turbine is being developed for a turbopump to be used in an advanced upper stage rocket engine. The advanced engine will use a hydrogen expander cycle and achieve high performance through efficient combustion of hydrogen/oxygen propellants, high combustion pressure, and high area ratio exhaust nozzle expansion. Engine performance goals require that the turbopump drive turbines achieve high efficiency at low gas flow rates. The low mass flow rates and high operating pressures result in very small airfoil heights and diameters. The high efficiency and small size requirements present a challenging turbine design problem. The shrouded axial turbine blades are 50 percent reaction with a maximum thickness to chord ratio near 1. At 6 deg from the tangential direction, the nozzle and blade exit flow angles are well below the traditional design minimum limits. The blade turning angle of 160 deg also exceeds the maximum limits used in traditional turbine designs.

Progress and prospects for blood-stage malaria vaccines.

PubMed

Miura, Kazutoyo

2016-06-01

There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.

Core compressor exit stage study. Volume 1: Blading design. [turbofan engines

NASA Technical Reports Server (NTRS)

Wisler, D. C.

1977-01-01

A baseline compressor test stage was designed as well as a candidate rotor and two candidate stators that have the potential of reducing endwall losses relative to the baseline stage. These test stages are typical of those required in the rear stages of advanced, highly-loaded core compressors. The baseline Stage A is a low-speed model of Stage 7 of the 10 stage AMAC compressor. Candidate Rotor B uses a type of meanline in the tip region that unloads the leading edge and loads the trailing edge relative to the baseline Rotor A design. Candidate Stator B embodies twist gradients in the endwall region. Candidate Stator C embodies airfoil sections near the endwalls that have reduced trailing edge loading relative to Stator A. Tests will be conducted using four identical stages of blading so that the designs described will operate in a true multistage environment.

Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients.

PubMed

Shiels, Meredith S; Copeland, Glenn; Goodman, Marc T; Harrell, Janna; Lynch, Charles F; Pawlish, Karen; Pfeiffer, Ruth M; Engels, Eric A

2015-06-15

It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. Because cancer stage is influenced both by tumor biology and medical surveillance, the authors assessed cancer stage in individuals infected with the human immunodeficiency virus (HIV) and solid organ transplant recipients, 2 immunosuppressed groups with differences in their health care use. The authors used data on all cases of 15 cancer types diagnosed during 1996 through 2010 in 2 studies that linked US cancer registries with HIV and transplant registries. Odds ratios (ORs) for advanced (vs local) disease were estimated comparing HIV and transplant populations with immunocompetent individuals in polytomous logistic regression models adjusted for age, sex, race, registry, and year. A total of 8411 of 4.5 million cancer cases occurred in HIV-infected individuals and 7322 of 6.4 million cancer cases occurred in transplant recipients. Compared with immunocompetent patients with cancer, those infected with HIV were more likely to be diagnosed with distant stage lung (OR, 1.13), female breast (OR, 1.99), and prostate (OR, 1.57) cancers, whereas transplant recipients had fewer distant stage lung (OR, 0.54), female breast (OR, 0.75), and prostate (OR, 0.72) cancers. Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs of 1.97 for HIV-infected individuals and 1.82 for transplant recipients) and bladder cancer (ORs of 1.42 for HIV-infected individuals and 1.54 for transplant recipients). Bladder cancer and melanoma were more likely to be diagnosed at a nonlocal stage in both HIV-infected individuals and transplant recipients, suggesting a role for immunosuppression in their progression. In addition, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, which is consistent with differential access to medical care or surveillance. © 2015 American Cancer Society.

Advanced wastewater treatment simplified through research

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

Souther, R.H.

A waste water treatment plant was built based on results of a small-scale pilot plant study, conducted largely in a search for efficiency as well as economy. Results were that 98 percent carbonaceous BOD (BOD/sub C/) and nitrogenous BOD (BOD/sub N/) were removed in a simplified, low-cost, single-stage advanced treatment process surpassing even some of the most sophisticated advanced complex waste treatment methods. The single-stage process treats domestic waste alone or combined with very high amounts of textile, electroplating, chemical, food, and other processing industrial wastewater. The process removed 100 percent of the sulfides above 98 percent of NH/sub 3/-N,more » over 90 percent of COD and phenols; chromium was converted from highly toxic hexavalent CrVI to nearly nontoxic trivalent chrome (CrIII). A pH up to 12 may be tolerated if no free hydroxyl (OH) ions are present. Equalization ponds, primary settling tanks, trickling filters, extra nitrogen removal tanks, carbon columns, and chemical treatment are not required. Color removal is excellent with clear effluent suitable for recycling after chlorination to water supply lakes. The construction cost of the single-stage advanced treatment plant is surprisingly low, about /sup 1///sub 2/ to /sup 1///sub 6/ as much as most conventional ineffective complex plants. This simplified, innovative process developed in independent research at Guilford College is considered by some a breakthrough in waste treatment efficiency and economy. (MU)« less

A Gas-Spring-Loaded X-Y-Z Stage System for X-ray Microdiffraction Sample Manipulation

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

Shu Deming; Cai Zhonghou; Lai, Barry

2007-01-19

We have designed and constructed a gas-spring-loaded x-y-z stage system for x-ray microdiffraction sample manipulation at the Advanced Photon Source XOR 2-ID-D station. The stage system includes three DC-motor-driven linear stages and a gas-spring-based heavy preloading structure, which provides antigravity forces to ensure that the stage system keeps high-positioning performance under variable goniometer orientation. Microdiffraction experiments with this new stage system showed significant sample manipulation performance improvement.

A Gas-Spring-Loaded X-Y-Z Stage System for X-ray Microdiffraction Sample Manipulation

NASA Astrophysics Data System (ADS)

Shu, Deming; Cai, Zhonghou; Lai, Barry

2007-01-01

We have designed and constructed a gas-spring-loaded x-y-z stage system for x-ray microdiffraction sample manipulation at the Advanced Photon Source XOR 2-ID-D station. The stage system includes three DC-motor-driven linear stages and a gas-spring-based heavy preloading structure, which provides antigravity forces to ensure that the stage system keeps high-positioning performance under variable goniometer orientation. Microdiffraction experiments with this new stage system showed significant sample manipulation performance improvement.

Economic implications of using bendamustine, alemtuzumab, or chlorambucil as a first-line therapy for chronic lymphocytic leukemia in the US: a cost-effectiveness analysis.

PubMed

Kongnakorn, Thitima; Sterchele, James A; Salvador, Christopher G; Getsios, Denis; Mwamburi, Mkaya

2014-01-01

The objective of this analysis was to evaluate the cost-effectiveness of using bendamustine versus alemtuzumab or bendamustine versus chlorambucil as a first-line therapy in patients with Binet stage B or C chronic lymphocytic leukemia (CLL) in the US. A discrete event simulation of the disease course of CLL was developed to evaluate the economic implications of single-agent treatment with bendamustine, alemtuzumab, or chlorambucil, which are indicated for a treatment-naïve patient population with Binet stage B or C CLL. Data from clinical trials were used to create a simulated patient population, risk equations for progression-free survival and survival post disease progression, response rates, and rates of adverse events. Costs from a US health care payer perspective in 2012 US dollars, survival (life years), and quality-adjusted life years (QALYs) were estimated over a patient's lifetime; all were discounted at 3% per year. Compared with alemtuzumab, bendamustine was considered to be a dominant treatment providing greater benefit (6.10 versus 5.37 life years and 4.02 versus 3.45 QALYs) at lower cost ($78,776 versus $121,441). Compared with chlorambucil, bendamustine was associated with higher costs ($78,776 versus $42,337) but with improved health outcomes (6.10 versus 5.21 life years and 4.02 versus 3.30 QALYs), resulting in incremental cost-effectiveness ratios of $40,971 per life year gained and $50,619 per QALY gained. Bendamustine is expected to provide cost savings and greater health benefit than alemtuzumab in treatment-naïve patients with CLL. Furthermore, it can be considered as a cost-effective treatment providing health benefits at an acceptable cost versus chlorambucil in the US.

A novel wavelet neural network based pathological stage detection technique for an oral precancerous condition

PubMed Central

Paul, R R; Mukherjee, A; Dutta, P K; Banerjee, S; Pal, M; Chatterjee, J; Chaudhuri, K; Mukkerjee, K

2005-01-01

Aim: To describe a novel neural network based oral precancer (oral submucous fibrosis; OSF) stage detection method. Method: The wavelet coefficients of transmission electron microscopy images of collagen fibres from normal oral submucosa and OSF tissues were used to choose the feature vector which, in turn, was used to train the artificial neural network. Results: The trained network was able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. Conclusions: The results obtained from this proposed technique were promising and suggest that with further optimisation this method could be used to detect and stage OSF, and could be adapted for other conditions. PMID:16126873

Herbal medicines for advanced colorectal cancer.

PubMed

Guo, Zhongning; Jia, Xiaoqiang; Liu, Jian Ping; Liao, Juan; Yang, Yufei

2012-05-16

Herbal medicine has been widely used in patients with advanced colorectal cancer in China, but its efficacy has not been confirmed. To evaluate the beneficial effect and safety on Chinese herbal medicine therapy for advanced stage colorectal cancer, and it's influence on the patients' quality of life. The following electronic databases were searched: BIOSIS Previews, Cochrane Controlled Trials Register, Medline EMBASE, Biological Abstracts, until Aug. 2011. Manual searching was performed on 16 types of Chinese journals which started from their respective first publication dates, as well as unpublished conference proceedings. No language restriction was applied. Randomized or quasi-randomised controlled trials on the treatment of advanced stage colorectal cancer by herbal medicines or herbal medicines combined with chemotherapy, regardless of blinding. The data were extracted independently by two reviewers. Methodological quality of the included in trials was assessed according to the following parameters: randomisation, allocation concealment, double blinding, and drop-out rates. A total of 20 randomised controlled trials with 1304 participants were identified. All the 20 trials compared the use of herbal medicines with chemotherapy and chemotherapy alone in the treatment of advanced stage colorectal cancers.Compared with chemotherapy alone, the use of Quxie capsule combined with chemotherapy could decrease mortality rate (RR 0.17, 95% CI 0.03 to 0.97); the use of Jianpi Jiedu formula, Xiaozheng formula and Yiqi Huoxue herbal medicine combined with chemotherapy respectively could improve 1-year survival rate significantly; the use of Xiaozheng Formula in conjunction with chemotherapy could improve 3-year survival rate. There were 10 herbal medicines showing benefit in improving quality of life. Herbal medicines did not show additional benefit in response rate or stability rate. No trials reported serious adverse effect from herbal medicine. Some herbal medicines

Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia.

PubMed

Han, Kwang-Hyub; Kudo, Masatochi; Ye, Sheng-Long; Choi, Jong Young; Poon, Roonni Tung-Ping; Seong, Jinsil; Park, Joong-Won; Ichida, Takafumi; Chung, Jin Wook; Chow, Pierce; Cheng, Ann-Lii

2011-01-01

Hepatocellular carcinoma (HCC) is a highly prevalent disease in many Asian countries, accounting for 80% of victims worldwide. Screening programs improve the detection of early HCC and have a positive impact on survival, but the majority of HCC patients in Asia still present with advanced stage disease. The treatment outcomes of HCC are affected by multiple variables, including liver function, performance status of the patient, and tumor stage. Therefore, it is not easy to apply a multidisciplinary therapeutic approach for optimal management. At present, limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia. Therefore, most patients are eligible for only palliative treatments. For optimal management, the treatment choice is guided by staging systems and treatment guidelines. Numerous staging systems have been proposed and treatment guidelines vary by region. According to the Barcelona Clinic Liver Cancer (BCLC) guideline based on evidence from randomized clinical trials, only transarterial chemoembolization (TACE) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC. However, treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach, hepatic arterial infusion chemotherapy, external radiation, and their combinations based on clinical experiences for intermediate and advanced stage HCC. Although TACE is the main therapeutic modality in the intermediate stage, overall therapeutic outcomes depend on the tumor size. In the advanced stage, the prognosis depends on the tumor status, e.g. major vessel invasion or extrahepatic spread. Thus, a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence-based data, which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC. Copyright �

Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Symptoms, Tests, Prognosis, Stages (PDQ®)—Patient Version

Cancer.gov

Ovarian epithelial, fallopian tube, and primary peritoneal cancers form in the same type of tissue and use the same staging system. Risk factors include family history and inherited gene mutations. Learn more about why ovarian cancers are often found at advanced stages and the tests to diagnose and stage the cancer.

Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

ClinicalTrials.gov

2018-03-28

Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

Situational variation in moral judgment: In a stage or on a stage?

