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Sample records for early-stage grade 1-2

  1. Clinical, functional and pathological correspondence in early stage idiopathic pulmonary fibrosis: evidence for small airway obstruction 1-2.

    PubMed

    Myre, M; Allard, S; Bernard, C; Martin, R R

    1988-01-01

    We describe the clinical, physiological and pathological features of 23 subjects with early stage idiopathic pulmonary fibrosis. Thirteen subjects who had no symptoms had been fortuitously recruited by a routine chest radiograph, whereas the 10 other subjects complained of dyspnea. Twenty-one subjects showed only light to moderate extent of abnormalities on the chest radiograph. Fourteen subjects had a reduced vital capacity whereas 16 and 17 showed a reduced pulmonary compliance and an increase in lung elastic recoil, respectively. Transfer factor was significantly reduced in 18 subjects. Evidence for significant airway obstruction, mainly located at the peripheral level, was demonstrated by a reduced specific lung conductance and upstream conductance in 13 subjects. Airway obstruction was not associated with smoking habits. Bronchial hyperresponsiveness was noted in 50% of the 18 subjects studied. Although fibrosis was mild to moderate in 15 instances, it was only focal, i.e. at least one zone of normal parenchyma in the lung specimen in 17 subjects. Peribronchial fibrosis was established in 8/11 satisfactory biopsy specimens. Significant correlations were observed between rales, the radiological score, some functional indices and the characteristics of fibrosis. We conclude that small airway obstruction documented by physiological and pathological means is frequent in early stage idiopathic pulmonary fibrosis. PMID:3420306

  2. The D-Optimality Item Selection Criterion in the Early Stage of CAT: A Study with the Graded Response Model

    ERIC Educational Resources Information Center

    Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E. S.

    2008-01-01

    During the early stage of computerized adaptive testing (CAT), item selection criteria based on Fisher"s information often produce less stable latent trait estimates than the Kullback-Leibler global information criterion. Robustness against early stage instability has been reported for the D-optimality criterion in a polytomous CAT with the…

  3. FGFR1, 2 and 3 protein overexpression and molecular aberrations of FGFR3 in early stage non‐small cell lung cancer

    PubMed Central

    Mittempergher, Lorenza; Willems, Stefan M; Bosma, Astrid J; Peters, Dennis DGC; van der Noort, Vincent; Japenga, Eva J; Peeters, Ton; Koole, Koos; Šuštić, Tonći; Blaauwgeers, JL; van Noesel, Carel J; Bernards, René

    2016-01-01

    Abstract This study aimed to determine protein expression levels of fibroblast growth factor receptors (FGFR) 1, 2 and 3 in early stage non‐small cell lung cancer (NSCLC). Additionally, a screen to define the frequency of FGFR3‐TACC3 translocation and FGFR3 amplification was performed. Archived tissues from 653 NSCLC samples (adenocarcinoma (AC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC)) were analysed with immunohistochemistry (IHC) for expression of FGFR1, 2 and 3. Expression levels of FGFR1, 2 and 3 were correlated with clinicopathological features. The presence of FGFR3‐TACC3 translocation was detected by RT‐PCR and FGFR3 amplification was detected by fluorescence in situ hybridization. FGFR1, 2 and 3 proteins were highly expressed in 64 (10.6%), 76 (12.9%) and 20 (3.3%) NSCLC tumour samples, respectively. Protein expression of FGFR1 was significantly related to worse overall survival in NSCLC. Furthermore, FGFR1 protein expression was associated with light smoking and histological subtype (AC), FGFR2 protein expression with female gender, younger age, histological subtype (AC) and lower tumour stage, and FGFR3 protein was significantly overexpressed in tumours of older patients and SCC histology. The FGFR3‐TACC3 fusion was detected in 3.0% (6/200) of NSCLC samples and the FGFR3 gene was amplified in 4.7% of IHC positive NSCLC samples (2/43). FGFR1, 2 and 3 proteins are expressed in a high number of early stage NSCLC and FGFR1 protein expression may serve as a prognostic biomarker. Recurrent translocations and amplifications in FGFR3 can be found in NSCLC. This study shows that FGFR family members are frequently aberrant in NSCLC and could be interesting therapeutic targets for the treatment of NSCLC.

  4. Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells

    PubMed Central

    2013-01-01

    Background The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. Methods To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0–2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Results Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. Conclusions These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway

  5. GDP-fucose:GM1 alpha 1----2fucosyltransferase is activated in parenchymal cells of rat liver during early stages of N-2-acetylaminofluorene induced hepatocarcinogenesis.

    PubMed

    Holmes, E H

    1990-01-01

    Gangliosides from liver parenchymal and non-parenchymal cells were isolated from Fischer 344 rats that had been fed normal diet or a diet supplemented with 0.03% N-2-acetylaminofluorene (AAF) for 4 weeks. Gangliosides from liver cell fractions were characterized by an induction of both II3NeuAcIV3 alpha GalIV2FucGg4 and GM3 synthesis in the parenchymal cells of AAF-fed animals which were missing in parenchymal cells from animals fed normal diet. In addition, new bands corresponding to GM1 and GD1a were observed in cell fractions of AAF-fed animals. The activity of the GM1-specific alpha 1----2fucosyltransferase induced after AAF feeding was found to be enriched 5- to 6-fold in the parenchymal cell fraction of AAF-fed animals and correlated with the parenchymal cell marker enzyme glucose-6-phosphatase in these cell fractions. Feeding animals the hepatotoxin acetaminophen at 1.87% in the diet for 10 weeks resulted in no increase in the levels of the alpha 1----2fucosyltransferase. Antibodies specific for II3NeuAcIV3 alpha GalIV2FucGg4 were produced and utilized in tissue localization studies. These results indicated little or no staining of normal liver tissue or that after acetaminophen feeding was observed. In contrast, focal areas of staining of liver tissue from animals after 3 weeks of 0.03% AAF feeding were readily apparent. These results indicate that induction of alpha 1----2fucosyltransferase and fucoganglioside synthesis is most probably a property of liver parenchymal cells and is associated with events occurring during early stages of AAF-induced carcinogenesis. PMID:2295130

  6. Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3-13C]Glucose Breath Tests

    PubMed Central

    Kijima, Sho; Tanaka, Hideki

    2016-01-01

    This study aimed to evaluate changes in glucose metabolism at the early stage and onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Specifically, after the oral administration of [1, 2, 3-13C]glucose, the levels of exhaled 13CO2, which most likely originated from pyruvate decarboxylation and tricarboxylic acid, were measured. Eight OLETF rats and eight control rats (Long-Evans Tokushima Otsuka [LETO]) were administered 13C-glucose. Three types of 13C-glucose breath tests were performed thrice in each period at 2-week intervals. [3-13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule, which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13CO2 excretion in OLETF rats was delayed in all three breath tests compared to that in control rats, suggesting that OLETF rats had a lower glucose metabolism than control rats. In addition, overall glucose metabolism increased with age in both groups. The utilization of [2-13C]glucose was suppressed in OLETF rats at 6–12 weeks of age, but they showed higher [3-13C]glucose oxidation than control rats at 22–25 weeks of age. In the [1-13C]glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC180) were observed between OLETF and LETO rats of any age. Glucose metabolism kinetics were different between the age groups and two groups of rats; however, these differences were not significant based on the overall AUC180 of [1-13C]glucose. We conclude that breath 13CO2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats. PMID:27483133

  7. The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas.

    PubMed

    Graflund, Marianne; Sorbe, B; Bryne, M; Karlsson, M

    2002-01-01

    This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients. PMID:11975674

  8. Elementary Physical Education Weekly Lesson Plan. Grades 1, 2.

    ERIC Educational Resources Information Center

    Anchorage Borough School District, AK.

    This curriculum guide provides weekly lesson plans for the physical education of first and second grade students and lists specific activities along with organization and teaching procedures for each. Warm-up activities, safety procedures, modifications and athletic equipment are described for each activity. (CJ)

  9. CURRICULUM GUIDE FOR SOCIAL STUDIES, KINDERGARTEN, GRADES 1, 2.

    ERIC Educational Resources Information Center

    BOWERS, CATHERINE; AND OTHERS

    EXTENSIVE RESOURCE MATERIALS ARE PRESENTED FOR A COMPLETE SOCIAL STUDIES COURSE IN GRADES KINDERGARTEN, ONE, AND TWO. RECOGNITION IS GIVEN TO THE FACT THAT TODAY'S EDUCATION MUST BE MULTI-CULTURAL AND CROSS-CULTURAL. EMPHASIS IS PLACED UPON TEACHING OF AMERICAN IDEALS BY PROVIDING MATERIALS AND EXPERIENCES FROM THE VARIOUS DISCIPLINES OF THE…

  10. Creative Prescriptions Unlimited, Grades 1-2. Evaluation Program Needs.

    ERIC Educational Resources Information Center

    East Whittier City School District, CA.

    The document provides lesson plans for strengthening the thought processes, including problem solving and creative abilities, of first and second grade mentally gifted children. The lessons are organized within the five operations of the mind as defined by J. Guilford's Structure of Intellect (SOI): cognition (10 lessons), memory (3 lessons),…

  11. Early stage of nanocrystal growth

    SciTech Connect

    2012-01-01

    Berkeley Lab researchers at the Molecular Foundry have elucidated important mechanisms behind oriented attachment, the phenomenon that drives biomineralization and the growth of nanocrystals. This electron microscopy movie shows the early stage of nanocrystal growth. Nanoparticles make transient contact at many points and orientations until their lattices are perfectly matched. The particles then make a sudden jump-to-contact to form attached aggregates. (Movie courtesy of Jim DeYoreo)

  12. Morphogenesis of early stage melanoma

    NASA Astrophysics Data System (ADS)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  13. Collateral Benefits of an Interactive Literacy Program for Grade 1/2 Students and Their Teachers.

    ERIC Educational Resources Information Center

    Ross, John A.; Hogaboam-Gray, Anne; Hannay, Lynne

    This study examined the collateral effects of WiggleWorks, an interactive literacy program, in two settings: a cohort study comparing random samples of grade 1-2 students (n=452) before and after software implementation and a longitudinal sample tracing students from Kindergarten to grade 1 (n=126). WiggleWorks contributed to greater student use…

  14. Dislocation generation during early stage sintering.

    NASA Technical Reports Server (NTRS)

    Sheehan, J. E.; Lenel, F. V.; Ansell, G. S.

    1973-01-01

    Discussion of the effects of capillarity-induced stresses on dislocations during early stage sintering. A special version of Hirth's (1963) theoretical calculation procedures modified to describe dislocation nucleation on planes meeting the sintering body's neck surface obliquely is shown to predict plastic flow at stress levels know to exist between micron size metal particles in the early stages of sintering.

  15. Education for Survival; A Social Studies and Science Curriculum Guide for Grades 1, 2, 3.

    ERIC Educational Resources Information Center

    Grubman, Ruth W.; And Others

    This book is one of a series on Education For Survival and integrates a conservation curriculum into a social studies and science program for grades 1, 2, and 3. It was developed to help lead young people to an awareness of environmental problems which confront our society. The first chapter presents a resume of all social science curriculum units…

  16. Guide for Teaching Science Problems 1-2, Grade XI or XII. Second Edition.

    ERIC Educational Resources Information Center

    Fredrickson, Clifford T.

    Science Problems 1-2 is a terminal course for eleventh and twelfth grade students with limited science background and generally below average reading levels. The guide is intended as a supplement to the detailed teacher's guide prepared by the publishers of the textbook used in the course. It is assumed that no teacher is expert in all subject…

  17. Endoscopic options for early stage esophageal cancer

    PubMed Central

    Shah, Pari M.

    2015-01-01

    Surgery has traditionally been the preferred treatment for early stage esophageal cancer. Recent advances in endoscopic treatments have been shown to be effective and safe. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow endoscopists to remove small, superficial lesions, providing tumor specimen that can be examined for accurate pathologic tumor staging and assessment of adequacy of resection. Endoscopic ablation procedures, including photodynamic therapy (PDT) and radio frequency ablation (RFA), have also been shown to safely and effectively treat esophageal dysplasia and early stage neoplasia, with excellent long-term disease control. Both approaches are becoming more widely available around the world, and provide an alternative, safe, low risk strategy for treating early stage disease, making combined endoscopic therapy the recommended treatment of choice for early stage esophageal cancers. PMID:25642334

  18. Treatment of early stage vocal cord carcinoma

    SciTech Connect

    Ayers, G.

    1989-03-01

    The cure rates for early stage vocal cord cancer are excellent with primary radiotherapy. Voice quality remains as good or becomes better than prior to treatment. For the local failures that do occur, surgical salvage will yield ultimate cure rates of about 95% for T1 and 90% for T2 tumors.

  19. Using In-Depth Science Instruction to Accelerate Student Achievement in Science and Reading Comprehension in Grades 1-2

    ERIC Educational Resources Information Center

    Vitale, Michael R.; Romance, Nancy R.

    2012-01-01

    This study focused on accelerating development of science knowledge and understanding at the primary level (grades 1-2) as a means for enhancing reading comprehension (i.e. early literacy). An adaptation of a grade 3-5 cognitive-science-based, instructional model ("Science IDEAS") that integrated science with reading and writing, this year-long…

  20. Suicide in the Early Stage of Schizophrenia.

    PubMed

    Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

    2016-01-01

    Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects with subthreshold psychotic experiences. Factors associated with the risk of suicide in the early phase of schizophrenia are previous suicidal attempts and social aspects: the lack of social support and stable relationships, social drift after the first episode, and social impairment. Also, several psychotic symptoms (suspiciousness, paranoid delusions, mental disintegration and agitation, negative symptoms, depression and hopelessness, and command hallucinations) and substance abuse are associated with higher risk of suicide. It has been described that perfectionism and good levels of insight among individuals who have recently developed psychotic symptoms are significantly associated with higher numbers of suicidal attempts. Moreover, recent evidences show that prefrontal cortex-based circuit dysfunction may be related to suicide in the early stage of schizophrenia. This narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed. PMID:27445872

  1. Suicide in the Early Stage of Schizophrenia

    PubMed Central

    Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

    2016-01-01

    Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects with subthreshold psychotic experiences. Factors associated with the risk of suicide in the early phase of schizophrenia are previous suicidal attempts and social aspects: the lack of social support and stable relationships, social drift after the first episode, and social impairment. Also, several psychotic symptoms (suspiciousness, paranoid delusions, mental disintegration and agitation, negative symptoms, depression and hopelessness, and command hallucinations) and substance abuse are associated with higher risk of suicide. It has been described that perfectionism and good levels of insight among individuals who have recently developed psychotic symptoms are significantly associated with higher numbers of suicidal attempts. Moreover, recent evidences show that prefrontal cortex-based circuit dysfunction may be related to suicide in the early stage of schizophrenia. This narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed. PMID:27445872

  2. Early-Stage Breast Cancer Treatment Fact Sheet

    MedlinePlus

    ... breast cancer treatment fact sheet ePublications Early-stage breast cancer treatment fact sheet Print this fact sheet Early-stage breast cancer treatment fact sheet (PDF, 943 KB) Related information ...

  3. Career Education: Some Essential Learner Outcomes. Primary Grades K, 1, 2, 3.

    ERIC Educational Resources Information Center

    Tennyson, W. Wesley; And Others

    This guide, one of a series for various grade levels, contains Some Essential Learner Outcomes (SELOs) for career education in the primary grades in Minnesota. (The SELOs are selected samples of knowledge statements considered as essential learning outcomes for students in each of the subject areas taught in schools.) These SELOs for the primary…

  4. Whole Language across the Curriculum: Grades 1, 2, 3. Language and Literacy Series.

    ERIC Educational Resources Information Center

    Raines, Shirley C., Ed.

    Applying the whole language perspective across the primary-grade curriculum, this book presents 10 essays that describe first-, second-, and third-grade classrooms where teachers find authentic, meaningful ways for children to communicate about their lives and what they are learning. Essays in the book demonstrate numerous whole language…

  5. Effects of nicotine on a rat model of early stage osteoarthritis

    PubMed Central

    Gu, Qiangrong; Li, Dong; Wei, Bo; Guo, Yang; Yan, Junwei; Mao, Fengyong; Zhang, Xiang; Wang, Liming

    2015-01-01

    The objective of the study was to investigate the effects of nicotine on articular cartilage degeneration and inflammation in a rat model of early stage osteoarthritis (OA), using T2 mapping. In this study, a rat model of early stage OA was established by immobilizing the left knee joints of adult male rats for two weeks. Subsequently, rats were fed with nicotine for two and four weeks. Changes in the articular cartilage from the medial femoral condylar region of the knee were evaluated by gross observation and histological grading with the contents of cartilage matrix detected. T2 values of the articular cartilage were estimated through high-field magnetic resonance imaging (MRI) (7.0T). Levels of serum tumor necrosis factor-α (TNF-α) were assessed by ELISA. The expression of TNF-α and the cholinergic receptor, α7nAChR, in the synovial tissue was measured by RT-PCR. Nicotine treatment ameliorated cartilage destruction, promoted matrix production, reduced the serum level of TNF-α and the expression of TNF-α in the synovial tissue, and increased the expression of α7nAChR in the synovial tissue in the rat model of early stage OA. In conclusion, nicotine prevented cartilage damage and had an anti-inflammatory effect in a rat model of early stage OA. Thus nicotine may have potential as a therapeutic strategy for early stage OA. PMID:26097542

  6. Follow Through in Oklahoma: A Process Curriculum in Early Childhood Education, Grades K, 1, 2, 3.

    ERIC Educational Resources Information Center

    Oklahoma State Dept. of Education, Oklahoma City.

    Follow Through, which builds on the foundation provided by Head Start and similar preschool programs, is a program designed for children in the early primary grades. The Follow Through curriculum presented in this document is based on certain assumptions about children and the learning process, among them the understanding of the importance of…

  7. Total abdominal and pelvic radiotherapy in the management of early stage ovarian carcinoma

    SciTech Connect

    Macbeth, F.R.; Macdonald, H.; Williams, C.J.

    1988-08-01

    In a prospective study, 57 women with early stage ovarian carcinoma received total abdominal and pelvic radiotherapy (TAPR) following radical surgery. The whole abdomen received 22.5 Gy m.p.d. by large opposed fields in 18 fractions over 4 1/2 weeks, with 8 MeV X rays, followed by a further 22.5 Gy in 10 fractions over 2 weeks to the pelvis alone, using a dosage and technique similar to that described from the Princess Margaret Hospital, Toronto. The actuarial 5-year relapse-free and overall survival figures were 49 and 57% respectively, which appear to be significantly worse than those reported from Toronto (73% and 75%). The incidence of severe bowel toxicity (7%) was higher. There was no correlation between survival and FIGO stage at laparotomy, but a significant correlation with histological grade. These data do not seem to support the idea of a curative role for post-operative irradiation at this dosage in these patients.

  8. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    PubMed Central

    Hong, Yu; Long, Jiang; Li, Hai; Chen, Shuhong; Liu, Qiqi; Zhang, Bei; He, Xiaomin; Wang, Yan; Li, Hongyi; Li, Yimei; Zhang, Tao; Lu, Chenzhen; Yan, Hao; Zhang, Minli; Li, Qing; Cao, Bangwei; Bai, Zhigang; Wang, Jin; Zhang, Zhongtao; Zhu, Shengtao; Zheng, Jiasheng; Ou, Xiaojuan; Ma, Hong; Jia, Jidong; You, Hong; Wang, Shengqi; Huang, Jian

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. Findings Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. Interpretation Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID:26137588

  9. ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

    PubMed

    Wahl, Andrew O; Gaffney, David K; Jhingran, Anuja; Yashar, Catheryn M; Biagioli, Matthew; Elshaikh, Mohamed A; Jolly, Shruti; Kidd, Elizabeth; Lee, Larissa J; Li, Linna; Moore, David H; Rao, Gautam G; Williams, Ned L; Small, William

    2016-09-15

    These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer. PMID:27633412

  10. Adjuvant platinum-based chemotherapy for early stage cervical cancer

    PubMed Central

    Rosa, Daniela D; Medeiros, Lídia RF; Edelweiss, Maria I; Pohlmann, Paula R; Stein, Airton T

    2014-01-01

    compared chemotherapy combined with radiotherapy to radiotherapy alone; and one trial compared chemotherapy followed by radiotherapy to radiotherapy alone. It was not possible to perform subgroup analyses by stage or tumour size. Compared with adjuvant radiotherapy, chemotherapy combined with radiotherapy significantly reduced the risk of death (two trials, 297 women; hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.36 to 0.87) and disease progression (two trials, 297 women; HR = 0.47, 95% CI 0.30 to 0.74), with no heterogeneity between trials (I2 = 0% for both meta-analyses). Acute grade 4 toxicity occurred significantly more frequently in the chemotherapy plus radiotherapy group than in the radiotherapy group (risk ratio (RR) 5.66, 95% CI 2.14 to 14.98). We considered this evidence to be of a moderate quality due to small numbers and limited follow-up in the included studies. In addition, it was not possible to separate data for bulky early stage disease. In the one small trial that compared adjuvant chemotherapy followed by radiotherapy with adjuvant radiotherapy alone there was no significant difference in disease recurrence between the groups (HR = 1.34; 95% CI 0.24 to 7.66) and OS was not reported. We considered this evidence to be of a low quality. No trials compared adjuvant platinum-based chemotherapy with no adjuvant chemotherapy after surgery for early cervical cancer with risk factors for recurrence. Authors’ conclusions The addition of platinum-based chemotherapy to adjuvant radiotherapy (chemoradiation) may improve survival in women with early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant chemoradiation is associated with an increased risk of severe acute toxicity, although it is not clear whether this toxicity is significant in the long-term due to a lack of long-term data. This evidence is limited by the small numbers and poor methodological quality of included studies. We await the results of three ongoing trials

  11. Prognostic factors in early-stage ovarian cancer

    PubMed Central

    Tognon, Germana; Carnazza, Mario; Ragnoli, Monica; Calza, Stefano; Ferrari, Federico; Gambino, Angela; Zizioli, Valentina; Notaro, Sara; Sostegni, Benedetta; Sartori, Enrico

    2013-01-01

    The purpose of this study was to identify the main prognostic factors in patients with early-stage epithelial ovarian cancer. Data were extracted from 222 patients with initial stage (I–IIA) invasive epithelial ovarian cancer treated with primary surgery followed or not followed by adjuvant therapy, from 1 January 1980 to 31 December 2008, at the Division of Obstetrics and Gynecology, Spedali Civili, Brescia, Italy; the median follow-up was 79 months (SD ± 35,945, range 20–250 months). The negative prognostic factors that were statistically significant (p<0.050) in univariate analysis were grade 2, 3, and X (clear cell in our study); stage IB, IC, IIA; positive peritoneal cytology, age equal to/greater than 54; dense adhesions; capsule rupture (pre-operative or intra-operative) and endometrioid histotype (only for disease-free survival (DFS)). Positive cytology was strongly associated with peritoneal relapses, while adhesions were associated with pelvic relapses. A positive prognosis was associated with the mucinous histotype. Conservative treatment had been carried out in 52% of patients under 40 years of age, and we detected only two relapses and three completions of surgery after a few weeks among 31 women in total. Our study indicated a possible execution in patients with patients with cancer stage IA G1–G2 (p=0.030) or IC G1 (p=0.050), provided well staged. Adjuvant chemotherapy improved the survival of cancers that were not IA G1. The positive prognostic role of taxanes must be emphasised, when used in combination with platino. PMID:23781280

  12. Long-term outcomes after breast conservation therapy for early stage breast cancer in a community setting.

    PubMed

    McCloskey, Susan A; Botnick, Leslie E; Rose, Christopher M; Malcolm, Arnold W; Ozohan, Mary Lou; Mena, Raul; Llamas, Lupe; Tao, May Lin

    2006-01-01

    We, as a large community practice, retrospectively reviewed our experience in treating early stage breast cancer to determine rates of breast-conserving therapy (BCT), disease outcomes after such treatment, and risk factors for local recurrence. A hospital tumor registry was used to identify breast cancer cases diagnosed between 1987 and 2003. Rates of BCT and radiotherapy were examined using primary treatment data. For subsequent disease outcomes analyses, cases were limited to only those treated between 1987 and 1994 to allow for adequate follow-up. For the subset of 521 T1-2N0 patients treated with BCT, we calculated crude rates of first failure at 8 years, with outcomes classified as local failure (LF), distant or regional node failure (DNF), dead without failure (DWF), or alive without failure (AWF). Polychotomous logistic regression was done to assess the influence of age at diagnosis, tumor grade, total radiation dose to the tumor bed, and use of systemic therapy. From 1987 to 2003, rates of BCT went from 69% to 89% and the rate of radiation after breast-conserving surgery was 90%. For the subset of 521 T1-2N0 patients treated with BCT who had at least 8 years of follow-up, median age was 58 years, 15% had grade 1 tumors, 83% had T1 tumors, 4.6% had positive margins, 83% got a total radiation dose >or=60 Gy to the tumor bed, and 51% had systemic therapy. At 8 years, 7% of patients had LF, 8% DNF, 10% were DWF, and 75% were AWF. Patient age (p = 0.076), tumor grade (p = 0.056), use of systemic therapy (p = 0.077), and radiation dose (p = 0.127) had borderline significant effects on the risk of LF versus AWF. The majority of patients in this community were treated with BCT and most received radiotherapy. Local control was excellent and comparable to that seen in large academic centers.

  13. High-Dose and Extended-Field Intensity Modulated Radiation Therapy for Early-Stage NK/T-Cell Lymphoma of Waldeyer's Ring: Dosimetric Analysis and Clinical Outcome

    SciTech Connect

    Bi, Xi-Wen; Li, Ye-Xiong Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong

    2013-12-01

    Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.

  14. Supportive seminar groups: an intervention for early stage dementia patients.

    PubMed

    Snyder, L; Quayhagen, M P; Shepherd, S; Bower, D

    1995-10-01

    A supportive seminar group was developed and conducted for individuals with early stage dementia and their caregivers. The eight sessions focused on pertinent topics, namely, coping with memory problems, daily living, self-esteem, relationships, health, legal, and financial concerns. Content analysis of the evaluative statements from nine men and six women patients revealed positive themes of feelings of purposefulness, gratification, belongingness, and survival, while other themes reflected the turmoil of the disease, namely, feelings of helplessness, devaluation, and unpredictability. These preliminary findings lend support to the feasibility of a group approach for early stage dementia patients.

  15. Outcomes in Patients With Early-Stage Hypopharyngeal Cancer Treated With Radiotherapy

    SciTech Connect

    Yoshimura, Ryo-ichi; Kagami, Yoshikazu; Ito, Yoshinori; Asai, Masao; Mayahara, Hiroshi; Sumi, Minako; Itami, Jun

    2010-07-15

    Purpose: To analyze the outcome in patients with early-stage hypopharyngeal cancer (HPC) who were treated with radiotherapy (RT). Methods and Materials: Between February 1988 and February 2007, 77 patients with Stage I or Stage II HPC underwent definitive RT in the Division of Radiation Oncology at the National Cancer Center Hospital. Eleven of the patients received local irradiation, and the other 66 patients received elective bilateral neck irradiation and booster irradiation to the primary lesion. The median follow-up period for all the patients was 33 months from the start of RT, ranging from 3 to 229 months. Results: The rates of overall survival, HPC-specific survival, HPC recurrence-free survival, and local control with laryngeal voice preservation for the 77 patients at 5 years were 47%, 74%, 57%, and 70%, respectively. The survival rates were not affected by the patient characteristics or treatment factors, but the RT field was significantly correlated with local control in a multivariate analysis. Seven of the patients had Grade 3 or greater complications, but these complications occurred after salvage surgery in 6 of the patients. Of the 77 patients, 83% had synchronous or metachronous malignancies, but these malignancies did not influence the survival of the patients if the malignancies were detected at an early stage. Conclusion: RT is an appropriate treatment method for early-stage HPC. However, because synchronous or metachronous malignancies occur at a relatively high frequency, careful follow-up and the early detection of such malignancies are critical.

  16. Radiation Plus Chemotherapy in Early-Stage Hodgkin Lymphoma

    Cancer.gov

    Adding radiation therapy to chemotherapy may improve outcomes in patients with early-stage Hodgkin lymphoma, according to a paper published in the Cochrane Database of Systematic Reviews in February 2011, but the long-term effects of this regimen are not

  17. 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.

  18. Early Stages of the Evolution of Life: a Cybernetic Approach

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  19. Ultrastructure of basement membranes in monkey and shark teeth at an early stage of development.

    PubMed

    Sawada, Takashi

    2003-12-01

    The basement membrane, which separates the inner enamel epithelium from the dental papilla in the early stages of tooth development, is known to play a significant role in odontogenesis. In this review article, this basement membrane was described in detail based on our recent findings with the use of high-resolution electron microscopy. Tooth germs of a monkey (Macaca fuscata) and a shark (Cephaloscyllium umbratile) were processed for thin-section observations. During the early stage of development, the basement membrane of the inner enamel (dental) epithelium was composed of a lamina lucida, lamina densa, and much wider lamina fibroreticularis. At higher magnification, the lamina densa in both species was made up of a fine network of cords, which are generally the main constituents of the basement membranes. In the monkey tooth, the lamina fibroreticularis was rich in fibrils, which were now characterized as basotubules, 10-nm-wide microfibril-like structures. The space between the basotubules was filled with a cord network that extended from the lamina densa. Dental papilla cell processes were inserted into the lamina fibroreticularis, and their surface was closely associated with numerous parallel basotubules via 1.5- to 3-nm-wide filaments. In the shark tooth during its early stage of development, the basotubules were absent in the lamina fibroreticularis and only narrow extensions, 60-90 nm wide and 1-2 microm long, of the cord network of the lamina densa were present. The dental papilla cells were immobilized by means of the binding of their processes to the extensions. These results indicate that basement membranes in both monkey and shark teeth at early stage of development are specialized for functions as anchoring and firm binding, which are essential for the successful differentiation of the odontoblasts.

  20. Genome-Based Risk Prediction for Early Stage Breast Cancer

    PubMed Central

    Adaniel, Christina; Jhaveri, Komal; Heguy, Adriana

    2014-01-01

    Tests to better characterize tumor genomic architecture are quickly becoming a standard of care in oncology. For breast cancer, the use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. In the last 5 years, more assays have become available to the practicing oncologist. Given the rapidity with which this field has evolved, it is prudent to review the tests, their indications, and the studies from which they have been validated. We present a comprehensive review of the available gene expression assays for early stage breast cancer. We review data for several individual tests and comparative studies looking at risk prediction and cost-effectiveness. PMID:25187476

  1. Folding of Polymer Chains in Early Stage of Crystallization

    NASA Astrophysics Data System (ADS)

    Yuan, Shichen; Miyoshi, Toshikazu

    Understanding the structural formation of long polymer chains in the early stage of crystallization is one of the long-standing problems in polymer science. Using solid state NMR, we investigated chain trajectory of isotactic polypropylene in the mesomorphic nano-domains formed via rapid and deep quenching. Comparison of experimental and simulated 13C-13C Double Quantum (DQ) buildup curves demonstrated that instead of random re-entry models and solidification models, individual chains in the mesomorphic form iPP adopt adjacent reentry sequences with an average folding number of = 3-4 (assuming an adjacent re-entry fraction of of 100%) during mesomorphic formation process via nucleation and growth in the early stage. This work was financially supported by the National Science Foundation (Grant DMR-1105829 and 1408855) and startup funds from the UA.

  2. Effects of genistein on early-stage cutaneous wound healing

    SciTech Connect

    Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung; Lim, Yunsook; Kim, Jung-Hyun

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  3. Complement Factor H Autoantibodies are Associated with Early Stage NSCLC

    PubMed Central

    Amornsiripanitch, Nita; Hong, Shaolin; Campa, Michael J.; Frank, Michael M.; Gottlin, Elizabeth B.; Patz, Edward F.