PubMed

Carpendale, J I; Krebs, D L

1992-04-01

Two issues were examined in this study-the consistency of moral judgment across different types of dilemma and different social contexts, and the relationship between the structure (stage) of moral judgment and the content of moral decisions. Forty subjects were given two hypothetical dilemmas about business decisions and two standard Kohlberg dilemmas. Half the subjects directed their responses to a business audience, half to a philosophical audience. Responses to the moral dilemmas were scored in accordance with the Colby and Kohlberg (1987) scoring manual. Stage of moral reasoning was found to be significantly higher on the Kohlberg dilemmas than on the business dilemmas. A significant interaction between type of dilemma and audience was attributed to the tendency of subjects directing their responses to a business audience to interpret one of the business dilemmas in terms of the moral order of business, but for subjects directing their responses to a philosophy audience to treat it as a philosophical dilemma. The other business dilemma evoked uniformly low-level moral judgments. The amount of selfishness intrinsic in subjects' moral choices on the business dilemmas was significantly negatively correlated with moral maturity on the business dilemmas, but not with their moral maturity on Kohlberg's test. These results are interpreted as more consistent with models of moral development such as those advanced by C. G. Levine ([1979] "Stage Acquisition and Stage Use: An Appraisal of Stage Displacement Explanations of Variation in Moral Reasoning, " Human Development, Vol. 22, pp. 145-164), J. Rest ([1983] "Morality," in: P. H. Mussen [ed.], J. H. Flavell and E. Markman [Vol. eds.], Handbook of Child Psychology [Vol. 3, 4th ed.], John Wiley & Sons, New York), and R. Harré ([1984]) Personal Being: A Theory for Individual Psychology, Harvard University Press, Cambridge, Massachusetts), which posit a relatively wide range of within-person stage use and emphasize the

Advanced rocket propulsion

NASA Technical Reports Server (NTRS)

Obrien, Charles J.

1993-01-01

Existing NASA research contracts are supporting development of advanced reinforced polymer and metal matrix composites for use in liquid rocket engines of the future. Advanced rocket propulsion concepts, such as modular platelet engines, dual-fuel dual-expander engines, and variable mixture ratio engines, require advanced materials and structures to reduce overall vehicle weight as well as address specific propulsion system problems related to elevated operating temperatures, new engine components, and unique operating processes. High performance propulsion systems with improved manufacturability and maintainability are needed for single stage to orbit vehicles and other high performance mission applications. One way to satisfy these needs is to develop a small engine which can be clustered in modules to provide required levels of total thrust. This approach should reduce development schedule and cost requirements by lowering hardware lead times and permitting the use of existing test facilities. Modular engines should also reduce operational costs associated with maintenance and parts inventories.

Enabling Exploration Missions Now: Applications of On-orbit Staging

NASA Technical Reports Server (NTRS)

Folta, David C.; Vaughn, Frank; Westmeyer, Paul; Rawitscher, Gary; Bordi, Francesco

2005-01-01

Future NASA Exploration goals are difficult to meet using current launch vehicle implementations and techniques. We introduce a concept of On-Orbit Staging (OOS) using multiple launches into a Low Earth orbit (LEO) staging area to increase payload mass and reduce overall cost for exploration initiative missions. This concept is a forward-looking implementation of ideas put forth by Oberth and Von Braun to address the total mission design. Applying staging throughout the mission and utilizing technological advances in propulsion efficiency and architecture enable us to show that exploration goals can be met in the next decade. As part of this architecture, we assume the readiness of automated rendezvous, docking, and assembly technology.

Stage of cancer diagnoses among migrants from the former Soviet Union in comparison to the German population - are diagnoses among migrants delayed?

PubMed

Cho, An Bin; Jaehn, Philipp; Holleczek, Bernd; Becher, Heiko; Winkler, Volker

2018-01-17

In this study, we compared stage at diagnosis, standardized incidence ratio (SIR) and standardized mortality ratio (SMR) of most frequent cancer diagnoses between re-settlers (Aussiedler) from the former Soviet Union and the general population in the Saarland in Germany to assess possible delays in diagnosis of cancer among this migrant group. Lung cancer, colorectal cancer, breast cancer, prostate cancer, malignant melanoma of the skin and stomach cancer diagnoses among a cohort of 18,619 re-settlers living in the Saarland between 1990 and 2009 were identified by the federal state's cancer registry. Vital status was available for the respective time-period and used to calculate SIR and SMR in comparison to the autochthonous population. Tumor stages were condensed into local and advanced stages. Odds ratios (OR) for an advanced tumor stage were modeled in dependence of re-settler-status and relevant covariates by logistic regression. Missing values were addressed in a sensitivity analysis. The influence of duration of stay in Germany on advanced stage diagnosis was analyzed among re-settlers. SIR and SMR of lung and breast cancer were lower among female re-settlers, while SIR and SMR of colorectal and prostate cancer were lower among male re-settlers. SIR and SMR of stomach cancer were elevated among both sexes. Female re-settlers showed an elevated OR for being diagnosed with advanced stage breast cancer. Both male and female re-settlers showed an elevated OR when observing all six sites combined (OR among males 1.47, p = 0.04; OR among females 1.37, p = 0.05). The result of elevated ORs was supported in the sensitivity analysis. Finally, male re-settlers showed a weak association between duration of stay in Germany and reduced risk for advanced stage diagnosis. Re-settlers were more likely to be diagnosed at an advanced tumor stage. These findings are in line with previous research having shown unfavorable health care utilization of re-settlers. Overall

Results of an Advanced Fan Stage Operating Over a Wide Range of Speed and Bypass Ratio. Part 1; Fan Stage Design and Experimental Results

NASA Technical Reports Server (NTRS)

Suder, Kenneth L.; Prahst, Patricia S.; Thorp, Scott A.

2011-01-01

NASA s Fundamental Aeronautics Program is investigating turbine-based combined cycle (TBCC) propulsion systems for access to space because it provides the potential for aircraft-like, space-launch operations that may significantly reduce launch costs and improve safety. To this end, National Aeronautics and Space Administration (NASA) and General Electric (GE) teamed to design a Mach 4 variable cycle turbofan/ramjet engine for access to space. To enable the wide operating range of a Mach 4+ variable cycle turbofan ramjet required the development of a unique fan stage design capable of multi-point operation to accommodate variations in bypass ratio (10 ), fan speed (7 ), inlet mass flow (3.5 ), inlet pressure (8 ), and inlet temperature (3 ). In this paper, NASA has set out to characterize a TBCC engine fan stage aerodynamic performance and stability limits over a wide operating range including power-on and hypersonic-unique "windmill" operation. Herein, we will present the fan stage design, and the experimental test results of the fan stage operating from 15 to 100 percent corrected design speed. Whereas, in the companion paper, we will provide an assessment of NASA s APNASA code s ability to predict the fan stage performance and operability over a wide range of speed and bypass ratio.

The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

PubMed

In, Haejin; Ravetch, Ethan; Langdon-Embry, Marisa; Palis, Bryan; Ajani, Jaffer A; Hofstetter, Wayne L; Kelsen, David P; Sano, Takeshi

2018-01-01

New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p < 0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index = 0.81, 95% CI, 0.79-0.83; ypStage: c index = 0.80, 95% CI, 0.73-0.87). The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.

Ares I First Stage Propulsion System Status

NASA Technical Reports Server (NTRS)

Priskos, Alex S.

2010-01-01

With the retirement of the Space Shuttle inevitable, the US is faced with the need to loft a reliable cost-effective, technologically viable solution to bring the nation s fleet of spacecraft back up to industry standard. It must not only support the International Space Station (ISS), it must also be capable of supporting human exploration beyond low Earth orbit (LEO). NASA created the Constellation Program to develop a new fleet including the launch vehicles, the spacecraft, and the mission architecture to meet those objectives. The Ares First Stage Team is tasked with developing a propulsion system capable of safely, dependably and repeatedly lofting that new fleet. To minimize technical risks and development costs, the Solid Rocket Boosters (SRBs) of Shuttle were used as a starting point in the design and production of a new first stage element. While the first stage will provide the foundation, the structural backbone, power, and control for launch, the new propulsive element will also provide a greater total impulse to loft a safer, more powerful, fleet of space flight vehicles. Substantial design and system upgrades were required to meet the mass and trajectory requisites of the new fleet. Noteworthy innovations and design features include new forward structures, new propellant grain geometry, a new internal insulation system, and a state-of-the art avionics system. Additional advances were in materials and composite structures development, case bond liners, and thermal protection systems. Significant progress has been made in the design, development and testing of the propulsion and avionics systems for the new first stage element. Challenges, such as those anticipated with thrust oscillation, have been better characterized, and are being effectively mitigated. The test firing of the first development motor (DM-1) was a success that validated much of the engineering development to date. Substantive data has been collected and analyzed, allowing the Ares

Evaluation of 122 advanced-stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies.

PubMed

Al-Rohil, Rami N; Tarasen, Ashley J; Carlson, J Andrew; Wang, Kai; Johnson, Adrienne; Yelensky, Roman; Lipson, Doron; Elvin, Julia A; Vergilio, Jo-Anne; Ali, Siraj M; Suh, James; Miller, Vincent A; Stephens, Philip J; Ganesan, Prasanth; Janku, Filip; Karp, Daniel D; Subbiah, Vivek; Mihm, Martin C; Ross, Jeffrey S

2016-01-15

The authors hypothesized that comprehensive genomic profiling of advanced-stage cutaneous squamous cell carcinoma (cSCC) could identify genomic-derived drug targets of therapy for patients with conventional therapy-resistant disease. Comprehensive genomic profiling of 315 cancer genes was applied to 50 ng of DNA from 122 cSCC cases for the evaluation of all classes of genomic alterations (GAs). Clinically relevant genomic alterations (CRGAs) were defined as those identifying anticancer drugs on the market or in registered clinical trials. There were 21 women (17%) and 101 men (83%) with a median age of 64.9 years (range, 21-87 years). Eleven cSCC cases (9%) were histologic AJCC grade 1, 69 (57%) were grade 2, and 42 (34%) were grade 3. The primary cSCC was used for sequencing in 77 cases (63%). Metastatic lesions were sequenced in 37% of cases. There were 1120 total GAs identified (average of 9.2 GAs per tumor), with 100% of cases harboring at least 1 alteration. Of the 122 cSCCs, 107 (88%) harbored at least 1 CRGA (2.5 CRGAs per cSCC) includingNOTCH1 (43%); patched 1 (PTCH1) (11%); BRCA2 (10%); HRAS (8%); ataxia telangiectasia mutated (ATM) (7%); erb-B2 receptor tyrosine kinase 4 (ERBB4) (7%); neurofibromatosis type 1 (NF1) (7%); erb-B2 receptor tyrosine kinase 2 (ERBB2) (6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) (6%); cyclin D1 (CCND1) (6%); epidermal growth factor receptor (EGFR) (5%); and F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) (5%). In the current study, approximately 88% of patients with cSCC were found to harbor clinically relevant GAs that have the potential to guide the treatment of patients with advanced-stage tumors with targeted therapeutic agents. Cancer 2016;122:249-257. © 2015 American Cancer Society. © 2015 American Cancer Society.

Progress and prospects for blood-stage malaria vaccines

PubMed Central

Miura, Kazutoyo

2016-01-01

ABSTRACT There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part. PMID:26760062

Esophageal cancer: anatomic particularities, staging, and imaging techniques.

PubMed

Encinas de la Iglesia, J; Corral de la Calle, M A; Fernández Pérez, G C; Ruano Pérez, R; Álvarez Delgado, A

2016-01-01

Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

NExT: Advancing Promising Cancer Therapies

Cancer.gov

The NCI Experimental Therapeutics (NExT) program works with researchers and top scientific experts to advance promising or novel cancer therapies from the earliest stages of research to clinical trials. Learn about recent successes from NExT in this Cancer Currents blog post.

Nuclear Thermal Propulsion for Advanced Space Exploration

NASA Technical Reports Server (NTRS)

Houts, M. G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

Worldwide Esophageal Cancer Collaboration: clinical staging data.

PubMed

Rice, T W; Apperson-Hansen, C; DiPaola, L M; Semple, M E; Lerut, T E M R; Orringer, M B; Chen, L-Q; Hofstetter, W L; Smithers, B M; Rusch, V W; Wijnhoven, B P L; Chen, K N; Davies, A R; D'Journo, X B; Kesler, K A; Luketich, J D; Ferguson, M K; Räsänen, J V; van Hillegersberg, R; Fang, W; Durand, L; Allum, W H; Cecconello, I; Cerfolio, R J; Pera, M; Griffin, S M; Burger, R; Liu, J-F; Allen, M S; Law, S; Watson, T J; Darling, G E; Scott, W J; Duranceau, A; Denlinger, C E; Schipper, P H; Ishwaran, H; Blackstone, E H

2016-10-01

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg 2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. © 2016 International Society for Diseases of the Esophagus.

Worldwide Esophageal Cancer Collaboration: clinical staging data

PubMed Central

Rice, T. W.; Apperson-Hansen, C.; DiPaola, L. M.; Semple, M. E.; Lerut, T. E. M. R.; Orringer, M. B.; Chen, L.-Q.; Hofstetter, W. L.; Smithers, B. M.; Rusch, V. W.; Wijnhoven, B. P. L.; Chen, K. N.; Davies, A. R.; D’Journo, X. B.; Kesler, K. A.; Luketich, J. D.; Ferguson, M. K.; Räsänen, J. V.; van Hillegersberg, R.; Fang, W.; Durand, L.; Allum, W. H.; Cecconello, I.; Cerfolio, R. J.; Pera, M.; Griffin, S. M.; Burger, R.; Liu, J.-F; Allen, M. S.; Law, S.; Watson, T. J.; Darling, G. E.; Scott, W. J.; Duranceau, A.; Denlinger, C. E.; Schipper, P. H.; Ishwaran, H.; Blackstone, E. H.

2017-01-01

SUMMARY To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data—simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival—for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5–25 mg/kg2, 47%), little weight loss (2.4 ± 7.8 kg), 0–1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cNO (44%), cMO (95%), and cG2–G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cNO versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. PMID:27731549

Conceptual design of a two stage to orbit spacecraft

NASA Technical Reports Server (NTRS)

Armiger, Scott C.; Kwarta, Jennifer S.; Horsley, Kevin B.; Snow, Glenn A.; Koe, Eric C.; Single, Thomas G.

1993-01-01

This project, undertaken through the Advanced Space Design Program, developed a 'Conceptual Design of a Two Stage To Orbit Spacecraft (TSTO).' The design developed utilizes a combination of air breathing and rocket propulsion systems and is fully reusable, with horizontal takeoff and landing capability. The orbiter is carried in an aerodynamically designed bay in the aft section of the booster vehicle to the staging altitude. This TSTO Spacecraft design meets the requirements of replacing the aging Space Shuttle system with a more easily maintained vehicle with more flexible mission capability.

Health system delay and its effect on clinical stage of breast cancer: Multicenter study.

PubMed

Unger-Saldaña, Karla; Miranda, Alfonso; Zarco-Espinosa, Gelasio; Mainero-Ratchelous, Fernando; Bargalló-Rocha, Enrique; Miguel Lázaro-León, Jesús

2015-07-01

The objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer. This was a cross-sectional study of 886 patients who were referred to 4 of the largest public cancer hospitals in Mexico City for the evaluation of a probable breast cancer. Data on time intervals, sociodemographic factors, and clinical stage at diagnosis were retrieved. A logistic regression model was used to estimate the average marginal effects of delay on the probability of being diagnosed with advanced breast cancer (stages III and IV). The median time between problem identification and the beginning of treatment was 7 months. The subinterval with the largest delay was that between the first medical consultation and diagnosis (median, 4 months). Only 15% of the patients who had cancer were diagnosed with stage 0 and I disease, and 48% were diagnosed with stage III and IV disease. Multivariate analyses confirmed independent correlations for the means of problem identification, patient delay, health system delay, and age with a higher probability that patients would begin cancer treatment in an advanced stage. In the sample studied, the majority of patients with breast cancer began treatment after a delay. Both patient delays and provider delays were associated with advanced disease. Research aimed at identifying specific access barriers to medical services is much needed to guide the design of tailored health policies that go beyond the promotion of breast care awareness and screening participation to include improvements in health services that facilitate access to timely diagnosis and treatment. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

2015-01-01

This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

[Neoadjuvant Radiochemotherapy Followed by Curative Resection in Patients with Advanced Non-Small Cell Lung Cancer in Stage IIIA/IIIB: Prognostic Factors and Results].

PubMed

Schreiner, W; Dudek, W; Lettmaier, S; Gavrychenkova, S; Rieker, R; Fietkau, R; Sirbu, H

2016-06-01

The role of surgical lung resection following neo-adjuvant radio-chemotherapy (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet not clearly defined. The aim of our study was to analyze the postoperative survival and to identify relevant prognostic factors. 46 patients underwent curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB) between February 2008 and February 2015. A retrospective data analysis regarding preoperative regression status, perioperative mortality, postoperative survival, patho-histological remission, relapse pattern and other prognostic factors was performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45-60] Gy was performed in 44 (96 %) patients. Partial and/or complete regression was observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients. The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The overall and progression free 5-year survival rate was 47 % and respectively 45 % [in median 58 months]. The 5-year survival rate of 64 % in the "responder"-group was significantly better when compared with 24 % in the "non-responder"-group (p = 0.038). The tri-modality therapy improved the prognosis in patients with locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological remission is an important prognostic factor for better long term survival. Dividing the patients in "responder" and "non-responder" after neo-adjuvant RCT may have large therapeutically consequences in the future. Georg Thieme Verlag KG Stuttgart · New York.

Winning Strategies in Challenging Times for Advancing Small Colleges.

ERIC Educational Resources Information Center

Willmer, Wesley K., Ed.

This volume contains nine papers on advancement issues and strategies for small colleges in the context of this decade's economic and social challenges. Chapter 1, "Setting the Stage" (Wesley K. Willmer), reports on a study of the advancement programs of smaller colleges in 1990-91, the third in a series of studies beginning in 1977-78. Chapter 2,…

Implementation of Extensive Cytoreduction Resulted in Improved Survival Outcomes for Patients with Newly Diagnosed Advanced-Stage Ovarian, Tubal, and Peritoneal Cancers.

PubMed

Raspagliesi, Francesco; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Chiappa, Valentina; Borghi, Chiara; Scaffa, Cono; Morano, Federica; Maltese, Giuseppa; Lorusso, Domenica

2017-10-01

Residual disease (RD) after primary debulking surgery (PDS) is one of the main factors driving ovarian cancer prognosis. The primary end point of this study was assessment of the impact that surgery had on survival outcomes for patients with advanced ovarian cancer. Data on the effect of newly diagnosed advanced-stage ovarian, tubal, and peritoneal cancers were analyzed during two study periods (T1: 2001-2006 and T2: 2007-2012), in which the concepts of optimal and complete cytoreduction were introduced and implemented. In this study, 260 patients (36%) had surgery during T1 and 462 patients (64%) had surgery during T2. The rate of PDS increased, from 55.4% (144/260) during T1 to 85.5% (395/462) during T2 (p < 0.001). At the time of PDS, complete resection (RD0) was achieved for 45.1% of the patients during T1 and 76.7% of the patients during T2 (p < 0.001), whereas optimal resection (RD < 1 cm) was achieved for 60.4% of the patients during T1 and 85.3% of the patients during T2 (p < 0.001). Disease-free survival improved during the study periods (p = 0.006). Overall survival was similar in T1 and T2 (p = 0.18). The preoperative CA125 level, disease stage, and RD remained independently associated with disease-free survival (p ≤ 0.05). The performance of interval debulking surgery (IDS) instead of PDS correlated with worse survival outcomes (hazard ratio [HR] 1.47; 95% confidence interval [CI] 1.24-1.92; p = 0.02), whereas achievement of RD0 and RD < 1 cm independently improved overall survival (HR 0.45; 95% CI 0.22-0.91; p = 0.02 for RD0 and HR 0.47; 95% CI 0.23-0.96; p = 0.03 for RD0). The implementation of extensive cytoreduction allows improvement of patient outcomes. Further studies are needed to assess the risk-to-benefit ratio between PDS and IDS and to identify patients who benefit much more from one treatment method than from another.

Composite engines for application to a single-stage-to-orbit vehicle

NASA Technical Reports Server (NTRS)

Bendot, J. G.; Brown, P. N.; Piercy, T. G.

1975-01-01

Seven composite engines were designed for application to a reusable single-stage-to-orbit vehicle. The engine designs were variations of the supercharged ejector ramjet engine. The resulting performance, weight, and drawings of each engine form a data base for establishing a potential of this class of composite engine to various missions, including the single-stage-to-orbit application. The impact of advanced technology in the design of the critical fan turbine was established.

Advanced small launch vehicle study

NASA Technical Reports Server (NTRS)

Reins, G. E.; Alvis, J. F.

1972-01-01

A conceptual design study was conducted to determine the most economical (lowest cost/launch) approach for the development of an advanced small launch vehicle (ASLV) for use over the next decade. The ASLV design objective was to place a 340 kg (750 lb) payload into a 556 km (300 n.mi.) circular orbit when launched due east from Wallops Island, Virginia. The investigation encompassed improvements to the current Scout launch vehicle; use of existing military and NASA launch vehicle stages; and new, optionally staged vehicles. Staging analyses included use of liquid, solid, and hybrid propellants. Improvements in guidance, controls, interstages, telemetry, and payload shroud were also considered. It was concluded that the most economical approach is to progressively improve the Scout launch vehicle in three phased steps which are discussed.

Intravoxel Incoherent Motion MR Imaging for Staging of Hepatic Fibrosis.

PubMed

Zhang, Bin; Liang, Long; Dong, Yuhao; Lian, Zhouyang; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

2016-01-01

To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83-4.09, P = 0.006; WMD 13.10, 95% CI 9.53-16.67, P < 0.001; WMD 14.34, 95% CI 10.26-18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06-3.18, P = 0.027; WMD 5.63, 95% CI 2.74-8.52, P < 0.001; WMD 3.30, 95% CI 2.10-4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF.

CAREGIVERS’ DIFFERING NEEDS ACROSS KEY EXPERIENCES OF THE ADVANCED CANCER DISEASE TRAJECTORY

PubMed Central

Bernard-DuBenske, Lori L.; Wen, Kuang-Yi; Gustafson, David H.; Guarnaccia, Charles A.; Cleary, James F.; Dinauer, Susan K.; McTavish, Fiona M.

2013-01-01

Familial caregivers are providing increasing amounts of care to advanced cancer patients. Increased understanding of caregivers’ needs is vital in providing necessary support to lessen caregiver burden and morbidity. Current literature has identified caregiver and patient needs at broad stages of the cancer trajectory; however, such broad stages may be too general to inform a practice of targeting specific interventions when they have the greatest utility. This study examines a variety of particular needs across a number of more discrete illness-related transition experiences specifically in the advanced cancer disease trajectory. One hundred fifty-nine female informal caregivers of people with advanced cancer completed a needs assessment survey. Analyses of these cross-sectional retrospective-report data reveal that cancer caregiver needs vary across specific key experiences occurring within the broader stages of illness identified by current literature. Furthermore, caregivers have unique needs during bereavement. While the sample characteristics are demographically limited, this study provides preliminary evidence that the broad stages are not specific enough increments for effectively examining caregiver needs, and supports the need for more precise distribution of cancer-related information at more discrete times in the illness course. PMID:18662420

Fifteen years' review of advanced childhood neuroblastoma from a single institution in Hong Kong.

PubMed

Leung, C K

1998-05-01

To assess the progress in the treatment of advanced childhood neuroblastoma. From 1981 to 1996, there were 32 children with neuroblastoma (NB) diagnosed, staged and treated in our institution. There were 4 patients with stage II NB (12%), 5 stage III (16%), 21 stage IV (66%) and 2 stage IV s (6%). The NBs were excised if CT scan indicated that the tumors were operable. For advanced NB, stages III and IV, multiple drug chemotherapy was started first and operability was assessed with serial CT scan examinations. Once the X-ray imaging indicated the tumors were operable, surgical interventions were done. The medical records of the advanced NB were reviewed. In the initial period of the study, 9 patients were treated using the VAC protocol [vincristine (vcr), adriamycin (adria) and cyclophosphamide (cyc)]. No patient was convertible to operable and all died with a mean survival of 10 months. OPEC [vcr, cyc, VM26, cisplatin (cis)], Rapid COJEC (carboplatin, VP16, vcr, cis and cyc) and more recently N6 protocol (cyc, adria, vcr, VP16, cis) was used for 17 patients. 80% of them were converted to operable. In 4 patients, surgical specimens showed only necrotic tissue without viable tumor tissue and 6 (35%) tumors were converted to ganglioneuroma or ganglioneuroblastoma. Although 2 (12%) patients died of fungal septicemia and 1 (6%) developed Fanconi's syndrome after chemotherapy, the mean survival period increased to 27 months. In the 10 survivors (60%), 4 had megatherapy with melphalan followed by autologous peripheral blood stem cell (PBSC) transplantation and 2 were waiting for transplantation. There is a high percentage of advanced NB on presentation in Hong Kong. With more potent multiple drug chemotherapy for advanced stage NB there are (1) improvement in the survival of these patients, (2) opportunities for more operations for tumor excision and (3) opportunities for autologous PBSC transplantation for better tumor eradication.

Esophageal dysfunction in different stages of Parkinson's disease.

PubMed

Suttrup, I; Suttrup, J; Suntrup-Krueger, S; Siemer, M-L; Bauer, J; Hamacher, C; Oelenberg, S; Domagk, D; Dziewas, R; Warnecke, T

2017-01-01

Dysphagia is a clinically relevant symptom in patients with Parkinson's disease (PD) leading to pronounced reduction in quality of life and other severe complications. Parkinson's disease-related dysphagia may affect the oral and pharyngeal, as well as the esophageal phase of swallowing. To examine the nature and extend of esophageal dysphagia in different stages of PD and their relation to oropharyngeal dysfunction, we examined 65 PD patients (mean age 66.3±9.7 years, mean disease duration 7.9±5.8 years, mean Hoehn & Yahr [H&Y] stage 2.89±0.91) and divided into three groups (early [H&Y I+II; n=21], intermediate [H&Y III; n=25], and advanced stadium [H&Y IV+V; n=19]), using esophageal high-resolution manometry (HRM) to detect esophageal motor disorders. Oropharyngeal impairment was assessed using fiberoptic endoscopic evaluation of swallowing. Major esophageal motor disorders were detected in nearly one third of the PD patients. Minor impairment of the esophageal body was present in 95% of participants and throughout all disease stages with pathological findings especially in peristalsis and intrabolus pressure (IBP). The IBP was found to significantly increase in the advanced stadium. Although dysfunction of the upper and lower esophageal sphincters was observed in individual patients, alterations in these esophageal segments revealed no statistical significance compared with normative data. No clear association was found between the occurrence of oropharyngeal dysphagia and esophageal impairment. Esophageal body impairment in PD is a frequent phenomenon during all disease stages, which possibly reflects α-synucleinopathy in the enteric nervous system. © 2016 John Wiley & Sons Ltd.

Two stage low noise advanced technology fan. 1: Aerodynamic, structural, and acoustic design

NASA Technical Reports Server (NTRS)

Messenger, H. E.; Ruschak, J. T.; Sofrin, T. G.