    2010-01-01

    Purpose In order to discover diagnostic biomarkers associated with early stage non-small cell lung cancer (NSCLC), we searched for autoantibodies preferentially present in stage I patients compared to patients with advanced stage disease. Here we describe an autoantibody against complement factor H (CFH) and its association with early stage NSCLC. Experimental Design Immunoblots were used to detect autoantibodies in the sera of stage I NSCLC patients. An autoantibody recognizing a 150 kDa protein was discovered and the protein was identified by mass spectrometry. The association of the autoantibody with early stage disease was suggested by the results of immunoblot analysis with sera from 28 stage I patients and 28 stage III/IV patients. This association was confirmed by protein microarray of sera from 125 NSCLC patients of all stages as well as 125 age, gender, and smoking history matched controls. Results The immunoreactive protein was identified as CFH. By immunoblot analysis, anti-CFH autoantibody was found in 50% of stage I NSCLC patients and 11% of late stage NSCLC patients (P=0.003). By protein microarray analysis, patients with stage I NSCLC had a significantly higher incidence of anti-CFH antibody than those with late stage NSCLC (P=0.0051). The percentage of sera with a positive level of CFH autoantibody was 30.4% in stage I, 21.1% in stage II, 12.5% in stage III, 7.4% in stage IV and 8.0% in the control group. Conclusions These findings suggest that in patients with NSCLC, CFH autoantibody is a molecular marker associated with early stage disease. PMID:20515868

  4. Acoustic determination of early stages of intravascular blood coagulation.

    PubMed

    Uzlova, Svetlana G; Guria, Konstantin G; Guria, Georgy Th

    2008-10-13

    The blood coagulation system (BCS) is a complex biological system playing a principal role in the maintenance of haemostasis. Insufficient activity of the BCS may lead to bleeding and blood loss (e.g. in the case of haemophilia). On the other hand, excessive activity may cause intravascular blood coagulation, thromboses and embolization. Most of the methods currently used for BCS monitoring suffer from the major disadvantage of being invasive. The purpose of the present work is to demonstrate the feasibility of using ultrasonic methods for non-invasive registration of the early stages of blood coagulation processes in intensive flows. With this purpose, a special experimental set-up was designed, facilitating the simultaneous detection of optical and acoustic signals during the clotting process. It was shown that (i) as microemboli appear in the flow during the early stage of blood coagulation, the intensity of the Doppler signal increases twofold, and (ii) microemboli formation in the early stages of blood clotting always reveals itself through an acoustic contrast. Both of these effects are well defined, so we hope that they may be used for non-invasive BCS monitoring in clinical practice.

  5. Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health

    PubMed Central

    Ahmed, Usman; Anwar, Attia; Savage, Richard S.; Costa, Matthew L.; Mackay, Nicola; Filer, Andrew; Raza, Karim; Watts, Richard A.; Winyard, Paul G.; Tarr, Joanna; Haigh, Richard C.; Thornalley, Paul J.; Rabbani, Naila

    2015-01-01

    There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti–cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti–CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity. PMID:25788417

  6. Easy as 1, 2, 3: Exploring the Implementation of Standards-Based Grading in Wake County Elementary Schools

    ERIC Educational Resources Information Center

    Paeplow, Colleen Graham

    2011-01-01

    Wake County Public School System's (WCPSS) 102 elementary schools have implemented standards-based grading. This grading practice is aligned with North Carolina's Student Accountability Standards and the WCPSS Promotion/Intervention policy. Standards-based report cards were designed to reflect student mastery of state standards and provide an…

  7. Surgical Treatment of Early-Stage Cervical Cancer.

    PubMed

    Brucker, Sara Y; Ulrich, Uwe A

    2016-01-01

    Surgical treatment of cervical cancer has been a cornerstone in the management of this malignancy for more than 100 years. Today, for early-stage and low-risk cervical cancer, surgery is still considered the gold standard. If the preoperative assessment of the tumor reveals a situation prompting postoperative adjuvant radiochemotherapy, the latter should be planned as the primary treatment option, being preceded by staging laparoscopy including pelvic and paraaortic lymph node dissection. As an alternative to the open approach, the definitive surgical treatment should be either performed laparoscopically, or be laparoscopic-assisted, or laparoscopically robotic-assisted. PMID:27614875

  8. Early stage of superradiance from Bose-Einstein condensates

    SciTech Connect

    Buchmann, L. F.; Lambropoulos, P.; Nikolopoulos, G. M.; Zobay, O.

    2010-08-15

    We investigate the dynamics of matter and optical waves at the early stage of superradiant Rayleigh scattering from Bose-Einstein condensates. Our analysis is within a spatially dependent quantum model which is capable of providing analytic solutions for the operators of interest. The predictions of the present model are compared to the predictions of a closely related mean-field model, and we provide a procedure that allows one to calculate quantum expectation values by averaging over semiclassical solutions. The coherence properties of the outgoing scattered light are also analyzed, and it is shown that the corresponding correlation functions may provide detailed information about the internal dynamics of the system.

  9. Radical Hysterectomy for Early Stage Cervical Cancer: Laparoscopy Versus Laparotomy

    PubMed Central

    McBee, William C.; Richard, Scott D.; Edwards, Robert P.

    2011-01-01

    Objectives: Gynecologic oncologists have recently begun using laparoscopic techniques to treat early stage cervical cancer. We evaluated a single institution's experience of laparoscopic radical hysterectomy and staging compared with laparotomy. Methods: A retrospective chart review identified stage IA2 and IB1 cervical cancer patients who underwent laparoscopic radical hysterectomy and pelvic lymph node dissection from July 2003 to April 2009. A 2:1 cohort of patients treated with laparotomy were matched by stage. Results: Nine laparoscopic patients (3 stage IA2, 6 stage IB1) with 18 matched controls (6 and 12) were identified. Demographics for each group were similar. None had positive margins or lymph nodes. An average of 11.2 vs.13.9 pelvic lymph nodes (P=0.237) were removed. Average operating time was 231.7 vs. 207.2 minutes (P=0.434), and average estimated blood loss was 161.1 vs. 394.4mL (P=0.059). Average length of stay was 2.9 vs. 5.5 days (P=0.012). No transfusions or operative complications were noted in the laparoscopic group vs. 3 each in the open group (P=0.194). No laparoscopic patients and 5 open patients had a postoperative wound infection (P=0.079). No recurrences were noted. Conclusions: Laparoscopic radical hysterectomy is a feasible alternative to laparotomy for early stage cervical cancer. Similar surgical outcomes are achieved with significantly less morbidity. PMID:21902978

  10. Early stages during plasma nitriding of pure iron

    SciTech Connect

    Palacios, M.D.; Martinez, O.; Oseguera, J.

    1995-12-31

    The sequence of nitride formation during the early stages of plasma nitriding of pure iron was studied by optical microscopy, SEM, TEM and x-ray diffraction. Plasma nitriding at {approximately}490 C in a 25 vol.%H{sub 2} + 75 vol.%N{sub 2} mixture starts with the formation of {gamma}{prime}-Fe{sub 4}N after 40s. Once {gamma}{prime} nucleates, it mainly spreads laterally due to diffusion shortcuts in the discontinuous surface nitride layer. Before {gamma}{prime} is continuous on the surface, {epsilon} nucleates on top of it shortly after 40S. Epsilon is then observed to grow, both inwardly and laterally along with {gamma}{prime}. A compact {gamma}{prime}/{epsilon} bilayer forms on the surface at around 100s. The kinetics of nucleation, growth and compactation of the nitrides observed in the present work was significantly more rapid than in any of the nitriding process reported in the literature, including plasma nitriding. The acceleration of the nitriding kinetics in the early stages of plasma nitriding may be attributed to enhanced diffusion resulting from a high nitrogen flux from the plasma atmosphere. The results presented are consistent with the findings of a companion work on modeling the kinetics of nitride layer growth.

  11. An Early-Stage Atherosclerosis Research Model Based on Microfluidics.

    PubMed

    Zheng, Wenfu; Huang, Rong; Jiang, Bo; Zhao, Yuyun; Zhang, Wei; Jiang, Xingyu

    2016-04-01

    The arterial microenvironment plays a vital role in the pathology of atherosclerosis (AS). However, the interplay between the arterial microenvironment and atherogenesis remains unclear, partially due to the gap between cell culture and animal experiments. Addressing this problem, the present study reports a microfluidic AS model reconstituting early-stage AS. Physiological or AS-prone hemodynamic conditions are recapitulated on the model. The on-chip model recaptures the atherogenic responses of endothelial cells (ECs) in ways that the Petri dish could not. Significant cytotoxicity of a clinical anti-atherosclerotic drug probucol is discovered on the model, which does not appear on Petri dish but is supported by previous clinical evidence. Moreover, the anti-AS efficiency of platinum-nanoparticles (Pt-NPs) on the model shows excellent consistency with animal experiments. The early-stage AS model shows an excellent connection between Petri dish and animal experiments and highlights its promising role in bridging fundamental AS research, drug screening, and clinical trials. PMID:26890624

  12. Motor-cortical oscillations in early stages of Parkinson's disease

    PubMed Central

    Pollok, B; Krause, V; Martsch, W; Wach, C; Schnitzler, A; Südmeyer, M

    2012-01-01

    Pathophysiological changes in basal ganglia-thalamo-cortical circuits are well established in idiopathic Parkinson's disease (PD). However, it remains open whether such alterations already occur at early stages representing a characteristic neurophysiological marker of PD. Therefore, the present study aims at elucidating changes of synchronised oscillatory activity in early PD patients. In this study, we performed whole-head magnetoencephalography (MEG) in a resting condition and during steady state contraction of the more severely affected forearm in 10 drug–naive, de novo patients, in 10 early-stage patients with chronic medication and in 10 age-matched control subjects. While cortico-muscular coherence (CMC) did not differ between groups, patients showed increased sensori-motor cortical power at beta frequency (13–30 Hz) during rest as well as during isometric contraction compared to controls. In healthy control subjects the power of the contralateral hemisphere was significantly suppressed during isometric contraction. By contrast, both hemispheres were activated equally strongly in de novo patients. In medicated patients, the pattern was found to be reversed. Contralateral beta power was significantly correlated with motor impairment during isometric contraction but not during rest. The present results suggest that the reduced ability of the primary motor cortex to disengage from increased beta band oscillations during the execution of movements is an early marker of PD. PMID:22547636

  13. Yours Truly: A Closer Look at Our Special Selves. Grades 1-2. Tapestries for Learning Series.

    ERIC Educational Resources Information Center

    McDonald, Heather

    This thematic unit involves 1st and 2nd grade students in exploration of their own unique and special qualities. The interdisciplinary unit connects knowledge related to art, language arts, applied mathematics, social studies, and science. Lesson activities focus on topics of family, friends, health, and emotions. The unit encourages students to…

  14. Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

    SciTech Connect

    Woolston, Caroline M.; Al-Attar, Ahmad; Storr, Sarah J.; Ellis, Ian O.; Morgan, David A.L.; Martin, Stewart G.

    2011-04-01

    Purpose: Early-stage invasive breast cancer patients have commonly undergone breast-conserving surgery and radiotherapy. In a large majority of these patients, the treatment is effective; however, a proportion will develop local recurrence. Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Therefore, the expression of redox proteins was examined in tumor specimens from this defined cohort to determine whether such expression could predict response. Methods and Materials: The nuclear and cytoplasmic expression of nine redox proteins (glutathione, glutathione reductase, glutaredoxin, glutathione peroxidase 1, 3, and 4, and glutathione S-transferase-{theta}, -{pi}, and -{alpha}) was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors. Results: A high cytoplasmic expression of glutathione S-transferase-{theta} significantly correlated with a greater risk of local recurrence (p = .008) and, when combined with a low nuclear expression (p = .009), became an independent predictive factor (p = .002) for local recurrence. High cytoplasmic expression of glutathione S-transferase-{theta} also correlated with a worse overall survival (p = .009). Low nuclear and cytoplasmic expression of glutathione peroxidase 3 (p = .002) correlated with a greater risk of local recurrence and was an independent predictive factor (p = .005). These proteins did not correlate with tumor grade, suggesting their function might be specific to the regulation of oxidative stress rather than alterations of tumor phenotype. Only nuclear (p = .005) and cytoplasmic (p = .001) expression of glutathione peroxidase 4 correlated with the tumor grade. Conclusions: Our results support the use of redox protein expression, namely glutathione S-transferase-{theta} and glutathione peroxidase 3, to predict the response to radiotherapy in early-stage breast cancer patients. If incorporated into

  15. Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy

    PubMed Central

    Kobayashi, Takaaki; Moody, Sandra; Komori, Masafumi; Jibatake, Akira; Yaegashi, Makito

    2015-01-01

    Relapsing polychondritis is a rare inflammation of cartilaginous tissues, the diagnosis of which is usually delayed by a mean period of 2.9 years from symptom onset. We present the case of a 36-year-old man with nasal pain and fever. Physical examination of the nose was grossly unremarkable, but there was significant tenderness of the nasal bridge. Acute sinusitis was initially diagnosed due to thickened left frontal sinus mucosa on computed tomography (CT); however, there was no improvement after antibiotic intake. Repeat CT showed edematous inflammation of the nasal septum; biopsy of this site demonstrated erosion and infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils in the hyaline cartilage. Relapsing polychondritis was confirmed by the modified McAdam's criteria and can be diagnosed at an early stage by nasal septum biopsy; it should be considered as a differential diagnosis in patients presenting with nasal symptoms alone or persistent sinus symptoms. PMID:26843866

  16. Systemic immune system alterations in early stages of Alzheimer's disease.

    PubMed

    Zhang, Rongzhen; Miller, Robert G; Madison, Catherine; Jin, Xia; Honrada, Ronald; Harris, Will; Katz, Jonathan; Forshew, Dallas A; McGrath, Michael S

    2013-03-15

    Immune activation and inflammation play significant roles in the pathogenesis of Alzheimer's disease (AD). To test whether AD patients showed systemic manifestations of inflammation, blood from 41 patients with early stages of AD and 31 aged-match elderly controls were evaluated. Cellular markers for monocyte/macrophage (MO) activation and CD8 T lymphocyte were increased in early AD patients. Expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), was decreased; however, plasma MCP-1 levels were significantly increased and were related to the degree of MO activation in AD. These findings suggest that AD pathogenesis may be influenced by systemic immunologic dysfunction and provides potential immunologic targets for therapeutic intervention.

  17. Discovery of potent wall teichoic acid early stage inhibitors.

    PubMed

    Labroli, Marc A; Caldwell, John P; Yang, Christine; Lee, Sang Ho; Wang, Hao; Koseoglu, Sandra; Mann, Paul; Yang, Shu-Wei; Xiao, Jing; Garlisi, Charles G; Tan, Christopher; Roemer, Terry; Su, Jing

    2016-08-15

    The widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current β-lactam antibiotics and created an urgent need for novel treatment options. Using an S. aureus phenotypic screening strategy, we have identified small molecule early stage wall teichoic acid (WTA) pathway-specific inhibitors predicted to be chemically synergistic with β-lactams. These previously disclosed inhibitors, termed tarocins, demonstrate by genetic and biochemical means inhibition of TarO, the first step in WTA biosynthesis. Tarocins demonstrate potent bactericidal synergy in combination with broad spectrum β-lactam antibiotics across diverse clinical isolates of methicillin-resistant Staphylococci. The synthesis and structure-activity relationships (SAR) of a tarocin series will be detailed. Tarocins and other WTA inhibitors may provide a rational strategy to develop Gram-positive bactericidal β-lactam combination agents active against methicillin-resistant Staphylococci. PMID:27436582

  18. Frontiers in Radiotherapy for Early-Stage Invasive Breast Cancer

    PubMed Central

    Fisher, Christine M.; Rabinovitch, Rachel

    2014-01-01

    The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies. PMID:25113764

  19. SBRT in operable early stage lung cancer patients

    PubMed Central

    Andratschke, Nicolaus; Guckenberger, Matthias

    2014-01-01

    Since decades the gold standard for treatment of early stage non-small cell lung cancer (NSCLC) is surgical lobectomy plus mediastinal lymph node dissection. Patients in worse health status are treated with sublobar resection or radiation treatment. With development of stereotactic-body-radiotherapy (SBRT), outcome of patients treated with radiation was substantially improved. Comparison of SBRT and surgical techniques is difficult due to the lack of randomized trials. However, all available evidence in form of case control studies of population based studies show equivalence between sublobar resection and SBRT indicating that SBRT—when performed by a trained and experienced team—should be offered to all high-risk surgical patients. For patients not willing to take the risk of lobectomy and therefore refusing surgery, SBRT is an excellent treatment option. PMID:25806303

  20. Flame acceleration in the early stages of burning in tubes

    SciTech Connect

    Bychkov, Vitaly; Fru, Gordon; Petchenko, Arkady; Akkerman, V'yacheslav; Eriksson, Lars-Erik

    2007-09-15

    Acceleration of premixed laminar flames in the early stages of burning in long tubes is considered. The acceleration mechanism was suggested earlier by Clanet and Searby [Combust. Flame 105 (1996) 225]. Acceleration happens due to the initial ignition geometry at the tube axis when a flame develops to a finger-shaped front, with surface area growing exponentially in time. Flame surface area grows quite fast but only for a short time. The analytical theory of flame acceleration is developed, which determines the growth rate, the total acceleration time, and the maximal increase of the flame surface area. Direct numerical simulations of the process are performed for the complete set of combustion equations. The simulations results and the theory are in good agreement with the previous experiments. The numerical simulations also demonstrate flame deceleration, which follows acceleration, and the so-called ''tulip flames''. (author)

  1. Point pressure sensitivity in early stage Parkinson's disease.

    PubMed

    Doty, Richard L; Gandhi, Shifa S; Osman, Allen; Hurtig, Howard I; Pawasarat, Ian; Beals, Evan; Chung, Inna; Dubroff, Jacob; Newberg, Andrew; Ying, Gui-Shang; Leon-Sarmiento, Fidias E

    2015-01-01

    A number of sensory changes occur in the earliest stages of Parkinson's disease (PD), some of which precede the expression of the classic motor phenotype by years (e.g., olfactory dysfunction). Whether point pressure sensitivity (PPS), a cutaneous measure of light touch mediated by myelinated Aβ fibers, is altered in early PD is not clear. Prior studies on this point are contradictory and are based on non-forced-choice threshold tests that confound the sensitivity measure with the response criterion. While α-synuclein pathology, a defining feature of PD, is present in the skin of PD patients, it is restricted to unmyelinated nerve fibers, suggesting PPS may be spared in this disease. We determined PPS thresholds using a state-of-the-art forced-choice staircase threshold test paradigm in 29 early stage PD patients and 29 matched controls at 11 body sites: the center of the forehead and the left and right forearms, index fingers, palms, medial soles of the feet, and plantar halluces. The patients were tested, in counterbalanced sessions, both on and off dopamine-related medications (DRMs). PPS was not influenced by PD and did not correlate with DRM l-DOPA equivalents, scores on the Unified Parkinson's Disease Rating Scale, side of the major motor disturbances, or SPECT imaging of the striatal dopamine transporter, as measured by technetium-99m TRODAT. However, PPS thresholds were lower on the left than on the right side of the body (p=0.008) and on the upper extremities relative to the toes and feet (ps<0.0001). Positive correlations were evident among the thresholds obtained across all body sectors, even though disparate regions of the body differed in terms of absolute sensitivity. This study indicates that PPS is not influenced in early stage PD regardless of whether patients are on or off DRMs. PMID:25447476

  2. Graded Ca2+/calmodulin-dependent coupling of voltage-gated CaV1.2 channels

    PubMed Central

    Dixon, Rose E; Moreno, Claudia M; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Navedo, Manuel F; Santana, Luis F

    2015-01-01

    In the heart, reliable activation of Ca2+ release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1.2 channels. Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear. Here, we demonstrate that CaV1.2 channels form clusters that undergo dynamic, reciprocal, allosteric interactions. This ‘functional coupling’ facilitates Ca2+ influx by increasing activation of adjoined channels and occurs through C-terminal-to-C-terminal interactions. These interactions are initiated by binding of incoming Ca2+ to calmodulin (CaM) and proceed through Ca2+/CaM binding to the CaV1.2 pre-IQ domain. Coupling fades as [Ca2+]i decreases, but persists longer than the current that evoked it, providing evidence for ‘molecular memory’. Our findings suggest a model for CaV1.2 channel gating and Ca2+-influx amplification that unifies diverse observations about Ca2+ signaling in the heart, and challenges the long-held view that voltage-gated channels open and close independently. DOI: http://dx.doi.org/10.7554/eLife.05608.001 PMID:25714924

  3. Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

    PubMed

    Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

    2012-09-20

    Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood.

  4. Metamorphic density controls on early-stage subduction dynamics

    NASA Astrophysics Data System (ADS)

    Duesterhoeft, Erik; Oberhänsli, Roland; Bousquet, Romain

    2013-04-01

    contribution to the slab pull, where eclogitization does not occur. Thus, the lithospheric mantle acts as additional ballast below the sinking slab shortly after the initiation of subduction. Our calculation shows that the dogma of eclogitized basaltic, oceanic crust as the driving force of slab pull is overestimated during the early stage of subduction. These results improve our understanding of the force budget for slab pull during the intial and early stage of subduction. Therefore, the complex metamorphic structure of a slab and mantle wedge has an important impact on the development and dynamics of subduction zones. Further Reading: Duesterhoeft, Oberhänsli & Bousquet (2013), submitted to Earth and Planetary Science Letters

  5. Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

    PubMed Central

    Tan, Daryl; Horning, Sandra J.; Hoppe, Richard T.; Levy, Ronald; Rosenberg, Saul A.; Sigal, Bronislava M.; Warnke, Roger A.; Natkunam, Yasodha; Han, Summer S.; Yuen, Alan; Plevritis, Sylvia K.

    2013-01-01

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1 to 2 FL treated at Stanford University from 1960-2003 were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n = 180); era 2, anthracycline (1976-1986, n = 426); era 3, aggressive chemotherapy/purine analogs (1987-1996, n = 471); and era 4, rituximab (1997-2003, n = 257). Clinical characteristics, patterns of care, and survival were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at the time of diagnosis. The median OS was 13.6 years. Age, gender, and stage did not differ across the eras. Although primary treatment varied, event-free survival after the first treatment did not differ between eras (P = .17). Median OS improved from 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (P < .001), with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement. PMID:23777769

  6. High-throughput quantification of early stages of phagocytosis.

    PubMed

    Yeo, Jeremy Changyu; Wall, Adam Alexander; Stow, Jennifer Lea; Hamilton, Nicholas Ahti

    2013-09-01

    Phagocytosis--the engulfment of cells and foreign bodies--is an important cellular process in innate immunity, development, and disease. Quantification of various stages of phagocytosis, especially in a rapid screening fashion, is an invaluable tool for elucidating protein function during this process. However, current methods for assessing phagocytosis are largely limited to flow cytometry and manual image-based assays, providing limited information. Here, we present an image-based, semi-automated phagocytosis assay to rapidly quantitate three distinct stages during the early engulfment of opsonized beads. Captured images are analyzed using the image-processing software ImageJ and quantified using a macro. Modifications to this method allowed quantification of phagocytosis only in fluorescently labeled transfected cells. Additionally, the time course of bead internalization could be measured using this approach. The assay could discriminate perturbations to stages of phagocytosis induced by known pharmacological inhibitors of filamentous actin and phosphoinositol-3-kinase. Our methodology offers the ability to automatically categorize large amounts of image data into the three early stages of phagocytosis within minutes, clearly demonstrating its potential value in investigating aberrant phagocytosis when manipulating proteins of interest in drug screens and disease.

  7. Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats.

    PubMed

    Jo, Woori; Yu, Eun-Sil; Chang, Minsun; Park, Hyun-Kyu; Choi, Hyun-Ji; Ryu, Jae-Eun; Jang, Sungwoong; Lee, Hyo-Ju; Jang, Ja-June; Son, Woo-Chan

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma‑specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S‑transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK‑dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high‑risk patients, including chronic hepatitis and cirrhosis.

  8. Multiscale Investigations of the Early Stage Oxidation on Cu Surfaces

    NASA Astrophysics Data System (ADS)

    Zhu, Qing; Xiao, Penghao; Lian, Xin; Yang, Shen-Che; Henkelman, Grame; Saidi, Wissam; Yang, Judith; University of Pittsburgh Team; University of Texas at Austin Team

    Previous in situ TEM experiments have shown that the oxidation of the three low index Cu surfaces (100), (110) and (111) exhibit different oxide nucleation rates, and the resulting oxides have 3-dimensional (3D) island shapes or 2D rafts under different conditions. In order to better understand these results, we have investigated the early stages of Cu oxidation using a multiscale computational approach that employs density functional theory (DFT), reactive force field (ReaxFF), and kinetic Mote Carlo (KMC). With DFT calculation, we have compared O2 dissociation barriers on Cu (100), (110) and (111) surfaces at high oxygen coverage to evaluate the kinetic barrier of sublayer oxidization. We found that O2 dissociation barriers on Cu(111) surface are all lower than those on (110) and (100) surfaces. This trend agrees with experimental observations that (111) surface is easier to oxidize. These DFT calculated energy barriers are then incorporated into KMC simulations. The large scale ReaxFF molecular dynamics and KMC simulations detail the oxidation dynamics of the different Cu surfaces, and show the formation of various oxide morphologies that are consistent with experimental observations.

  9. Affective Motives for Smoking Among Early Stage Smokers

    PubMed Central

    Wahlquist, Amy E.; Garrett-Mayer, Elizabeth; Gray, Kevin M.; Saladin, Michael E.; Carpenter, Matthew J.

    2014-01-01

    Background: As most smokers initiate smoking during adolescence, assessment of smoking motives that underlie trajectories of dependence is critical for both prevention and cessation efforts. In the current study, we expected participants with higher nicotine dependence would smoke (a) less for positive reinforcement (PR) and (b) more for negative reinforcement (NR) motives. We secondarily assessed the relative contribution of PR to NR motives across levels of dependence. Methods: Data were drawn from a study on cue-elicited craving among occasional versus daily adolescent smokers aged 16–20 years (N = 111). Smoking motives were assessed in relation to 3 commonly used measures of nicotine dependence: (a) Fagerström Test for Nicotine Dependence (FTND), (b) Autonomy over Smoking Scale (AUTOS), and (c) Nicotine Dependence Syndrome Scale (NDSS). Results: Compared to occasional smokers, daily smokers had significantly higher scores on each dependence measure and endorsed more prominent NR smoking motives. Each measure of nicotine dependence was strongly associated with NR motives for smoking, although measures differed in their association with PR motives. As expected, the FTND, AUTOS, and NDSS each significantly predicted smoking motive difference score (PR − NR), such that higher dependence was associated with more prominent NR motives for smoking. Conclusions: Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. PMID:24924155

  10. Metformin inhibits early stage diethylnitrosamine-induced hepatocarcinogenesis in rats

    PubMed Central

    JO, WOORI; YU, EUN-SIL; CHANG, MINSUN; PARK, HYUN-KYU; CHOI, HYUN-JI; RYU, JAE-EUN; JANG, SUNGWOONG; LEE, HYO-JU; JANG, JA-JUNE; SON, WOO-CHAN

    2016-01-01

    Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)-induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma-specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S-transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK-dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high-risk patients, including chronic hepatitis and cirrhosis. PMID:26548419

  11. Blood biomarkers in the early stage of cerebral ischemia.

    PubMed

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  12. The relationship between local recurrence and death in early-stage breast cancer.

    PubMed

    Sopik, Victoria; Nofech-Mozes, Sharon; Sun, Ping; Narod, Steven A

    2016-01-01

    To examine the relationship between local recurrence and breast cancer mortality in women with early-stage breast cancer. We studied 1675 women with stage 0 (DCIS), stage I or stage II breast cancer who were treated with breast-conserving surgery at Women's College Hospital between 1987 and 2009. For each patient, we obtained information on age at diagnosis, tumour size, lymph node status, tumour grade, lymphovascular invasion, oestrogen receptor status, progesterone receptor status, HER2 status and treatments received (radiotherapy, chemotherapy and tamoxifen). Patients were followed from the date of diagnosis until local recurrence, death from breast cancer or the date of last follow-up. We used the Kaplan-Meier method to estimate 15-year local recurrence-free and breast cancer-specific survival rates for each stage at diagnosis. For each stage, the two rates were compared. After a mean follow-up of 13.1 years, 243 women (14.5 %) experienced a local recurrence and 281 women (16.8 %) died of breast cancer. The 15-year actuarial rate of local recurrence was 16 % for women with DCIS, 15 % for women with stage I cancer and 16 % for women with stage II cancer. The 15-year breast cancer-specific mortality rate was 3 % for women with DCIS, 10 % for women with stage I breast cancer and 30 % for women with stage II breast cancer. After experiencing a local recurrence, the 15-year breast cancer mortality rate was 16 % for women with DCIS, 32 % for women with stage I breast cancer and 59 % for women with stage II breast cancer. Across the spectrum of the early stages of breast cancer, the risk of local recurrence does not correlate with the risk of death from breast cancer. After local recurrence, the risk of death from breast cancer depends on the initial stage at diagnosis.

  13. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  14. Is Ovarian Preservation Feasible in Early-Stage Adenocarcinoma of the Cervix?

    PubMed Central

    Lu, Huaiwu; Li, Jing; Wang, Lijuan; Zhou, Hui; Liu, Yunyun; Wang, Dongyan; Lin, Zhongqiu

    2016-01-01

    Background In cervical adenocarcinoma, surgical treatment involves bilateral oophorectomy, which affects the long-term quality of life. The aim of our study was to access the incidence of ovarian metastasis in early-stage cervical adenocarcinoma and to suggest an algorithm for the triage of these patients to preserve the ovaries. Material/Methods A total 101 patients with cervical adenocarcinoma who had undergone radical hysterectomy with pelvic lymphadenectomy and bilateral oophorectomy were included in this study. Data on the clinicopathologic characteristics of the cases were collected and low risk factors for ovarian metastasis in early-stage cervical adenocarcinoma were analyzed. Results The ovary metastasis rate of cervical adenocarcinoma in this study was 4.95%, while it is only 2% in stage IB1. Pathological grade, LSVI, lymph node status, tumor size, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis, while LSVI, lymph node status, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis in stage IB. Multivariate analysis revealed that LVSI and lymph node metastasis were independent risk factors for ovarian metastasis in all stages of cervical adenocarcinoma, but involvement of the junction of the cervix and the body of the uterus was an independent risk factor for ovarian metastasis in stage IB. Conclusions The incidence of ovarian metastasis in cervical adenocarcinoma is low. Our study suggests that ovarian preservation is safe and feasible in patients with no risk factors for ovarian metastasis. Further prospective studies are warranted. PMID:26852916

  15. The role of norepinephrine and insulin resistance in an early stage of hypertension.

    PubMed

    Penesova, Adela; Radikova, Zofia; Cizmarova, Eva; Kvetnanský, Richard; Blazicek, Pavel; Vlcek, Miroslav; Koska, Juraj; Vigas, Milan

    2008-12-01

    The interrelationship between activity of sympathetic nervous system and metabolic risk factors in youth with hypertension (HT) has been poorly studied. The aim of our present study was to assess the interrelationship between metabolic risk factors, such as insulin resistance, concentration of plasminogen activator inhibitor (PAI)-1, and catecholamines in an early stage of HT onset. An oral glucose tolerance test was performed in 17 young males with early-diagnosed nontreated HT grade 1 and 16 gender-, age-, and BMI-matched normotensive controls. Concentrations of glucose, insulin, epinephrine, norepinephrine, PAI-1, and plasma renin activity (PRA) were determined in venous plasma. Insulin sensitivity indices (ISIs) proposed by Cederholm, Matsuda, and Gutt were calculated. HT had higher baseline levels of norepinephrine, insulin (P= 0.02), and PAI-1 (P= 0.04). ISIs were lower in HT subjects (P < 0.001). Baseline concentrations of epinephrine were negatively associated with HDL cholesterol (r=-0.415, P= 0.02), ISI Matsuda (r=-0.361, P= 0.04), ISI Cederholm (r=-0.354, P= 0.04), and ISI Gutt (r=-0.429, P= 0.01), and positively with PRA (r= 0.609, P < 0.0001). Positive association was found between baseline concentrations of norepinephrine and PAI-1 (r= 0.418, P= 0.02). The sympathetic overactivity, which occurs in the early stage of HT may contribute to reduced insulin sensitivity even in young patients and intensify the undesirable development of metabolic cardiovascular risk factors and progress of the disease. PMID:19120146

  16. Involved Node Radiation Therapy: An Effective Alternative in Early-Stage Hodgkin Lymphoma

    SciTech Connect

    Maraldo, Maja V.; Aznar, Marianne C.; Vogelius, Ivan R.; Petersen, Peter M.; Specht, Lena

    2013-03-15

    Purpose: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy in a cohort of 97 clinical stage I-II HL patients. Methods and Materials: Patients were staged with positron emission tomography/computed tomography scans, treated with adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy, and given INRT (prechemotherapy involved nodes to 30 Gy, residual masses to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. Results: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7 malignancies were diagnosed, and 5 patients developed heart disease. Conclusions: INRT offers excellent tumor control and represents an effective alternative to more extended radiation therapy in the combined modality treatment for early-stage HL.

  17. AJAP1 is Dysregulated at an Early Stage of Gliomagenesis and Suppresses Invasion Through Cytoskeleton Reorganization

    PubMed Central

    Han, Lei; Zhang, Kai-Liang; Zhang, Jun-Xia; Zeng, Liang; Di, Chun-Hui; Fee, Brian E.; Rivas, Miriam; Bao, Zhao-Shi; Jiang, Tao; Bigner, Darrell; Kang, Chun-Sheng; Adamson, David Cory

    2015-01-01

    SUMMARY Aims Down-regulation of AJAP1 in glioblastoma multiforme (GBM) has been reported. However, the expression profiles of AJAP1 in gliomas and the underlying mechanisms of AJAP1 function on invasion are still poorly understood. Methods The gene profiles of AJAP1 in glioma patients were studied among four independent cohorts. Confocal imaging was used to analyze the AJAP1 localization. After AJAP1 overexpression in GBM cell lines, cellular polarity, cytoskeleton distribution, and antitumor effect were investigated in vitro and in vivo. Results AJAP1 expression was significantly decreased in gliomas compared with normal brain in REMBRANDT and CGCA cohorts. Additionally, low AJAP1 expression was associated with worse survival in GBMs in REMBRANDT and TCGA U133A cohorts and was significantly associated with classical and mesenchymal subtypes of GBMs among four cohorts. Confocal imaging indicated AJAP1 localized in cell membranes in low-grade gliomas and AJAP1-overexpressing GBM cells, but difficult to assess in high-grade gliomas due to its absence. AJAP1 overexpression altered the cytoskeleton and cellular polarity in vitro and inhibited the tumor growth in vivo. Conclusions AJAP1 is dysregulated at an early stage of gliomagenesis and may suppress glioma cell invasion and proliferation, which suggests that AJAP1 may be a potential diagnostic and prognostic marker for gliomas. PMID:24483339

  18. Locomotor function in the early stage of Parkinson's disease.

    PubMed

    Carpinella, Ilaria; Crenna, Paolo; Calabrese, Elena; Rabuffetti, Marco; Mazzoleni, Paolo; Nemni, Raffaello; Ferrarin, Maurizio

    2007-12-01

    The cardinal motor symptoms of Parkinson's disease (PD) have been widely investigated with particular reference to abnormalities of steady-state walking. The great majority of studies, however are related to severe forms of PD patients (phases > = 3 of Hoehn and Yahr scale), where locomotor abnormalities are clearly manifested. Goal of the present study was to quantitatively describe locomotor symptoms in subjects with mild PD. Accordingly, a multitask protocol involving instrumental analysis of steady-state linear walking, initiation of gait, and turning while walking was applied to a group of patients with idiopathic PD in their early clinical stage (phases 1 and 2 of Hoehn and Yahr scale), as well as in age-matched elderly controls. Kinematic, kinetic, and myoelectric measures were obtained by optoelectronic motion analysis, force platform, and telemetric electromyography. Results in PD patients showed a tendency to bradykinetic gait, with reduction of walking speed and cadence. Impairments of gait initiation consisted in reduction of the backward shift of the center of pressure (CoP) and prolongation of the stepping phase. Alterations of the turning task were more consistent and included delayed reorientation of the head toward the new direction, altered head-upper trunk rotational strategy, and adoption of a greater number of steps to complete the turning. It is concluded that patients in the early stage of PD reveal mild alterations of steady-state linear walking and more significant anomalies in the transitional conditions, especially during changes in the travel direction. Quantitative analysis of nonstationary locomotor tasks might be a potentially useful starting point for further studies on the pathophysiology of PD.

  19. Native language change during early stages of second language learning.

    PubMed

    Bice, Kinsey; Kroll, Judith F

    2015-11-11

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill.

  20. Native language change during early stages of second language learning.

    PubMed

    Bice, Kinsey; Kroll, Judith F

    2015-11-11

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill. PMID:26351964

  1. Protein dynamics modulated electron transfer kinetics in early stage photosynthesis

    NASA Astrophysics Data System (ADS)

    Kundu, Prasanta; Dua, Arti

    2013-01-01

    A recent experiment has probed the electron transfer kinetics in the early stage of photosynthesis in Rhodobacter sphaeroides for the reaction center of wild type and different mutants [Science 316, 747 (2007)]. By monitoring the changes in the transient absorption of the donor-acceptor pair at 280 and 930 nm, both of which show non-exponential temporal decay, the experiment has provided a strong evidence that the initial electron transfer kinetics is modulated by the dynamics of protein backbone. In this work, we present a model where the electron transfer kinetics of the donor-acceptor pair is described along the reaction coordinate associated with the distance fluctuations in a protein backbone. The stochastic evolution of the reaction coordinate is described in terms of a non-Markovian generalized Langevin equation with a memory kernel and Gaussian colored noise, both of which are completely described in terms of the microscopics of the protein normal modes. This model provides excellent fits to the transient absorption signals at 280 and 930 nm associated with protein distance fluctuations and protein dynamics modulated electron transfer reaction, respectively. In contrast to previous models, the present work explains the microscopic origins of the non-exponential decay of the transient absorption curve at 280 nm in terms of multiple time scales of relaxation of the protein normal modes. Dynamic disorder in the reaction pathway due to protein conformational fluctuations which occur on time scales slower than or comparable to the electron transfer kinetics explains the microscopic origin of the non-exponential nature of the transient absorption decay at 930 nm. The theoretical estimates for the relative driving force for five different mutants are in close agreement with the experimental estimates obtained using electrochemical measurements.

  2. Alteration of Brain Functional Networks in Early-Stage Parkinson’s Disease: A Resting-State fMRI Study

    PubMed Central

    Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Wang, Jian; Qiu, Mingguo

    2015-01-01

    Although alterations of topological organization have previously been reported in the brain functional network of Parkinson’s disease (PD) patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2) and 30 age-matched normal controls were scanned using resting-state functional MRI. Subsequently, graph theoretical analysis was employed to investigate the abnormal topological configuration of the brain network in early-stage PD patients. We found that both the PD patient and control groups showed small-world properties in their functional brain networks. However, compared with the controls, the early-stage PD patients exhibited abnormal global properties, characterized by lower global efficiency. Moreover, the modular structure and the hub distribution were markedly altered in early-stage PD patients. Furthermore, PD patients exhibited increased nodal centrality, primarily in the bilateral pallidum, the inferior parietal lobule, and the medial superior frontal gyrus, and decreased nodal centrality in the caudate nucleus, the supplementary motor areas, the precentral gyrus, and the middle frontal gyrus. There were significant negative correlations between the Unified Parkinson Disease Rating Scale motor scores and nodal centralities of superior parietal gyrus. These results suggest that the topological organization of the brain functional network was altered in early-stage PD patients who received antiparkinson treatment, and we speculated that the antiparkinson treatment may affect the efficiency of the brain network to effectively relieve clinical symptoms of PD. PMID:26517128

  3. Tangential Radiotherapy Without Axillary Surgery in Early-Stage Breast Cancer: Results of a Prospective Trial

    SciTech Connect

    Wong, Julia S.; Winer, Eric P.

    2008-11-01

    Purpose: To determine the risk of regional-nodal recurrence in patients with early-stage, invasive breast cancer, with clinically negative axillary nodes, who were treated with breast-conserving surgery, 'high tangential' breast radiotherapy, and hormonal therapy, without axillary surgery or the use of a separate nodal radiation field. Methods and Materials: Between September 1998 and November 2003, 74 patients who were {>=}55 years of age with Stage I-II clinically node-negative, hormone-receptor-positive breast cancer underwent tumor excision to negative margins without axillary surgery as a part of a multi-institutional prospective study. Postoperatively, all underwent high-tangential, whole-breast radiotherapy with a boost to the tumor bed, followed by 5 years of hormonal therapy. Results: For the 74 patients enrolled, the median age was 74.5 years, and the median pathologic tumor size was 1.2 cm. Lymphatic vessel invasion was present in 5 patients (7%). At a median follow-up of 52 months, no regional-nodal failures or ipsilateral breast recurrences had been identified (95% confidence interval, 0-4%). Eight patients died, one of metastatic disease and seven of other causes. Conclusion: In this select group of mainly older patients with early-stage hormone-responsive breast cancer and clinically negative axillary nodes, treatment with high-tangential breast radiotherapy and hormonal therapy, without axillary surgery, yielded a low regional recurrence rate. Such patients might be spared more extensive axillary treatment (axillary surgery, including sentinel node biopsy, or a separate nodal radiation field), with its associated time, expense, and morbidity.

  4. Active compressive intraoceanic deformation: early stages of ophiolites emplacement?

    NASA Astrophysics Data System (ADS)

    Chamot-Rooke, Nicolas; Delescluse, Matthias; Montési, Laurent

    2010-05-01

    investigate the very early stages of formation of faulted oceanic bodies that may further be incorporated into mountain belts as ophiolites. They allow to discuss rates and duration of deformation, diffuse vs localized deformation, re-activation vs neo-formed faults, serpentinization and thermal regime, spacing of minor and major thrust faults. Delescluse, M., L. G. J. Montesi, and N. Chamot-Rooke (2008) Fault reactivation and selective abandonment in the oceanic lithosphere. Geophys. Res. Lett., v. 35. Delescluse, M., and N. Chamot-Rooke (2008) Serpentinization pulse in the actively deforming Central Indian Basin. Earth Planet. Sci. Lett., v. 276, p. 140-151. Eittreim, S. L., and J. Ewing (1972), Mid-Plate Tectonics in the Indian Ocean, J. Geophys. Res., 77(32), 6413-6421.

  5. 77 FR 74908 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-18

    ... . Read only examples of these forms may be found at www.sba.gov/content/application-forms . III. Early... will allocate available leverage across all FY 2013 Early Stage SBICs on a pro rata basis. Early Stage....gov/content/earlystage-model-partnership-agreement . Applicants must use the Model LPA as a...

  6. Degradation phase of apoptosis during the early stages of human metanephros development.

    PubMed

    Wagner, Filip; Erdösová, Bela; Kylarová, Dana

    2004-12-01

    Apoptosis as a vital process is necessary for human intrauterine development. Not only the induction and course of apoptosis, but engulfment of the apoptotic cells (bodies) were the centre of our interest. Macrophages were detected in the early stages of human intrauterine development and the role of macrophages in the clearance of apoptotic cells in the early stages of human metanephros development was confirmed.

  7. NGS-based BRCA1/2 mutation testing of high-grade serous ovarian cancer tissue: results and conclusions of the first international round robin trial.

    PubMed

    Endris, Volker; Stenzinger, Albrecht; Pfarr, Nicole; Penzel, Roland; Möbs, Markus; Lenze, Dido; Darb-Esfahani, Silvia; Hummel, Michael; Sabine-Merkelbach-Bruse; Jung, Andreas; Lehmann, Ulrich; Kreipe, Hans; Kirchner, Thomas; Büttner, Reinhard; Jochum, Wolfram; Höfler, Gerald; Dietel, Manfred; Weichert, Wilko; Schirmacher, Peter

    2016-06-01

    With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advances in routine tumor test methodologies due to the large size of both genes and the lack of mutational hot spots. Classical focused screening approaches, like Sanger sequencing, do not allow for a sensitive, rapid, and economic analysis of tumor tissue. Next-generation sequencing (NGS) approaches employing targeted panels for BRCA1/2 to interrogate formalin-fixed and paraffin-embedded tumor samples from either surgical resection or biopsy specimens can overcome these limitations. Although focused NGS methods have been implemented by few centers in routine molecular diagnostics for the analysis of some druggable oncogenic mutations, the reliable diagnostic testing of the entire coding regions of BRCA1 and BRCA2 was a new challenge requiring extensive technological improvement and quality management. Here, we describe the implementation and results of the first round robin trial for BRCA1/2 mutation testing in tumor tissue that was conducted in central Europe on May 2015, shortly after the approval and prior to the official release of olaparib. The high success rate of 81 % (21/26 test centers) demonstrates that BRCA1/2 multicenter mutation testing is well feasible in FFPE tumor tissue, extending to other tumor entities beyond ovarian cancer. The high number of test centers passing the trial demonstrates the success of the concerted efforts by German, Swiss, and Austrian pathology centers to ensure quality-controlled NGS-based testing and proves the potential of this technology in routine molecular pathology. On the basis of our results, we provide recommendations for predictive testing of tumor tissue for BRCA1/2 to clinical decision making in ovarian cancer patients.

  8. [Cytological finding in the pre- and early stages of cervix carcinoma--a contribution to the evaluation of Papanicolau III].

    PubMed

    Bader, G; Büttner, H H; Neumann, H G; Rhode, E; Beust, M

    1977-01-01

    Cytologic findings and the histologic diagnosis are compared in 326 cervical cones. We have found following ratio of the groups Papanicolaou (Pap) III: Pap IV--in dysplasia 1: 1: 1, in "more dysplasia than carcinoma in situ (CIS)" 1:2:2. The Pap IV dominates in "pure" CIS and in cones with "more CIS than dysplasia". We take out of the Pap III ("with cytologic control") cases named "Pap III with necessity for histologic diagnosis". We have found in this subgroup of Pap III prestages or early stages of cervical carcinoma.

  9. [Rehabilitation method for churg-strauss syndrome from early stage: considering functional prognosis of mononeuritis multiplex].

    PubMed

    Hashida, Goichi; Kan, Akiko; Inoue, Satoru; Abe, Kazuo

    2006-05-01

    We report our rehabilitation experience for two patients with Churg-Strauss syndrome (CSS). To improve their functional prognoses, we started rehabilitation program compensating for their activity of daily livings from their early stage. Also, we paid special attention to prescribed drug effect and adverse effect. Since patients with the mononeuritis multiplex have restricted weakness in the muscles ruled by a specific nerve, rehabilitation approaches including orthoses should start to improve the compensatory ability of normal adjacent muscles even in their early stages. In addition, since functional improvement may be gradual and take some years from onset, we should start rehabilitation in their early stage to improve their functional prognoses.

  10. Radiotherapy Alone for Early-Stage Squamous Cell Carcinoma of the Larynx and Hypopharynx

    SciTech Connect

    Foote, Robert L.

    2007-10-01

    Purpose: To describe and illustrate examples of early-stage larynx and hypopharynx cancer that can be successfully treated with radiotherapy alone. Methods and Materials: Review of the NCCN and ASCO practice guidelines. Representative examples are included. Results: Early-stage larynx and hypopharynx cancer is defined by tumor extent based on physical and imaging examination. Conclusions: Radiotherapy alone is appropriate treatment for properly selected early-stage squamous cell carcinoma of the larynx and hypopharynx. The NCCN and ASCO practice guidelines can be an aid to the clinician in identifying favorable cancers that can be successfully treated with radiotherapy alone with preservation of organ function.

  11. EARLY-STAGE MASSIVE STAR FORMATION NEAR THE GALACTIC CENTER: Sgr C

    SciTech Connect

    Kendrew, S.; Johnston, K.; Beuther, H.; Ginsburg, A.; Bally, J.; Battersby, C.; Cyganowski, C. J.

    2013-10-01

    We present near-infrared spectroscopy and 1 mm line and continuum observations of a recently identified site of high mass star formation likely to be located in the Central Molecular Zone (CMZ) near Sgr C. Located on the outskirts of the massive evolved H II region associated with Sgr C, the area is characterized by an Extended Green Object (EGO) measuring ∼10'' in size (0.4 pc), whose observational characteristics suggest the presence of an embedded massive protostar driving an outflow. Our data confirm that early-stage star formation is taking place on the periphery of the Sgr C H II region, with detections of two protostellar cores and several knots of H{sub 2} and Brackett γ emission alongside a previously detected compact radio source. We calculate the cores' joint mass to be ∼10{sup 3} M {sub ☉}, with column densities of 1-2 × 10{sup 24} cm{sup –2}. We show the host molecular cloud to hold ∼10{sup 5} M {sub ☉} of gas and dust with temperatures and column densities favorable for massive star formation to occur, however, there is no evidence of star formation outside of the EGO, indicating that the cloud is predominantly quiescent. Given its mass, density, and temperature, the cloud is comparable to other remarkable non-star-forming clouds such as G0.253 in the eastern CMZ.

  12. Dynamic drying in the early-stage coalescence of droplets sitting on a plate

    NASA Astrophysics Data System (ADS)

    Narhe, R. D.; Beysens, D. A.; Pomeau, Y.

    2008-02-01

    The early-stage coalescence of two sessile drops is investigated theoretically and experimentally. The coalescence of small sessile drops of diethylene glycol on silicon wafer is induced either by condensation or syringe deposition. The bridge geometry in directions parallel and perpendicular to the substrate, the bridge contact angle and the direct fluid velocity are simultaneously analyzed. The process is characterized by the nucleation and growth of a bridge between the two drops. Three stages are identified. i) An initial stage of dynamic drying where the capillary number Ca>0.02 and the contact line does not move appreciably. The bridge does not wet the solid and its size grows as time t perpendicularly to the substrate and as t1/2 parallel to the substrate. ii) A late stage where the contact line starts to move and where the bridge relaxes exponentially, making eventually the composite drop to be ellipsis like. This stage is followed by iii) a very slow evolution limited by the contact line motion where the drop relaxes to a circular shape with a dynamics that is 6 to 7 orders larger than bulk hydrodynamics predicts.

  13. Hepatoma-derived growth factor upregulation is correlated with prognostic factors of early-stage cervical adenocarcinoma.

    PubMed

    Tsai, Ching-Chou; Huang, Shun-Chen; Tai, Ming Hong; Chien, Chan-Chao Chang; Huang, Chao-Cheng; Hsu, Yi-Chiang

    2014-11-21

    Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor that plays an important role in the progression of different types of cancer. A total of 63 patients with early-stage cervical adenocarcinoma (Cx) were enrolled in this retrospective study. The expression of HDGF was significantly increased compared with adjacent non-tumor tissue samples (p < 0.001). Moreover, elevated nuclear HDGF levels were correlated with lymph-vascular space invasion (LVSI; p < 0.05), lymph node metastasis (LNM; p < 0.001), recurrence (p < 0.001) and advanced grade (AG; p < 0.001). The growth of cervical cancer cells (Hela cells) was enhanced by HDGF treatment. The HDGF mRNA and protein level were significantly higher in malignant cervical cancer cells compared with primary ones. By adenovirus gene delivery, HDGF overexpression enhanced, whereas HDGF knockdown perturbed the tumorigenic behaviors of cervical cancer cells. HDGF overexpression is common in early-stage cervical adenocarcinoma and is involved in the carcinogenesis of cervical adenocarcinoma. Cytoplasmic HDGF expression is strongly correlated with pelvic lymph node metastasis and recurrence, indicating that HDGF may serve as a novel prognostic marker for patients with Cx.

  14. Treatment of early-stage erythematotelangiectatic rosacea with a Q-switched 595-nm Nd:YAG laser.

    PubMed

    Goo, Boncheol Leo; Kang, Jin-Soo; Cho, Sung Bin

    2015-06-01

    Erythematotelangiectatic rosacea presents as persistent erythema and telangiectasia with frequent flushing and blushing on the facial and extrafacial skin. Additionally, papulopustular rosacea shows acneiform papules, pustules, and nodules with persistent plaque-form edema. Despite garnering only grade-C or -D level recommendations, a 585-nm or 595-nm flashlamp-pumped pulsed-dye laser can be considered as an effective therapeutic modality for the treatment of rosacea in patients who are refractory to topical and/or systemic treatments. In this report, treatment with a Q-switched 595-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with low non-purpuragenic fluence proved to be safe and effective in treating early-stage erythematotelangiectatic rosacea in two female Korean patients. Laser treatment for rosacea was delivered with the settings of pulse energy of 0.4-0.5 J/cm(2), pulse duration of 5-10 ns, 5-mm spot size, 5 Hz, and 500 shots. Additionally, we found that remarkable therapeutic effects were achieved for both rosacea and melasma by combining Q-switched quick pulse-to-pulse 1,064-nm Nd:YAG and Q-switched 595-nm Nd:YAG laser treatments, which required only the changing of handpieces equipped with solid dye. In conclusion, we suggest that treatment with a Q-switched 595-nm Nd:YAG laser with low fluence may provide an additional therapeutic option for treating early-stage erythematotelangiectatic rosacea.

  15. Adoption of Hypofractionated Whole-Breast Irradiation for Early-Stage Breast Cancer: A National Cancer Data Base Analysis

    SciTech Connect

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Rutter, Charles E.; Evans, Suzanne B.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2014-12-01

    Purpose: To evaluate the relationship of patient, hospital, and cancer characteristics with the adoption of hypofractionation in a national sample of patients diagnosed with early-stage breast cancer. Methods and Materials: We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs conventional fractionation). Results: We identified 13,271 women (11.7%) and 99,996 women (88.3%) with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P<.001 for trend). Patients living ≥50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (odds ratio 1.57 [95% confidence interval 1.44-1.72], P<.001). Adoption of hypofractionation was associated with treatment at an academic center (P<.001) and living in an area with high median income (P<.001). Hypofractionation was less likely to be used in patients with high-risk disease, such as increased tumor size (P<.001) or poorly differentiated histologic grade (P<.001). Conclusions: The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and nonclinical concerns.

  16. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

    Cancer.gov

    The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

  17. Dutasteride May Slow the Growth of Early-Stage Prostate Cancer | Division of Cancer Prevention

    Cancer.gov

    For men who are undergoing active surveillance for early-stage prostate cancer, the drug dutasteride (Avodart) could help control the disease and prevent the need for more aggressive treatments. |

  18. Late Effects May Not Warrant Using Radiation to Treat Early-Stage Hodgkin Lymphoma

    Cancer.gov

    Patients with early-stage Hodgkin lymphoma who were treated with multidrug chemotherapy alone were more likely to be alive 12 years later than patients who received treatment that included radiation therapy, according to findings from a clinical trial.

  19. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD).

    PubMed

    Baruth, Joshua M; Casanova, Manuel F; Sears, Lonnie; Sokhadze, Estate

    2010-06-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors.

  20. Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

    SciTech Connect

    Pogribny, Igor P. Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

    2007-11-15

    Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G{sub 1} to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen.

  1. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS.

  2. A profile of identity in early-stage dementia and a comparison with healthy older people.

    PubMed

    Caddell, Lisa S; Clare, Linda

    2013-01-01

    The aim of the study was to determine whether people in the early stages of dementia experience their sense of identity differently to healthy older people and to examine whether different aspects of identity are related to each other in each group. This was a cross-sectional questionnaire-based study; 50 people with early-stage dementia and 50 age-matched people without dementia completed measures pertaining to different aspects of identity. Measures of mood and self-esteem were also included so that any differences could be taken into account in the analysis. There were very few differences in identity between the groups. After differences in levels of anxiety were accounted for, there were no differences in scores on most measures of identity. However, people in the early stages of dementia scored significantly lower on one subtotal for one measure of identity, whereas healthy older adults reported significantly more identity-related distress than people in the early stages of dementia. For both groups, there were no associations between different aspects of identity. People in the early stages of dementia do not differ much from healthy older adults in terms of their identity. Since healthy older people experience more distress relating to identity, they may be more likely to benefit from some sort of intervention than people in the early stages of dementia. It might be useful to consider identity as consisting of multiple components in future studies, rather than assuming that one aspect of identity represents the overall experience of identity.

  3. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    PubMed

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS. PMID:23126275

  4. Early stages of oxidative stress-induced membrane permeabilization: a neutron reflectometry study.

    PubMed

    Smith, Hillary L; Howland, Michael C; Szmodis, Alan W; Li, Qijuan; Daemen, Luke L; Parikh, Atul N; Majewski, Jaroslaw

    2009-03-18

    Neutron reflectometry was used to probe in situ the structure of supported lipid bilayers at the solid-liquid interface during the early stages of UV-induced oxidative degradation. Single-component supported lipid bilayers composed of gel phase, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and fluid phase, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), phospholipids were exposed to low-dose oxidative stress generated by UV light and their structures were examined by neutron reflectometry. An interrupted illumination mode, involving exposures in 15 min increments with 2 h intervals between subsequent exposures, and a continuous mode involving a single 60 (or 90) min exposure period were employed. In both cases, pronounced differences in the structure of the lipid bilayer after exposure were observed. Interrupted exposure led to a substantial decrease in membrane coverage but preserved its total thickness at reduced scattering length densities. These results indicate that the initial phase during UV-induced membrane degradation involves the formation of hydrophilic channels within the membrane. This is consistent with the loss of some lipid molecules we observe and attendant reorganization of residual lipids forming hemimicellar edges of the hydrophilic channels. In contrast, continuous illumination produced a graded interface of continuously varied scattering length density (and hence hydrocarbon density) extending 100-150 A into the liquid phase. Exposure of a DPPC bilayer to UV light in the presence of a reservoir of unfused vesicles showed low net membrane disintegration during oxidative stress, presumably because of surface back-filling from the bulk reservoir. Chemical evidence for membrane degradation was obtained by mass spectrometry and Fourier transform infrared spectroscopy. Further evidence for the formation of hydrophilic channels was furnished by fluorescence microscopy and imaging ellipsometry data.

  5. Early Stages of Oxidative Stress-Induced Membrane Permeabilization: A Neutron Reflectometry Study

    PubMed Central

    Smith, Hillary L.; Howland, Michael C.; Szmodis, Alan W.; Li, Qijuan; Daemen, Luke L.; Parikh, Atul N.; Majewski, Jaroslaw

    2009-01-01

    Neutron reflectometry was used to probe in situ the structure of supported lipid bilayers at the solid–liquid interface during the early stages of UV-induced oxidative degradation. Single-component supported lipid bilayers composed of gel phase, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and fluid phase, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), phospholipids were exposed to low-dose oxidative stress generated by UV light and their structures were examined by neutron reflectometry. An interrupted illumination mode, involving exposures in 15 min increments with 2 h intervals between subsequent exposures, and a continuous mode involving a single 60 (or 90) min exposure period were employed. In both cases, pronounced differences in the structure of the lipid bilayer after exposure were observed. Interrupted exposure led to a substantial decrease in membrane coverage but preserved its total thickness at reduced scattering length densities. These results indicate that the initial phase during UV-induced membrane degradation involves the formation of hydrophilic channels within the membrane. This is consistent with the loss of some lipid molecules we observe and attendant reorganization of residual lipids forming hemimicellar edges of the hydrophilic channels. In contrast, continuous illumination produced a graded interface of continuously varied scattering length density (and hence hydrocarbon density) extending 100–150 Å into the liquid phase. Exposure of a DPPC bilayer to UV light in the presence of a reservoir of unfused vesicles showed low net membrane disintegration during oxidative stress, presumably because of surface back-filling from the bulk reservoir. Chemical evidence for membrane degradation was obtained by mass spectrometry and Fourier transform infrared spectroscopy. Further evidence for the formation of hydrophilic channels was furnished by fluorescence microscopy and imaging ellipsometry data. PMID:19275260

  6. Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

    SciTech Connect

    Lemanski, Claire; Azria, David; Gourgon-Bourgade, Sophie; Gutowski, Marian; Rouanet, Phillippe; Saint-Aubert, Bernard; Ailleres, Norbert; Fenoglietto, Pascal; Dubois, Jean-Bernard

    2010-03-01

    Purpose: We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. Methods and Materials: We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. Results: The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. Conclusion: Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

  7. Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival.

    PubMed

    Makanji, Yogeshwar; Tagler, David; Pahnke, Jennifer; Shea, Lonnie D; Woodruff, Teresa K

    2014-04-15

    Oxygen tension is critical for follicle growth and metabolism, especially for early-stage follicles, where vascularity is limited. Its role and underlying mechanism in the in vitro activation and maturation of immature to ovulatory follicles is largely unknown. In this study, early secondary (110 μm) murine follicles were isolated and encapsulated in alginate hydrogels to replicate the in vivo environment of the growing/maturing follicle. Encapsulated follicles were cultured for 8 days at either 2.5 or 20% O2. Survival (2.6-fold) and growth (1.2-fold) were significantly higher for follicles cultured at 2.5% compared with 20% O2. Using a mouse hypoxia-signaling pathway qRT-PCR array and GeneGo Metacore analysis, we found that direct target genes of the hypoxia-activated HIF1-complex were significantly upregulated in follicles cultured for 8 days at 2.5% compared with 20% O2, including the carbohydrate transport and metabolism genes Slc2a3, Vegfa, Slc2a1, Edn1, Pgk1, Ldha, and Hmox1. Other upregulated genes included carbohydrate transporters (Slc2a1, Slc2a3, and Slc16a3) and enzymes essential for glycolysis (Pgk1, Hmox1, Hk2, Gpi1, Pfkl, Pfkp, Aldoa, Gapdh, Pgam1, Eno1, Pkm2, and Ldha). For follicles cultured at 2.5% O2, a 7.2-fold upregulation of Vegfa correlated to an 18-fold increase in VEGFA levels, and a 3.2-fold upregulation of Ldha correlated to a 4.8-fold increase in lactate levels. Both VEGFA and lactate levels were significantly higher in follicles cultured at 2.5% compared with 20% O2. Therefore, enhanced hypoxia-mediated glycolysis is essential for growth and survival of early secondary follicles and provides vital insights into improving in vitro culture conditions.

  8. Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: results of long-term follow-up.

    PubMed

    Odunsi, K; Moneke, V; Tammela, J; Ghamande, S; Seago, P; Driscoll, D; Marchetti, D; Baker, T; Lele, S

    2004-01-01

    Data on adjuvant chemotherapy in early-stage uterine sarcomas are conflicting and most often based on small patient groups with relatively short duration of follow-up. Approximately 60% of patients present with stage I disease with an overall 5-year survival of 30-50% when treated with surgery alone. This study examines the efficacy and results of long-term follow-up of a multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma. Between 1982 and 1999, 24 evaluable patients with completely staged uterine sarcomas received adjuvant multiagent chemotherapy with vincristine sulfate (1mg /m(2)) on days 1 and 4, doxorubicin (40 mg /m(2)) and cyclophosphamide (400 mg /m(2)) on day 2, and dacarbazine (200 mg /m(2)) on days 1 through 4 for a total of nine monthly cycles or until recurrence of disease was documented. Survival distributions were calculated by the Kaplan-Meier method, and statistical significance was determined with the log-rank test. Factors significant on univariate analysis were analyzed in a multivariate fashion using Cox proportional hazards model. The histologic distribution of patients was 46% leiomyosarcoma, 33% mixed mullerian tumors, 13% stromal sarcomas, 4% adenosarcomas, and 4% hemangiosarcoma. The patients received 206 of a planned 216 cycles of chemotherapy. The median follow-up of the patient population was 93 months (range 11-213 months). Eight patients (33%) developed recurrent disease. The median time to recurrence was 19 months (range 7-184 months). The estimated survival for the entire group was 88, 75, and 69% at 2, 5, and 15 years, respectively. Factors that did not affect survival included age, histology, and tumor grade. Four patients required dose reductions secondary to grade 2-3 toxicities (hematologic). Grade 1 neurotoxicity was observed in six patients (25%) and grade 2 neurotoxicity in one patient (4%). Adjuvant CYVADIC

  9. Cognitive and behavioral assessment in the early stages of neurodegenerative extrapyramidal syndromes.

    PubMed

    Borroni, B; Turla, M; Bertasi, V; Agosti, C; Gilberti, N; Padovani, A

    2008-01-01

    Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration Syndrome (CBDS) are the most common neurodegenerative extrapyramidal syndromes. Beyond motor symptoms, cognitive dysfunctions and behavioral disturbances are reported. Neuropsychological and neuropsychiatry features in the early stages, however, are under-investigated, and few comparison studies are available yet. The aim of the present study was to evaluate the cognitive and behavioral profile in the early stages of neurodegenerative extrapyramidal syndromes. Thirty-nine PD, 27 DLB, 16 CBDS, and 24 PSP were recruited. Groups were matched for global cognitive and motor impairment. The overall sample showed a common neuropsychological core characterized by visuospatial deficits. Although in the early stage of the disease, a high presence of behavioral disturbances was detected, depression and anxiety were the most common disorders, followed by apathy and sleep disturbances. The observation of overlapping clinical entities points the attention on the need of adjunctive diagnostic markers for early differential diagnosis.