1974-01-01

A two-stage fan was designed to reduce noise 20 db below current requirements. The first-stage rotor has a design tip speed of 365.8 m/sec and a hub/tip ratio of 0.4. The fan was designed to deliver a pressure ratio of 1.9 with an adiabatic efficiency of 85.3 percent at a specific inlet corrected flow of 209.2kg/sec/sq m. Noise reduction devices include acoustically treated casing walls, a flowpath exit acoustic splitter, a translating centerbody sonic inlet device, widely spaced blade rows, and the proper ratio of blades and vanes. Multiple-circular-arc rotor airfoils, resettable stators, split outer casings, and capability to go to close blade-row spacing are also included.

Perspectives on current tumor-node-metastasis (TNM) staging of cancers of the colon and rectum.

PubMed

Hu, Huankai; Krasinskas, Alyssa; Willis, Joseph

2011-08-01

Improvements in classifications of cancers based on discovery and validation of important histopathological parameters and new molecular markers continue unabated. Though still not perfect, recent updates of classification schemes in gastrointestinal oncology by the American Joint Commission on Cancer (tumor-node-metastasis [TNM] staging) and the World Health Organization further stratify patients and guide optimization of treatment strategies and better predict patient outcomes. These updates recognize the heterogeneity of patient populations with significant subgrouping of each tumor stage and use of tumor deposits to significantly "up-stage" some cancers; change staging parameters for subsets of IIIB and IIIC cancers; and introduce of several new subtypes of colon carcinomas. By the nature of the process, recent discoveries that are important to improving even routine standards of patient care, especially new advances in molecular medicine, are not incorporated into these systems. Nonetheless, these classifications significantly advance clinical standards and are welcome enhancements to our current methods of cancer reporting. Copyright © 2011 Elsevier Inc. All rights reserved.

Advanced expander test bed program

NASA Technical Reports Server (NTRS)

Riccardi, D. P.; Mitchell, J. C.

1993-01-01

The Advanced Expander Test Bed (AETB) is a key element in NASA's Space Chemical Engine Technology Program for development and demonstration of expander cycle oxygen/hydrogen engine and advanced component technologies applicable to space engines as well as launch vehicle upper stage engines. The AETB will be used to validate the high-pressure expander cycle concept, investigate system interactions, and conduct investigations of advanced mission focused components and new health monitoring techniques in an engine system environment. The split expander cycle AETB will operate at combustion chamber pressures up to 1200 psia with propellant flow rates equivalent to 20,000 lbf vacuum thrust. Contract work began 27 Apr. 1990. During 1992, a major milestone was achieved with the review of the final design of the oxidizer turbopump in Sep. 1992.

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

ClinicalTrials.gov

2018-06-08

Advanced Malignant Solid Neoplasm; KRAS Gene Mutation; Metastatic Malignant Solid Neoplasm; NRAS Gene Mutation; Recurrent Colorectal Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Malignant Neoplasm

Evaluation of advanced air bag deployment algorithm performance using event data recorders.

PubMed

Gabler, Hampton C; Hinch, John

2008-10-01

This paper characterizes the field performance of occupant restraint systems designed with advanced air bag features including those specified in the US Federal Motor Vehicle Safety Standard (FMVSS) No. 208 for advanced air bags, through the use of Event Data Recorders (EDRs). Although advanced restraint systems have been extensively tested in the laboratory, we are only beginning to understand the performance of these systems in the field. Because EDRs record many of the inputs to the advanced air bag control module, these devices can provide unique insights into the characteristics of field performance of air bags. The study was based on 164 advanced air bag cases extracted from NASS/CDS 2002-2006 with associated EDR data. In this dataset, advanced driver air bags were observed to deploy with a 50% probability at a longitudinal delta-V of 9 mph for the first stage, and at 26 mph for both inflator stages. In general, advanced air bag performance was as expected, however, the study identified cases of air bag deployments at delta-Vs as low as 3-4 mph, non-deployments at delta-Vs over 26 mph, and possible delayed air bag deployments.

Evaluation of Advanced Air Bag Deployment Algorithm Performance using Event Data Recorders

PubMed Central

Gabler, Hampton C.; Hinch, John

2008-01-01

This paper characterizes the field performance of occupant restraint systems designed with advanced air bag features including those specified in the US Federal Motor Vehicle Safety Standard (FMVSS) No. 208 for advanced air bags, through the use of Event Data Recorders (EDRs). Although advanced restraint systems have been extensively tested in the laboratory, we are only beginning to understand the performance of these systems in the field. Because EDRs record many of the inputs to the advanced air bag control module, these devices can provide unique insights into the characteristics of field performance of air bags. The study was based on 164 advanced air bag cases extracted from NASS/CDS 2002-2006 with associated EDR data. In this dataset, advanced driver air bags were observed to deploy with a 50% probability at a longitudinal delta-V of 9 mph for the first stage, and at 26 mph for both inflator stages. In general, advanced air bag performance was as expected, however, the study identified cases of air bag deployments at delta-Vs as low as 3-4 mph, non-deployments at delta-Vs over 26 mph, and possible delayed air bag deployments. PMID:19026234

Clinical effectiveness of multimodality treatment on advanced pediatric hepatoblastoma.

PubMed

Zhang, Y; Zhang, W-L; Huang, D-S; Hong, L; Wang, Y-Z; Zhu, X; Hu, H-M; Zhang, P-W; Yi, Y; Han, T

2014-01-01

To investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma and the factors affecting the prognosis. 35 childhood patients were treated with multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. Patients were followed up every month. 33 patients completed the follow-up, of which 17 were in complete remission, 5 were in partial remission, 1 case got worse, and 10 died. The remission rate was 66.7% (22/33), and the overall survival rate was 69.7% (23/33). 1 patient with advanced hepatoblastoma got high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (APBSCT) treatment, and a primary lesion by 18 x 15 x 9 cm reduced to 10 x 8 x 4 cm. Remote metastases significantly alleviated, and partial remission reached six months. The overall survival was 9 months after transplantation. Patients with the mixed phenotype of hepatoblastoma had a worse prognosis than with the epithelial phenotype (p < 0.001), and patients in stage IV had a lower survival rate than in stage III (p < 0.001). Multimodality treatment can effectively improve remission rate and prolong the survival of children with the advanced hepatoblastoma. In addition, alpha-fetoprotein (AFP), hepatoblastoma pathological classification and staging are of great use in prediction of prognosis.

Advanced technology and future earth-orbit transportation systems

NASA Technical Reports Server (NTRS)

Henry, B. Z.; Eldred, C. H.

1977-01-01

The paper is concerned with the identification and evaluation of technology developments which offer potential for high return on investment when applied to advanced transportation systems. These procedures are applied in a study of winged single-stage-to-orbit (SSTO) vehicles, which are considered feasible by the 1990s. Advanced technology is considered a key element in achieving improved economics, and near term investment in selected technology areas is recommended.

Advanced Foreign Language Learning: A Challenge to College Programs. Issues in Language Program Direction.

ERIC Educational Resources Information Center

Byrnes, Heidi, Ed.; Maxim, Hiram H., Ed.

This book includes the following chapters: "Literacy and Advanced Foreign Language Learning: Rethinking he Curriculum" (Richard G. Kern); "A Template for Advanced Learner Tasks: Staging Genre Reading and Cultural Literacy Through the Precis" (Janet Swaffar); "Fostering Advanced L2 Literacy: A Genre-Based, Cognitive…

Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma

ClinicalTrials.gov

2018-06-07

Advanced Pleural Malignant Mesothelioma; HLA-A*0201 Positive Cells Present; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; WT1 Positive

Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma.

PubMed

Skoetz, Nicole; Will, Andrea; Monsef, Ina; Brillant, Corinne; Engert, Andreas; von Tresckow, Bastian

2017-05-25

There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen. To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment. We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to July 2013 and for the update to March 2017) and Embase (1985 to November 2008). Moreover we searched trial registries (March 2017; www.controlled-trials.com, www.clinicaltrialsregister.eu/ctr-search/search, clinicaltrials.gov, www.eortc.be, www.ghsg.org, www.ctc.usyd.edu.au, www.trialscentral.org/index.html) SELECTION CRITERIA: We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared with chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL. The effect measures we used were hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and freedom from first progression.We used risk ratios (RRs) relative risks to analyse harms: treatment-related mortality, secondary malignancies (including myeloid dysplastic syndrome (MDS) or acute myeloid leukaemia (AML)), infertility and adverse events.Quality of life was not reported in any trial, therefore not analysed. Two review authors independently extracted data and assessed quality of trials. We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We

Clinical stages in patients with primary and subsequent cancers based on the czech cancer registry 1976-2005.

PubMed

Geryk, Edvard; Stampach, Radim; Dítě, Petr; Kozel, Jiří; Horváth, Teodor; Kubíček, Petr

2013-01-01

Of 1,486,984 new cancers registered in the Czech Cancer Registry in 1976-2005, 290,312 (19.5%) were multiple malignant neoplasms (MMNs), of which there were 65,292 primary and 89,796 subsequent cases in men and 59,970 primary and 75,254 subsequent cases in women. The duplicities were higher in women, and the triplicities and others (3-6 MMNs) were higher in men. The most frequent diagnoses were the primary cancers of skin, gastrointestinal and urinary tract, male genital organs, respiratory tract in men, and cancers of skin, breast, female genital organs, and gastrointestinal tract in women. The analysis of the early and advanced clinical stages shows that the number of subsequent advanced stages increased after primary advanced stages. Their time-age-space distributions visualized maps of MMNs in 14 Czech regions. These results support the improvement of algorithms of dispensary care for the early detection of the subsequent neoplasms.

[Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

PubMed

Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

2013-10-01

A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Future Perspectives for Management of Stage A Heart Failure.

PubMed

Tanaka, Hidekazu

2018-05-07

Patients with Stage A heart failure (HF) show no HF symptoms but have related comorbid diseases with a high risk of progressing to HF. Screening for comorbid diseases warrants closer attention because of the growing interest in addressing Stage A HF as the best means of preventing eventual progression to overt HF such as Stages C and D. The identification of individuals of Stage A HF is potentially useful for the implementation of HF-prevention strategies; however, not all Stage A HF patients develop left ventricular (LV) structural heart disease or symptomatic HF, which lead to advanced HF stages. Therefore, Stage A HF requires management with the long-term goal of avoiding HF development; likewise, Stage B HF patients are ideal targets for HF prevention. Although the early detection of subclinical LV dysfunction is, thus, essential for delaying the progression to HF, the assessment of subclinical LV dysfunction can be challenging. Global longitudinal strain (GLS) as assessed by speckle-tracking echocardiography has recently been reported to be a sensitive marker of early subtle LV myocardial abnormalities, helpful for the prediction of the outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS reflects LV longitudinal myocardial systolic function, and can be assessed usually by means of two-dimensional speckle-tracking. This article reviews the importance of the assessment of subclinical LV dysfunction in Stage A HF patients by means of GLS, and its current potential to prevent progression to later stage HF.

Lung cancer staging now and in the future.

PubMed

Liam, Chong-Kin; Andarini, Sita; Lee, Pyng; Ho, James Chung-Man; Chau, Ngo Quy; Tscheikuna, Jamsak

2015-05-01

For a long time lung cancer was associated with a fatalistic approach by healthcare professionals. In recent years, advances in imaging, improved diagnostic techniques and more effective treatment modalities are reasons for optimism. Accurate lung cancer staging is vitally important because treatment options and prognosis differ significantly by stage. The staging algorithm should include a contrast computed tomography (CT) of the chest and the upper abdomen including adrenals, positron emission tomography/CT for staging the mediastinum and to rule out extrathoracic metastasis in patients considered for surgical resection, endosonography-guided needle sampling procedure replacing mediastinoscopy for near complete mediastinal staging, and brain imaging as clinically indicated. Applicability of evidence-based guidelines for staging of lung cancer depends on the available expertise and level of resources and is directly impacted by financial issues. Considering the diversity of healthcare infrastructure and economic performance of Asian countries, optimal and cost-effective use of staging methods appropriate to the available resources is prudent. The pulmonologist plays a central role in the multidisciplinary approach to lung cancer diagnosis, staging and management. Regional respiratory societies such as the Asian Pacific Society of Respirology should work with national respiratory societies to strive for uniform standards of care. For developing countries, a minimum set of care standards should be formulated. Cost-effective delivery of optimal care for lung cancer patients, including staging within the various healthcare systems, should be encouraged and most importantly, tobacco control implementation should receive an absolute priority status in all countries in Asia. © 2015 Asian Pacific Society of Respirology.

Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer

ClinicalTrials.gov

2017-10-26

Advanced Malignant Solid Neoplasm; Bile Duct Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer

MRI in local staging of rectal cancer: an update

PubMed Central

Tapan, Ümit; Özbayrak, Mustafa; Tatlı, Servet

2014-01-01

Preoperative imaging for staging of rectal cancer has become an important aspect of current approach to rectal cancer management, because it helps to select suitable patients for neoadjuvant chemoradiotherapy and determine the appropriate surgical technique. Imaging modalities such as endoscopic ultrasonography, computed tomography, and magnetic resonance imaging (MRI) play an important role in assessing the depth of tumor penetration, lymph node involvement, mesorectal fascia and anal sphincter invasion, and presence of distant metastatic diseases. Currently, there is no consensus on a preferred imaging technique for preoperative staging of rectal cancer. However, high-resolution phased-array MRI is recommended as a standard imaging modality for preoperative local staging of rectal cancer, with excellent soft tissue contrast, multiplanar capability, and absence of ionizing radiation. This review will mainly focus on the role of MRI in preoperative local staging of rectal cancer and discuss recent advancements in MRI technique such as diffusion-weighted imaging and dynamic contrast-enhanced MRI. PMID:25010367

CD30 expression utilization for the accuracy of classical Hodgkin's lymphoma staging.

PubMed

Flangea, Corina; Potencz, Elena; Mihăescu, Rodica; Anghel, A; Gîju, S; Motoc, Marilena; Dogaru, C

2006-01-01

The presence of Reed-Sternberg malignant cells is absolutely necessary for Hodgkin's lymphoma diagnostic, but it is not always sufficient because can be observed Reed-Sternberg-like cells in other malignant and benign diseases, too. The CD30 expression at Hodgkin and Reed-Sternberg level can give us supplementary information in differential diagnostic and can be used as progressive disease factor. Our study was composed from 63 cases histopathological diagnosed with Hodgkin's lymphoma and hospitalized in Hematology Department of County Hospital Timişoara. CD30 expression was immunohistochemical semi-quantitative evaluated using clone BerH2 as primary antibody and APAAP-New Fuchsin as visualization system. The increasing of CD30 expression occurs in the same time with advanced stages and the disease progression (p =0.001). For I and II stages CD30 expression does not overcome (-/+) category while the III and IV stages, all the cases are situated in (+/-) and (+) categories. No connection can be noticed between histological type and CD30 expression (p < or = 1). We consider that using this staining, although less used in Romania, must be done in all Hodgkin's lymphoma and Hodgkin's lymphoma-like cases. We say that because the main cause of relapses is represented by inadequate clinical staging and diagnostic. In our study, the increasing of CD30 expression is associated with advanced disease stage. We recommend reinvestigating and restaging all cases that was included into an incipient stages and they have a CD30 expression situated in (+/-) and (+) intervals because some lymph nodes could be overlooked.

Progranulin Is a Novel Independent Predictor of Disease Progression and Overall Survival in Chronic Lymphocytic Leukemia

PubMed Central

Göbel, Maria; Eisele, Lewin; Möllmann, Michael; Hüttmann, Andreas; Johansson, Patricia; Scholtysik, René; Bergmann, Manuela; Busch, Raymonde; Döhner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; Dührsen, Ulrich; Dürig, Jan

2013-01-01

Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38+ZAP-70+ as compared to indolent CD38−ZAP-70− chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13–3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05–10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09–3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA. PMID:24009671

Progranulin is a novel independent predictor of disease progression and overall survival in chronic lymphocytic leukemia.

PubMed

Göbel, Maria; Eisele, Lewin; Möllmann, Michael; Hüttmann, Andreas; Johansson, Patricia; Scholtysik, René; Bergmann, Manuela; Busch, Raymonde; Döhner, Hartmut; Hallek, Michael; Seiler, Till; Stilgenbauer, Stephan; Klein-Hitpass, Ludger; Dührsen, Ulrich; Dürig, Jan

2013-01-01

Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome. We found that high Pgrn plasma levels were strongly associated with adverse risk factors including unmutated IGHV status, expression of CD38 and ZAP-70, poor risk cytogenetics (11q-, 17p-) as detected by flourescence in situ hybridization (FISH) and high Binet stage. Pgrn as well as the aforementioned risk factors were prognostic for time to first treatment and overall survival in this series. Importantly, these results could be confirmed in the independent multicentric CLL1 cohort of untreated Binet stage A patients (n = 163). Here, multivariate analysis of time to first treatment revealed that high risk Pgrn (HR = 2.06, 95%-CI = 1.13-3.76, p = 0.018), unmutated IGHV status (HR = 5.63, 95%-CI = 3.05-10.38, p<0.001), high risk as defined by the study protocol (HR = 2.06, 95%-CI = 1.09-3.89, p = 0.026) but not poor risk cytogenetics were independent prognostic markers. In summary our results suggest that Pgrn is a novel, robust and independent prognostic marker in CLL that can be easily measured by ELISA.

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

ClinicalTrials.gov

2018-06-01

Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

[Diagnosis and treatment of depression in the advanced stage of cancer].

PubMed

Ronson, A

2002-10-01

The diagnosis of depression in patients with advanced cancer is a particularly complex task. The lack of diagnostic tools specifically developed for this patient population, the difficulty of interpreting neurovegetative symptoms of depression--which can result from the neoplastic disease--and the "normal and understandable" nature of many symptoms or signs of psychological distress are among the main obstacles to a clear-cut diagnosis of depression. Things go even more complex when it comes about to discuss whether one should treat patients displaying psychological distress that does not meet established criteria for the diagnosis of a depressive illness. When the indication to treat is finally acknowledged, the choice of the optimal antidepressant will depend upon a series of parameters including survival expectancy, tolerance profile and drug interactions. Though we currently lack prospective data about the efficacy and safety of antidepressants in depressed patients with advanced cancer, extrapolation of data available from other patient populations with severe medical conditions and clinical experience allow to draw guidelines aimed at helping healthcare professionals faced with those problems to improve the quality of life of their patients. These elements are presented and discussed in this paper in the light of the recent developments resulting from the growing interest of the medical community to the care to patients with terminal illness.

Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

PubMed

Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

2000-11-01

Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study.

PubMed

Ippolito, Antonio Massimo; Milella, Michele; Messina, Vincenzo; Conti, Fabio; Cozzolongo, Raffaele; Morisco, Filomena; Brancaccio, Giuseppina; Barone, Michele; Santantonio, Teresa; Masetti, Chiara; Tundo, Paolo; Smedile, Antonina; Carretta, Vito; Gatti, Pietro; Termite, Antonio Patrizio; Valvano, Maria Rosa; Bruno, Giuseppe; Fabrizio, Claudia; Andreone, Pietro; Zappimbulso, Marianna; Gaeta, Giovanni Battista; Napoli, Nicola; Fontanella, Luca; Lauletta, Gianfranco; Cuccorese, Giuseppe; Metrangolo, Antonio; Francavilla, Ruggiero; Ciracì, Emanuela; Rizzo, Salvatore; Andriulli, Angelo

2017-09-01

Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D'Amico might provide new insights on timing for antiviral therapy. We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n=575) or cirrhosis (n=2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3-5) who are at greatest risk and have the most to gain from therapy. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

ClinicalTrials.gov

2018-04-03

Advanced Adult Hepatocellular Carcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Hepatocellular Carcinoma AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7

Optimization of multi-stage dynamic treatment regimes utilizing accumulated data.

PubMed

Huang, Xuelin; Choi, Sangbum; Wang, Lu; Thall, Peter F

2015-11-20

In medical therapies involving multiple stages, a physician's choice of a subject's treatment at each stage depends on the subject's history of previous treatments and outcomes. The sequence of decisions is known as a dynamic treatment regime or treatment policy. We consider dynamic treatment regimes in settings where each subject's final outcome can be defined as the sum of longitudinally observed values, each corresponding to a stage of the regime. Q-learning, which is a backward induction method, is used to first optimize the last stage treatment then sequentially optimize each previous stage treatment until the first stage treatment is optimized. During this process, model-based expectations of outcomes of late stages are used in the optimization of earlier stages. When the outcome models are misspecified, bias can accumulate from stage to stage and become severe, especially when the number of treatment stages is large. We demonstrate that a modification of standard Q-learning can help reduce the accumulated bias. We provide a computational algorithm, estimators, and closed-form variance formulas. Simulation studies show that the modified Q-learning method has a higher probability of identifying the optimal treatment regime even in settings with misspecified models for outcomes. It is applied to identify optimal treatment regimes in a study for advanced prostate cancer and to estimate and compare the final mean rewards of all the possible discrete two-stage treatment sequences. Copyright © 2015 John Wiley & Sons, Ltd.

Advanced Teleprocessing Systems

DTIC Science & Technology

1981-09-30

Univur’iiy of Califtri ABSTRACT The network technologies developed over the past decade. due lagly to incredibe advances in integrated chip production. have...seo the stage for an enormous DP revolution the impact of which will soon be felt in the businms community and in the home and consumer markets . We have...most common of (which has already begun). At the top of this the bus architectures is perhaps the well- chain we see the integrated chip from which

Impact of chronic kidney disease stage on lower-extremity arthroplasty.

PubMed

Deegan, Brian F; Richard, Raveesh D; Bowen, Thomas R; Perkins, Robert M; Graham, Jove H; Foltzer, Michael A

2014-07-01

End-stage renal disease and dialysis is commonly associated with poor outcomes after joint replacement surgery. The goal of this study was to evaluate postoperative complications in patients with less advanced chronic kidney disease undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients who underwent THA or TKA between 2004 and 2011 with stage 1, 2, or 3 chronic kidney disease were retrospectively reviewed via an electronic medical record. The authors compared 377 patients who had stage 1 to 2 chronic kidney disease with 402 patients who had stage 3 chronic kidney disease. No significant differences in 90-day readmission or revision rates were found between the stage 1 to 2 and stage 3 patient groups. For patients with stage 3 chronic kidney disease, the overall mortality rate was greater than that in patients with stage 1 to 2 chronic kidney disease. However, when adjusted for comorbid disease, no significant increases were seen in joint infection, readmission, or early revision between patients with stage 1 to 2 chronic kidney disease vs patients with stage 3 chronic kidney disease. The overall incidence of infection was high (3.5%) but far less than reported for patients with end-stage renal disease, dialysis, and kidney transplant. In conclusion, patients with stage 1, 2, or 3 chronic kidney disease may have a higher than expected rate of prosthetic joint infection (3.5%) after total joint arthroplasty. Patients with stage 3 chronic kidney disease are at higher risk for postoperative mortality compared with those with lesser stages of kidney disease. Copyright 2014, SLACK Incorporated.

Ecology of Postlarval Stages of Chigger Mites.

DTIC Science & Technology

1985-12-05

or during prolonged droughts . Adults of T. autumnalis have been collected at depths of 30.5-45.7 cm (Cockings 1948), and Richards (1950) reported...study were all Pinus spp. in advanced stages of decay, and could easily be torn apart by hand. Much of the wood in 9r - --- - decomposing tree stumps...floridana L.), Red Cedar (Juniperus virginiana L.), Loblolly Pine ( Pinus taeda L.), and Hawthorne (Crataegus sp.). Shrubs consisted predominantly of

Tumor Stage-Related Role of Radiotherapy in Patients with an External Auditory Canal and Middle Ear Carcinoma.

PubMed

Choi, Jinhyun; Kim, Se-Heon; Koh, Yoon Woo; Choi, Eun Chang; Lee, Chang Geol; Keum, Ki Chang

2017-01-01

The purpose of this study was to evaluate the clinical outcomes of patients treated with radiotherapy (RT) for a carcinoma of the external auditory canal (EAC) and middle ear. The records of 32 patients who received RT from 1990 to 2013 were reviewed retrospectively. The Pittsburgh classification was used to stage all the cancers (early stage, T1/T2 [n=12]; advanced stage, T3/T4 or N positive [n=20]). Twenty-one patients (65.6%) were treated with postoperative RT and 11 patients (34.4%) were treated with definitive RT. The median radiation doses for postoperative and definitive RT were 60 Gy and 64.8 Gy, respectively. Chemotherapy was administered to seven patients (21.9%). The 5-year overall survival and disease-free survival rates for all patients were 57% and 52%, respectively. The disease control rates for the patients with early stage versus advanced stage carcinomawere 55.6% (5/9) and 50% (6/12) in the postoperative RT group and 66.7% (2/3) and 37.5% (3/8) in the definitive RT group, respectively. Overall, 15 cases (14 patients, 46.7%) experienced treatment failure; these failures were classified as local in four cases, regional in one case, and distant in 10 cases. The median follow-up period after RT was 51 months (range, 7 to 286 months). Patients with early stage carcinoma achieved better outcomes when definitive RT was used. Advanced stage carcinoma patients experienced better outcomes with postoperative RT. The high rate of distant failure after RT, with or without surgery, reflected the lack of a consensus regarding the best therapeutic approach for treating carcinoma of the EAC and middle ear.

[Asthenia in advanced cancer and the use of psychostimulants].

PubMed

Portela Tejedor, M A; Sanz Rubiales, A; Martínez, M; Centeno Cortés, C

2011-01-01

Asthenia is the most frequent symptom in patients with advanced cancer and is probably what most affects the quality of life of oncology patients since it interferes in their physical and social activity. Treatment in the majority of cases is symptomatic. There is growing interest in the use of psychostimulants for treating asthenia. Methylphenidate and modafinil are two psychostimulants that have already been tested in controlled studies on asthenia of the patient with advanced cancer; they have proved to be efficient, particularly in patients in very advanced stages who are very tired.

National Trends and Predictors of Locally Advanced Penile Cancer in the United States (1998-2012).

PubMed

Chipollini, Juan; Chaing, Sharon; Peyton, Charles C; Sharma, Pranav; Kidd, Laura C; Giuliano, Anna R; Johnstone, Peter A; Spiess, Philippe E

2017-08-12

We analyzed the trends in presentation of squamous cell carcinoma (SCC) of the penis and determined the socioeconomic predictors for locally advanced (cT3-cT4) disease in the United States. The National Cancer Database was queried for patients with clinically nonmetastatic penile SCC and staging available from 1998 to 2012. Temporal trends per tumor stage were evaluated, and a multivariable logistic regression model was used to identify predictors for advanced presentation during the study period. A total of 5767 patients with stage ≤ T1-T2 (n = 5423) and T3-T4 (n = 344) disease were identified. Increasing trends were noted in all stages of penile SCC with a greater proportion of advanced cases over time (P = .001). Significant predictors of advanced presentation were age > 55 years, the presence of comorbidities, and Medicaid or no insurance (P < .05 for all). More penile SCC is being detected in the United States. Our results have demonstrated older age, presence of comorbidities, and Medicaid or no insurance as potential barriers to early access of care in the male population. Understanding the current socioeconomic gaps could help guide targeted interventions in vulnerable populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Current advances in T-cell-based cancer immunotherapy

PubMed Central

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

Current advances in T-cell-based cancer immunotherapy.