  10. [Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

    PubMed

    Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

    2013-01-01

    A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

  11. All-optical photoacoustic imaging and detection of early-stage dental caries

    NASA Astrophysics Data System (ADS)

    Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

    2015-02-01

    Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

  12. Toxicity and Patterns of Failure of Adaptive/Ablative Proton Therapy for Early-Stage, Medically Inoperable Non-Small Cell Lung Cancer

    SciTech Connect

    Chang, Joe Y.; Komaki, Ritsuko; Wen, Hong Y.; De Gracia, Beth; Bluett, Jaques B.; McAleer, Mary F.; Swisher, Stephen G.; Cox, James D.

    2011-08-01

    Purpose: To analyze the toxicity and patterns of failure of proton therapy given in ablative doses for medically inoperable early-stage non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients with medically inoperable T1N0M0 (central location) or T2-3N0M0 (any location) NSCLC were treated with proton therapy at 87.5 Gy (relative biological effectiveness) at 2.5 Gy /fraction in this Phase I/II study. All patients underwent treatment simulation with four-dimensional CT; internal gross tumor volumes were delineated on maximal intensity projection images and modified by visual verification of the target volume in 10 breathing phases. The internal gross tumor volumes with maximal intensity projection density was used to design compensators and apertures to account for tumor motion. Therapy consisted of passively scattered protons. All patients underwent repeat four-dimensional CT simulations during treatment to assess the need for adaptive replanning. Results: At a median follow-up time of 16.3 months (range, 4.8-36.3 months), no patient had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (Grade 2, 67%; Grade 3, 17%), followed by Grade 2 fatigue (44%), Grade 2 pneumonitis (11%), Grade 2 esophagitis (6%), and Grade 2 chest wall pain (6%). Rates of local control were 88.9%, regional lymph node failure 11.1%, and distant metastasis 27.8%. Twelve patients (67%) were still alive at the last follow-up; five had died of metastatic disease and one of preexisting cardiac disease. Conclusions: Proton therapy to ablative doses is well tolerated and produces promising local control rates for medically inoperable early-stage NSCLC.

  13. Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

    PubMed Central

    Boer, R H de; Smith, I E; Pastorino, U; O'Brien, M E R; Ramage, F; Ashley, S; Goldstraw, P

    1999-01-01

    Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaign PMID:10188899

  14. Expression patterns of the immunomodulatory enzyme arginase 1 in blood, lymph nodes and tumor tissue of early-stage breast cancer patients.

    PubMed

    de Boniface, Jana; Mao, Yumeng; Schmidt-Mende, Jan; Kiessling, Rolf; Poschke, Isabel

    2012-11-01

    Arginase 1 (ARG1) is an important enzyme in amino acid metabolism that also exerts immunoregulatory function. High ARG1 expression, which is associated with cell cycle arrest and functional unresponsiveness in T cells, has been observed after trauma, infections and in cancer patients. We studied ARG1 expression in early-stage breast cancer patients (stage 1, n = 20; stage 2, n = 23) by multi-parametric flow cytometry and immunohistochemistry. Despite a low tumor burden, ARG1 expression was significantly increased in blood-derived myeloid cells of breast cancer patients compared with healthy controls. The ARG1(hi) myeloid population in the blood of cancer patients contained a high frequency of CD14(+) cells and was, therefore, distinct from the granulocytic ARG1(+) population observed in control individuals. Expression of ARG1 in patient blood cells correlated with tumor grade and was significantly reduced after surgical tumor removal. ARG1(+) myeloid cells could also be detected in tumors and tumor-draining lymph nodes, where ARG1 expression levels exceeded those measured in the blood. We conclude that even patients with early-stage breast cancer exhibit tumor-related changes of ARG1 expression. The level of ARG1-mediated immunomodulation at this early stage remains to be determined. However, high ARG1 expression is likely to interfere with antitumor T-cell responses and immunotherapeutic interventions, making ARG1 or its downstream effector interesting therapeutic targets.

  15. Elective Inguinal Node Irradiation in Early-Stage T2N0 Anal Cancer: Prognostic Impact on Locoregional Control

    SciTech Connect

    Zilli, Thomas; Betz, Michael; Bieri, Sabine; Ris, Frederic; Roche, Bruno; Roth, Arnaud D.; Allal, Abdelkarim S.

    2013-09-01

    Purpose: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. Methods and Materials: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. Results: Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC, cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). Conclusions: In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.

  16. Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer

    PubMed Central

    Misawa, Kiyoshi; Mochizuki, Daiki; Imai, Atsushi; Endo, Shiori; Mima, Masato; Misawa, Yuki; Kanazawa, Takeharu; Carey, Thomas E.; Mineta, Hiroyuki

    2016-01-01

    Staging and pathological grading are useful, but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly, molecular biomarkers that predict the risk of recurrence are necessary to improve clinical outcomes. The methylation statuses of the promoters of 11 tumor-related genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST, and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation-specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was lower in patients with 6–11 methylated genes than in those with 0–5 methylated genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated with poor survival, with hazard ratios of 4.474 (95% CI, 1.241–16.124). In a joint analysis of these four genes, patients with 2–4 methylated genes had a significantly lower survival rate than those with 0–1 methylated genes in early-stage HNSCC. Importantly, the methylation of some genes was closely related to poor prognosis in early-stage HNSCC, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. PMID:27027429

  17. Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer.

    PubMed

    Misawa, Kiyoshi; Mochizuki, Daiki; Imai, Atsushi; Endo, Shiori; Mima, Masato; Misawa, Yuki; Kanazawa, Takeharu; Carey, Thomas E; Mineta, Hiroyuki

    2016-05-01

    Staging and pathological grading are useful, but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly, molecular biomarkers that predict the risk of recurrence are necessary to improve clinical outcomes. The methylation statuses of the promoters of 11 tumor-related genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST, and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation-specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was lower in patients with 6-11 methylated genes than in those with 0-5 methylated genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated with poor survival, with hazard ratios of 4.474 (95% CI, 1.241-16.124). In a joint analysis of these four genes, patients with 2-4 methylated genes had a significantly lower survival rate than those with 0-1 methylated genes in early-stage HNSCC. Importantly, the methylation of some genes was closely related to poor prognosis in early-stage HNSCC, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. PMID:27027429

  18. Test Design Optimization in CAT Early Stage with the Nominal Response Model

    ERIC Educational Resources Information Center

    Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

    2007-01-01

    The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

  19. Early-stage visual processing abnormalities in high-functioning autism spectrum disorder (ASD)

    PubMed Central

    Baruth, Joshua M.; Casanova, Manuel F.; Sears, Lonnie; Sokhadze, Estate

    2012-01-01

    It has been reported that individuals with autism spectrum disorder (ASD) have abnormal responses to the sensory environment. For these individuals sensory overload can impair functioning, raise physiological stress, and adversely affect social interaction. Early-stage (i.e. within 200ms of stimulus onset) auditory processing abnormalities have been widely examined in ASD using event-related potentials (ERP), while ERP studies investigating early-stage visual processing in ASD are less frequent. We wanted to test the hypothesis of early-stage visual processing abnormalities in ASD by investigating ERPs elicited in a visual oddball task using illusory figures. Our results indicate that individuals with ASD have abnormally large cortical responses to task irrelevant stimuli over both parieto-occipital and frontal regions-of-interest (ROI) during early stages of visual processing compared to the control group. Furthermore, ASD patients showed signs of an overall disruption in stimulus discrimination, and had a significantly higher rate of motor response errors. PMID:22563527

  20. Memory Club: A Group Intervention for People with Early-Stage Dementia and Their Care Partners

    ERIC Educational Resources Information Center

    Zarit, Steven H.; Femia, Elia E.; Watson, Jennifer; Rice-Oeschger, Laura; Kakos, Bernadette

    2004-01-01

    Purpose: Diagnosis of dementia in its early stages presents a window of opportunity for examining the immediate and long-term consequences of the illness at a point when the individual with memory loss can still participate in decision making. Design and Methods: Memory Club is a l0-session group program designed to provide information about…

  1. Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

    ERIC Educational Resources Information Center

    Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

    2014-01-01

    Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

  2. Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

    ERIC Educational Resources Information Center

    Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

    2005-01-01

    This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

  3. Validity of linear analysis in early-stage spinodal decomposition of a polymer mixture

    NASA Astrophysics Data System (ADS)

    Hayashi, Masaki; Jinnai, Hiroshi; Hashimoto, Takeji

    2000-08-01

    A two-step phase separation was imposed to a binary mixture of deuterated polybutadiene and protonated polyisoprene with nearly critical composition in the following way: the system was first subjected to phase separation via spinodal decomposition (SD) so that the system developed coexisting two phases characteristics of the late stage of SD (the first-step phase separation). It was then brought into a deeper quench so that both two phases again fell into spinodal region and hence further SD took place within each phase (the second-step phase separation at T2). In the very early stage after this second-step phase separation, the two-phase structure developed in the first-step phase separation was almost unchanged with time, but the composition fluctuation was newly developed within each phase, giving rise to an excess light scattering (LS) at large scattering vectors. The very early stage in this second-step phase separation process was studied by time-resolved LS. We found that the early-stage SD after the second-step phase separation at T2 can be well described by the linearized theory of SD. However the characteristic parameters, especially the collective diffusivity, obtained from the linear analysis, were different from those obtained by the single-step SD at T2 for the corresponding single-phase mixtures. The results unveil an intriguing effect of initial structure or space confinement on early stage SD, reflecting an intrinsically nonlinear phenomenon.

  4. Early-Stage Chunking of Finger Tapping Sequences by Persons Who Stutter and Fluent Speakers

    ERIC Educational Resources Information Center

    Smits-Bandstra, Sarah; De Nil, Luc F.

    2013-01-01

    This research note explored the hypothesis that chunking differences underlie the slow finger-tap sequencing performance reported in the literature for persons who stutter (PWS) relative to fluent speakers (PNS). Early-stage chunking was defined as an immediate and spontaneous tendency to organize a long sequence into pauses, for motor planning,…

  5. Sydney, Australia Community Meets Classroom: Celebrating Families and Difference in the Early Stages of Primary Education

    ERIC Educational Resources Information Center

    Burns, Kellie

    2006-01-01

    Teachers and teacher educators are often hard pressed to find resources that creatively integrate lesbian, gay, bisexual, transgender (LGBT), and intersex issues into the early stages of primary education. While there is a growing number of academics who stress the importance of addressing topics of sexual and gender diversity during the early…

  6. A Comparison of Item Selection Rules at the Early Stages of Computerized Adaptive Testing.

    ERIC Educational Resources Information Center

    Chen, Shu-Ying; Ankenmann, Robert D.; Chang, Hua-Hua

    2000-01-01

    Compared five item selection rules with respect to the efficiency and precision of trait (theta) estimation at the early stages of computerized adaptive testing (CAT). The Fisher interval information, Fisher information with a posterior distribution, Kullback-Leibler information, and Kullback-Leibler information with a posterior distribution…

  7. Dyadic Intervention for Family Caregivers and Care Receivers in Early-Stage Dementia

    ERIC Educational Resources Information Center

    Whitlatch, Carol J.; Judge, Katherine; Zarit, Steven H.; Femia, Elia

    2006-01-01

    Purpose: The Early Diagnosis Dyadic Intervention (EDDI) program provides a structured, time-limited protocol of one-on-one and dyadic counseling for family caregivers and care receivers who are in the early stages of dementia. The goals and procedures of EDDI are based on previous research suggesting that dyads would benefit from an intervention…

  8. Prolonged Exposure Therapy for a Vietnam Veteran with PTSD and Early-Stage Dementia

    ERIC Educational Resources Information Center

    Duax, Jeanne M.; Waldron-Perrine, Brigid; Rauch, Sheila A. M.; Adams, Kenneth M.

    2013-01-01

    Although prolonged exposure therapy (PE) is considered an evidence-based treatment for PTSD, there has been little published about the use of this treatment for older adults with comorbid early-stage dementia. As the number of older adults in the United States continues to grow, so will their unique mental health needs. The present article…

  9. Differentially expressed protein-coding genes and long noncoding RNA in early-stage lung cancer.

    PubMed

    Li, Ming; Qiu, Mantang; Xu, Youtao; Mao, Qixing; Wang, Jie; Dong, Gaochao; Xia, Wenjia; Yin, Rong; Xu, Lin

    2015-12-01

    Due to the application of low-dose computed tomography screening, more and more early-stage lung cancers have been diagnosed. Thus, it is essential to characterize the gene expression profile of early-stage lung cancer to develop potential biomarkers for early diagnosis and therapeutic targets. Here, we analyzed microarray data of 181 early-stage lung cancer patients. By comparing gene expression between different tumor and lymph node metastasis stages, we identified various differentially expressed protein-coding genes and long noncoding RNA (lncRNA) in the comparisons of T2 vs. T2 and N1- vs. N0-stage lung cancer. Functional analyses revealed that these differentially expressed genes were enriched in various tumorigenesis or metastasis-related pathways. Survival analysis indicated that two protein-coding genes, C7 and SCN7A, were significantly associated survival of lung cancer. Notably, a novel lncRNA, LINC00313, was highly expressed in both T2- and N1-stage lung cancers. On the other hand, LINC00313 was also upregulated in lung cancer and metastasized lung cancer tissues, compared with adjacent lung tissues and primary lung cancer tissues. Additionally, higher expression level of LINC00313 indicated poor prognosis of lung cancer (hazard ratio = 0.658). Overall, we characterized the expression profiles of protein-coding genes and lncRNA in early-stage lung cancer and found that LINC00313 could be a biomarker for lung cancer.

  10. The Night before the LHC -thoughts about expectations in the early stage and beyond-

    SciTech Connect

    Nojiri, Mihoko M.

    2008-11-23

    I review recent developments on the use of m{sub T2} variables for SUSY parameter study, which might be useful for analyses of the data in the early stage of the LHC experiments. I will also mention some of recent interesting studies relevant to the SUSY analysis.

  11. 77 FR 25775 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-01

    ... also review the information at www.sba.gov/inv/earlystage which includes a list of frequently asked... Regulatory Capital, up to a maximum of $50 million. Early Stage SBICs must invest at least 50% of their... governing these SBICs may be found at www.sba.gov/inv/earlystage . DATES: In order to expedite licensing...

  12. 76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-09

    ... provide early stage venture capital financing to small businesses. The standard debenture is generally... operating history may qualify under this definition. The venture capital industry employs various... investment fund draws its initial capital from investors). Because of the cyclical nature of venture...

  13. 77 FR 25042 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... assets or cash flow for traditional bank funding. Although the venture capital industry provided over $22... form of SBA- guaranteed debentures to SBICs that plan to provide early stage venture capital financing... such as the Institutional Limited Partners Association, the National Venture Capital Association,...

  14. Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what?

    PubMed Central

    Kong, Feng-Ming (Spring)

    2015-01-01

    More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternative treatments now available. These alternative treatments include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous cryoablation therapy (PCT), photodynamic therapy (PDT) and external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy. We describe the established alternatives to surgical resection, their advantages and disadvantages, potential complications and efficacy. We then describe the optimal treatment approach for patients with early-stage NSCLC based on tumor operability, size and location. Finally, we discuss future directions and whether any alternative therapies will challenge surgical resection as the treatment of choice for patients with operable early-stage lung cancer. PMID:26380185

  15. 76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ...- creating startups and small firms, accelerate research, and address barriers to success for entrepreneurs... From the Federal Register Online via the Government Publishing Office ] SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage SBICs; Public Webinars AGENCY:...

  16. Apathy in untreated early-stage Parkinson disease: relationship with other non-motor symptoms.

    PubMed

    Dujardin, Kathy; Langlois, Carole; Plomhause, Lucie; Carette, Anne-Sophie; Delliaux, Marie; Duhamel, Alain; Defebvre, Luc

    2014-12-01

    Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment-naive patients with early-stage PD has not been extensively investigated. Moreover, whether apathy is related to other non-motor symptoms in early-stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment-naive patients with early-stage PD. Ninety-five treatment-naive patients with early-stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non-apathetic patients. When considering non-motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non-apathetic patients. In treatment-naive patients with early-stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anhedonia.

  17. Regulation of cap-dependent translation initiation in the early stage porcine parthenotes.

    PubMed

    Susor, Andrej; Jelínková, Lucie; Karabínová, Pavla; Torner, Helmut; Tomek, Wolfgang; Kovárová, Hana; Kubelka, Michal

    2008-12-01

    The binding of mRNAs to ribosomes is mediated by the protein complex eIF4F in conjunction with eIF4B (eukaryotic initiation factor 4F and 4B). EIF4F is a three subunit complex consisting of eIF4A (RNA helicase), eIF4E (mRNA cap binding protein), and eIF4G (bridging protein). The crucial role is played by eIF4E, which directly binds the 5'-cap structure of the mRNA and facilitates the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. EIF4E binding to mRNA and to other initiation factors is regulated on several levels, including its phosphorylation on Ser-209, and association with its regulatory protein 4E-binding protein (4E-BP1). In this study we document that both the translation initiation factor eIF4E and its regulator 4E-BP1 become dephosphorylated in the early stage porcine zygotes already 8 hr post-activation. Similarly, the activities of ERK1/2 MAP and Mnk1 kinases, which are both involved in eIF4E phosphorylation, gradually decrease during this period with the timing similar to that of eIF4E dephosphorylation. The formation of an active eIF4F complex is also diminished after 9-15 hr post-activation, although substantial amounts of this complex have been detected also 24 hr post-activation (2-cell stage). The overall protein synthesis in the parthenotes decreases gradually from 12 hr post-activation reaching a minimum after 48 hr (4-cell stage). Although the translation is gradually decreasing during early preimplantation development, the eIF4F complex, which is temporarily formed, might be a premise for the translation of a small subset of mRNAs at this period of development.

  18. Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

    SciTech Connect

    Filippi, Andrea Riccardo; Ciammella, Patrizia; Piva, Cristina; Ragona, Riccardo; Botto, Barbara; Gavarotti, Paolo; Merli, Francesco; Vitolo, Umberto; Iotti, Cinzia; Ricardi, Umberto

    2014-06-01

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. Methods and Materials: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. Results: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). Conclusions: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete

  19. Correlation of polymorphism of IL-8 and MMP-7 with occurrence and lymph node metastasis of early stage cervical cancer.

    PubMed

    Wu, Suhui; Lu, Shi; Tao, Huijuan; Zhang, Li; Lin, Weifeng; Shang, Haixia; Xie, Jun

    2011-02-01

    The IL-8 and MMP-7 genes participate in the carcinogenesis of many malignancies, but the role of both genes in cervical cancer is not fully elucidated. The aim of this study was to determine the frequency of IL-8 and MMP-7 gene mutations and to assess their effects on the risk of early stage cervical cancer and lymph node metastasis. The clinical stage and histological grade of cervical cancer were also studied. The peripheral blood from the patients with early stage cervical cancers and normal controls was collected and the DNA was extracted. The incidence of IL-8 and MMP-7 gene mutations was assessed by using tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS PCR) and restriction fragment length polymorphism (RFLP). The data were statistically analyzed by x2 test. The results showed that: (1) The genotype frequency of IL-8 -251AT and TT was significantly higher in the cervical cancer group than in the normal control group (OR=2.290 and 2.619 respectively, P=0.001), and it was also higher in the lymphatic metastasis group than that without metastasis (OR=2.917, P=0.035); (2) The frequency of MMP-7 -181G/G genotype was significantly higher in the cervical cancer group and in the lymphatic metastasis group (P<0.05); (3) The incidence of IL-8 mutation was two times higher in IIa cervical cancer group than in Ib1 and Ib2 cervical cancer group (P=0.006). For the MMP-7 gene, there was statistically significant difference in the incidence of mutation between the Ib1, Ib2 and the IIa (P=0.000); (4) Different histological types and different grades of cervical cancer had different incidence of mutations, statistically. It was suggested that there was significant difference in the genotype of IL-8 -251TT and MMP-7 -181GG polymorphism between the cervical cancer group and the lymph node metastasis group. Moreover, individuals with IL-8 T allele or MMP-7 G allele carriers were at significantly higher risk of cervical cancer, particularly the

  20. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta.

    PubMed

    Liu, X Y; Yan, F; Niu, L L; Chen, Q N; Zheng, H R; Li, J Y

    2016-04-01

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery. PMID:26972797

  1. Following iron speciation in the early stages of magnetite magnetosome biomineralization

    DOE PAGESBeta

    Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; Faivre, Damien; Prozorov, Tanya

    2016-02-26

    Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structure withmore » a majority of iron present as Fe3+ and trace amounts of Fe2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.« less

  2. Morphological changes to early stage Taenia solium cysticerci following oxfendazole treatment.

    PubMed

    Liu, Yong-Jie; Li, Qing-Zhang; Hao, Yan-Hong

    2003-01-01

    The progressive morphological changes to early stage Taenia solium cysticerci following the treatment of pigs with a single therapeutic dose of oxfendazole (30 mg/kg), are described. On Day 1 after treatment, no obvious changes occurred in the general appearance of the larvae but alternations were seen by electron microscope, with an apparent reduction in the number of microtriches, and a complete disappearance of the tegument. Numerous granules were seen to have accumulated in the tegument cells. As treatment progressed, damage to the cysticerci was more serious and, by five days, all cysticerci were seen to be in an advanced stage of degeneration. By 45 days post-treatment, all cysts were calcified. These results suggest that oxfendazole is a highly effective drug against T. solium cysticerci in the early stages of development.

  3. Laparoscopic surgery on broken points for uterine sarcoma in the early stage decrease prognosis.

    PubMed

    Liu, Hong; Zhu, Yi; Zhang, Guo-Nan; Wang, Chang; Li, Chao; Shi, Yu

    2016-01-01

    Uterine sarcoma, a rare solid tumor in uterus, is difficult to identify in the early stage from some benign uterine tumors, such as uterine fibroids. Hence, uterine sarcoma may be treated in the same way as uterine fibroids; and this may not be found until pathological diagnosis. Consequently, this can lead to tumor's abdominal spread, planting and local invasive growth, resulting in an early uterine sarcoma, an increased relapse rate after surgery and a decreased survival. Therefore, it's important to avoid these unintended and iatrogenic complications through an accurate diagnosis and an appropriate surgical approach. The surgical staging and a complete resection of the tumor are both important for patients' prognosis. In this review, we will discuss the laparoscopic surgery for uterine sarcoma in the early stage and patients' prognosis. PMID:27503773

  4. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

    2016-03-01

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

  5. Early stages of precipitation in Mg-RE alloys studied by positron annihilation spectroscopy

    NASA Astrophysics Data System (ADS)

    Vlček, M.; Čížek, J.; Melikhova, O.; Hruška, P.; Procházka, I.; Vlach, M.; Stulíková, I.; Smola, B.

    2016-01-01

    Magnesium alloys with rare earth (RE) elements are promising structural materials exhibiting favourable mechanical properties at elevated temperatures. However, the processes occurring during early stages of precipitation in these alloys are still not completely understood. In this work positron lifetime spectroscopy combined with coincidence Doppler broadening was employed for investigation of early stages of precipitation in Mg-RE alloys. Presence of quenched-in vacancy clusters was observed after solution treatment of studied alloys. These quenched-in vacancy clusters are bound to RE solutes and thereby stabilized at room temperature. During natural aging, RE clusters are formed by vacancy-assisted long-range diffusion. In addition, hardness of studied materials increases and quenched-in vacancy clusters are annealed out during the course of natural aging. Simple model was developed to describe hardening during natural aging.

  6. Analysis on Gene Expression Profile in Oncospheres and Early Stage Metacestodes from Echinococcus multilocularis

    PubMed Central

    Dang, Zhisheng; Suzuki, Yutaka; Horiuchi, Terumi; Yagi, Kinpei; Kouguchi, Hirokazu; Irie, Takao; Kim, Kyeongsoon; Oku, Yuzaburo

    2016-01-01

    Alveolar echinococcosis is a worldwide zoonosis of great public health concern. Analysis of genome data for Echinococcus multilocularis has identified antigen families that can be used in diagnostic assays and vaccine development. However, little gene expression data is available for antigens of the egg and early larval stages. To address this information gap, we used a Next-Generation Sequencing approach to investigate three different stages (non-activated and activated oncospheres, and early stage metacestodes) of E. multilocularis (Nemuro strain). Transcriptome data analysis revealed that some diagnostic antigen gp50 isoforms and the antigen Eg95 family dominated in activated oncospheres, and the antigen B family dominated in early stage metacestodes. Furthermore, heat shock proteins and antigen II/3 are constantly expressed in the three stages. The expression pattern of various known antigens in E. multilocularis may give fundamental information for choosing candidate genes used in diagnosis and vaccine development. PMID:27092774

  7. Analysis on Gene Expression Profile in Oncospheres and Early Stage Metacestodes from Echinococcus multilocularis.

    PubMed

    Huang, Fuqiang; Dang, Zhisheng; Suzuki, Yutaka; Horiuchi, Terumi; Yagi, Kinpei; Kouguchi, Hirokazu; Irie, Takao; Kim, Kyeongsoon; Oku, Yuzaburo

    2016-04-01

    Alveolar echinococcosis is a worldwide zoonosis of great public health concern. Analysis of genome data for Echinococcus multilocularis has identified antigen families that can be used in diagnostic assays and vaccine development. However, little gene expression data is available for antigens of the egg and early larval stages. To address this information gap, we used a Next-Generation Sequencing approach to investigate three different stages (non-activated and activated oncospheres, and early stage metacestodes) of E. multilocularis (Nemuro strain). Transcriptome data analysis revealed that some diagnostic antigen gp50 isoforms and the antigen Eg95 family dominated in activated oncospheres, and the antigen B family dominated in early stage metacestodes. Furthermore, heat shock proteins and antigen II/3 are constantly expressed in the three stages. The expression pattern of various known antigens in E. multilocularis may give fundamental information for choosing candidate genes used in diagnosis and vaccine development. PMID:27092774

  8. Treatment of Early Stage Non-Small Cell Lung Cancer: Surgery or Stereotactic Ablative Radiotherapy?

    PubMed Central

    Uzel, Esengül Koçak; Abacıoğlu, Ufuk

    2015-01-01

    The management of early-stage Non-small Cell Lung Cancer (NSCLC) has improved recently due to advances in surgical and radiation modalities. Minimally-invasive procedures like Video-assisted thoracoscopic surgery (VATS) lobectomy decreases the morbidity of surgery, while the numerous methods of staging the mediastinum such as endobronchial and endoscopic ultrasound-guided biopsies are helping to achieve the objectives much more effectively. Stereotactic Ablative Radiotherapy (SABR) has become the frontrunner as the standard of care in medically inoperable early stage NSCLC patients, and has also been branded as tolerable and highly effective. Ongoing researches using SABR are continuously validating the optimal dosing and fractionation schemes, while at the same time instituting its role for both inoperable and operable patients. PMID:25759766

  9. The δ-cyclin expression at early stages of embryogenesis of Brassica rapa L. under clinorotation

    NASA Astrophysics Data System (ADS)

    Artemenko, O. A.; Popova, A. F.

    We present some results of comparison studying of Brassica embryo development and the δ-cyclin genes expression under slow horizontal clinorotation and in the laboratory control. Some backlog of the δ1-cyclin genes expression at early stages of embryogenesis under clinorotation was revealed in comparison with the laboratory control. The similar level of the δ3-cyclin expression at all stages of embryo formation (from one to nine days) in both variants is shown. Some delays in the rate of Brassica rapa embryo development under clinorotation in comparison with the laboratory control can be a result of decrease of a level and some backlog of the δ1-cyclin expression at early stages of embryogenesis.

  10. Laparoscopic surgery on broken points for uterine sarcoma in the early stage decrease prognosis

    PubMed Central

    Liu, Hong; Zhu, Yi; Zhang, Guo-Nan; Wang, Chang; Li, Chao; Shi, Yu

    2016-01-01

    Uterine sarcoma, a rare solid tumor in uterus, is difficult to identify in the early stage from some benign uterine tumors, such as uterine fibroids. Hence, uterine sarcoma may be treated in the same way as uterine fibroids; and this may not be found until pathological diagnosis. Consequently, this can lead to tumor’s abdominal spread, planting and local invasive growth, resulting in an early uterine sarcoma, an increased relapse rate after surgery and a decreased survival. Therefore, it’s important to avoid these unintended and iatrogenic complications through an accurate diagnosis and an appropriate surgical approach. The surgical staging and a complete resection of the tumor are both important for patients’ prognosis. In this review, we will discuss the laparoscopic surgery for uterine sarcoma in the early stage and patients’ prognosis. PMID:27503773

  11. Proteomic Analysis of Phosphoproteins in the Rice Nucleus During the Early Stage of Seed Germination.

    PubMed

    Li, Ming; Yin, Xiaojian; Sakata, Katsumi; Yang, Pingfang; Komatsu, Setsuko

    2015-07-01

    The early stage of seed germination is the first step in the plant life cycle without visible morphological change. To investigate the mechanism controlling the early stage of rice seed germination, we performed gel-and label-free nuclear phosphoproteomics. A total of 3467 phosphopeptides belonging to 102 nuclear phosphoproteins from rice embryos were identified. Protein-synthesis-related proteins were mainly phosphorylated. During the first 24 h following imbibition, 115 nuclear phosphoproteins were identified, and significant changes in the phosphorylation level over time were observed in 29 phosphoproteins. Cluster analysis indicated that nucleotide-binding proteins and zinc finger CCCH- and BED-type proteins increased in abundance during the first 12 h of imbibition and then decreased. The in silico protein-protein interactions for 29 nuclear phosphoproteins indicated that the Sas10/Utp3 protein, which functions in snoRNA binding and gene silencing, was the center of the phosphoprotein network in nuclei. The germination rate of seeds was significantly slowed with phosphatase inhibitor treatment. The mRNA expression of the zinc finger CCCH-type protein did not change, and the zinc finger BED-type protein was upregulated in rice embryos during the early stage of germination with phosphatase inhibitor treatment. These results suggest that the phosphorylation and dephosphorylation of nuclear proteins are involved in rice seed germination. Furthermore, transcription factors such as zinc finger CCCH- and BED-type proteins might play a key role through nuclear phosphoproteins, and Sas10/Utp3 protein might interact with nuclear phosphoproteins in rice embryos to mediate the early stage of seed germination.

  12. Robotic surgery for early stage cervical cancer: Evolution and current trends.

    PubMed

    Medlin, Erin E; Kushner, David M; Barroilhet, Lisa

    2015-12-01

    The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy.

  13. Robotic surgery for early stage cervical cancer: Evolution and current trends.

    PubMed

    Medlin, Erin E; Kushner, David M; Barroilhet, Lisa

    2015-12-01

    The management of early stage cervical cancer often includes surgery in the form of radical hysterectomy, radical trachelectomy, or radical parametrectomy. Surgical techniques have evolved to include minimal invasive approaches, and more recently, to include robotic assisted techniques. This review highlights the evolution of surgical management of early cervical cancer and specifically explores robotic assisted radical hysterectomy, radical trachelectomy, radical parametrectomy, and the role of neoadjuvant chemotherapy. PMID:26768315

  14. [Retraction of: Diagnostics and treatment of early stages of oral cancer].

    PubMed

    Warloe, Trond; Aamdal, Steinar; Reith, Albrecht; Bryne, Magne

    2006-09-01

    The undersigned, who are co-authors of the article Diagnostics and treatment of early stages of oral cancer, wish to retract it. The reason is that the basis for the review article has been shown to be false. A review committee, that has assessed the research activity of the main author, has concluded that the data in this article are fabricated. We can no longer stand behind the article and hereby retract it. PMID:16967079

  15. Gadolinium metallo nanocongregates as potential magnetosensors for detecting early stage cancers

    SciTech Connect

    Dutta, Ranu; Pandey, Avinash C.

    2015-04-27

    Gadolinium chelates and gadolinium based inorganic nanoparticles have been extensively studied, because of the high magnetic moment of gadolinium. Here, metallic gadolinium nanocongregates have been developed. Upon injecting these nanoparticles in the mice, they initially circulate in the blood stream and are localized at the cancer site, which could be visualized upon application of magnetic field hence acting as small magnetic nanosensors searching for even small cancers, detecting cancers at a very early stage.

  16. Evaluation and treatment of high-risk patients with early-stage lung cancer.

    PubMed

    Mehta, Hiren J; Ross, Christopher; Silvestri, Gerard A; Decker, Roy H

    2011-12-01

    Standard therapy for early-stage non-small cell lung cancer is lobectomy for patients who are able to tolerate such surgery. However, the risk of postoperative morbidity is not trivial, with a 30% to 40% incidence of postoperative complications and a 1% to 5% incidence of operative mortality. Some patients, though technically resectable, refuse surgery or are considered medically inoperable because of insufficient respiratory reserve, cardiovascular disease, or general frailty. This group is considered either "high risk" or "medically inoperable."