PubMed

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

The effect of marital status on stage and survival of prostate cancer patients treated with radical prostatectomy: a population-based study.

PubMed

Abdollah, Firas; Sun, Maxine; Thuret, Rodolphe; Abdo, Al'a; Morgan, Monica; Jeldres, Claudio; Shariat, Shahrokh F; Perrotte, Paul; Montorsi, Francesco; Karakiewicz, Pierre I

2011-08-01

The detrimental effect of unmarried marital status on stage and survival has been confirmed in several malignancies. We set to test whether this applied to patients diagnosed with prostate cancer (PCa) treated with radical prostatectomy (RP). We identified 163,697 non-metastatic PCa patients treated with RP, within 17 Surveillance, Epidemiology, and End Results registries. Logistic regression analyses focused on the rate of locally advanced stage (pT3-4/pN1) at RP. Cox regression analyses tested the relationship between marital status and cancer-specific (CSM), as well as all-cause mortality (ACM). Respectively, 9.1 and 7.8% of individuals were separated/divorced/widowed (SDW) and never married. SDW men had more advanced stage at surgery (odds ratio: 1.1; p < 0.001), higher CSM and ACM (both hazard ratio [HR]: 1.3; p < 0.001) than married men. Similarly, never married marital status portended to a higher ACM rate (HR:1.2, p = 0.001). These findings were consistent when analyses were stratified according to organ confined vs. locally advanced stages. Being SDW significantly increased the risk of more advanced stage at RP. Following surgery, SDW men portended to a higher CSM and ACM rate than married men. Consequently, these individuals may benefit from a more focused health care throughout the natural history of their disease.

In vivo staging of regional amyloid deposition.

PubMed

Grothe, Michel J; Barthel, Henryk; Sepulcre, Jorge; Dyrba, Martin; Sabri, Osama; Teipel, Stefan J

2017-11-14

To estimate a regional progression pattern of amyloid deposition from cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo staging of an individual's amyloid pathology. Multiregional analysis of florbetapir ( 18 F-AV45)-PET data was used to determine individual amyloid distribution profiles in a sample of 667 participants from the Alzheimer's Disease Neuroimaging Initiative cohort, including cognitively normal older individuals (CN) as well as patients with mild cognitive impairment and Alzheimer disease (AD) dementia. The frequency of regional amyloid positivity across CN individuals was used to construct a 4-stage model of progressing amyloid pathology, and individual distribution profiles were used to evaluate the consistency of this hierarchical stage model across the full cohort. According to a 4-stage model, amyloid deposition begins in temporobasal and frontomedial areas, and successively affects the remaining associative neocortex, primary sensory-motor areas and the medial temporal lobe, and finally the striatum. Amyloid deposition in these brain regions showed a highly consistent hierarchical nesting across participants, where only 2% exhibited distribution profiles that deviated from the staging scheme. The earliest in vivo amyloid stages were mostly missed by conventional dichotomous classification approaches based on global florbetapir-PET signal, but were associated with significantly reduced CSF Aβ42 levels. Advanced in vivo amyloid stages were most frequent in patients with AD and correlated with cognitive impairment in individuals without dementia. The highly consistent regional hierarchy of PET-evidenced amyloid deposition across participants resembles neuropathologic observations and suggests a predictable regional sequence that may be used to stage an individual's progress of amyloid pathology in vivo. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Relations of Transtheoretical Model Stage, Self-Efficacy, and Voluntary Physical Activity in African American Preadolescents

ERIC Educational Resources Information Center

Annesi, James J.; Faigenbaum, Avery D.; Westcott, Wayne L.

2010-01-01

The transtheoretical model (TTM; Prochaska, DiClemente, & Norcross, 1992) suggests that, at any point, an individual is in one of five stages-of-change related to adopting a behavior. People sequentially advance in stage but may also maintain or even regress, based on personal and environmental factors (Nigg, 2005). A classic study published in…

The STAR trial protocol: a randomised multi-stage phase II/III study of Sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic Renal Cancer

PubMed Central

2012-01-01

Background Over recent years a number of novel therapies have shown promise in advanced renal cell carcinoma (RCC). Internationally the standard of care of first-line therapy is sunitinib™, after a clear survival benefit was demonstrated over interferon-α. Convention dictates that sunitinib is continued until evidence of disease progression, assuming tolerability, although there is no evidence that this approach is superior to intermittent periods of treatment. The purpose of the STAR trial is to compare the standard treatment strategy (conventional continuation strategy, CCS) with a novel drug free interval strategy (DFIS) which includes planned treatment breaks. Methods/Design The STAR trial is an NIHR HTA-funded UK pragmatic randomised phase II/III clinical trial in the first-line treatment of advanced RCC. Participants will be randomised (1:1) to either a sunitinib CCS or a DFIS. The overall aim of the trial is to determine whether a DFIS is non-inferior, in terms of 2-year overall survival (OS) and quality adjusted life years (QALY) (averaged over treatment and follow up), compared to a CCS. The QALY primary endpoint was selected to assess whether any detriment in terms of OS could be balanced with improvements in quality of life (QoL). This is a complex trial with a number of design challenges, and to address these issues a feasibility stage is incorporated into the trial design. Predetermined recruitment (stage A) and efficacy (stage B) intermediary endpoints must be met to allow continuation to the overall phase III trial (stage C). An integral qualitative patient preference and understanding study will occur alongside the feasibility stage to investigate patients’ feelings regarding participation or non-participation in the trial. Discussion The optimal duration of continuing sunitinib in advanced RCC is unknown. Novel targeted therapies do not always have the same constraints to treatment duration as standard chemotherapeutic agents and currently

Shaking Up the Debate: Ensuring the Ethical Use of DBS Intervention Criteria for Mid-Stage Parkinson's Patients.

PubMed

Eijkholt, Marleen; Cabrera, Laura Y; Ramirez-Zamora, Adolfo; Pilitsis, Julie G

2017-07-01

Deep brain stimulation (DBS) is a well-established treatment for the management of severe motor fluctuations in advanced Parkinson's disease (PD). Until recently, device regulation, medical, and insurance practices limited DBS to patients with advanced stages of PD. In February 2016 this changed, however, when the US Food and Drug Administration (FDA) granted formal approval for the use of brain stimulator in mid-stage PD patients. In this article, we examine whether DBS in mid-stage PD can be ethically justified beyond the FDA approval. We scrutinize the current risk-benefit profile, the costs-benefit profile, and the capacity for informed consent requirement, to ask if use of subthalamic nucleus (STN) in mid-stage DBS is ethically appropriate. We propose that mid-stage DBS decisions could be appropriate under a shared decision-making model, which embraces a broad quality of life perspective. Although it might be too premature to know how the FDA decision will affect medical and insurance practices, we conclude by arguing that revisions to persisting guidelines seems justified both on scientific and ethical grounds. © 2017 International Neuromodulation Society.

Facial affect recognition in early and late-stage schizophrenia patients.

PubMed

Romero-Ferreiro, María Verónica; Aguado, Luis; Rodriguez-Torresano, Javier; Palomo, Tomás; Rodriguez-Jimenez, Roberto; Pedreira-Massa, José Luis

2016-04-01

Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps<.01) and an increased misattribution of emotional meaning to neutral faces. PANSS scores of FEP patients on Depressed factor correlated positively with the accuracy to recognize fearful expressions (r=.473). For the MES group fear recognition correlated positively with negative PANSS factor (r=.498) and recognition of sad and neutral expressions was inversely correlated with disorganized PANSS factor (r=-.461 and r=-.541, respectively). These results provide evidence that a generalized impairment of affect recognition is observed in advanced-stage patients and is not characteristic of the early stages of schizophrenia. Moreover, the finding that anomalous attribution of emotional meaning to neutral faces is observed only in MES patients suggests that an increased attribution of salience to social stimuli is a characteristic of social cognition in advanced stages of the disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Multimodal imaging evaluation in staging of rectal cancer

PubMed Central

Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Yong Yeon; Kang, Heoung-Keun

2014-01-01

Rectal cancer is a common cancer and a major cause of mortality in Western countries. Accurate staging is essential for determining the optimal treatment strategies and planning appropriate surgical procedures to control rectal cancer. Endorectal ultrasonography (EUS) is suitable for assessing the extent of tumor invasion, particularly in early-stage or superficial rectal cancer cases. In advanced cases with distant metastases, computed tomography (CT) is the primary approach used to evaluate the disease. Magnetic resonance imaging (MRI) is often used to assess preoperative staging and the circumferential resection margin involvement, which assists in evaluating a patient’s risk of recurrence and their optimal therapeutic strategy. Positron emission tomography (PET)-CT may be useful in detecting occult synchronous tumors or metastases at the time of initial presentation. Restaging after neoadjuvant chemoradiotherapy (CRT) remains a challenge with all modalities because it is difficult to reliably differentiate between the tumor mass and other radiation-induced changes in the images. EUS does not appear to have a useful role in post-therapeutic response assessments. Although CT is most commonly used to evaluate treatment responses, its utility for identifying and following-up metastatic lesions is limited. Preoperative high-resolution MRI in combination with diffusion-weighted imaging, and/or PET-CT could provide valuable prognostic information for rectal cancer patients with locally advanced disease receiving preoperative CRT. Based on these results, we conclude that a combination of multimodal imaging methods should be used to precisely assess the restaging of rectal cancer following CRT. PMID:24764662

Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV.

PubMed

Kerr, Stephen J; Puthanakit, Thanyawee; Vibol, Ung; Aurpibul, Linda; Vonthanak, Sophan; Kosalaraksa, Pope; Kanjanavanit, Suparat; Hansudewechakul, Rawiwan; Wongsawat, Jurai; Luesomboon, Wicharn; Ratanadilok, Kattiya; Prasitsuebsai, Wasana; Pruksakaew, Kanchana; van der Lugt, Jasper; Paul, Robert; Ananworanich, Jintanat; Valcour, Victor

2014-01-01

Human immunodeficiency virus (HIV)-negative children born to HIV-infected mothers may exhibit differences in neurodevelopment (ND) compared to age- and gender-matched controls whose lives have not been affected by HIV. This could occur due to exposure to HIV and antiretroviral agents in utero and perinatally, or differences in the environment in which they grow up. This study assessed neurodevelopmental outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children enrolled as controls in a multicenter ND study from Thailand and Cambodia. One hundred sixty HEU and 167 HUU children completed a neurodevelopmental assessment using the Beery Visual Motor Integration (VMI) test, Color Trails, Perdue Pegboard, and Child Behavior Checklist (CBCL). Thai children (n = 202) also completed the Wechsler Intelligence Scale (IQ) and Stanford-Binet II memory tests. In analyses adjusted for caregiver education, parent as caregiver, household income, age, and ethnicity, statistically significant lower scores were seen on verbal IQ (VIQ), full-scale IQ (FSIQ), and Binet Bead Memory among HEU compared to HUU. The mean (95% CI) differences were -6.13 (-10.3 to -1.96), p = 0.004; -4.57 (-8.80 to -0.35), p = 0.03; and -3.72 (-6.57 to -0.88), p = 0.01 for VIQ, FSIQ, and Binet Bead Memory, respectively. We observed no significant differences in performance IQ, other Binet memory domains, Color Trail, Perdue Pegboard, Beery VMI, or CBCL test scores. We conclude that HEU children evidence reductions in some neurodevelopmental outcomes compared to HUU; however, these differences are small and it remains unclear to what extent they have immediate and long-term clinical significance.

The development and piloting of the REnal specific Advanced Communication Training (REACT) programme to improve Advance Care Planning for renal patients.

PubMed

Bristowe, Katherine; Shepherd, Kate; Bryan, Liz; Brown, Heather; Carey, Irene; Matthews, Beverley; O'Donoghue, Donal; Vinen, Katie; Murtagh, Fliss E M

2014-04-01

In recent years, the End-Stage Kidney Disease population has increased and is ever more frail, elderly and co-morbid. A care-focused approach needs to be incorporated alongside the disease focus, to identify those who are deteriorating and improve communication about preferences and future care. Yet many renal professionals feel unprepared for such discussions. To develop and pilot a REnal specific Advanced Communication Training (REACT) programme to address the needs of End-Stage Kidney Disease patients and renal professionals. Two-part study: (1) development of the REnal specific Advanced Communication Training programme informed by multi-professional focus group and patient survey and (2) piloting of the programme. The REnal specific Advanced Communication Training programme was piloted with 16 participants (9 renal nurses/health-care assistants and 7 renal consultants) in two UK teaching hospitals. The focus group identified the need for better information about end-of-life phase, improved awareness of patient perspectives, skills to manage challenging discussions, 'hands on' practice in a safe environment and follow-up to discuss experiences. The patient survey demonstrated a need to improve communication about concerns, treatment plans and decisions. The developed REnal specific Advanced Communication Training programme was acceptable and feasible and was associated with a non-significant increase in confidence in communicating about end-of-life issues (pre-training: 6.6/10, 95% confidence interval: 5.7-7.4; post-training: 6.9/10, 95% confidence interval: 6.1-7.7, unpaired t-test - p = 0.56), maintained at 3 months. There is a need to improve end-of-life care for End-Stage Kidney Disease patients, to enable them to make informed decisions about future care. Challenges include prioritising communication training among service providers.