  17. Polymorphism in rice amylases at an early stage of seed germination.

    PubMed

    Mitsunaga, S; Kawakami, O; Numata, T; Yamaguchi, J; Fukui, K; Mitsui, T

    2001-03-01

    A polymorphism in rice amylases at an early stage of seed germination is analyzed by zymogram. In non-glutinous cultivars of rice, alpha-amylase isozymes are mainly confirmed in germinating seeds. However, in glutinous cultivars, beta-amylase isozymes, which are not confirmed in nonglutinous cultivars, make up the major part of the total amylase activity and the expression of alpha-amylases are repressed. PMID:11330685

  18. Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

    PubMed Central

    2014-01-01

    Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

  19. Comparison of Favorable Early-Stage Hodgkin's Lymphoma Treatments: A Single-Institution Review

    SciTech Connect

    Samant, Rajiv; Alomary, Ibraheem; Alsaeed, Eyad; Al-jasir, Badr; Bence-Bruckler, Isabelle; Cross, Peter; Genest, Paul; Huebsch, Lothar

    2010-03-15

    Purpose: To compare outcomes of patients receiving combined-modality chemotherapy and radiation (CMT) vs. other approaches for early-stage Hodgkin's lymphoma (HL). Methods and Materials: A review of patients with nonbulky, early-stage (IA/IIA) HL treated between 1984 and 2002 was performed to determine the treatment approaches used and the outcomes obtained. Results: There were 173 adult patients with newly diagnosed early-stage HL (49% men, 51% women, median age 33 [range 17-82] years). Treatment was as follows: extended-field radiotherapy alone (EFRT) 49%; chemotherapy alone (CTA) 13%; and CMT 38%. Among CMT patients, 36% received abbreviated doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy (three to four cycles) followed by involved-field radiotherapy. With a median follow-up of 8.3 years, the estimated 10-year relapse-free survival (RFS) and overall survival (OS) rates for the entire cohort were 78% and 85%, respectively. The 10-year RFS and OS rates for the various groups were as follows: 69% and 81% for EFRT; 78% and 84% for CTA; and 87% and 89% for CMT. The 10-year RFS rate was significantly higher (p < 0.01) among CMT patients. The use of EFRT has diminished from approximately 90% in the 1980s to virtually no use at present, whereas the use of CTA and CMT has increased significantly (p < 0.01). Conclusion: Early-stage HL treatment has changed dramatically over the past 2 decades, and our results support the superiority and continued use of CMT, specifically abbreviated-course chemotherapy and involved-field radiotherapy, as an appropriate treatment approach.

  20. Therapeutic role of systematic lymphadenectomy in early-stage endometrial cancer: A systematic review

    PubMed Central

    LI, MEI-YI; HU, XIAO-XIA; ZHONG, JIAN-HONG; CHEN, LU-LU; LIN, YONG-XIU

    2016-01-01

    The purpose of the current review was to examine whether systematic lymphadenectomy is safe and effective for treating early-stage endometrial cancer. PubMed, Embase, the Cochrane Library and the China National Knowledge Infrastructure databases were systematically searched during April 2014 to identify studies comparing the use of systematic lymphadenectomy and no systematic lymphadenectomy in parallel for the treatment of early-stage endometrial cancer. A total of 13 eligible studies involving 51,155 patients were included in this review. The median overall survival (OS) rate at 5 years following lymphadenectomy was 90% (range, 73.1–98.3%) for patients undergoing the systematic procedure and 88.2% (range, 68–98.4%) for patients not undergoing the systematic procedure. For the two types of lymphadenectomy, OS has tended to improve over the last 20 years. The combined rate of disease-free and progression-free survival was higher in patients who underwent systematic lymphadenectomy, and the recurrence rate was lower. In particular, systematic lymphadenectomy was associated with markedly higher OS than the non-systematic procedure for patients with intermediate- and high-risk endometrial cancer when ≥11 lymph nodes were removed. Systematic lymphadenectomy demonstrates clinical benefit in patients with early-stage endometrial cancer and should thus be a standard treatment option. In conclusion, systematic lymphadenectomy leads to higher OS than no systematic lymphadenectomy in intermediate- and high-risk patients with early-stage endometrial cancer, particularly when the procedure removes ≥11 lymph nodes. PMID:27313706

  1. [Signal exchange between plants and Arbuscular Mycorrhizae fungi during the early stage of symbiosis - A review].

    PubMed

    Duan, Qianqian; Yang, Xiaohong; Huang, Xianzhi

    2015-07-01

    Much is known about Arbuscular Mycorrhizae (AM), an important component of the ecosystem, whereas little is known about the signal exchange that allows mutual recognition and reprograming for the anticipated physical interaction. This review addresses the latest advances of signal exchange between plants and AM, including signal substances and their function, related genes and regulation function in the early stage of plant-fungal symbiosis.

  2. Funding opportunities for clinical investigators in the early stages of career development in cardiovascular research.

    PubMed

    Mentz, Robert J; Becker, Richard C

    2013-11-01

    Contemporary cardiovascular research offers junior investigators the opportunity to explore the gamut of biomedical questions. Despite the recent reduction in the availability of funding mechanisms that have historically served as the primary pathways for investigators in the early stages of career development, there remain numerous traditional and non-traditional funding opportunities. This article highlights these opportunities in order to assist early career investigators in the development of a personalized research trajectory, which optimizes the potential for career success.

  3. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

    PubMed Central

    Jang, Ye-Rang; Kim, Hyeyoung; Lee, Jeong-Moo; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

  4. Characterization of early stage cartilage degradation using diffuse reflectance near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Brown, C. P.; Jayadev, C.; Glyn-Jones, S.; Carr, A. J.; Murray, D. W.; Price, A. J.; Gill, H. S.

    2011-04-01

    Interest in localized and early stage treatment technologies for joint conditions such as osteoarthritis is growing rapidly. It has therefore become important to develop objective measures capable of characterizing the earliest (non-visible) changes associated with degeneration to aid treatment procedures. In addition to assessing tissue before treatment, it is further important to develop an effective, non-destructive means of monitoring post-treatment tissue healing, and of providing the high-quality data needed for trials of developing treatment methods. To investigate its ability to detect the early stages of degeneration in cartilage-on-bone, diffuse reflectance near infrared spectroscopy was applied to normal and osteoarthritic joints. A discriminating function was developed to relate absorbance peaks of interest and track degradation around focal osteoarthritic defects. The function could distinguish between normal and degraded tissue (100% separation of normal tissue from that within 25 mm of a defect) and between different stages of osteoarthritic progression (p < 0.05). This technique allows simple, practical and non-destructive assessment of component-level properties over the full depth of the tissue. It has the potential to increase our understanding of the underlying etiologic and pathogenic processes in early stage degeneration, to assist classification and the development of new treatment methods.

  5. Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    PubMed

    Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

    2011-01-01

    Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

  6. Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    PubMed

    Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

    2011-01-01

    Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base. PMID:21822050

  7. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis

    PubMed Central

    López-Góngora, Mariana; Escartín, Antonio; Martínez-Horta, Saul; Fernández-Bobadilla, Ramón; Querol, Luis; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-01-01

    Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes. PMID:26322632

  8. Population-based Estimate of the Prevalence of HER-2 Positive Breast Cancer Tumors for Early Stage Patients in the US

    PubMed Central

    Cronin, Kathleen A.; Harlan, Linda C.; Dodd, Kevin W.; Abrams, Jeffrey S.; Ballard-Barbash, Rachel

    2010-01-01

    The goal of this study was to estimate prevalence of HER-2 positive tumors in a population-based sample of 1026 women diagnosed in 2005 with early stage breast cancer. We modeled the relationship between patient and tumor characteristics and HER-2. HER-2 positive estimates were 19% for women aged ≤49 years and 15% aged ≥50 years. HER-2 varied by tumor grade and size in women aged ≤49 years but was not significant in multivariate analysis. Tumor grade and race were associated with HER-2 for women aged ≥50 years after controlling for other variables. HER-2 varies by age and by race and tumor in older women. PMID:20690807

  9. Whole Reproductive System Non-Negative Matrix Factorization Mass Spectrometry Imaging of an Early-Stage Ovarian Cancer Mouse Model

    PubMed Central

    Kim, Jaeyeon; Bennett, Rachel V.; Parry, R. Mitchell; Gaul, David A.; Wang, May D.; Matzuk, Martin M.; Fernández, Facundo M.

    2016-01-01

    High-grade serous carcinoma (HGSC) is the most common and deadliest form of ovarian cancer. Yet it is largely asymptomatic in its initial stages. Studying the origin and early progression of this disease is thus critical in identifying markers for early detection and screening purposes. Tissue-based mass spectrometry imaging (MSI) can be employed as an unbiased way of examining localized metabolic changes between healthy and cancerous tissue directly, at the onset of disease. In this study, we describe MSI results from Dicer-Pten double-knockout (DKO) mice, a mouse model faithfully reproducing the clinical nature of human HGSC. By using non-negative matrix factorization (NMF) for the unsupervised analysis of desorption electrospray ionization (DESI) datasets, tissue regions are segregated based on spectral components in an unbiased manner, with alterations related to HGSC highlighted. Results obtained by combining NMF with DESI-MSI revealed several metabolic species elevated in the tumor tissue and/or surrounding blood-filled cyst including ceramides, sphingomyelins, bilirubin, cholesterol sulfate, and various lysophospholipids. Multiple metabolites identified within the imaging study were also detected at altered levels within serum in a previous metabolomic study of the same mouse model. As an example workflow, features identified in this study were used to build an oPLS-DA model capable of discriminating between DKO mice with early-stage tumors and controls with up to 88% accuracy. PMID:27159635

  10. Whole Reproductive System Non-Negative Matrix Factorization Mass Spectrometry Imaging of an Early-Stage Ovarian Cancer Mouse Model.

    PubMed

    Paine, Martin R L; Kim, Jaeyeon; Bennett, Rachel V; Parry, R Mitchell; Gaul, David A; Wang, May D; Matzuk, Martin M; Fernández, Facundo M

    2016-01-01

    High-grade serous carcinoma (HGSC) is the most common and deadliest form of ovarian cancer. Yet it is largely asymptomatic in its initial stages. Studying the origin and early progression of this disease is thus critical in identifying markers for early detection and screening purposes. Tissue-based mass spectrometry imaging (MSI) can be employed as an unbiased way of examining localized metabolic changes between healthy and cancerous tissue directly, at the onset of disease. In this study, we describe MSI results from Dicer-Pten double-knockout (DKO) mice, a mouse model faithfully reproducing the clinical nature of human HGSC. By using non-negative matrix factorization (NMF) for the unsupervised analysis of desorption electrospray ionization (DESI) datasets, tissue regions are segregated based on spectral components in an unbiased manner, with alterations related to HGSC highlighted. Results obtained by combining NMF with DESI-MSI revealed several metabolic species elevated in the tumor tissue and/or surrounding blood-filled cyst including ceramides, sphingomyelins, bilirubin, cholesterol sulfate, and various lysophospholipids. Multiple metabolites identified within the imaging study were also detected at altered levels within serum in a previous metabolomic study of the same mouse model. As an example workflow, features identified in this study were used to build an oPLS-DA model capable of discriminating between DKO mice with early-stage tumors and controls with up to 88% accuracy. PMID:27159635

  11. Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice

    PubMed Central

    Pollock, Zemmie; Harrod, Kevin S.; Xu, Fadi

    2016-01-01

    H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal) or HK486 (non-lethal) virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min) and hypercapnia (HCVR; 7% CO2 for 5 min) were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi) and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR) of substance P (SP-IR) in the nodose ganglion or tyrosine hydroxylase (TH-IR) in the carotid body coupled with the nucleoprotein of influenza A (NP-IR) was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1) both viral infections failed to alter body temperature and weight, V˙CO2, or induce viremia while producing similarly high lung viral titers; 2) HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3) only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death. PMID:26808681

  12. Predictors of locoregional recurrence in early stage oral cavity cancer with free surgical margins.

    PubMed

    Huang, Tsai-Ying; Hsu, Lee-Ping; Wen, Yu-Hsuan; Huang, Tung-Tsun; Chou, Yu-Fu; Lee, Chia-Fong; Yang, Miao-Chun; Chang, Yi-Kuo; Chen, Peir-Rong

    2010-01-01

    Locoregional recurrence in patients with early stage oral cavity squamous cell carcinoma (ESOSCC) after surgery remains a problem and can affect their survival. We sought to identify new high-risk factors in these patients, who need further adjuvant therapy. We retrospectively reviewed records for 148 patients who underwent surgery for ESOSCC between 2002 and 2006 with negative surgical margins. The primary endpoint was locoregional recurrence. Recurrence-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Univariate and multivariate analyses were used to identify independent predictors of locoregional recurrence. All patients were grouped into the low- and high-risk groups according to the odds ratios (OR) of the predictors. Recurrence rates of the low- and high-risk groups were then predicted. Recurrence was observed in 17 of 148 (11.5%) patients at the end of this study. None of the patients received postoperative radiotherapy or chemotherapy. At 3 years, the RFS rate was 89.7% and the OS rate at 3 years was 84.1%. Univariate analysis of the RFS revealed three significant prognostic factors: lymphovascular permeation (LVP, p<0.001), perineural infiltration (PNI, p=0.08), and non-T4 muscular invasion (non-T4MI, p<0.005). Multivariate analysis demonstrated that LVP (p=0.007, OR=10.7) and non-T4 MI (p=0.001, OR=8.347) were independent predictors. The recurrence rate was 1.96% in patients without LVP or non-T4MI, and it increased to 26.47% in patients with non-T4MI, to 50% in patients with LVP, and to 50% in patients with both. According to the status of LVP and non-T4MI, patients were divided into two groups: low-risk (no factors present) and high-risk (one or both factors present) groups. The 2-year RFS was lower in the high-risk group (84.13%) than in the low-risk group (93.91%); the 3-year RFS was also lower in the high-risk group (70.49%) than in the low-risk group (91.99%) (p=0.008). Subgroup analysis revealed that

  13. Dosimetric and Clinical Outcomes of Involved-Field Intensity-Modulated Radiotherapy After Chemotherapy for Early-Stage Hodgkin's Lymphoma With Mediastinal Involvement

    SciTech Connect

    Lu Ningning; Li Yexiong; Wu Runye; Zhang Ximei; Wang Weihu; Jin Jing; Song Yongwen; Fang Hui; Ren Hua; Wang Shulian; Liu Yueping; Liu Xinfan; Chen Bo; Dai Jianrong; Yu Zihao

    2012-09-01

    Purpose: To evaluate the dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy (IF-IMRT) for patients with early-stage Hodgkin's lymphoma (HL) with mediastinal involvement. Methods and Materials: Fifty-two patients with early-stage HL that involved the mediastinum were reviewed. Eight patients had Stage I disease, and 44 patients had Stage II disease. Twenty-three patients (44%) presented with a bulky mediastinum, whereas 42 patients (81%) had involvement of both the mediastinum and either cervical or axillary nodes. All patients received combination chemotherapy followed by IF-IMRT. The prescribed radiation dose was 30-40 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated. Results: The median mean dose to the primary involved regions (planning target volume, PTV1) and boost area (PTV2) was 37.5 Gy and 42.1 Gy, respectively. Only 0.4% and 1.3% of the PTV1 and 0.1% and 0.5% of the PTV2 received less than 90% and 95% of the prescribed dose, indicating excellent PTV coverage. The median mean lung dose and V20 to the lungs were 13.8 Gy and 25.9%, respectively. The 3-year overall survival, local control, and progression-free survival rates were 100%, 97.9%, and 96%, respectively. No Grade 4 or 5 acute or late toxicities were reported. Conclusions: Despite the large target volume, IF-IMRT gave excellent dose coverage and a favorable prognosis, with mild toxicity in patients with early-stage mediastinal HL.

  14. 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

  15. [Retrospective analysis for 104 cases of early-stage Hodgkin's Lymphoma treated with different modality therapies].

    PubMed

    Du, Ting-Ting; Xiao, Xiu-Bin; Su, Hang; Da, Yong; Chen, Xin-Lin; Zhong, Kai-Li; Zhao, Shi-Hua; Lu, Yun; Wang, Shuang; Zhang, Wei-Jing

    2012-04-01

    This paper explored the curative effect of combined modality therapy and extended field radiotherapy for early-stage Hodgkin's Lymphoma. 104 cases of early-stage Hodgkin's Lymphoma from Jan 1987 to Dec 2010 in PLA Hospital 307 were retrospectively analyzed, including 76 cases in combined modality therapy group and 28 cases in extended field radiotherapy group, and the long-term efficacy and toxicity of two therapy modalities were evaluated. The results showed that the median survival time of 104 cases was 85.42 months, the complete remission rates of combined modality therapy and extended field radiotherapy groups were 72.4 and 71.4 respectively (P = 0.924); the overall response rates of combined modality therapy and extended field radiotherapy groups were 97.4 and 96.4 respectively (P = 0.779); the 5-year overall survival (OS) rates in the 2 groups were 89.5 and 89.1 respectively, and the 8-year OS rates of the 2 groups were 81.3 and 70.6. No statistical difference was found in above-mentioned 2 groups. Moreover, the 5-year progression free survival (PFS) rates of these 2 groups were 84.2 and 69.0 (P = 0.04), and 8-year PFS rates of these 2 groups were 80.0 and 55.5 (P = 0.04) respectively, the 5-year relapse rates of these 2 groups were 28.1 and 45.6 (P = 0.023) respectively. It is concluded that the combined modality therapy can raise the PFS rate and reduce the relapse rate as compared with extended field radiotherapy for early-stage Hodgkin's Lymphoma, but there is no difference in the overall survival rate between the 2 groups.

  16. Prediction of motor outcome by shoulder subluxation at early stage of stroke

    PubMed Central

    Jang, Sung Ho; Yi, Ji Hyun; Chang, Chul Hoon; Jung, Young Jin; Kim, Seong Ho; Lee, Jun; Seo, Jeong Pyo

    2016-01-01

    Abstract We attempted to determine whether shoulder subluxation at the early stage of stroke can predict motor outcome in relation to the corticospinal tract (CST) state on diffusion tensor tractography. Fifty-nine stroke patients with severe hemiparesis were recruited. The patients were classified according to the distance of shoulder subluxation (group A: ≥2 cm, group B: <2 cm) and the affected CST on diffusion tensor tractography at the first evaluation (CST type A—the CST was discontinued at the stroke lesion; CST type B—the integrity of the CST was preserved). Motor function of the patients was evaluated twice (first: beginning of rehabilitation—24.1 ± 16.6 days; second: discharge after first rehabilitation—58.5 ± 24.1 days) using the Medical Research Council score, Motricity Index, and Modified Brunnstrom Classification. Regarding the improvement of the Medical Research Council for the finger extensor and upper Motricity Index, the order in terms of better recovery was as follows: group B–type B, group A–type B, group B–type A, and group A–type A (P < 0.05). The distance of shoulder subluxation showed significant correlation with improvement of the finger extensor (moderate negative correlation, r = −0.37) and improvement of the Modified Brunnstrom Classification (weak negative correlation, r = −0.29) (P < 0.05). The presence of shoulder subluxation at the early stage of stroke can be a predictor of motor outcome of the affected upper extremity and the degree of shoulder subluxation can be a predictor of the motor function of the affected hand. Therefore, our results suggest that shoulder subluxation in relation to the affected CST state at the early stage of stroke can be a prognostic factor for motor outcome. PMID:27512873

  17. Impact of diabetes mellitus on oncological outcomes after radical hysterectomy for early stage cervical cancer

    PubMed Central

    2016-01-01

    Objective To evaluate the relationship between type 2 diabetes mellitus (DM) and oncological outcomes in early stage cervical cancer patients who underwent radical surgical resection. Methods Patients with early stage cervical cancer diagnosed between 2001 and 2014 were retrospectively enrolled. We assessed the outcomes of 402 non-DM and 42 DM patients with cervical cancer. We tested the prognostic value of DM via Cox proportional hazard modeling. Results Patients with DM were more likely to be older and overweight. In the DM group, 20 and 22 patients were and were not taking metformin, respectively. The 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) rate for the whole study population were 88.49% and 96.34%, respectively. In the DM group, there was no evidence that metformin affected the RFS (p=0.553) or the OS (p=0.429). In multivariate analysis, age (p=0.007), histology (p=0.006), and deep stromal invasion (p=0.007) were independent adverse prognostic factors for RFS. There was a borderline significant association of increased RFS with DM (p=0.051). However, a time-varying-effect Cox model revealed that the DM was associated with a worse RFS (hazard ratio, 11.15; 95% CI, 2.00 to 62.08, p=0.022) after 5 years. DM (p=0.008), age (p=0.009), and node status (p=0.001) were the only 3 independent prognostic factors for OS. Conclusion Early stage cervical cancer patients with type 2 DM have a poorer oncological outcome than patients without DM. PMID:27029749

  18. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    PubMed

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  19. Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

    PubMed Central

    Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

    2016-01-01

    Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

  20. Qualitative evaluation of a self-management intervention for people in the early stage of dementia.

    PubMed

    Martin, Faith; Turner, Andrew; Wallace, Louise M; Stanley, Damian; Jesuthasan, Jana; Bradbury, Nicola

    2015-07-01

    Self-management programs are effective for people living with chronic illnesses. However, there has been little research addressing self-management for people with dementia in the early stages. This study presents a qualitative evaluation of the experiences of attending a novel self-management program and initial process evaluation. The program was designed with and for people with dementia. It addresses: (a) relationship with family, (b) maintenance of an active lifestyle, (c) psychological well-being, (d) techniques to cope with memory changes and (e) information about dementia. Six participants with early stage dementia completed the intervention that was co-delivered by lay and clinical professional tutors. Participants and tutors attended focus group and interviews at the end of the program to explore their perceptions of the intervention. These were audio-recorded, transcribed verbatim and analysed thematically. Participants reported enjoyment and benefits from the intervention. This was despite some reporting concerns relating to their memory difficulties. The program's flexible nature, focus on strengths and the opportunity to spend time with other people living with dementia were particularly well received. Participants and tutors outlined areas for further improvement. The program was feasible and its flexible delivery appeared to facilitate participant benefit. Emphasis should be placed on maintaining activity and relationships, improving positive well-being and social interaction during the program. Memory of the pleasant experience and strengths focus was evidenced, which may impact positively on quality of life. The results highlight the usefulness and acceptability of self-management for people with early stage dementia and provide initial support for the program's structure and content.

  1. Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

    SciTech Connect

    Torok, Jordan A.; Wu, Yuan; Prosnitz, Leonard R.; Kim, Grace J.; Beaven, Anne W.; Diehl, Louis F.; Kelsey, Chris R.

    2015-05-01

    Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

  2. Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

    PubMed Central

    Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

    2015-01-01

    Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

  3. Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

    PubMed Central

    Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

    2012-01-01

    Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

  4. Cryopreservation of In Vitro-Produced Early-Stage Porcine Embryos in a Closed System

    PubMed Central

    Men, Hongsheng; Spate, Lee D.; Murphy, Clifton N.; Prather, Randall S.

    2015-01-01

    Abstract Cryostorage of porcine embryos in a closed pathogen-free system is essential for the maintenance and safeguard of swine models. Previously, we reported a protocol for the successful cryopreservation of porcine embryos at the blastocyst stage in 0.25 mL ministraws. In this experiment, we aimed at developing a protocol to apply the same concept for the cryopreservation of early-stage porcine embryos. Porcine embryos from day 2 through day 4 were delipidated by using a modified two-step centrifugation method and were then cryopreserved in sealed 0.25 mL straws by using a slow cooling method. Control groups included open pulled straw (OPS) vitrified embryos after delipidation and noncryopreserved embryos without delipidation. There were no significant differences in cryosurvival between embryos frozen in 0.25 mL straws and OPS vitrified embryos across all the stages (two cell to morula) examined (p>0.05). Similarly, in all groups examined, the blastocyst rates were not different between the two cryopreserved groups. However, the blastocyst rates from the cryopreserved groups were significantly lower than the noncryopreserved controls (p<0.05). This experiment demonstrated that early-stage porcine embryos can survive cryopreservation in a closed system by using a slow cooling method at a comparable rate to those vitrified by using an ultrarapid cooling method (p>0.05). However, the developmental competence was significantly reduced after cryopreservation compared to noncryopreserved embryos. Further research is needed to optimize the protocol to improve the developmental potential of cryopreserved early-stage porcine embryos in sealed straws. PMID:26309801

  5. Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

    PubMed Central

    Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

    2015-01-01

    ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

  6. A Model of Isotope Separation in Cells at the Early Stages of Evolution.

    PubMed

    Melkikh, A V; Bokunyaeva, A O

    2016-03-01

    The separation of the isotopes of certain ions can serve as an important criterion for the presence of life in the early stages of its evolution. A model of the separation of isotopes during their transport through the cell membrane is constructed. The dependence of the selection coefficient on various parameters is found. In particular, it is shown that the maximum efficiency of the transport of ions corresponds to the minimum enrichment coefficient. At the maximum enrichment, the efficiency of the transport system approaches ½. Calculated enrichment coefficients are compared with experimentally obtained values for different types of cells, and the comparison shows a qualitative agreement between these quantities.

  7. [Current situation and confusion of sublobar resection for early stage lung cancer].

    PubMed

    Yang, Fan; Wang, Jun

    2015-10-01

    Lobectomy with lymph node dissection has long been the standard surgical procedure for non-small cell lung cancer. However, the increased identification of smaller and smaller and even more indolent tumors by advanced imaging screening rekindled the interest of sublobar resection. Still, existing evidence only supports sublobar resection for radiologically or pathologically "very-early" stage tumors or high-risk patients. Ongoing randomized controlled trials in America, Japan and Europe will address the issue of "radical" application of sublobar resection, as well as an elderly patient trial for "compromized" application initiated by us. These efforts will delineate the utility of sublobar resection in patients with non-small cell lung cancer.

  8. 'Making the best you can of it': living with early-stage Alzheimer's disease.

    PubMed

    Macrae, Hazel

    2008-04-01

    Drawing upon data from a qualitative study of persons who are in the early stage of the condition, this paper examines the meaning of Alzheimer's disease. It contrasts the meaning of the disease as portrayed in popular culture with its meaning as interpreted by persons living with it. Findings show that persons with the illness do not necessarily accept the negative cultural meaning of the disease, nor the helpless 'victim' role in which they are generally cast. With a determination to 'make the best of it', strategies such as humour, normalisation, present-time orientation, and life review are employed to create a meaningful life. PMID:18298633

  9. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer's disease.

    PubMed

    Krasodomska, Kamila; Lubiński, Wojciech; Potemkowski, Andrzej; Honczarenko, Krystyna

    2010-10-01

    Alzheimer's disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)--the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These

  10. Composition effects on the early-stage oxidation kinetics of (001) Cu-Au alloys

    NASA Astrophysics Data System (ADS)

    Zhou, G.-W.; Eastman, J. A.; Birtcher, R. C.; Baldo, P. M.; Pearson, J. E.; Thompson, L. J.; Wang, L.; Yang, J. C.

    2007-02-01

    An in situ environmental transmission electron microscopy study of the nucleation and growth of oxide islands during the early-stage oxidation of (001) Cu1-xAux alloys (x⩽38at.%) was undertaken in order to investigate the effects of alloying on oxide island nucleation behavior and growth kinetics. The kinetic data reveal that Au enhances the nucleation density of oxide islands and suppresses their growth rate. Our results provide insight into reasons for the decreased passivation properties of Cu when alloyed with Au.

  11. Microstructural evolution of 7012 alloy during the early stages of artificial ageing

    SciTech Connect

    Ferragut, R.; Somoza, A.; Tolley, A.

    1999-11-26

    A study of the microstructural evolution of a commercial 7012 (Al-Zn-Mg-Cu) age-hardenable alloy following artificial ageing by high resolution and conventional transmission electron microscopy and positron annihilation lifetime spectroscopy is presented. At the early stages of decomposition, the microstructure included precipitation of either pre-precipitate solute clusters or Guinier-Preston zones and semi-coherent {eta}{prime} precipitates, with typical sizes between 1 and 10 nm. Quantitative information on the size, number density and morphology of the particles present in the microstructure was obtained. The results were correlated with those obtained using positron annihilation lifetime spectroscopy.

  12. 'Making the best you can of it': living with early-stage Alzheimer's disease.

    PubMed

    Macrae, Hazel

    2008-04-01

    Drawing upon data from a qualitative study of persons who are in the early stage of the condition, this paper examines the meaning of Alzheimer's disease. It contrasts the meaning of the disease as portrayed in popular culture with its meaning as interpreted by persons living with it. Findings show that persons with the illness do not necessarily accept the negative cultural meaning of the disease, nor the helpless 'victim' role in which they are generally cast. With a determination to 'make the best of it', strategies such as humour, normalisation, present-time orientation, and life review are employed to create a meaningful life.

  13. Origin of the Directed Movement of Protocells in the Early Stages of the Evolution of Life

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.; Chesnokova, Oksana I.

    2012-08-01

    The origin of the directed motion of protocells during the early stages of evolution was discussed. The expenditures for movement, space orientation, and reception of information about the environment were taken into consideration, and it was shown that directed movement is evolutionarily advantageous in the following cases: when opposite gradients of different resources (for example, matter and energy) are great enough and when there is a rapid change in environmental parameters. It was also shown that the advantage of directed movement strategies depends greatly on how information about the environment is obtained by a protocell.

  14. Origin of the directed movement of protocells in the early stages of the evolution of life.

    PubMed

    Melkikh, Alexey V; Chesnokova, Oksana I

    2012-08-01

    The origin of the directed motion of protocells during the early stages of evolution was discussed. The expenditures for movement, space orientation, and reception of information about the environment were taken into consideration, and it was shown that directed movement is evolutionarily advantageous in the following cases: when opposite gradients of different resources (for example, matter and energy) are great enough and when there is a rapid change in environmental parameters. It was also shown that the advantage of directed movement strategies depends greatly on how information about the environment is obtained by a protocell. PMID:22772806

  15. Mitochondrial response to oxidative and nitrosative stress in early stages of diabetes.

    PubMed

    Noriega-Cisneros, Ruth; Cortés-Rojo, Christian; Manzo-Avalos, Salvador; Clemente-Guerrero, Mónica; Calderón-Cortés, Elizabeth; Salgado-Garciglia, Rafael; Montoya-Pérez, Rocío; Boldogh, Istvan; Saavedra-Molina, Alfredo

    2013-11-01

    Diabetes mellitus (DM) is associated with increased production of reactive oxygen and nitrogen species; consequently, an increase in lipid peroxidation and a decrease in antioxidants resulting in mitochondrial dysfunction. Using a rat model of DM induced by streptozotocin, we show the opposite: an increase in NO levels, S-nitrosylation, aconitase activity, and total glutathione and a decrease in lipid peroxidation at early stages of diabetes. These data imply that the decrease in lipid peroxidation is a vital early response to hyperglycemia to prevent escalation of ROS generation in mitochondria. These results also suggest a need for novel therapeutic targets to prevent the neurological consequences of diabetes.

  16. Clean Energy Finance: Challenges and Opportunities of Early-Stage Energy Investing (Presentation)

    SciTech Connect

    Heap, D.; Pless, J.; Aieta, N.

    2013-12-01

    Characterized by a changing landscape and new opportunities, today's increasingly complex energy decision space will need innovative financing and investment models to appropriately assess risk and profitability. This report provides an overview of the current state of clean energy finance across the entire spectrum but with a focus on early stage investing, and it includes insights from investors across all investment classes. Further, this report aims to provide a roadmap with the mechanisms, limitations, and considerations involved in making successful investments by identifying risks, challenges, and opportunities in the clean energy sector.

  17. Modeling the early stages of self-assembly in nanophase materials.

    PubMed

    Kozak, John J; Nicolis, C; Nicolis, G

    2007-04-21

    The early stages of self-assembly of the elementary building blocks of nanophase materials are studied. The relative roles of entropic and energetic factors in determining the relative abundance of the final products present is analyzed using both a kinetic mean field model and a mesoscopic approach in which self-assembly is viewed as an encounter-controlled process on a discrete lattice. The relevance of the results in zeolite synthesis in connection with the ordered liquid phases recently discovered in these materials is discussed.

  18. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA.

  19. Advances in Medical Management of Early Stage and Advanced Breast Cancer: 2015.

    PubMed

    Witherby, Sabrina; Rizack, Tina; Sakr, Bachir J; Legare, Robert D; Sikov, William M

    2016-01-01

    Standard management of early stage and advanced breast cancer has been improved over the past few years by knowledge gained about the biology of the disease, results from a number of eagerly anticipated clinical trials and the development of novel agents that offer our patients options for improved outcomes or reduced toxicity or both. This review highlights recent major developments affecting the systemic therapy of breast cancer, broken down by clinically relevant patient subgroups and disease stage, and briefly discusses some of the ongoing controversies in the treatment of breast cancer and promising therapies on the horizon.

  20. A Model of Isotope Separation in Cells at the Early Stages of Evolution

    NASA Astrophysics Data System (ADS)

    Melkikh, A. V.; Bokunyaeva, A. O.

    2016-03-01

    The separation of the isotopes of certain ions can serve as an important criterion for the presence of life in the early stages of its evolution. A model of the separation of isotopes during their transport through the cell membrane is constructed. The dependence of the selection coefficient on various parameters is found. In particular, it is shown that the maximum efficiency of the transport of ions corresponds to the minimum enrichment coefficient. At the maximum enrichment, the efficiency of the transport system approaches ½. Calculated enrichment coefficients are compared with experimentally obtained values for different types of cells, and the comparison shows a qualitative agreement between these quantities.

  1. Prognostic modeling in early stage lung cancer: an evolving process from histopathology to genomics.

    PubMed

    Harpole, David H

    2007-05-01

    The goal is to validate a molecular-based tumor model that identifies patients at low-risk for cancer recurrence and who will not benefit from adjuvant chemotherapy. The remaining patients will be randomized to observation (present standard of care) or adjuvant chemotherapy to determine efficacy of adjuvant in this population. Investigators have focused on the identification of markers that may predict poor prognosis as a way to "enrich" the population by separating those likely to have early recurrence and cancer death from those not needing additional treatment after resection. The initial projects refined predictive models of cancer recurrence after resection for patients with early stage non-small cell lung cancer.

  2. [Treatment of non-small cell lung carcinoma in early stages].

    PubMed

    Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

    2013-12-01

    Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. PMID:23829961

  3. Transforming the work of early-stage drug discovery through bioprocess informatics.

    PubMed

    Holzman, Thomas F; Hebert, Eric J

    2005-01-01

    Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of the early-stages of target development in drug discovery. We contrast our approach to strategies that have recently evolved at startup biotechnology companies who use similar technological approaches to drug development but who are less encumbered by precedent and history.

  4. Similar Survival With Breast Conservation Therapy or Mastectomy in the Management of Young Women With Early-Stage Breast Cancer

    SciTech Connect

    Mahmood, Usama; Morris, Christopher; Neuner, Geoffrey; Koshy, Matthew; Kesmodel, Susan; Buras, Robert; Chumsri, Saranya; Bao Ting; Tkaczuk, Katherine; Feigenberg, Steven

    2012-08-01

    Purpose: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. Results: A total of 14,764 women were identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5-, 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). Conclusions: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival.

  5. TH-A-BRF-04: Intra-Fraction Motion Characterization for Early Stage Rectal Cancer Using Cine-MRI

    SciTech Connect

    Kleijnen, J; Asselen, B; Burbach, M; Intven, M; Reerink, O; Philippens, M; Lagendijk, J; Raaymakers, B

    2014-06-15

    Purpose: To investigate the intra-fraction motion in patients with early stage rectal cancer using cine-MRI. Methods: Sixteen patient diagnosed with early stage rectal cancer underwent 1.5 T MR imaging prior to each treatment fraction of their short course radiotherapy (n=76). During each scan session, three 2D sagittal cine-MRIs were performed: at the beginning (Start), after 9:30 minutes (Mid), and after 18 minutes (End). Each cine-MRI has a duration of one minute at 2Hz temporal resolution, resulting in a total of 3:48 hours of cine-MRI. Additionally, standard T2-weighted (T2w) imaging was performed. Clinical target volume (CTV) an tumor (GTV) were delineated on the T2w scan and transferred to the first time-point of each cine-MRI scan. Within each cine-MRI, the first frame was registered to the remaining frames of the scan, using a non-rigid B-spline registration. To investigate potential drifts, a similar registration was performed between the first frame of the Start and End scans.To evaluate the motion, the distances by which the edge pixels of the delineations move in anterior-posterior (AP) and cranial-caudal (CC) direction, were determined using the deformation field of the registrations. The distance which incorporated 95% of these edge pixels (dist95%) was determined within each cine-MRI, and between Start- End scans, respectively. Results: Within a cine-MRI, we observed an average dist95% for the CTV of 1.3mm/1.5mm (SD=0.7mm/0.6mm) and for the GTV of 1.2mm/1.5mm (SD=0.8mm/0.9mm), in respectively AP/CC. For the CTV motion between the Start and End scan, an average dist95% of 5.5mm/5.3mm (SD=3.1mm/2.5mm) was found, in respectively AP/CC. For the GTV motion, an average dist95% of 3.6mm/3.9mm (SD=2.2mm/2.5mm) was found in AP/CC, respectively. Conclusion: Although intra-fraction motion within a one minute cine-MRI is limited, substantial intra-fraction motion was observed within the 18 minute time period between the Start and End cine-MRI.

  6. The Problems of Replication in the Early Stages of Evolution: Enumeration of Variants and Spatial Configurations of Replicators

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.

    2014-12-01

    Two main problems of replication in the early stages of evolution are discussed: the problem of exponentially large number of conformational degrees of freedom and the problem of enumeration of variants.

  7. Targeted labeling of an early-stage tumor spheroid in a chorioallantoic membrane model with upconversion nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Holz, Jasmin A.; Ding, Yadan; Liu, Xiaomin; Zhang, Youlin; Tu, Langping; Kong, Xianggui; Priem, Bram; Nadort, Annemarie; Lambrechts, Saskia A. G.; Aalders, Maurice C. G.; Buma, Wybren Jan; Liu, Yichun; Zhang, Hong

    2015-01-01

    In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb).In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb). Electronic supplementary information (ESI) available: Details of experimental procedures for the sample preparation and characterization, Chick CAM model, 3-D multicellular tumor spheroids, UCNPs circulating in CAM. See DOI: 10.1039/c4nr05638h

  8. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

    PubMed Central

    An, Chansik; Choi, Youn Ah; Choi, Dongil; Paik, Yong Han; Ahn, Sang Hoon; Kim, Myeong-Jin; Paik, Seung Woon; Han, Kwang-Hyub

    2015-01-01

    Background/Aims The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. Methods Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. Results The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). Conclusions The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC. PMID:26523271

  9. Effects of cigarette smoke exposure on early stage embryos in the rat

    SciTech Connect

    Tachi, Norihide; Aoyama, Mitsuko )

    1989-09-01

    It is well recognized that cigarette smoking in pregnant women exerts many deleterious effects on their progenies; intrauterine growth retardation, and increases in perinatal mortality and premature births. The fetal growth retardation also has been reported in animals exposed to cigarette smoke. The authors previously demonstrated that cigarette smoke exposure in pregnant rats retarded the growth of fetuses from mid to late stages of pregnancy. In addition, the weight of uteri containing embryos in animals inhaling the smoke was smaller, although not significant, than that in the control on day 7 of pregnancy. Based on these findings, it was suggested that the growth of embryos in early stage seemed to be harmfully affected as well as during mid and late stages of pregnancy. However, since the uterine weight in early pregnancy was measured in the previous study instead of the direct observation of early stage embryos, it remained unclear whether the early development of embryos was really influenced by cigarette smoke exposure or not. The present study was designed to observe the effects of cigarette smoke inhalation by pregnant rats on early development of embryos from fertilization to implantation.

  10. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma.

    PubMed

    Zhang, Xindong; Gao, Lin; Liu, Zhi-Ping; Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  11. Treatment of early stage breast cancer by limited surgery and radical irradiation

    SciTech Connect

    Chu, A.M.; Cope, O.; Russo, R.; Wang, C.C.; Schulz, M.D.; Wang, C.; Rodkey, G.

    1980-01-01

    Eighty-five female patients with early stage breast cancer, i.e., Stage I and II were treated by limited surgery followed by radical radiation therapy at Massachusetts General Hospital between January, 1956 and December, 1974. Patients included those who were medically inoperable or who refused mastectomy. The 5-year survival rate was 83% and 76% for Stage I and II, respectively. The corresponding disease free survival (absolute) was 67% and 42%. Although the number of patients so treated is small, there was no significant difference in survival from the results of the radical mastectomy series at the same institution. No major complications were encountered. Seventeen of eighty-five patients developed minor problems; mostly fibrosis and minimal arm lymphedema stemmming from older orthovoltage equipment and treatment techniques. With the current availability of megavoltage equipment, improvements in techniques and dosimetry, complications should decrease. Combined limited surgery and radical radiation therapy should be considered in those patients where a radical mastectomy is not feasible because of psychological or medical problems. Since this procedure results in a cosmetically acceptable breast, radical radiation in early stage breast cancer seems a reasonable alternative to radical mastectomy.

  12. Discovery of piRNAs Pathway Associated with Early-Stage Spermatogenesis in Chicken

    PubMed Central

    Chang, Guobin; Guo, Qixin; Liu, Xiangping; Bi, Yulin; Zhang, Yu; Wang, Hongzhi; Li, Zhiteng; Guo, Xiaoming; Wan, Fang; Zhang, Yang; Xu, Qi; Chen, Guohong

    2016-01-01

    Piwi-interacting RNAs (piRNAs) play a key role in spermatogenesis. Here, we describe the piRNAs profiling of primordial germ cells (PGCs), spermatogonial stem cells (SSCs), and the spermatogonium (Sp) during early-stage spermatogenesis in chicken. We obtained 31,361,989 reads from PGCs, 31,757,666 reads from SSCs, and 46,448,327 reads from Sp cells. The length distribution of piRNAs in the three samples showed peaks at 33 nt. The resulting genes were subsequently annotated against the Gene Ontology (GO) database. Five genes (RPL7A, HSPA8, Pum1, CPXM2, and PRKCA) were found to be involved in cellular processes. Interactive pathway analysis (IPA) further revealed three important pathways in early-stage spermatogenesis including the FGF, Wnt, and EGF receptor signaling pathways. The gene Pum1 was found to promote germline stem cell proliferation, but it also plays a role in spermatogenesis. In conclusion, we revealed characteristics of piRNAs during early spermatogonial development in chicken and provided the basis for future research. PMID:27045806

  13. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

    2015-01-01

    One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

  14. Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy.

    PubMed

    Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul

    2010-03-01

    The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg.

  15. Molecular Mechanism of the Early Stage of Amyloidogenic Hexapeptides (NFGAIL) Aggregation

    NASA Astrophysics Data System (ADS)

    Shi, Bi-Yun; Zhou, Bo; Cai, Zhuo-Wei; Xiu, Peng; Yang, Zai-Xing

    2013-10-01

    Peptides/proteins aggregation can give rise to pathological conditions of many human diseases. Small partially ordered oligomers formed in the early stage of aggregation, rather than mature fibrils, are thought to be the main toxicity agent for the living cell. Thus, understanding the pathway and the underlying physical mechanism in the early stage of aggregation is very important for prevention and treatment of these protein functional diseases. Herein we use all-atom molecular dynamics simulations to study the aggregation of four NFGAIL hexapeptides (NFGAIL peptide is a core segment of human islet amyloid polypeptide and exhibits similar aggregation kinetics as the full-length polypeptide). We observe that the peptide monomers in water mainly adopt non-structural coil configurations; the four peptides which are randomly placed in water aggregate spontaneously to partially ordered oligomer (β-sheets) through dimerization or trimerization, with the dimerization predominated. Both parallel and anti-parallel β-sheets are observed. The hydrophobic interactions drive the initial peptides associations, and the subsequent conformational fluctuations promote the formation of more hydrogen bonds between the dangling hydrogen sites in the main chains of peptides.

  16. Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice.

    PubMed

    Good, Jeffrey M; Handel, Mary Ann; Nachman, Michael W

    2008-01-01

    House mice offer a powerful system for dissecting the genetic basis of phenotypes that isolate species in the early stages of speciation. We used a series of reciprocal crosses between wild-derived strains of Mus musculus and M. domesticus to examine F(1) hybrid male sterility, one of the primary phenotypes thought to isolate these species. We report four main results. First, we found significantly smaller testes and fewer sperm in hybrid male progeny of most crosses. Second, in some crosses hybrid male sterility was asymmetric and depended on the species origin of the X chromosome. These observations confirm and extend previous findings, underscoring the central role that the M. musculus X chromosome plays in reproductive isolation. Third, comparisons among reciprocal crosses revealed polymorphism at one or more hybrid incompatibilities within M. musculus. Fourth, the spermatogenic phenotype of this polymorphic interaction appears distinct from previously described hybrid incompatibilities between these species. These data build on previous studies of speciation in house mice and show that the genetic basis of hybrid male sterility is fairly complex, even at this early stage of divergence.

  17. Transcriptome profile of the early stages of breast cancer tumoral spheroids

    PubMed Central

    Pacheco-Marín, Rosario; Melendez-Zajgla, Jorge; Castillo-Rojas, Gonzalo; Mandujano-Tinoco, Edna; Garcia-Venzor, Alfredo; Uribe-Carvajal, Salvador; Cabrera-Orefice, Alfredo; Gonzalez-Torres, Carolina; Gaytan-Cervantes, Javier; Mitre-Aguilar, Irma B.; Maldonado, Vilma

    2016-01-01

    Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to reliably mimic the initial growth of primary and metastatic cancer cells. However, cancer cell growth during the initial stages has not been fully explored using a genome-wide approach. Thus, in the present study, we investigated the transcriptome of breast cancer cells during the initial stages of tumoral growth using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses showed that a metastatic signature was enriched as several adhesion molecules were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which were further supported by an increase in cell migration. Interestingly, we also found that the cancer cells at this stage of growth exhibited a paradoxical hyperactivation of oxidative mitochondrial metabolism. In addition, we found a large number of regulated (long non coding RNA) lncRNAs, several of which were co-regulated with neighboring genes. The regulatory role of some of these lncRNAs on mRNA expression was demonstrated with gain of function assays. This is the first report of an early-stage MTS transcriptome, which not only reveals a complex expression landscape, but points toward an important contribution of long non-coding RNAs in the final phenotype of three-dimensional cellular models. PMID:27021602

  18. Early-Stage Capital Cost Estimation of Biorefinery Processes: A Comparative Study of Heuristic Techniques.

    PubMed

    Tsagkari, Mirela; Couturier, Jean-Luc; Kokossis, Antonis; Dubois, Jean-Luc

    2016-09-01

    Biorefineries offer a promising alternative to fossil-based processing industries and have undergone rapid development in recent years. Limited financial resources and stringent company budgets necessitate quick capital estimation of pioneering biorefinery projects at the early stages of their conception to screen process alternatives, decide on project viability, and allocate resources to the most promising cases. Biorefineries are capital-intensive projects that involve state-of-the-art technologies for which there is no prior experience or sufficient historical data. This work reviews existing rapid cost estimation practices, which can be used by researchers with no previous cost estimating experience. It also comprises a comparative study of six cost methods on three well-documented biorefinery processes to evaluate their accuracy and precision. The results illustrate discrepancies among the methods because their extrapolation on biorefinery data often violates inherent assumptions. This study recommends the most appropriate rapid cost methods and urges the development of an improved early-stage capital cost estimation tool suitable for biorefinery processes.

  19. Early stage spin-state transition in LaCoO3 investigated by first principles

    NASA Astrophysics Data System (ADS)

    Leighton, C.; Hsu, H.; Cococcioni, M.; Wentzcovitch, R. M.

    2009-12-01

    Thermal-induced spin-state transition in LaCoO3 has been a highly debated phenomenon. The point in controversy is whether the intermediate-spin (IS) state can stably exist, and whether the intermediate-spin or high-spin (HS) state is the first excited state. In our calculation, we have successfully stabilized isolated HS and IS Co in an array of low-spin (LS) Co in LaCoO3 using the local density approximation + Hubbard U (LDA+U) method. The HS/LS (or IS/LS) Co population ratio is set to 1:7, so that the early stage of spin-state transition is properly approximated. The Hubbard U is self-consistently determined by first principles, so that the equation of state and the energy of Co in each spin state can be determined with better accuracy. We show that at low temperature, isolated IS Co has higher energy than isolated HS Co. We also show that low concentration of isolated IS Co can lead to metallic LaCoO3. Therefore, the early stage spin-state transition in LaCoO3 is LS-to-HS transition. This work was supported primarily by the MRSEC Program of the National Science Foundation under Award Number DMR-0212302 and DMR-0819885. It was also partially supported by NSF grants ITR-0426757 (VLab) and EAR 0757903. Calculations were performed at Minnesota Supercomputing Institute (MSI).

  20. Early-stage comparative sustainability assessment of new bio-based processes.

    PubMed

    Patel, Akshay D; Meesters, Koen; den Uil, Herman; de Jong, Ed; Worrell, Ernst; Patel, Martin K

    2013-09-01

    Our increasing demand for materials and energy has put critical roadblocks on our path towards a sustainable society. To remove these roadblocks, it is important to engage in smart research and development (R&D). We present an early-stage sustainability assessment framework that is used to analyze eight new bio-based process alternatives developed within the CatchBio research consortium in the Netherlands. This assessment relies on a multi-criteria approach, integrating the performance of chemical conversions based on five indicators into an index value. These indicators encompass economics, environmental impact, hazards and risks thereby incorporating elements of green chemistry principles, and techno-economic and life cycle assessments. The analyzed bio-based options target the production of fuels and chemicals through chemical catalysis. For each bio-based process, two R&D stages (current laboratory and expected future) are assessed against a comparable conventional process. The multi-criteria assessment in combination with the uncertainty and scenario analysis shows that the chemical production processes using biomass as feedstock can provide potential sustainability benefits over conventional alternatives. However, further development is necessary to realize the potential benefits from biomass gasification and pyrolysis processes for fuel production. This early stage assessment is intended as an input for R&D decision making to support optimal allocation and utilization of resources to further develop promising bio-based processes. PMID:24078179

  1. Early-Stage Capital Cost Estimation of Biorefinery Processes: A Comparative Study of Heuristic Techniques.

    PubMed

    Tsagkari, Mirela; Couturier, Jean-Luc; Kokossis, Antonis; Dubois, Jean-Luc

    2016-09-01

    Biorefineries offer a promising alternative to fossil-based processing industries and have undergone rapid development in recent years. Limited financial resources and stringent company budgets necessitate quick capital estimation of pioneering biorefinery projects at the early stages of their conception to screen process alternatives, decide on project viability, and allocate resources to the most promising cases. Biorefineries are capital-intensive projects that involve state-of-the-art technologies for which there is no prior experience or sufficient historical data. This work reviews existing rapid cost estimation practices, which can be used by researchers with no previous cost estimating experience. It also comprises a comparative study of six cost methods on three well-documented biorefinery processes to evaluate their accuracy and precision. The results illustrate discrepancies among the methods because their extrapolation on biorefinery data often violates inherent assumptions. This study recommends the most appropriate rapid cost methods and urges the development of an improved early-stage capital cost estimation tool suitable for biorefinery processes. PMID:27484398

  2. Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer's disease.

    PubMed

    Duplan, L; Michel, B; Boucraut, J; Barthellémy, S; Desplat-Jego, S; Marin, V; Gambarelli, D; Bernard, D; Berthézène, P; Alescio-Lautier, B; Verdier, J M

    2001-01-01

    According to one of the theories formulated to explain the etiology of Alzheimer's disease (AD), amylosis may reflect a specific inflammatory response. Two inflammatory proteins, lithostathine and PAP, were evidenced by immunohistochemistry in senile plaques and neurofibrillary tangles of patients with AD. In addition, lithostathine and PAP were significantly increased in the cerebrospinal fluid of patients with AD when compared to patients with multiple sclerosis, another inflammatory disease, and to normal control subjects. However, no correlation was observed with age of occurrence. Furthermore, lithostathine and PAP were increased even at the very early stages of AD, and their level remained elevated during the course of the AD unlike TNFalpha whose level, very high at very early stages, regularly decreased. Finally, if part of lithostathine and PAP are synthesized in the brain, a large part comes from serum by passage over the blood-brain barrier. These results indicate (i) the existence of an acute phase response followed by a chronic inflammation in AD, and (ii) that lithostathine and PAP are involved even at the first pre-clinical biochemical events of AD. In addition, because lithostathine undergoes an autolytic cleavage leading to its precipitation and the formation of fibrils, we believe that it may be involved in amyloidosis and tangles by allowing heterogeneous precipitation of other proteins.

  3. Robotic Compartment-Based Radical Surgery in Early-Stage Cervical Cancer

    PubMed Central

    Toptas, Tayfun; Uysal, Aysel; Ureyen, Isin; Erol, Onur; Simsek, Tayup

    2016-01-01

    A radical hysterectomy with pelvic lymphadenectomy is the recommended treatment option in patients with early-stage cervical cancer. Although various classifications were developed in order to define the resection margins of this operation, no clear standardization could be achieved both in the nomenclature and in the extent of the surgery. Total mesometrial resection (TMMR) is a novel procedure which aims to remove all components of the compartment formed by Müllerian duct in which female reproductive organs develop. TMMR differs from the conventional radical hysterectomy techniques in that its surgical philosophy, terminology, and partly resection borders are different. In this paper, a TMMR with therapeutic pelvic lymphadenectomy operation that we performed for the first time with robot-assisted laparoscopic (robotic) approach in an early-stage cervical cancer patient was presented. This procedure has already been described in open surgery by Michael Höckel and translated to the robotic surgery by Rainer Kimmig. Our report is the second paper, to our knowledge, to present the initial experience regarding robotic TMMR in the English literature. PMID:27195167

  4. Thermodynamics, morphology, and kinetics of early- stage self-assembly of pi-conjugated oligopeptides

    NASA Astrophysics Data System (ADS)

    Thurston, Bryce; Tovar, John; Ferguson, Andrew

    Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate self-assembly. At low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ~ - 25kB T . Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini. We model simulations of hundereds of monomers as a continuous-time Markov process. We infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates. Supported by U.S. Department of Energy, Office of Science, Basic Energy Sciences, Award DE-SC0004857. Molecular simulations partially conducted on University of Illinois Computational Science and Engineering Program parallel computing resources.

  5. Social Network Effects of Nonlifesaving Early-Stage Breast Cancer Detection on Mammography Rates

    PubMed Central

    Parker, Andrew M.

    2014-01-01

    Objectives. We estimated the effect of anecdotes of early-stage, screen-detected cancer for which screening was not lifesaving on the demand for mammography. Methods. We constructed an agent-based model of mammography decisions, in which 10 000 agents that represent women aged 40 to 100 years were linked together on a social network, which was parameterized with a survey of 716 women conducted through the RAND American Life Panel. Our model represents a population in equilibrium, with demographics reflecting the current US population based on the most recent available census data. Results. The aggregate effect of women learning about 1 category of cancers—those that would be detected but would not be lethal in the absence of screening—was a 13.8 percentage point increase in annual screening rates. Conclusions. Anecdotes of detection of early-stage cancers relayed through social networks may substantially increase demand for a screening test even when the detection through screening was nonlifesaving. PMID:25322304

  6. Time-resolved EUV spectroscopy in the early stage of laser ablation of carbon

    NASA Astrophysics Data System (ADS)

    Loiseleur, Pierre; Hansen, Tue N.; Larour, Jean; Lunney, James G.

    2002-09-01

    In the early stages of laser ablation the combination of high density and optical opacity makes it difficult to use visible spectroscopy for plasma diagnosis. However, these problems can be overcome by working at shorter wavelengths in the EUV. We have used time-resolved EUV emission spectroscopy to study the early stages (1-30 ns) of plasma development in the laser ablation of carbon at an irradiance of 5 GW cm -2. The ablation was done using a 6 ns Nd:YAG laser at 1.06 μm. The spectra were recorded using a grazing incidence spectrometer with a 5 ns-gated micro-channel plate (MCP) detector. An ion probe operating in the time-of-flight mode was used to measure the ion velocity distribution of the plasma outflow. In the 10-35 nm region the predominant line emission was due to Li-like carbon. The temporal variation of the electron density and temperature was deduced by fitting the observed spectrum to a synthetic spectrum calculated using the FLY numerical model of the plasma ionisation and excitation. The temperature deduced from spectroscopy was in good agreement with the estimation from the measured ion velocity distribution in the plasma outflow.

  7. Experimental early-stage coalification of a peat sample and a peatified wood sample from Indonesia

    USGS Publications Warehouse

    Orem, W.H.; Neuzil, S.G.; Lerch, H.E.; Cecil, C.B.

    1996-01-01

    Experimental coalification of a peat sample and a buried wood sample from domed peat deposits in Indonesia was carried out to examine chemical structural changes in organic matter during early-stage coalification. The experiment (125 C, 408 atm lithostatic pressure, and 177 atm fluid pressure for 75 days) was designed to maintain both lithostatic and fluid pressure on the sample, but allow by-products that may retard coalification to escape. We refer to this design as a geologically open system. Changes in the elemental composition, and 13C NMR and FTIR spectra of the peat and wood after experimental coalification suggest preferential thermal decomposition of O-containing aliphatic organic compounds (probably cellulose) during early-stage coalification. The elemental compositions and 13C NMR spectra of the experimentally coalified peat and wood were generally similar to those of Miocene coal and coalified wood samples from Indonesia. Yields of lignin phenols in the peat and wood samples decreased following experimental coalification; the wood sample exhibited a larger change. Lignin phenol yields from the experimentally coalified peat and wood were comparable to yields of lignin phenols from Miocene Indonesian lignite and coalified wood. Changes in syringyl/vanillyl and p-hydroxy/vanillyl ratios suggest direct demethoxylation as a secondary process to demethylation of methoxyl groups during early coalification, and changes in lignin phenol yields and acid/aldehyde ratios point to a coupling between demethoxylation processes and reactions in the alkyl side chain bonds of the ??-carbon in lignin phenols.

  8. Multifactor-surface-tests of organic insulating materials in the early stage of degradation

    SciTech Connect

    Kloes, H.J.; Koenig, D.

    1996-12-31

    Ageing due to multifactor stresses of the surface of organic materials has to be divided into two different stages named early and late stage of ageing. While standardized tests such as the inclined plane test or the rotating wheel dip test aim at verifying only the performance of insulating materials in the late stage of ageing, growing interest of scientists recently focuses on the early stage of ageing, characterized by a loss of hydrophobicity and an increase of leakage current as well as the appearance of surface partial discharges. To assess the phenomena in the early stage of ageing several new test facilities and diagnostic tools have been developed and applied, such as the inverse climatic chamber generating continuous condensation, the cold fog chamber and the modified rotating wheel dip test arrangement. This paper presents some new test results of polymer resin materials achieved in above mentioned test facilities and enables a comparison and assessment of the efficiency and the advantages of relevant test procedures.

  9. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  10. Upregulation of α3β1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy

    PubMed Central

    Sawada, Kaichiro; Kaneyama, Noriko; Shiraiwa, Sawako; Moriya, Hitomi; Miyatake, Han; Tanaka, Eitaro; Yamamoto, Naoyuki; Miyauchi, Masaaki; Kimura, Moritsugu; Wada, Takehiko; Fukagawa, Masafumi

    2016-01-01

    Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation of α3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels of α3β1-integrin in podocytes in early and advanced stages of DN. Methods. Surgical specimens from DN patients were examined by in situ hybridization, and the expression levels of α3- and β1-integrin subunits in glomeruli of early (n = 6) and advanced (n = 8) stages were compared with those of normal glomeruli (n = 5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined. Results. Podocytes of early-stage DN showed upregulation of α3- and β1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation of α3- and β1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhanced in vitro migration and attachment on collagen substrate. Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation of α3β1-integrin. PMID:27340677

  11. Dislocation Multiplication in the Early Stage of Deformation in Mo Single Crystals

    SciTech Connect

    Hsiung, L.; Lassila, D.H.

    2000-03-02

    Initial dislocation structure in annealed high-purity Mo single crystals and deformation substructure in a crystal subjected to 1% compression have been examined and studied using transmission electron microscopy (TEM) techniques in order to investigate dislocation multiplication mechanisms in the early stage of plastic deformation. The initial dislocation density is in a range of 10{sup 6} {approx} 10{sup 7} cm{sup -2}, and the dislocation structure is found to contain many grown-in superjogs along dislocation lines. The dislocation density increases to a range of 10{sup 8} {approx} 10{sup 9} cm{sup -2}, and the average jog height is also found to increase after compressing for a total strain of 1%. It is proposed that the preexisting jogged screw dislocations can act as (multiple) dislocation multiplication sources when deformed under quasi-static conditions. The jog height can increase by stress-induced jog coalescence, which takes place via the lateral migration (drift) of superjogs driven by unbalanced line-tension partials acting on link segments of unequal lengths. The coalescence of superjogs results in an increase of both link length and jog height. Applied shear stress begins to push each link segment to precede dislocation multiplication when link length and jog height are greater than critical lengths. This ''dynamic'' dislocation multiplication source is suggested to be crucial for the dislocation multiplication in the early stage of plastic deformation in Mo.

  12. Role of subchondral bone during early-stage experimental TMJ osteoarthritis.

    PubMed

    Embree, M; Ono, M; Kilts, T; Walker, D; Langguth, J; Mao, J; Bi, Y; Barth, J L; Young, M

    2011-11-01

    Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease that affects both cartilage and subchondral bone. We used microarray to identify changes in gene expression levels in the TMJ during early stages of the disease, using an established TMJ OA genetic mouse model deficient in 2 extracellular matrix proteins, biglycan and fibromodulin (bgn(-/0)fmod(-/-)). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn(-/0)fmod(-/-) TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn(-/0)fmod(-/-) TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn(-/0)fmod(-/-) TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn(-/0)fmod(-/-) TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn(-/0)fmod(-/-) TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn(-/0)fmod(-/-) TMJ subchondral bone are likely attributed to increased osteoclast activity. Analysis of these data shows that biglycan and fibromodulin are critical for TMJ subchondral bone integrity and reveal a potential role for TMJ subchondral bone turnover during the initial early stages of TMJ OA disease in this model. PMID:21917603

  13. Role of Subchondral Bone during Early-stage Experimental TMJ Osteoarthritis

    PubMed Central

    Embree, M.; Ono, M.; Kilts, T.; Walker, D.; Langguth, J.; Mao, J.; Bi, Y.; Barth, J.L.; Young, M.

    2011-01-01

    Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease that affects both cartilage and subchondral bone. We used microarray to identify changes in gene expression levels in the TMJ during early stages of the disease, using an established TMJ OA genetic mouse model deficient in 2 extracellular matrix proteins, biglycan and fibromodulin (bgn-/0fmod-/-). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn-/0fmod-/- TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn-/0fmod-/- TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn-/0fmod-/- TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn-/0fmod-/- TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn-/0fmod-/- TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn-/0fmod-/- TMJ subchondral bone are likely attributed to increased osteoclast activity. Analysis of these data shows that biglycan and fibromodulin are critical for TMJ subchondral bone integrity and reveal a potential role for TMJ subchondral bone turnover during the initial early stages of TMJ OA disease in this model. PMID:21917603

  14. Accelerated Partial Breast Irradiation Using Only Intraoperative Electron Radiation Therapy in Early Stage Breast Cancer

    SciTech Connect

    Maluta, Sergio; Dall'Oglio, Stefano; Marciai, Nadia; Gabbani, Milena; Franchini, Zeno; Pietrarota, Paolo; Meliado, Gabriele; Guariglia, Stefania; Cavedon, Carlo

    2012-10-01

    Background: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results: With a mean follow-up of 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.

  15. Aquaporin expression in the cerebral cortex is increased at early stages of Alzheimer disease.

    PubMed

    Pérez, Esther; Barrachina, Marta; Rodríguez, Agustín; Torrejón-Escribano, Benjamín; Boada, Mercé; Hernández, Isabel; Sánchez, Marisa; Ferrer, Isidre

    2007-01-12

    Abnormalities in the cerebral microvasculature are common in Alzheimer disease (AD). Expression levels of the water channels aquaporin 1 and aquaporin 4 (AQP1, AQP4) were examined in AD cases by gel electrophoresis and Western blotting, and densitometric values normalized with beta-actin were compared with corresponding values in age-matched controls processed in parallel. In addition, samples of cases with Pick disease (PiD) were examined for comparative purposes. A significant increase in the expression levels of AQP1 was observed in AD stage II (following Braak and Braak classification). Individual variations were seen in advanced stages which resulted in non-significant differences between AD stages V-VI and age-matched controls. No differences in AQP1 levels were observed between familial AD cases (FAD, all of them at advanced stages) and corresponding age-matched controls. Immunohistochemistry showed increased AQP1 in astrocytes at early stages of AD. Double-labelling immunofluorescence and confocal microscopy disclosed AQP1 immunoreactivity at the cell surface of astrocytes which were recognized with anti-glial fibrillary acidic protein antibodies. No differences in the levels of AQP4 were observed in AD, FAD and PiD when compared with corresponding controls. These results indicate abnormal expression of AQP1 in astrocytes in AD, and they add support to the idea that abnormal regulation of mechanisms involved in the control of water fluxes occurs at early stages in AD.