Pembrolizumab in Treating Participants With Metastatic, Recurrent or Locally Advanced Cancer and Genomic Instability

ClinicalTrials.gov

2018-03-22

BRCA1 Gene Mutation; BRCA2 Gene Mutation; Locally Advanced Solid Neoplasm; Metastatic Malignant Solid Neoplasm; POLD1 Gene Mutation; POLE Gene Mutation; Recurrent Malignant Solid Neoplasm; Recurrent Ovarian Carcinoma; Stage III Breast Cancer AJCC v7; Stage III Ovarian Cancer AJCC v8; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v8; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v8; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v8; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v8; Stage IVA Ovarian Cancer AJCC v8; Stage IVB Ovarian Cancer AJCC v8

Advances in aortic disease management: a year in review.

PubMed

Garg, Vinay; Ouzounian, Maral; Peterson, Mark D

2016-03-01

The medical and surgical management of aortic disease is continually changing in search for improved outcomes. Our objective is to highlight recent advances in a few select areas pertaining to aortic disease and aortic surgery: the genetics of aortopathy, medical therapy of aortic aneurysms, advances in cardiac imaging, and operative strategies for the aortic arch. As our understanding of the genetic basis for aortopathy continues to improve, routine genetic testing may be of value in assessing patients with genetically triggered forms of aortic disease. With regard to medical advances, treating patients with Marfan syndrome with either losartan or atenolol at an earlier stage in their disease course improves outcomes. In addition, novel imaging indices such as wall shear stress and aortic stiffness assessed by MRI may become useful markers of aortopathy and warrant further study. With regard to the optimal technique for cerebral perfusion in aortic arch surgery, high-quality data are still lacking. Finally, in patients with complex, multilevel aortic disease, the frozen elephant trunk is a viable single-stage option compared with the conventional elephant trunk, although with an increased risk for spinal cord injury. Based on recent advances, continued studies in genetics, cardiac imaging, and surgical trials will further elucidate the etiology of aortopathy and ultimately guide management, both medically and surgically.

Advances in pancreatic cancer research: moving towards early detection.

PubMed

He, Xiang-Yi; Yuan, Yao-Zong

2014-08-28

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

SEOM clinical guidelines in early-stage breast cancer 2015.

PubMed

Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

2015-12-01

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

Disparities in cancer stage at diagnosis and survival of Aboriginal and non-Aboriginal South Australians.

PubMed

Banham, David; Roder, David; Keefe, Dorothy; Farshid, Gelareh; Eckert, Marion; Cargo, Margaret; Brown, Alex

2017-06-01

This study tested the utility of retrospectively staging cancer registry data for comparing stage and stage-specific survivals of Aboriginal and non-Aboriginal people. Differences by area level factors were also explored. This test dataset comprised 950 Aboriginal cases and all other cases recorded on the South Australian cancer registry with a 1977-2010 diagnosis. A sub-set of 777 Aboriginal cases diagnosed in 1990-2010 were matched with randomly selected non-Aboriginal cases by year of birth, diagnostic year, sex, and primary site of cancer. Competing risk regression summarised associations of Aboriginal status, stage, and geographic attributes with risk of cancer death. Aboriginal cases were 10 years younger at diagnosis, more likely to present in recent diagnostic years, to be resident of remote areas, and have primary cancer sites of head & neck, lung, liver and cervix. Risk of cancer death was associated in the matched analysis with more advanced stage at diagnosis. More Aboriginal than non-Aboriginal cases had distant metastases at diagnosis (31.3% vs 22.0, p<0.001). After adjusting for stage, remote-living Aboriginal residents had higher risks of cancer death than Aboriginal residents of metropolitan areas. Non-Aboriginal cases had the lowest risk of cancer death. Retrospective staging proved to be feasible using registry data. Results indicated more advanced stages for Aboriginal than matched non-Aboriginal cases. Aboriginal people had higher risks of cancer death, which persisted after adjusting for stage, and applied irrespective of remoteness of residence, with highest risk of death occurring among Aboriginal people from remote areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Testing of polyimide second-stage rod seals for single-state applications in advanced aircraft hydraulic systems

NASA Technical Reports Server (NTRS)

Waterman, A. W.

1977-01-01

Machined polyimide second-stage rod seals were evaluated to determine their suitability for single-stage applications where full system pressure acts on the upstream side of the seal. The 6.35-cm (2.5-in.) K-section seal was tested in impulse screening tests where peak pressure was increased in 3.448-MPa (500-psi) increments each 20,000 cycles. Seal failure occurred at 37.92 MPa (5,500 psi), indicating a potential for acceptability in a 27.58-MPa (4,000-psi) system. Static pressurization for 600 sec at pressures in excess of 10.34 MPa (1,500 psi) revealed structural inadequacy of the seal cross section to resist fracture and extrusion. Endurance testing showed the seals capable of at least 65,000 1.27-cm (0.5-in.) cycles at 450 K (350 F) without leakage. It was concluded that the second-stage seals were proven to be exceptional in the 1.379-MPa (200-psi) applications for which they were designed, but polyimide material properties are not adequate for use in this design at pressure loading equivalent to that present in single-stage applications.

Core compressor exit stage study. 1: Aerodynamic and mechanical design

NASA Technical Reports Server (NTRS)

Burdsall, E. A.; Canal, E., Jr.; Lyons, K. A.

1979-01-01

The effect of aspect ratio on the performance of core compressor exit stages was demonstrated using two three stage, highly loaded, core compressors. Aspect ratio was identified as having a strong influence on compressors endwall loss. Both compressors simulated the last three stages of an advanced eight stage core compressor and were designed with the same 0.915 hub/tip ratio, 4.30 kg/sec (9.47 1bm/sec) inlet corrected flow, and 167 m/sec (547 ft/sec) corrected mean wheel speed. The first compressor had an aspect ratio of 0.81 and an overall pressure ratio of 1.357 at a design adiabatic efficiency of 88.3% with an average diffusion factor or 0.529. The aspect ratio of the second compressor was 1.22 with an overall pressure ratio of 1.324 at a design adiabatic efficiency of 88.7% with an average diffusion factor of 0.491.

Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer?

PubMed

Massuti, Bartomeu; Sanchez, Jose Miguel; Hernando-Trancho, Florentino; Karachaliou, Niki; Rosell, Rafael

2013-06-01

Lung cancer accounts for the majority of cancer-related deaths worldwide. At present, platinum-based therapy represents the standard of care in fit stage II and IIIA non-small cell lung cancer (NSCLC) patients following surgical resection. In advanced disease, personalized chemotherapy and targeted biologic therapy based on histological and molecular tumor profiling have already shown promise in terms of optimizing treatment efficacy. While disease stage is associated with outcome and is commonly used to determine adjuvant treatment eligibility, it is known that a subset of patients with early stage disease experience shorter survival than others with the same clinicopathological characteristics. Improved methods for identifying these individuals, at or near the time of initial diagnosis, may inform the decision to pursue adjuvant therapy options. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information, while real-time quantitative polymerase-chain reaction (RT-qPCR) strategy involving relatively small numbers of genes offers a practical alternative with high cross-platform performance. mRNA and/or protein expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M subunit 1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) are among the most promising potential biomarkers for early disease and their clinical utility is currently being evaluated in randomized phase II and III clinical trials. This review describes the most promising clinicopathological and molecular biomarkers with predictive and prognostic significance in lung cancer that have been identified through advanced research and which could influence adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine clinical practice.

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

PubMed

Lewintre, Eloisa Jantus; Martín, Cristina Reinoso; Ballesteros, Carlos García; Montaner, David; Rivera, Rosa Farrás; Mayans, José Ramón; García-Conde, Javier

2009-02-01

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.

Design study for a staged Very Large Hadron Collider

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

Peter J. Limon et al.

Advancing accelerator designs and technology to achieve the highest energies has enabled remarkable discoveries in particle physics. This report presents the results of a design study for a new collider at Fermilab that will create exceptional opportunities for particle physics--a two-stage very large hadron collider. In its first stage, the machine provides a facility for energy-frontier particle physics research, at an affordable cost and on a reasonable time scale. In a second-stage upgrade in the same tunnel, the VLHC offers the possibility of reaching 100 times the collision energy of the Tevatron. The existing Fermilab accelerator complex serves as themore » injector, and the collision halls are on the Fermilab site. The Stage-1 VLHC reaches a collision energy of 40 TeV and a luminosity comparable to that of the LHC, using robust superferric magnets of elegant simplicity housed in a large-circumference tunnel. The Stage-2 VLHC, constructed after the scientific potential of the first stage has been fully realized, reaches a collision energy of at least 175 TeV with the installation of high-field magnets in the same tunnel. It makes optimal use of the infrastructure developed for the Stage-1 machine, using the Stage-1 accelerator itself as the injector. The goals of this study, commissioned by the Fermilab Director in November 2000, are: to create reasonable designs for the Stage-1 and Stage-2 VLHC in the same tunnel; to discover the technical challenges and potential impediments to building such a facility at Fermilab; to determine the approximate costs of the major elements of the Stage-1 VLHC; and to identify areas requiring significant R and D to establish the basis for the design.« less

Denial, Conflagration, Pride: Three Stages in the Development of an Advanced Writing Requirement.

ERIC Educational Resources Information Center

Loux, Ann Kimble; Stoddart, Rebecca

General satisfaction with the achievements of an introductory writing-across-the-discipline program led faculty of Saint Mary's College (Indiana) to believe students were capable of sustaining comparable progress in their majors. Subsequently, the faculty spent between three and four years working out procedures for a new advanced writing…

Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

ClinicalTrials.gov

2014-12-29

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

Pathway Profiling and Rational Trial Design for Studies in Advanced Stage Cervical Carcinoma: A Review and a Perspective

PubMed Central

Scholl, Susy M. E.; Kenter, Gemma; Kurzeder, Christian; Beuzeboc, Philippe

2011-01-01

Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment. PMID:22091418

Treatment-related mortality in patients with advanced-stage hodgkin lymphoma: an analysis of the german hodgkin study group.

PubMed

Wongso, Diana; Fuchs, Michael; Plütschow, Annette; Klimm, Beate; Sasse, Stephanie; Hertenstein, Bernd; Maschmeyer, Georg; Vieler, Tom; Dührsen, Ulrich; Lindemann, Walter; Aulitzky, Walter; Diehl, Volker; Borchmann, Peter; Engert, Andreas

2013-08-01

The introduction of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPP(escalated). In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPP(escalated)-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPP(escalated) (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. The individual risk of TRM associated with BEACOPP(escalated) can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

Assessment of skeletal changes after post-mortem exposure to fire as an indicator of decomposition stage.

PubMed

Keough, N; L'Abbé, E N; Steyn, M; Pretorius, S

2015-01-01

Forensic anthropologists are tasked with interpreting the sequence of events from death to the discovery of a body. Burned bone often evokes questions as to the timing of burning events. The purpose of this study was to assess the progression of thermal damage on bones with advancement in decomposition. Twenty-five pigs in various stages of decomposition (fresh, early, advanced, early and late skeletonisation) were exposed to fire for 30 min. The scored heat-related features on bone included colour change (unaltered, charred, calcined), brown and heat borders, heat lines, delineation, greasy bone, joint shielding, predictable and minimal cracking, delamination and heat-induced fractures. Colour changes were scored according to a ranked percentage scale (0-3) and the remaining traits as absent or present (0/1). Kappa statistics was used to evaluate intra- and inter-observer error. Transition analysis was used to formulate probability mass functions [P(X=j|i)] to predict decomposition stage from the scored features of thermal destruction. Nine traits displayed potential to predict decomposition stage from burned remains. An increase in calcined and charred bone occurred synchronously with advancement of decomposition with subsequent decrease in unaltered surfaces. Greasy bone appeared more often in the early/fresh stages (fleshed bone). Heat borders, heat lines, delineation, joint shielding, predictable and minimal cracking are associated with advanced decomposition, when bone remains wet but lacks extensive soft tissue protection. Brown burn/borders, delamination and other heat-induced fractures are associated with early and late skeletonisation, showing that organic composition of bone and percentage of flesh present affect the manner in which it burns. No statistically significant difference was noted among observers for the majority of the traits, indicating that they can be scored reliably. Based on the data analysis, the pattern of heat-induced changes may

Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

PubMed

Bychkovsky, Brittany L; Lin, Nancy U

2017-02-01

Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Splenectomy combined with gastrectomy and immunotherapy for advanced gastric cancer.

PubMed

Miwa, H; Orita, K

1983-06-01

We studied the effects of a splenectomy in combination with immunotherapy on the survival of patients who had undergone a total gastrectomy. It was found that a splenectomy was not effective against advanced gastric cancer at stage III, and that the spleen should be retained for immunotherapy. Splenectomy for gastric cancer at terminal stage IV, particularly in combination with immunotherapy, produced not only augmentation of cellular immunity, but also increased survival.

IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD - a pilot study.

PubMed

Hagström, Hannes; Stål, Per; Hultcrantz, Rolf; Brismar, Kerstin; Ansurudeen, Ishrath

2017-12-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Advanced fibrosis (stage 3-4) is the most robust marker for future mortality, but diagnosis requires liver biopsy. Current non-invasive scoring systems aimed to identify advanced fibrosis are imperfect. Insulin-like growth factor I (IGF-I) and its binding protein IGFBP-1 are liver derived proteins, that are involved in various liver disorders. The aim of this study was to examine the possible association between advanced fibrosis and IGF-I and IGFBP-1 in NAFLD. Fasting blood samples were obtained from 52 patients diagnosed with NAFLD by liver biopsy. Total IGF-I and IGFBP-1 concentrations were determined in serum by in-house radio-immuno-assays. IGF-I levels were age-standardized (IGF-SD). A logistic regression model was used to investigate the association of IGF-SD and IGFBP-1 with advanced fibrosis (stage 3-4). Patients with advanced fibrosis (stage 3-4 vs. 0-2) had lower IGF-SD (-1.17 vs. 0.11, p = .01) and higher mean levels of IGFBP-1 (29.9 vs. 18.8 µg/l, p = .02). IGFBP-1 was associated with presence of advanced fibrosis (OR 1.04 per unit increase, 95%CI 1.0-1.07, p = .05), while IGF-1 was negatively associated with advanced fibrosis (OR 0.63 per standard deviation, 95%CI 0.44-0.92, p = .02). This pilot study suggests an association between serum IGFBP-1 and IGF-I levels with advanced fibrosis in NAFLD patients. IGFBP1 and IGF-1 could be of interest as future biomarkers. Similar studies in larger cohorts are needed.

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

PubMed Central

Jung, Jang Han; Lee, Hyun Jik; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Park, Jeong Youp; Park, Seung Woo; Song, Si Young; Bang, Seungmin

2017-01-01

AIM To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA). METHODS We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01). CONCLUSION NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability. PMID:28566890

Design and development of an advanced two-stage centrifugal compressor

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

Palmer, D.L.; Waterman, W.F.

1995-04-01

Small turboshaft engines require high-pressure-ratio, high-efficiency compressors to provide low engine fuel consumption. This paper describes the aeromechanical design and development of a 3.3 kg/s (7.3 lb/sec), 14:1 pressure ratio two-stage centrifugal compressor, which is used in the T800-LHT-800 helicopter engine. The design employs highly nonradial, splitter bladed impellers with swept leading edges and compact vaned diffusers to achieve high performance in a small and robust configuration. The development effort quantified the effects of impeller diffusion and passive inducer shroud bleed on surge margin as well as the effects of impeller loading on tip clearance sensitivity and the impact ofmore » sand erosion and shroud roughness on performance. The developed compressor exceeded its performance objectives with a minimum of 23% surge margin without variable geometry. The compressor provides a high-performance, rugged, low-cost configuration ideally suited for helicopter applications.« less

Phase 0 Trial of Itraconazole for Early-Stage Non-Small Cell Lung Cancer

DTIC Science & Technology

2015-10-01

63 Male Caucasian T1bN0M0 Stage IA Undifferentiated carcinoma , favor Large cell 63 Female Caucasian T1aN0N0 Stage IA squamous cell carcinoma ... carcinoma ; and possibly prolongs survival in advanced non-small cell lung cancer (NSCLC). Insight into itraconazole mechanism and biomarkers will...study team members in which itraconazole resulted in tumor regression and Hh pathway antagonism in basal cell carcinoma ; and (3) a clinical trial in

Single stage experimental evaluation of tandem-airfoil rotor and stator blading for compressors. Part 4: Data and performance for stage B

NASA Technical Reports Server (NTRS)

Brent, J. A.; Cheatham, J. G.

1973-01-01

Stage B, composed of tandem-airfoil rotor B and stator B, was tested with uniform inlet flow and with hub radial, tip radial and 90 degree one-per-revolution circumferential distortion of the inlet flow as part of an overall program to evaluate the effectiveness of tandem airfoils for increasing the design point loading capability and stable operating range of rotor and stator blading. The results of this series of tests provide overall performance and blade element data for evaluating: (1) the potential of tandem blading for extending the loading limit and stable operating range of a stage representative of a middle stage of an advanced high pressure compressor, (2) the effect of loading split between the two airfoils in tandem on the performance of tandem blading, and (3) the effects of inlet flow distortion on the stage performance. The rotor had an inlet hub/tip ratio of 0.8 and a design tip velocity of 757 ft/sec. With uniform inlet flow, rotor B achieved a maximum adiabatic efficiency of 88.4% at design equivalent rotor speed and a pressure ratio of 1.31. The stage maximum adiabatic efficiency at design equivalent rotor speed with uniform inlet flow was 82.5% at a pressure ratio of 1.28. Tip radial and circumferential distortion of the inlet flow caused substantial reductions in surge margin.

Sustainability of evidence-based healthcare: research agenda, methodological advances, and infrastructure support.

PubMed

Proctor, Enola; Luke, Douglas; Calhoun, Annaliese; McMillen, Curtis; Brownson, Ross; McCrary, Stacey; Padek, Margaret

2015-06-11

Little is known about how well or under what conditions health innovations are sustained and their gains maintained once they are put into practice. Implementation science typically focuses on uptake by early adopters of one healthcare innovation at a time. The later-stage challenges of scaling up and sustaining evidence-supported interventions receive too little attention. This project identifies the challenges associated with sustainability research and generates recommendations for accelerating and strengthening this work. A multi-method, multi-stage approach, was used: (1) identifying and recruiting experts in sustainability as participants, (2) conducting research on sustainability using concept mapping, (3) action planning during an intensive working conference of sustainability experts to expand the concept mapping quantitative results, and (4) consolidating results into a set of recommendations for research, methodological advances, and infrastructure building to advance understanding of sustainability. Participants comprised researchers, funders, and leaders in health, mental health, and public health with shared interest in the sustainability of evidence-based health care. Prompted to identify important issues for sustainability research, participants generated 91 distinct statements, for which a concept mapping process produced 11 conceptually distinct clusters. During the conference, participants built upon the concept mapping clusters to generate recommendations for sustainability research. The recommendations fell into three domains: (1) pursue high priority research questions as a unified agenda on sustainability; (2) advance methods for sustainability research; (3) advance infrastructure to support sustainability research. Implementation science needs to pursue later-stage translation research questions required for population impact. Priorities include conceptual consistency and operational clarity for measuring sustainability, developing evidence

Prognostic values of common clinical parameters in advanced pancreatic ductal adenocarcinoma: a large multicenter cohort study of ten years.

PubMed

Zhang, Chenyue; Dong, Shu; Wang, Lei; Yu, Songlin; Zheng, Yuwei; Geng, Yanyan; Shen, Xiaoheng; Ying, Haifeng; Guo, Yuanbiao; Yu, Jinming; Deng, Qinglong; Meng, Zhiqiang; Li, Zhaoshen; Chen, Hao; Shen, Yehua; Chen, Qiwen

2018-03-01

We conducted a multicenter cohort study to investigate the prognostic value of some commonly-used laboratory indices in advanced pancreatic ductal adenocarcinoma (PDAC). A multicenter cohort study was conducted from 2004 to 2013. The associations between laboratory indices and prognosis of advanced PDAC were examined. This cohort consisted of 553 females (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595 (39.0%) and 931 (61.0%), respectively. The median survival of stage III patients was 9.0 months, with 3-, 6-, and 12-month survival rates of 94.5%, 73.4%, and 28.5%, respectively. The median survival of stage IV patients was 5.4 months, with 3-, 6-, and 12-month survival rates of 79.3%, 42.9%, and 15.0%, respectively. In multivariate analyses, primary tumor diameter, low albumin, and elevated CA19-9 were associated with decreased survival for stage III patients. Age, smoking, primary tumor diameter, elevated ALT or AST, low albumin, and elevated CA19-9 were associated with decreased survival for stage IV patients. Elevated CA19-9 level, decreased albumin level, and tumor size were associated with worse survival in stage III patients. Meanwhile, advanced age, smoking, and ALT or AST level were negatively correlated to prognosis in stage IV patients.

Seismic isolation of Advanced LIGO: Review of strategy, instrumentation and performance

NASA Astrophysics Data System (ADS)

Matichard, F.; Lantz, B.; Mittleman, R.; Mason, K.; Kissel, J.; Abbott, B.; Biscans, S.; McIver, J.; Abbott, R.; Abbott, S.; Allwine, E.; Barnum, S.; Birch, J.; Celerier, C.; Clark, D.; Coyne, D.; DeBra, D.; DeRosa, R.; Evans, M.; Foley, S.; Fritschel, P.; Giaime, J. A.; Gray, C.; Grabeel, G.; Hanson, J.; Hardham, C.; Hillard, M.; Hua, W.; Kucharczyk, C.; Landry, M.; Le Roux, A.; Lhuillier, V.; Macleod, D.; Macinnis, M.; Mitchell, R.; O'Reilly, B.; Ottaway, D.; Paris, H.; Pele, A.; Puma, M.; Radkins, H.; Ramet, C.; Robinson, M.; Ruet, L.; Sarin, P.; Shoemaker, D.; Stein, A.; Thomas, J.; Vargas, M.; Venkateswara, K.; Warner, J.; Wen, S.

2015-09-01

The new generation of gravitational waves detectors require unprecedented levels of isolation from seismic noise. This article reviews the seismic isolation strategy and instrumentation developed for the Advanced LIGO observatories. It summarizes over a decade of research on active inertial isolation and shows the performance recently achieved at the Advanced LIGO observatories. The paper emphasizes the scientific and technical challenges of this endeavor and how they have been addressed. An overview of the isolation strategy is given. It combines multiple layers of passive and active inertial isolation to provide suitable rejection of seismic noise at all frequencies. A detailed presentation of the three active platforms that have been developed is given. They are the hydraulic pre-isolator, the single-stage internal isolator and the two-stage internal isolator. The architecture, instrumentation, control scheme and isolation results are presented for each of the three systems. Results show that the seismic isolation sub-system meets Advanced LIGO’s stringent requirements and robustly supports the operation of the two detectors.

Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

PubMed Central

Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

2016-01-01

Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

Simulated dynamic response of a multi-stage compressor with variable molecular weight flow medium

NASA Technical Reports Server (NTRS)

Babcock, Dale A.

1995-01-01

A mathematical model of a multi-stage compressor with variable molecular weight flow medium is derived. The modeled system consists of a five stage, six cylinder, double acting, piston type compressor. Each stage is followed by a water cooled heat exchanger which serves to transfer the heat of compression from the gas. A high molecular weight gas (CFC-12) mixed with air in varying proportions is introduced to the suction of the compressor. Condensation of the heavy gas may occur in the upper stage heat exchangers. The state equations for the system are integrated using the Advanced Continuous Simulation Language (ACSL) for determining the system's dynamic and steady state characteristics under varying operating conditions.

Space Launch System Launch Vehicle Stage Adapter Hardware Completes Manufacturing

NASA Image and Video Library

2017-08-28

The Launch Vehicle Stage Adapter for the first flight of the Space Launch System, NASA’s new deeps space rocket, recently completed manufacturing at NASA’s Marshal Space Flight Center in Huntsville, Alabama. The LVSA, the largest piece of the rocket welded together in Marshall’s Huntsville manufacturing area, will connect two major sections of SLS – the 27.6-foot diameter core stage and the 16.4-foot interim cryogenic propulsion stage – for the first integrated flight of SLS and the Orion spacecraft. Teledyne Brown Engineering of Huntsville, the prime contractor for the adapter, has completed manufacturing, and engineers are preparing to apply thermal insulation. It will be the largest piece of hardware that Marshall. The LVSA was moved from the NASA welding area to NASA’s Center for Advanced Manufacturing where the thermal protection system will be applied.

Clinical staging of Fibrodysplasia Ossificans Progressiva (FOP).

PubMed

Pignolo, Robert J; Kaplan, Frederick S

2018-04-01

Fibrodyplasia ossificans progressiva (FOP) is an ultra-rare genetic condition of heterotopic ossification (HO) that results in progressive loss of joint function, ultimately rendering movement impossible. Death is most commonly the result of thoracic insufficiency syndrome, or complications related to recurrent respiratory infections. There are no current treatments for FOP, but early and emerging clinical trials offer hope for this devastating disease. With the recent reporting of a comprehensive global natural history study, scales to assess joint dysfunction, and a more accurate prediction of joint survival, it is now possible to construct a conceptual framework for the clinical staging of FOP. Based on assessment of FOP features in seven areas, it is possible to assign five clinical stages. FOP features include flare-up activity, body regions affected, thoracic insufficiency, other complications, activities of daily living (ADLs), ambulatory status, and the cumulative joint involvement scale (CAJIS) score. Assessments of these features assign an individual with FOP to early/mild, moderate, severe, profound, or late-stage disease. These criteria seek to be flexible enough to be used by clinicians without reliance on advanced imaging or specialized testing, as well as by investigators involved in research or clinical trial studies who would have these tools available. These staging measures for FOP assess the influence of HO and accelerated joint dysfunction (due to congenital abnormalities) on the ability to perform common functional activities, and thus a delay or lack of progression from one stage to the next represents the ultimate test of efficacy for drug trials. This framework will serve both as a prediction tool for FOP progression as well as a critical opportunity to substantiate therapeutic interventions. The staging system proposed here will permit an accurate assessment of severity to appropriately develop or revise clinical plans of care, define

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

ClinicalTrials.gov

2017-08-01

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin

ClinicalTrials.gov

2018-04-23

Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Pleural Malignant Mesothelioma AJCC v7; Thymoma; Unresectable Solid Neoplasm

Advanced radial inflow turbine rotor program: Design and dynamic testing

NASA Technical Reports Server (NTRS)