  16. Proteomic analysis of liver tissue from HBx-transgenic mice at early stages of hepatocarcinogenesis.

    PubMed

    Kim, Sun-Young; Lee, Phil Young; Shin, Hye-Jun; Kim, Do Hyung; Kang, Sunghyun; Moon, Hyung-Bae; Kang, Sang Won; Kim, Jin-Man; Park, Sung Goo; Park, Byoung Chul; Yu, Dae-Yeul; Bae, Kwang-Hee; Lee, Sang Chul

    2009-11-01

    The hepatitis B virus X-protein (HBx), a multifunctional viral regulator, participates in the viral life cycle and in the development of hepatocellular carcinoma (HCC). We previously reported a high incidence of HCC in transgenic mice expressing HBx. In this study, proteomic analysis was performed to identify proteins that may be involved in hepatocarcinogenesis and/or that could be utilized as early detection biomarkers for HCC. Proteins from the liver tissue of HBx-transgenic mice at early stages of carcinogenesis (dysplasia and hepatocellular adenoma) were separated by 2-DE, and quantitative changes were analyzed. A total of 22 spots displaying significant quantitative changes were identified using LC-MS/MS. In particular, several proteins involved in glucose and fatty acid metabolism, such as mitochondrial 3-ketoacyl-CoA thiolase, intestinal fatty acid-binding protein 2 and cytoplasmic malate dehydrogenase, were differentially expressed, implying that significant metabolic alterations occurred during the early stages of hepatocarcinogenesis. The results of this proteomic analysis provide insights into the mechanism of HBx-mediated hepatocarcinogenesis. Additionally, this study identifies possible therapeutic targets for HCC diagnosis and novel drug development for treatment of the disease.

  17. Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

    2014-02-01

    The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

  18. Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

    PubMed Central

    Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

    2016-01-01

    Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

  19. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data.

  20. The Chromosomes of Turkey Embryos during Early Stages of Parthenogenetic Development

    PubMed Central

    Harada, Ko; Buss, Edward G.

    1981-01-01

    In the early stages of parthenogenetic development in turkey eggs, many blastoderms are mosaics of haploid, diploid and polyploid cells. The genome composition of these blastoderms can be identified by C-banding. They may be generally described as either A-Z/2A-ZZ/nA-nZ or A-W/2A-WW/nA-nW and are found in a nearly 1:1 ratio. The blastoderms showing the W body (W+) become lethal within two days of incubation. The haploid cell proportion decreases rapidly during the early stage of development, and, as haploid cells decrease, the proportion of polyploid cells appears to increase. At six days of incubation, various kinds of parthenogenetic development can be observed. Their genome compositions are either diploid (2A-ZZ) or mosaic (A-Z/2A-ZZ). These findings suggest that diploid parthenogenesis occurs by either suppression of meiosis II or chromosome doubling some time after the first cleavage division. The frequent occurrence of mosaic blastoderms indicates that the majority, if not all, of the parthenogenetic embryos initiate their development in haploid ova. PMID:7327389

  1. Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

    PubMed

    Kaiserova, Michaela; Prikrylova Vranova, Hana; Galuszka, Jan; Stejskal, David; Mensikova, Katerina; Zapletalova, Jana; Mares, Jan; Kanovsky, Petr

    2015-10-01

    An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD.

  2. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma.

    PubMed

    Kumar, Anita; Casulo, Carla; Yahalom, Joachim; Schöder, Heiko; Barr, Paul M; Caron, Philip; Chiu, April; Constine, Louis S; Drullinsky, Pamela; Friedberg, Jonathan W; Gerecitano, John F; Hamilton, Audrey; Hamlin, Paul A; Horwitz, Steven M; Jacob, Alexandra G; Matasar, Matthew J; McArthur, Gianna N; McCall, Susan J; Moskowitz, Alison J; Noy, Ariela; Palomba, Maria L; Portlock, Carol S; Straus, David J; VanderEls, Nicholas; Verwys, Stephanie L; Yang, Joanna; Younes, Anas; Zelenetz, Andrew D; Zhang, Zhigang; Moskowitz, Craig H

    2016-09-15

    This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD. Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV + AVD, and 25 patients BV + AVD + 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events (≥grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV + AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV + AVD + ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients (≥90%) achieved negative interim PET scans after 2 and 4 cycles of BV + AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was registered at www.clinicaltrials.gov as #NCT01868451.

  3. Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

    PubMed Central

    Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

    2016-01-01

    Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

  4. A Comparative Study of Daily 3-Gy Hypofractionated and 1.8-Gy Conventional Breast Irradiation in Early-Stage Breast Cancer

    PubMed Central

    Lee, Sea-Won; Kim, Yeon-Joo; Shin, Kyung Hwan; Kim, Kyubo; Chie, Eui Kyu; Han, Wonshik; Im, Seock-Ah; Jung, So-Youn; Lee, Keun Seok; Lee, Eun Sook

    2016-01-01

    Abstract We retrospectively compared accelerated hypofractionation (AHF) with conventional fractionation (CF) in the radiation therapy (RT) for early-stage breast cancer patients. Three hundred seventy-nine early-stage (pT1–2 and pN0–1a) breast cancer patients who received RT with AHF after breast-conserving surgery (BCS) were included. These patients were matched with 379 corresponding patients who received BCS and RT with CF at a different center with respect to the year BCS was performed, patient age (±3 years), and cancer stage. The AHF regimen consisted of 39 Gy in 13 fractions to the whole breast and a consecutive boost of 9 to 12 Gy in 3 to 4 fractions to the tumor bed. CF comprised whole-breast irradiation up to 50.4 Gy in 28 fractions and a boost of 9 to 14 Gy in 5 to 7 fractions to the tumor bed. The median follow-up period was 75 months (range, 3.8–110.8 months). There was no statistically significant difference between the AHF and CF groups in terms of age distribution, T and N stage, resection margin, and histologic grade. There were 5 ipsilateral breast tumor relapse (IBTR) cases in the AHF group compared with 7 cases in the CF group. Seven and eight locoregional relapse (LRR) cases were observed in the AHF and CF groups, respectively. The 7-year rates of IBTR-free survival, LRR-free survival, and disease-free survival were 98.9%, 98.4%, and 97.1% in the AHF group and 98.1%, 97.9%, and 96.0% in the CF group, respectively (P > 0.05). The incident rates of grade 3 edema, hyperpigmentation, or wet desquamation at the end of RT were higher in the CF group than in the AHF group (16.4% vs 0.2%, respectively; P < 0.01). AHF RT of 39 Gy to the whole breast plus a 9-Gy boost in 16 fractions showed excellent tumor control and tolerable skin toxicity, a finding that is comparable to CF RT in patients with early-stage breast cancer. PMID:27175630

  5. Investigating genetic discrimination in Australia: opportunities and challenges in the early stages.

    PubMed

    Taylor, Sandra D; Otlowski, Margaret F; Barlow-Stewart, Kristine K; Treloar, Susan A; Stranger, Mark; Chenoweth, Kellie

    2004-08-01

    Genetic discrimination, defined as the differential treatment of individuals or their relatives on the basis of actual or presumed genetic differences, is an emerging issue of interest in academic, clinical, social and legal contexts. While its potential significance has been discussed widely, verified empirical data are scarce. Genetic discrimination is a complex phenomenon to describe and investigate, as evidenced by the recent Australian Law Reform Commission inquiry in Australia. The authors research project, which commenced in 2002, aims to document the multiple perspectives and experiences regarding genetic discrimination in Australia and inform future policy development and law reform. Data are being collected from consumers, employers, insurers and the legal system. Attempted verification of alleged accounts of genetic discrimination will be a novel feature of the research. This paper overviews the early stages of the research, including conceptual challenges and their methodological implications. PMID:15460616

  6. Photoacoustic Molecular Imaging: From Multiscale Biomedical Applications Towards Early-Stage Theranostics.

    PubMed

    Liu, Yajing; Nie, Liming; Chen, Xiaoyuan

    2016-05-01

    Photoacoustic imaging (PAI) has ushered in a new era of observational biotechnology and has facilitated the exploration of fundamental biological mechanisms and clinical translational applications, which has attracted tremendous attention in recent years. By converting laser into ultrasound emission, PAI combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. This evolutional technique enables multiscale and multicontrast visualization from cells to organs, anatomy to function, and molecules to metabolism with high sensitivity and specificity. The state-of-the-art developments and applications of PAI are described in this review. Future prospects for clinical use are also highlighted. Collectively, PAI holds great promise to drive biomedical applications towards early-stage theranostics. PMID:26924233

  7. Direct Monte Carlo Simulations of the Intermediate Experimental Vehicle at Early Stages of Reentry

    NASA Astrophysics Data System (ADS)

    Banyai, T.; Torres, E.; Kashkovsky, A. V.; Vashchenkov, P. V.; Ivanov, M. S.; Rambaud, P.

    2011-05-01

    Within the European Space Agency (ESA) framework program FLPP Next Generation Launcher (NGL) preparatory activities on System, In-Flight Experimentation and Aerothermodynamics Period 1, Step 2, von Karman Institute (VKI) has to perform ground testing and numerical simulations to contribute to the aerothermodynamic database of the Intermediate eXperimental Vehicle (IXV) along its trajectory during re-entry. The present article summarizes the part of these activities in relation with the evaluation of the aerodynamic properties in the early stages of reentry. Due to the rarefied nature of the higher atmosphere, the computations were carried out by means of Direct Simulation of Monte Carlo (DSMC) method. The aim of this work was to a., validate the methodology used at VKI, b., perform computations at several points along the trajectory and c., assess the feasibility of joint simulation of rarefied flow and thrusters.

  8. Highly anisotropic and strongly dissipative hydrodynamics for early stages of relativistic heavy-ion collisions

    SciTech Connect

    Florkowski, Wojciech; Ryblewski, Radoslaw

    2011-03-15

    We introduce a new framework of highly anisotropic hydrodynamics that includes dissipation effects. Dissipation is defined by the form of the entropy source that depends on the pressure anisotropy and vanishes for the isotropic fluid. With a simple ansatz for the entropy source obeying general physical requirements, we are led to a nonlinear equation describing the time evolution of the anisotropy in purely longitudinal boost-invariant systems. Matter that is initially highly anisotropic approaches naturally the regime of the perfect fluid. Thus, the resulting evolution agrees with the expectations about the behavior of matter produced at the early stages of relativistic heavy-ion collisions. The equilibration is identified with the processes of entropy production.

  9. Early stages of superplasticity and positron lifetime spectroscopy in an Al-Mg-Cu alloy

    SciTech Connect

    Ayciriex, M.D.; Romero, R.; Somoza, A.

    1996-07-01

    In the present paper, by using positron lifetime technique, a careful study is carried out to analyze the microstructural changes induced on samples of an Al-based commercial alloy (Al-Mg-Cu-Mn-Cr) by superplastic deformation in the early stages of superplastic behavior of the alloy (strain range from 0.2% to 100%). These results are compared with those obtained on specimens only heat treated at the same temperature and for a time equivalent to the elapsed time during each tensile test, in order to evaluate the thermal contribution to the microstructural changes induced during the superplastic deformation process. Moreover, the positron results were linked with the microstructural evolution of the samples followed by means of optical microscopy and Vickers microhardness technique.

  10. Large scale surface migration of P. aeruginosa at early stages of biofilm formation

    NASA Astrophysics Data System (ADS)

    Gibiansky, Maxsim; Utada, Andy; Zhao, Kun; Xian, Wujing; Wong, Gerard

    2013-03-01

    Pseudomonas aeruginosa is a commonly-studied bacterium which can form biofilms, surface-bound aggregates which display increased resistance to various forms of stress, including a greatly enhanced antibiotic resistance. In the early stages of biofilm formation, free-swimming planktonic cells attach to the surface and form microcolonies, expressing a variety of adhesins and transitioning from reversible to irreversible attachment. By using particle tracking algorithms, we can in principle examine the full motility and division history of all cells in a microcolony. Here, we study the effects of the pel polysaccharides in microcolony formation by investigating how pel impacts the initial stages of biofilm formation by the P. aeruginosa PA14 strain. Specifically, we quantify the phenotypic effects of pel on initial attachment, microcolony formation, and biofilm morphology.

  11. Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients.

    PubMed

    Everaus, H; Lehtmaa, J; Luik, E; Kŏdar, H

    1992-11-01

    Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased beta 2-microglobulin (beta 2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy.

  12. Blood rheology and platelet function in untreated early-stage essential hypertensives complicated with metabolic syndrome.

    PubMed

    Sugimori, Hiroko; Tomoda, Fumihiro; Koike, Tsutomu; Kinuno, Hiroyuki; Kurosaki, Hiroko; Masutani, Toshitaka; Inoue, Hiroshi

    2012-01-01

    We examined whether hemorheology and platelet function are affected in essential hypertensives (EHTs) of the World Health Organization stage I when complicated with metabolic syndrome (Mets). In 156 untreated EHTs, blood viscosity and platelet surface markers were determined. Blood viscosity was significantly elevated in 54 subjects with Mets compared with 102 subjects without Mets. Hematocrit and plasma viscosity increased in the group with Mets, although red blood cell rigidity index "k" did not differ between groups. As a whole group, blood viscosity correlated positively with hematocrit and plasma viscosity. Additionally, plasma viscosity correlated positively with plasma leptin, triglyceride, homeostasis model assessment index, C-reactive protein, and plasma fibrinogen, but negatively with high-density lipoprotein cholesterol. In contrast, no differences were seen in platelet surface markers between groups. In conclusion, EHTs of the early stage complicated with Mets are characterized by increased blood viscosity due to hemoconcentration and increased plasma viscosity. PMID:22570768

  13. Complications of radical hysterectomy: clinical experience of 115 early stage cervical cancers.

    PubMed

    Zorlu, C G; Aydoğlu, T; Ergün, Y; Kuşçu, E; Cobanoğlu, O; Koçak, S

    1998-01-01

    We evaluated the clinical experience of 115 women with early stage cervical cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85 were in stage I, and 30 in stage II. Intraoperative complications occurred in 16 patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1 rectovaginal septum hematoma formation. Postoperative complications were observed in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6 urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and 1 incisional hernia. However, no death occurred due to intraoperative or postoperative complications. Pelvic lymph node metastases were observed in 32 patients of whom 17 had only unilateral involvement, most often in the obturator region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of whom were in stage II.

  14. Emission of spherical cesium-bearing particles from an early stage of the Fukushima nuclear accident

    PubMed Central

    Adachi, Kouji; Kajino, Mizuo; Zaizen, Yuji; Igarashi, Yasuhito

    2013-01-01

    The Fukushima nuclear accident released radioactive materials into the environment over the entire Northern Hemisphere in March 2011, and the Japanese government is spending large amounts of money to clean up the contaminated residential areas and agricultural fields. However, we still do not know the exact physical and chemical properties of the radioactive materials. This study directly observed spherical Cs-bearing particles emitted during a relatively early stage (March 14–15) of the accident. In contrast to the Cs-bearing radioactive materials that are currently assumed, these particles are larger, contain Fe, Zn, and Cs, and are water insoluble. Our simulation indicates that the spherical Cs-bearing particles mainly fell onto the ground by dry deposition. The finding of the spherical Cs particles will be a key to understand the processes of the accident and to accurately evaluate the health impacts and the residence time in the environment. PMID:23989894

  15. Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse

    SciTech Connect

    Xu Fang; Ji Jian; Li Li; Chen Rong; Hu Weicheng . E-mail: huweicheng@sdu.edu.cn

    2007-01-19

    The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.

  16. Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients.

    PubMed

    Everaus, H; Lehtmaa, J; Luik, E; Kŏdar, H

    1992-11-01

    Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased beta 2-microglobulin (beta 2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy. PMID:1457579

  17. Early-stage precipitation in Al-Zn-Mg-Cu alloy (7050)

    SciTech Connect

    Sha Gang; Cerezo, Alfred

    2004-09-06

    GP zone and metastable {eta}{sup '} formation during the early-stage precipitation of a 7050 Al alloy aged at 121 deg. C has been investigated using transmission electron microscopy, together with 3-dimensional atom probe analysis (of the chemistry and morphology) of individual precipitates. Small Mg-rich clusters (GPI zones) are found in the alloy after short ageing times at 121 deg. C, together with larger GPI zones (Zn/Mg=1.0). Zn-rich {eta}{sup '} platelets are seen to form mainly between 30 and 240 min ageing, coexisting with larger GPI zones. A significant fraction of <1 1 0> elongated clusters have also been observed over this period of ageing. The dominant mechanism for {eta}{sup '} formation at this stage is shown to be by transformation of small GPI zones, via these elongated clusters and not by nucleation on larger zones.

  18. An Analysis of Risk and Function Information in Early Stage Design

    NASA Technical Reports Server (NTRS)

    Barrientos, Francesca; Tumer, Irem; Grantham, Katie; VanWie, Michael; Stone, Robert

    2005-01-01

    The concept of function offers a high potential for thinking and reasoning about designs as well as providing a common thread for relating together other design information. This paper focuses specifically on the relation between function and risk by examining how this information is addressed for a design team conducting early stage design for space missions. Risk information is decomposed into a set of key attributes which are then used to scrutinize the risk information using three approaches from the pragmatics sub-field of linguistics: i) Gricean, ii) Relevance Theory, and Functional Analysis. Results of this linguistics-based approach descriptively account for the context of designer communication with respect to function and risk, and offer prescriptive guidelines for improving designer communication.

  19. Early stage second-language learning improves executive control: evidence from ERP.

    PubMed

    Sullivan, Margot D; Janus, Monika; Moreno, Sylvain; Astheimer, Lori; Bialystok, Ellen

    2014-12-01

    A growing body of research has reported a bilingual advantage in performance on executive control tasks, but it is not known at what point in emerging bilingualism these advantages first appear. The present study investigated the effect of early stage second-language training on executive control. Monolingual English-speaking students were tested on a go-nogo task, sentence judgment task, and verbal fluency, before and after 6 months of Spanish instruction. The training group (n = 25) consisted of students enrolled in introductory Spanish and the control group (n = 30) consisted of students enrolled in introductory Psychology. After training, the Spanish group showed larger P3 amplitude on the go-nogo task and smaller P600 amplitude on the judgment task, indicating enhanced performance, with no changes for the control group and no differences between groups on behavioral measures. Results are discussed in terms of neural changes underlying executive control after brief second-language learning. PMID:25463819

  20. The Utility of Cardiopulmonary Exercise Testing to Detect and Track Early-Stage Ischemic Heart Disease

    PubMed Central

    Chaudhry, Sundeep; Arena, Ross A.; Hansen, James E.; Lewis, Gregory D.; Myers, Jonathan N.; Sperling, Laurence S.; LaBudde, Brian D.; Wasserman, Karlman

    2010-01-01

    Evidence demonstrating the potential value of noninvasive cardiopulmonary exercise testing (CPET) to accurately detect exercise-induced myocardial ischemia is emerging. This case-based concept report describes CPET abnormalities in an asymptomatic at-risk man with suspected early-stage ischemic heart disease. When CPET was repeated 1 year after baseline assessment, his cardiovascular function had worsened, and an anti-atherosclerotic regimen was initiated. When the patient was retested after 3.3 years, the diminished left ventricular function had reversed with pharmacotherapy directed at decreasing cardiovascular events in patients with coronary artery disease. Thus, in addition to identifying appropriate patients in need of escalating therapy for atherosclerosis, CPET was useful in monitoring progression and reversal of abnormalities of the coronary circulation in a safe and cost-effective manner without the use of radiation. Serial CPET parameters may be useful to track changes marking the progression and/or regression of the underlying global ischemic burden. PMID:20884826

  1. Early stage second-language learning improves executive control: evidence from ERP.

    PubMed

    Sullivan, Margot D; Janus, Monika; Moreno, Sylvain; Astheimer, Lori; Bialystok, Ellen

    2014-12-01

    A growing body of research has reported a bilingual advantage in performance on executive control tasks, but it is not known at what point in emerging bilingualism these advantages first appear. The present study investigated the effect of early stage second-language training on executive control. Monolingual English-speaking students were tested on a go-nogo task, sentence judgment task, and verbal fluency, before and after 6 months of Spanish instruction. The training group (n = 25) consisted of students enrolled in introductory Spanish and the control group (n = 30) consisted of students enrolled in introductory Psychology. After training, the Spanish group showed larger P3 amplitude on the go-nogo task and smaller P600 amplitude on the judgment task, indicating enhanced performance, with no changes for the control group and no differences between groups on behavioral measures. Results are discussed in terms of neural changes underlying executive control after brief second-language learning.

  2. Detection of the early stage of recombinational DNA repair by silicon nanowire transistors.

    PubMed

    Chiesa, Marco; Cardenas, Paula P; Otón, Francisco; Martinez, Javier; Mas-Torrent, Marta; Garcia, Fernando; Alonso, Juan C; Rovira, Concepció; Garcia, Ricardo

    2012-03-14

    A silicon nanowire-based biosensor has been designed and applied for label-free and ultrasensitive detection of the early stage of recombinational DNA repair by RecA protein. Silicon nanowires transistors were fabricated by atomic force microscopy nanolithography and integrated into a microfluidic environment. The sensor operates by measuring the changes in the resistance of the nanowire as the biomolecular reactions proceed. We show that the nanoelectronic sensor can detect and differentiate several steps in the binding of RecA to a single-stranded DNA filament taking place on the nanowire-aqueous interface. We report relative changes in the resistance of 3.5% which are related to the interaction of 250 RecA·single-stranded DNA complexes. Spectroscopy data confirm the presence of the protein-DNA complexes on the functionalized silicon surfaces.

  3. Symptomatic Lymphocele Formation After Sentinel Lymph Node Biopsy for Early Stage Cervical Cancer.

    PubMed

    Dogan, Nasuh Utku; Garagozova, Nigar; Pfiffer, Tatiana; Beier, Anna; Köhler, Christhardt; Favero, Giovanni

    2016-01-01

    In early stage cervical cancer, nodal status is the most important prognostic factor, and execution of retroperitoneal lymphadenectomy is currently an integral part of surgical therapy. Sentinel lymph node biopsy has been progressively incorporated with surgical therapy and could reduce morbidity. However, the current incidence of complications exclusively related to the procedure is unknown. We report on a 29-year-old woman affected by cervical cancer (Fédération Internationale de Gynécologie et d'Obstétrique Stage 1b1), who underwent sentinel lymph node biopsy in combination with radical vaginal trachelectomy, and who later developed a symptomatic pelvic lymphocele that required surgical therapy. Conservative procedures in the pelvic lymph nodes are not free of complications, especially with regard to the formation of symptomatic lymphoceles. This report brings to light an important discussion about the exact magnitude of the complications associated with the procedure.

  4. Selective attention to signs of success: social dominance and early stage interpersonal perception.

    PubMed

    Maner, Jon K; DeWall, C Nathan; Gailliot, Matthew T

    2008-04-01

    Results from two experiments suggest that observers selectively attend to male, but not female, targets displaying signs of social dominance. Participants overestimated the frequency of dominant men in rapidly presented stimulus arrays (Study 1) and visually fixated on dominant men in an eyetracking experiment (Study 2). When viewing female targets, participants attended to signs of physical attractiveness rather than social dominance. Findings fit with evolutionary models of mating, which imply that dominance and physical attractiveness sometimes tend to be prioritized preferentially in judgments of men versus women, respectively. Findings suggest that sex differences in human mating are observed not only at the level of overt mating preferences and choices but also at early stages of interpersonal perception. This research demonstrates the utility of examining early-in-the-stream social cognition through the functionalist lens of adaptive thinking.

  5. Alternative to surgery in early stage NSCLC—interventional radiologic approaches

    PubMed Central

    Lee, Kyungmouk Steve

    2013-01-01

    Interventional radiologists have a variety of techniques in their armamentarium to treat pulmonary tumors. While most therapies are targeted to metastasis or palliation, percutaneous thermal ablation represents a potential therapy for not only palliation, but to treat inoperable early stage disease. Although radiofrequency ablation (RFA) is the most studied of these ablative techniques, newer technologies of thermal ablation, such as microwave and cryoablation have emerged as additional options. In this article, we will review the three different thermal ablative modalities, including patient selection, technique, outcomes, complications, and imaging follow-up. A brief discussion of state of the art techniques such as irreversible electroporation (IRE) and catheter directed therapies will also be included. PMID:25806253

  6. Production of stilbenoids and phenolic acids by the peanut plant at early stages of growth.

    PubMed

    Sobolev, Victor S; Horn, Bruce W; Potter, Thomas L; Deyrup, Stephen T; Gloer, James B

    2006-05-17

    The peanut plant (Arachis hypogaea) is known to produce stilbene phytoalexins as a defensive response to fungal invasion; however, the distribution of phytoalexins among different organs of the peanut plant at early stages of growth under axenic conditions has not been studied. Axenic plants produced a stilbenoid, resveratrol, as well as soluble bound and free phenolic acids, including 4-methoxycinnamic acid, which is reported in peanuts for the first time. Neither resveratrol nor phenolic acids were found in the root mucilage; the prenylated stilbenes were restricted to the mucilage and were not found in other organs of the peanut plant. These findings may lead to a better understanding of the defensive role of peanut stilbenes and phenolic acids.

  7. Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

    SciTech Connect

    Jeremic, Branislav . E-mail: b.jeremic@iaea.org; Milicic, Biljana; Dagovic, Aleksandar; Acimovic, Ljubisa; Milisavljevic, Slobodan

    2006-07-15

    Purpose: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. Patients and Methods: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n = 72). Results: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. Conclusions: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy.

  8. Narrowband Ultraviolet B Phototherapy of Early Stage Mycosis Fungoides in Korean Patients

    PubMed Central

    Jang, Min Soo; Baek, Jae Woo; Park, Jong Bin; Kang, Dong Young; Kang, Jin Seuk; Suh, Kee Suck

    2011-01-01

    Background Narrowband UVB (NBUVB) is currently used to treat early mycosis fungoides (MF). There are a number of reports on the efficacy and safety of NBUVB in Caucasians, but little data is available for Asians. Objective This study was designed to evaluate the effectiveness and safety of NBUVB for early stage MF in Korean patients. Methods We enrolled 14 patients (12 men, 2 women; age range, 10~64 years) with clinically and histologically proven MF. Three patients were stage IA, and the others were stage IB. The patients received NBUVB phototherapy three times a week. The starting dose was 70% of the minimal erythema dose and was increased in 20 percent increments if the previous treatment did not cause erythema. Clinical response, total number of treatments, total cumulative dose, duration of remission and side effects were investigated. Results Eleven of 14 patients (78.6%) achieved complete remission within a mean of 15.36±5.71 weeks (range, 5~27 weeks), 31.0±7.4 treatments (range, 16~39 treatments) and a mean cumulative UVB dose of 31.31±12.16 J/cm2 (range, 11.4~46.8 J/cm2). Three of the 14 patients (21.4%) achieved a partial remission. After discontinuation of treatment, 6 of 11 patients (54.5%) with complete remission relapsed after a mean of 8.5±4.09 months. No serious adverse effects were observed except for hyperpigmentation (7/14, 50%). Conclusion Our data suggest that NBUVB therapy is safe and effective for the treatment of early stage MF in Korean patients. PMID:22148015

  9. Similarity ratio analysis for early stage fault detection with optical emission spectrometer in plasma etching process.

    PubMed

    Yang, Jie; McArdle, Conor; Daniels, Stephen

    2014-01-01

    A Similarity Ratio Analysis (SRA) method is proposed for early-stage Fault Detection (FD) in plasma etching processes using real-time Optical Emission Spectrometer (OES) data as input. The SRA method can help to realise a highly precise control system by detecting abnormal etch-rate faults in real-time during an etching process. The method processes spectrum scans at successive time points and uses a windowing mechanism over the time series to alleviate problems with timing uncertainties due to process shift from one process run to another. A SRA library is first built to capture features of a healthy etching process. By comparing with the SRA library, a Similarity Ratio (SR) statistic is then calculated for each spectrum scan as the monitored process progresses. A fault detection mechanism, named 3-Warning-1-Alarm (3W1A), takes the SR values as inputs and triggers a system alarm when certain conditions are satisfied. This design reduces the chance of false alarm, and provides a reliable fault reporting service. The SRA method is demonstrated on a real semiconductor manufacturing dataset. The effectiveness of SRA-based fault detection is evaluated using a time-series SR test and also using a post-process SR test. The time-series SR provides an early-stage fault detection service, so less energy and materials will be wasted by faulty processing. The post-process SR provides a fault detection service with higher reliability than the time-series SR, but with fault testing conducted only after each process run completes. PMID:24755865

  10. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline

    PubMed Central

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a “pre-visible” stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65–84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  11. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    PubMed Central

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

  12. Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy.

    PubMed

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S; March, Keith L

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved "b" wave amplitude (as measured by electroretinogram) within 1-3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

  13. Radiofrequency ablation compared to resection in early-stage hepatocellular carcinoma

    PubMed Central

    Tohme, Samer; Geller, David A.; Cardinal, Jon S.; Chen, Hui-Wei; Packiam, Vignesh; Reddy, Srinevas; Steel, Jennifer; Marsh, James W.; Tsung, Allan

    2013-01-01

    Objectives: This study aimed to compare survival outcomes after hepatic resection (HR) and radiofrequency ablation (RFA) in early-stage hepatocellular carcinoma (HCC) at a Western hepatobiliary centre. Methods: Demographic details, clinicopathologic tumour characteristics and survival outcomes were compared among non-transplant candidate patients undergoing HR (n= 50) and RFA (n= 60) for early-stage HCC during 2001–2011. Results: Patients who underwent HR had larger tumours, a longer length of stay and a higher rate of postoperative complications. After a median follow-up of 29 months, there were no significant differences between the treatment groups in 1-, 3- and 5-year overall survival (OS) [RFA group: 86%, 50%, 35%, respectively; HR group: 88%, 68%, 47%, respectively (P= 0.222)] or disease-free survival (DFS) [RFA group: 68%, 42%, 28%, respectively; HR group: 66%, 42%, 34%, respectively (P= 0.823)]. The 58 patients who underwent RFA demonstrated ablation success on follow-up computed tomography at 3 months. Of these, 96.5% of patients showed sustained ablation success over the entire follow-up period. In a subgroup analysis of patients with tumours measuring 2–5 cm, no differences in OS or DFS emerged between the HR and RFA groups. Similarly, no significant differences in outcomes in patients with Child–Pugh class A cirrhosis were seen between the RFA and HR groups. Conclusions: Radiofrequency ablation is comparable with HR in terms of OS and DFS. It is a reasonable alternative as a first-line treatment for HCC in well-selected patients who are not candidates for transplant. PMID:23374361

  14. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline.

    PubMed

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a "pre-visible" stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  15. Partial Breast Irradiation Versus Whole Breast Radiotherapy for Early-Stage Breast Cancer: A Decision Analysis

    SciTech Connect

    Sher, David J.; Wittenberg, Eve; Taghian, Alphonse G.; Bellon, Jennifer R.; Punglia, Rinaa S.

    2008-02-01

    Purpose: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. Results: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. Conclusions: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.

  16. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma.

    PubMed

    Reichl, Patrick; Fang, Meng; Starlinger, Patrick; Staufer, Katharina; Nenutil, Rudolf; Muller, Petr; Greplova, Kristina; Valik, Dalibor; Dooley, Steven; Brostjan, Christine; Gruenberger, Thomas; Shen, Jiayun; Man, Kwan; Trauner, Michael; Yu, Jun; Gao, Chun Fang; Mikulits, Wolfgang

    2015-07-15

    If diagnosed at early stages, patients with hepatocellular carcinoma (HCC) can receive curative therapies, whereas therapeutic options at later stages are very limited. Here, we addressed the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. Serum concentrations of sAxl were significantly increased in HCC (18.575 ng/mL) as compared to healthy (13.388 ng/mL) or cirrhotic (12.169 ng/mL) controls. Receiver operating characteristic curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. α-Fetoprotein (AFP)-negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon. In summary, sAxl outperforms AFP in detecting very early HCC as compared to healthy or cirrhotic controls and shows high diagnostic accuracy for AFP-negative patients. sAxl is specific for HCC and suggested as a biomarker for routine clinical use.

  17. Development of Valpha4+ NK T cells in the early stages of embryogenesis.

    PubMed Central

    Makino, Y; Kanno, R; Koseki, H; Taniguchi, M

    1996-01-01

    The majority of T lymphocytes start to develop at around day 15 of gestation (d15)-d17 in the thymus and comprise the peripheral repertoire characterized by the expression of polymorphic T-cell antigen receptors (TCRs). Contrary to these conventional T cells, a subset of T cells, called natural killer (NK) T cells (most of them expressing an invariant TCR encoded by the Valpha14Jalpha281 gene with a 1-nt N-region), preferentially differentiates extrathymically and dominates the peripheral T-cell population at a high frequency (5% in splenic T cells and 40% in bone marrow T cells). Here, we investigated the development of NK T cells and found that the invariant Valpha14+ TCR transcripts and the circular DNA created by Valpha14 and Jalpha281 gene rearrangements can be detected in the embryo body at d9.5 of gestation and in the yolk sac and the fetal liver at d11.5-d13.5 of gestation, but not in the thymus, whereas T cells with Valpha1+ TCR expression, a major population in the thymus, were not observed at these early stages of gestation. Fluorescence-activated cell sorter analysis also demonstrated that there exist CD3+ alpha beta+ T cells, almost all of which are Valpha14/Vbeta8+ NK+ T cells, during early embryogenesis. To our knowledge, this demonstrates for the first time that a T lymphocyte subset develops in extrathymic tissues during the early stages of embryogenesis. Images Fig. 1 Fig. 4 PMID:8692847

  18. Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

    PubMed

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line.

  19. Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

    PubMed Central

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D.; Roca, Alfred L.

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire–dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5′- and 3′-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5′-LTR sequence was identical to the 3′-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

  20. Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells

    SciTech Connect

    Hong, Dun; Chen, Hai-Xiao; Yu, Hai-Qiang; Liang, Yong; Wang, Carrie; Lian, Qing-Quan; Deng, Hai-Teng; Ge, Ren-Shan

    2010-08-15

    Bone remodeling relies on a dynamic balance between bone formation and resorption, mediated by osteoblasts and osteoclasts, respectively. Under certain stimuli, osteoprogenitor cells may differentiate into premature osteoblasts and further into mature osteoblasts. This process is marked by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. In this study, we induced osteoblast differentiation in mouse osteoprogenitor MC3T3-E1 cells and divided the process into three stages. In the first stage (day 3), the MC3T3-E1 cell under osteoblast differentiation did not express ALP or deposit a mineralized nodule. In the second stage, the MC3T3-E1 cell expressed ALP but did not form a mineralized nodule. In the third stage, the MC3T3-E1 cell had ALP activity and formed mineralized nodules. In the present study, we focused on morphological and proteomic changes of MC3T3-E1 cells in the early stage of osteoblast differentiation - a period when premature osteoblasts transform into mature osteoblasts. We found that mean cell area and mean stress fiber density were increased in this stage due to enhanced cell spreading and decreased cell proliferation. We further analyzed the proteins in the signaling pathway of regulation of the cytoskeleton using a proteomic approach and found upregulation of IQGAP1, gelsolin, moesin, radixin, and Cfl1. After analyzing the focal adhesion signaling pathway, we found the upregulation of FLNA, LAMA1, LAMA5, COL1A1, COL3A1, COL4A6, and COL5A2 as well as the downregulation of COL4A1, COL4A2, and COL4A4. In conclusion, the signaling pathway of regulation of the cytoskeleton and focal adhesion play critical roles in regulating cell spreading and actin skeleton formation in the early stage of osteoblast differentiation.

  1. Regenerative Therapeutic Potential of Adipose Stromal Cells in Early Stage Diabetic Retinopathy

    PubMed Central

    Rajashekhar, Gangaraju; Ramadan, Ahmed; Abburi, Chandrika; Callaghan, Breedge; Traktuev, Dmitry O.; Evans-Molina, Carmella; Maturi, Raj; Harris, Alon; Kern, Timothy S.; March, Keith L.

    2014-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. PMID:24416262

  2. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia.

  3. Proliferation of endogenous retroviruses in the early stages of a host germ line invasion.

    PubMed

    Ishida, Yasuko; Zhao, Kai; Greenwood, Alex D; Roca, Alfred L

    2015-01-01

    Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire-dam-progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 5'- and 3'-long terminal repeats (LTRs) of a provirus can be used as a molecular clock. Within each of ten enKoRVs, the 5'-LTR sequence was identical to the 3'-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200-49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. PMID:25261407

  4. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia. PMID:27435496

  5. Electrolyte-carbohydrate beverage prevents water loss in the early stage of high altitude training.

    PubMed

    Yanagisawa, Kae; Ito, Osamu; Nagai, Satsuki; Onishi, Shohei

    2012-01-01

    To prevent water loss in the early stage of high altitude training, we focused on the effect of electrolyte-carbohydrate beverage (EC). Subjects were 16 male university students who belonged to a ski club. They had ski training at an altitude of 1,800 m. The water (WT) group drank only water, and the EC group drank only an electrolyte-carbohydrate beverage. They arrived at the training site in the late afternoon. The study started at 7 pm on the day of arrival and continued until noon of the 4(th) day. In the first 12 hours, 1 L of beverages were given. On the second and third days, 2.5 L of beverages were given. All subjects ate the same meals. Each morning while in fasting condition, subjects were weighed and blood was withdrawn for various parameters (hemoglobin, hematocrit, sodium, potassium and aldosterone). Urine was collected at 12 hour intervals for a total 60 hours (5 times). The urine volume, gravity, sodium and potassium concentrations were measured. Peripheral oxygen saturation and heart rate were measured during sleep with a pulse oximeter. Liquid intakes in both groups were similar, hence the electrolytes intake was higher in the EC group than in the WT group. The total urine volume was lower in the EC group than in the WT group, respectively (p<0.05). Plasma volume decreased in the WT group and increased in the EC group but a significant difference was not observed in the final value. Aldosterone concentration tended to be less in the EC group than in the WT group. Electrolyte-carbohydrate beverage in the early stage of high altitude training may be effective in decreasing urinary output and preventing loss of blood plasma volume.

  6. Hyper-connectivity of the Thalamus in during Early Stages following Mild Traumatic Brain Injury

    PubMed Central

    Sours, Chandler; George, Elijah O.; Zhuo, Jiachen; Roys, Steven; Gullapalli, Rao P.

    2015-01-01

    The thalamo-cortical resting state functional connectivity of 7 sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6±3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self-reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work. PMID:26153468

  7. Similarity ratio analysis for early stage fault detection with optical emission spectrometer in plasma etching process.

    PubMed

    Yang, Jie; McArdle, Conor; Daniels, Stephen

    2014-01-01

    A Similarity Ratio Analysis (SRA) method is proposed for early-stage Fault Detection (FD) in plasma etching processes using real-time Optical Emission Spectrometer (OES) data as input. The SRA method can help to realise a highly precise control system by detecting abnormal etch-rate faults in real-time during an etching process. The method processes spectrum scans at successive time points and uses a windowing mechanism over the time series to alleviate problems with timing uncertainties due to process shift from one process run to another. A SRA library is first built to capture features of a healthy etching process. By comparing with the SRA library, a Similarity Ratio (SR) statistic is then calculated for each spectrum scan as the monitored process progresses. A fault detection mechanism, named 3-Warning-1-Alarm (3W1A), takes the SR values as inputs and triggers a system alarm when certain conditions are satisfied. This design reduces the chance of false alarm, and provides a reliable fault reporting service. The SRA method is demonstrated on a real semiconductor manufacturing dataset. The effectiveness of SRA-based fault detection is evaluated using a time-series SR test and also using a post-process SR test. The time-series SR provides an early-stage fault detection service, so less energy and materials will be wasted by faulty processing. The post-process SR provides a fault detection service with higher reliability than the time-series SR, but with fault testing conducted only after each process run completes.

  8. Adoption of Intensity Modulated Radiation Therapy For Early-Stage Breast Cancer From 2004 Through 2011

    SciTech Connect

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Smith, Benjamin D.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2015-02-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials: We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results: We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions: The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.

  9. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

    PubMed Central

    Strickland, Kyle C.; Howitt, Brooke E.; Shukla, Sachet A.; Rodig, Scott; Ritterhouse, Lauren L.; Liu, Joyce F.; Garber, Judy E.; Chowdhury, Dipanjan; Wu, Catherine J.; D'Andrea, Alan D.; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.

    2016-01-01

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs. PMID

  10. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer.

    PubMed

    Strickland, Kyle C; Howitt, Brooke E; Shukla, Sachet A; Rodig, Scott; Ritterhouse, Lauren L; Liu, Joyce F; Garber, Judy E; Chowdhury, Dipanjan; Wu, Catherine J; D'Andrea, Alan D; Matulonis, Ursula A; Konstantinopoulos, Panagiotis A

    2016-03-22

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs.

  11. Characteristic patterns of dendritic remodeling in early-stage glaucoma: evidence from genetically identified retinal ganglion cell types.

    PubMed

    El-Danaf, Rana N; Huberman, Andrew D

    2015-02-11

    Retinal ganglion cell (RGC) loss is a hallmark of glaucoma and the second leading cause of blindness worldwide. The type and timing of cellular changes leading to RGC loss in glaucoma remain incompletely understood, including whether specific RGC subtypes are preferentially impacted at early stages of this disease. Here we applied the microbead occlusion model of glaucoma to different transgenic mouse lines, each expressing green fluorescent protein in 1-2 specific RGC subtypes. Targeted filling, reconstruction, and subsequent comparison of the genetically identified RGCs in control and bead-injected eyes revealed that some subtypes undergo significant dendritic rearrangements as early as 7 d following induction of elevated intraocular pressure (IOP). By comparing specific On-type, On-Off-type and Off-type RGCs, we found that RGCs that target the majority of their dendritic arbors to the scleral half or "Off" sublamina of the inner plexiform layer (IPL) undergo the greatest changes, whereas RGCs with the majority of their dendrites in the On sublamina did not alter their structure at this time point. Moreover, M1 intrinsically photosensitive RGCs, which functionally are On RGCs but structurally stratify their dendrites in the Off sublamina of the IPL, also underwent significant changes in dendritic structure 1 week after elevated IOP. Thus, our findings reveal that certain RGC subtypes manifest significant changes in dendritic structure after very brief exposure to elevated IOP. The observation that RGCs stratifying most of their dendrites in the Off sublamina are first to alter their structure may inform the development of new strategies to detect, monitor, and treat glaucoma in humans.

  12. Predictive Value of Molecular Subtyping for Locoregional Recurrence in Early-Stage Breast Cancer with N1 without Postmastectomy Radiotherapy

    PubMed Central

    Wen, Ge; Zhang, Jin-Shan; Zhu, Yu-Jia; Huang, Xiao-Bo; Guan, Xun-Xing

    2016-01-01

    Purpose This study was designed to investigate the relationship between molecular subtype and locoregional recurrence (LRR) in patients with early-stage breast cancer with 1–3 positive axillary lymph nodes (ALNs) and improve the individualized indications for postmastectomy radiotherapy (PMRT). Methods The records of 701 patients with pT1-2N1M0 breast cancer who did not undergo PMRT were retrospectively analyzed. Tumors were subclassified as follows: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and basal-like subtypes. Multivariate Cox analysis was used to determine the risk of LRR associated with the different subtypes and to adjust for clinicopathologic factors. Results Luminal A, luminal B, HER2-enriched, and basal-like subtypes accounted for 51.2%, 28.0%, 8.1%, and 12.7% of cases, respectively. The median follow-up duration was 67 months (range, 9–156 months). Univariate analysis revealed that, compared with the luminal A subtype, the HER2-enriched and basal-like subtypes were associated with significantly higher 5-year LRR rates (5.6% vs. 21.6% and vs.15.7% respectively; p=0.002 each), lower 5-year LRR-free survival (LRFS) rates (90.6% vs. 73.8% and 78.5%, respectively; p=0.001 each), and poorer 5-year breast cancer-specific survival (BCSS) rates (93.7% vs. 82.2% [p=0.002] and 84.9% [p=0.001], respectively). Multivariate analysis revealed that the HER2-enriched and basal-like subtypes, age ≤35 years, a medial tumor, and pT2 stage were poor prognostic factors for LRR and LRFS; furthermore, 2 to 3 positive ALNs represented an independent prognostic factor affecting LRR. The 10-year LRR rates of patients with 0, 1, 2, 3, and 4 risk factors were 1.0%, 6.9%, 14.3%, 30.4%, and 54.3%, respectively (p<0.001); the 10-year BCSS rates were 86.6%, 88.5%, 84.4%, 79.7%, and 38.8%, respectively (p<0.001). Conclusion Molecular subtyping allows for individualized evaluation of LRR risk in patients with pT1-2N1M0 breast cancer. PMRT

  13. Less radical surgery for early-stage cervical cancer: To what extent do we justify it?-Our belief.

    PubMed

    Thomakos, Nikolaos; Trachana, Sofia-Paraskevi; Davidovic-Grigoraki, Miona; Rodolakis, Alexandros

    2016-08-01

    Cancer of the uterine cervix, following breast cancer, is the second leading cause of death among gynecological cancers in the developed world. Traditionally, surgical management of early-stage cervical carcinoma is considered as a "sterilizing" procedure, since the uterus is removed. Nowadays, because of the postponement of childbearing to an older age, women younger than 45 years old who are diagnosed with early-stage cervical cancer have a strong desire to preserve fertility. Radical trachelectomy (vaginal or abdominal route) is used for fertility preservation in cases of early-stage (International Federation of Gynecology and Obstetrics Stages IA-IB1) cervical carcinomas with remarkable oncological and obstetrical outcomes. However, less radical approaches for ideal candidates may prove safe when fertility preservation is probably feasible. PMID:27590369

  14. Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma.

    PubMed

    Li, Tao; Wang, Shu-Kang; Zhi, Xu-Ting; Zhou, Jian; Dong, Zhao-Ru; Zhang, Zong-Li; Sun, Hui-Chuan; Ye, Qing-Hai; Fan, Jia

    2016-01-01

    Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04-1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13-2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients. PMID:27320390

  15. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    PubMed Central

    Niu, Chunhao; Sun, Xiaoying; Zhang, Weijing; Li, Han; Xu, Liqun; Li, Jun; Xu, Benke; Zhang, Yanna

    2016-01-01

    Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer. PMID:27775588

  16. In situ nanomechanical characterization of the early stages of swelling and degradation of a biodegradable polymer

    NASA Astrophysics Data System (ADS)

    Dumitru, A. C.; Espinosa, F. M.; Garcia, R.; Foschi, G.; Tortorella, S.; Valle, F.; Dallavalle, M.; Zerbetto, F.; Biscarini, F.

    2015-03-01

    The interactions of a biodegradable scaffold with cells or living tissues depend on the time-evolution of the nanoscale properties of the scaffold. We present an in situ quantitative study on the early-stage swelling and degradation of poly(lactic-co-glycolic acid) (PLGA). A novel metrology scheme based on force microscopy measurements of the patterns of PLGA nanostructures is developed to characterize the evolution of topography, volume and nanomechanical properties. The volume and nanoscale roughness show an oscillating behaviour during the first eight days of immersion; at a later stage, we observe a continuous decrease of the volume. The effective Young's modulus exhibits a monotonic decrease from an initial value of about 2.4 GPa down to 9 MPa at day 14. The oscillating behaviour of the volume before the onset of full degradation is explained by a coupled diffusion-swelling mechanism. The appearance of a second maximum in the volume evolution results from the competition between swelling and degradation.The interactions of a biodegradable scaffold with cells or living tissues depend on the time-evolution of the nanoscale properties of the scaffold. We present an in situ quantitative study on the early-stage swelling and degradation of poly(lactic-co-glycolic acid) (PLGA). A novel metrology scheme based on force microscopy measurements of the patterns of PLGA nanostructures is developed to characterize the evolution of topography, volume and nanomechanical properties. The volume and nanoscale roughness show an oscillating behaviour during the first eight days of immersion; at a later stage, we observe a continuous decrease of the volume. The effective Young's modulus exhibits a monotonic decrease from an initial value of about 2.4 GPa down to 9 MPa at day 14. The oscillating behaviour of the volume before the onset of full degradation is explained by a coupled diffusion-swelling mechanism. The appearance of a second maximum in the volume evolution results from

  17. Observations of Nucleation and Early Stage Growth of Amorphous Silica on Carboxyl-Terminated Model Biosubstrates

    NASA Astrophysics Data System (ADS)

    Wallace, A. F.; Dove, P. M.

    2005-12-01

    surface. While controlling solution chemistry, we can make in situ measurements of nucleation and early stage growth at these interfaces with Atomic Force Microscopy (AFM). Preliminary experiments show that at pH 4 to 7, and supersaturations of 0.76 to 1.45 (σ = ln([H4SiO4]/Ksp)), silica nucleates on carboxyl-terminated areas of the surface, that are less than 30 nm in diameter. The nuclei evolve during early stages of growth to spread over the surface into a sheet like form.

  18. Cost calculations at early stages of nuclear research facilities in the nordic countries

    SciTech Connect

    Iversen, Klaus; Salmenhaara, Seppo; Backe, Steinar; Cato, Anna; Lindskog, Staffan; Callander, Clas; Efraimsson, Henrik; Andersson, Inga; Sjoeblom, Rolf

    2007-07-01

    The Nordic countries Denmark, Norway and Sweden, and to some extent also Finland, had very large nuclear research and development programs for a few decades starting in the nineteen fifties. Today, only some of the facilities are in use. Some have been decommissioned and dismantled while others are at various stages of planning for shutdown. The perspective ranges from imminent to several decades. It eventually became realized that considerable planning for the future decommissioning is warranted and that an integral part of this planning is financial, including how financial funds should be acquired, used and allocated over time. This necessitates that accurate and reliable cost estimates be obtained at all stages. However, this is associated with fundamental difficulties and treacherous complexities, especially for the early ones. Eventually, Denmark and Norway decided not to build any nuclear power plants while Finland and Sweden did. This is reflected in the financing where the latter countries have established systems with special funds in which money is being collected now to cover the future costs for the decommissioning of the research facilities. Nonetheless, the needs for planning for the decommissioning of nuclear research facilities are very similar. However, they differ considerably from those of nuclear power reactors, especially with regard to cost calculations. It has become apparent in the course of work that summation types of cost estimation methodologies give rise to large systematic errors if applied at early stages, in which case comparison based assessments are less biased and may be more reliable. Therefore, in order to achieve the required quality of the cost calculations, it is necessary that data and experience from authentic cases be utilized in models for cost calculations. It also implies that this calculation process should include a well adopted learning process. Thus, a Nordic co-operation has been established for the exchange and

  19. Phytoplankton dynamics in contrasting early stage North Atlantic spring blooms: composition, succession, and potential drivers

    NASA Astrophysics Data System (ADS)

    Daniels, C. J.; Poulton, A. J.; Esposito, M.; Paulsen, M. L.; Bellerby, R.; St John, M.; Martin, A. P.

    2015-04-01

    The spring bloom is a key annual event in the phenology of pelagic ecosystems, making a major contribution to the oceanic biological carbon pump through the production and export of organic carbon. However, there is little consensus as to the main drivers of spring bloom formation, exacerbated by a lack of in situ observations of the phytoplankton community composition and its evolution during this critical period. We investigated the dynamics of the phytoplankton community structure at two contrasting sites in the Iceland and Norwegian basins during the early stage (25 March-25 April) of the 2012 North Atlantic spring bloom. The plankton composition and characteristics of the initial stages of the bloom were markedly different between the two basins. The Iceland Basin (ICB) appeared well mixed down to >400 m, yet surface chlorophyll a (0.27-2.2 mg m-3) and primary production (0.06-0.66 mmol C m-3 d-1) were elevated in the upper 100 m. Although the Norwegian Basin (NWB) had a persistently shallower mixed layer (<100 m), chlorophyll a (0.58-0.93 mg m-3) and primary production (0.08-0.15 mmol C m-3 d-1) remained lower than in the ICB, with picoplankton (<2 μm) dominating chlorophyll a biomass. The ICB phytoplankton composition appeared primarily driven by the physicochemical environment, with periodic events of increased mixing restricting further increases in biomass. In contrast, the NWB phytoplankton community was potentially limited by physicochemical and/or biological factors such as grazing. Diatoms dominated the ICB, with the genus Chaetoceros (1-166 cells mL-1) being succeeded by Pseudo-nitzschia (0.2-210 cells mL-1). However, large diatoms (>10 μm) were virtually absent (<0.5 cells mL-1) from the NWB, with only small nano-sized (<5 μm) diatoms (i.e. Minidiscus spp.) present (101-600 cells mL-1). We suggest microzooplankton grazing, potentially coupled with the lack of a seed population of bloom-forming diatoms, was restricting diatom growth in the NWB

  20. Phytoplankton dynamics in contrasting early stage North Atlantic spring blooms: composition, succession, and potential drivers

    NASA Astrophysics Data System (ADS)

    Daniels, C. J.; Poulton, A. J.; Esposito, M.; Paulsen, M. L.; Bellerby, R.; St. John, M.; Martin, A. P.

    2015-01-01

    The spring bloom is a key annual event in the phenology of pelagic ecosystems, making a major contribution to the oceanic biological carbon pump through the production and export of organic carbon. However, there is little consensus as to the main drivers of spring bloom formation, exacerbated by a lack of in situ observations of the phytoplankton community composition and its evolution during this critical period. We investigated the dynamics of the phytoplankton community structure at two contrasting sites in the Iceland and Norwegian Basins during the early stage (25 March-25 April) of the 2012 North Atlantic spring bloom. The plankton composition and characteristics of the initial stages of the bloom were markedly different between the two basins. The Iceland Basin (ICB) appeared well mixed to > 400 m, yet surface chlorophyll a (0.27-2.2 mg m-3) and primary production (0.06-0.66 mmol C m-3 d-1) were elevated in the upper 100 m. Although the Norwegian Basin (NWB) had a persistently shallower mixed layer (< 100 m), chlorophyll a (0.58-0.93 mg m-3) and primary production (0.08-0.15 mmol C m-3 d-1) remained lower than in the ICB, with picoplankton (> 2 μm) dominating chlorophyll a biomass. The ICB phytoplankton composition appeared primarily driven by the physicochemical environment, with periodic events of increased mixing restricting further increases in biomass. In contrast, the NWB phytoplankton community was potentially limited by physicochemical and/or biological factors such as grazing. Diatoms dominated the ICB, with the genus Chaetoceros (1-166 cells mL-1) being succeeded by Pseudo-nitzschia (0.2-210 cells mL-1). However, large diatoms (> 10 μm) were virtually absent (< 0.5 cells mL-1) from the NWB, with only small nanno-sized (< 5 μm) diatoms present (101-600 cells mL-1). We suggest micro-zooplankton grazing, potentially coupled with the lack of a seed population of bloom forming diatoms, was restricting diatom growth in the NWB, and that large diatoms

  1. Blue-Black or White-Gold? Early Stage Processing and the Color of 'The Dress'

    PubMed Central

    Rabin, Jeff

    2016-01-01

    Purpose In Feb 2015 an image of a dress posted on Tumblr triggered an internet phenomenon: Is the Dress blue and black (BB) or white and gold (WG)? Many claim BB and others insist WG while the true colors are BB. The prevailing theory is that assumptions about the illuminant govern perception of the Dress with WG due to bluish lighting and BB due to yellowish. Our purpose was to determine if early stage optical, retinal and/or neural factors also impact perception of the Dress. Methods Thirty-nine subjects were categorized as BB or WG based on their initial perception of the Dress and their perception reported when viewing the Dress on iPhone 5, iPad, and 22” LCD displays. Macular pigment optical density (MPOD) measured with the QuantifEye™ MPS II and visual brainwaves (VEPs) in response to brief presentations of a transparency of the Dress illuminated by a flashing light were measured on each subject and compared between BB and WG groups. Additionally, CIE chromaticity (color) and luminance (brightness) were measured from multiple areas of the Dress image to determine cone stimulation and contrast. Results Mean MPOD was higher in the WG group (0.49) vs. the BB (0.41, p = 0.04) and median values were higher as well (WG = 0.46, BB = 0.36, p = 0.03). There was no difference in VEP amplitude between groups (p > 0.85) but mean VEP latency was longer in WG (130 msec.) vs. the BB group (107 msec., p = 0.0005). Colorimetry of the Dress showed significantly greater stimulation of blue cones (contrast = 73%) vs. red and green sensitive cones (contrast = 13%). Conclusions Our findings indicate that observers with denser MPOD may be predisposed to perceive the Dress as WG due to great absorption of blue light by the macular pigment. Moreover, the novel, substantial stimulation of blue cones by the Dress may contribute to ambiguity and dichotomous perception since the blue cones are so sparse in the retina. Finally, the delayed WG VEPs indicate distinct neural processing

  2. Fertility-Preserving Surgery in Patients with Early Stage Cervical Carcinoma

    PubMed Central

    Kardakis, Spyridon

    2012-01-01

    Fertility preservation is an important issue for patients in reproductive age with early stage cervical cancer. In view of recent developments, our purpose was to review and discuss available surgical alternatives. A literature search was conducted using PUBMED, including papers between 1980 and December 2011. In patients with stage IA1 cervical cancer, conization is a valid alternative. Patients with stage IA2-IB1 disease can be conservatively treated by radical trachelectomy. This is as well-established conservative approach and appears to be safe and effective in allowing a high chance of conception. Prematurity is the most serious issue in pregnancies following trachelectomy. Less invasive options such as simple trachelectomy or conization seem to be feasible for stages IA2-IB1, but more and better evidence is needed. Neoadjuvant therapy might allow conservative surgery to be performed also in patients with more extensive lesions. Ovarian transposition is important when adjuvant radiation is needed. In conclusion, available literature shows that there are interesting fertility-sparing treatment alternatives to the “golden standard” for the management of early cervical cancer in young women. PMID:23320192

  3. Early stage breast cancer detection by means of time-domain ultra-wide band sensing

    NASA Astrophysics Data System (ADS)

    Zanoon, T. F.; Abdullah, M. Z.

    2011-11-01

    The interest in the use of ultra-wide band (UWB) impulses for medical imaging, particularly early stage breast cancer detection, is driven by safety advantage, super resolution capability, significant dielectric contrast between tumours and their surrounding tissues, patient convenience and low operating costs. However, inversion algorithms leading to recovery of the dielectric profile are complex in their nature, and vulnerable to noisy experimental conditions and environment. In this paper, we present a simplified yet robust gradient-based iterative image reconstruction technique to solve the nonlinear inverse scattering problem. The calculation is based on the Polak-Ribière's approach while the Broyden's formula is used to update the gradient in an iterative scheme. To validate this approach, both numerical and experimental results are presented. Animal derived biological targets in the form of chicken skin, beef and salted butter are used to construct an experimental breast phantom, while vegetable oil is used as a background media. UWB transceivers in the form of biconical antennas contour the breast forming a full view scanning geometry at a frequency range of 0-5 GHz. Results indicate the feasibility of experimental detection of millimetre scaled targets.

  4. Small pelagics in a changing ocean: biological responses of sardine early stages to warming.

    PubMed

    Faleiro, Filipa; Pimentel, Marta; Pegado, Maria Rita; Bispo, Regina; Lopes, Ana Rita; Diniz, Mário S; Rosa, Rui

    2016-01-01

    Small pelagic fishes are known to respond rapidly to changes in ocean climate. In this study, we evaluate the effects of future environmental warming (+2°C) during the early ontogeny of the European sardine, Sardina pilchardus. Warming reduced the survival of 30-day-old larvae by half. Length at hatching increased with temperature as expected, but no significant effect was observed on the length and growth at 30 days post-hatching. Warming did not significantly affect the thermal tolerance of sardine larvae, even though the mean lethal temperature increased by 1°C. In the warm conditions, sardine larvae showed signs of thermal stress, indicated by a pronounced increase in larval metabolism (Q 10 = 7.9) and a 45% increase in the heat shock response. Lipid peroxidation was not significantly affected by the higher temperature, even though the mean value doubled. Warming did not affect the time larvae spent swimming, but decreased by 36% the frequency of prey attacks. Given the key role of these small pelagics in the trophic dynamics off the Western Iberian upwelling ecosystem, the negative effects of warming on the early stages may have important implications for fish recruitment and ecosystem structure. PMID:27293764

  5. Early stages of growth and crystal structure evolution of boron nitride thin films

    NASA Astrophysics Data System (ADS)

    Henry, Anne; Chubarov, Mikhail; Czigány, Zsolt; Garbrecht, Magnus; Högberg, Hans

    2016-05-01

    A study of the nucleation and crystal structure evolution at the early stages of the growth of sp2-BN thin films on 6H-SiC and α-Al2O3 substrates is presented. The growth is performed at low pressure and high temperature in a hot wall CVD reactor, using ammonia and triethylboron as precursors, and H2 as carrier gas. From high-resolution transmission electron microscopy and X-ray thin film diffraction measurements we observe that polytype pure rhombohedral BN (r-BN) is obtained on 6H-SiC substrates. On α-Al2O3 an AlN buffer obtained by nitridation is needed to promote the growth of hexagonal BN (h-BN) to a thickness of around 4 nm followed by a transition to r-BN growth. In addition, when r-BN is obtained, triangular features show up in plan-view scanning electron microscopy which are not seen on thin h-BN layers. The formation of BN after already one minute of growth is confirmed by X-ray photoelectron spectroscopy.

  6. Do Diacritical Marks Play a Role at the Early Stages of Word Recognition in Arabic?

    PubMed Central

    Perea, Manuel; Abu Mallouh, Reem; Mohammed, Ahmed; Khalifa, Batoul; Carreiras, Manuel

    2016-01-01

    A crucial question in the domain of visual word recognition is whether letter similarity plays a role in the early stages of visual word processing. Here we focused on Arabic because in this language there are various groups of letters that share the same basic shape and only differ in the number/location of diacritical points. We conducted a masked priming lexical decision experiment in which a target word was preceded by: (i) an identity prime; (ii) a prime in which the critical letter was replaced by a letter with the same shape that differed in the number of diacritics (e.g., ); or (iii) a prime in which the critical letter was replaced by a letter with different shape (e.g., ). Results showed a sizable advantage of the identity condition over the two substituted-letter priming conditions (i.e., diacritical information is rapidly processed). Thus, diacritical marks play an essential role in the “feature letter” level of models of visual word recognition in Arabic. PMID:27597838

  7. Laser plasma plume structure and dynamics in the ambient air: The early stage of expansion

    SciTech Connect

    Cirisan, M.; Jouvard, J. M.; Lavisse, L.; Hallo, L.; Oltra, R.

    2011-05-15

    Laser ablation plasma plume expanding into the ambient atmosphere may be an efficient way to produce nanoparticles. From that reason it would be interesting to study the properties of these laser induced plasmas formed under conditions that are known to be favorable for nanoparticles production. In general, plume behavior can be described as a two-stage process: a 'violent' plume expansion due to the absorption of the laser beam energy (during the laser pulse) followed by a fast adiabatic expansion in the ambient gas (after the end of the laser pulse). Plasma plume may last a few microseconds and may have densities 10{sup -6} times lower than the solid densities at temperatures close to the ambient temperature. Expansion of the plasma plume induced by the impact of a nanosecond laser beam ({lambda} 1064 nm) on the surface of metallic samples in the open air has been investigated by means of fast photography. Spatio-temporal evolution of the plume at the early stage of its expansion (first 330 ns) has been recorded. Structure and dynamics of the plasma plume have been investigated and compared to numerical simulations obtained with a hydro-code, as well as some scaling laws. In addition, measurements using different sample materials (Al, Fe, and Ti) have been performed in order to analyze the influence of target material on plume expansion.

  8. [The psychopathological pictures of the early stages of dementia syndromes (vasogenic and of Alzheimer's type)].

    PubMed

    Bidzan, L

    1998-01-01

    The goal of the research is to determine the early symptoms predicting dementia syndromes both Vasogenic and Alzheimer type. The investigations covered: 36 people without any psychopathological syndrome, 32 people with dementia of Alzheimer type and 36 people with vasogenic dementia. DSM IV criteria were accepted as a basis for recognition of dementia syndromes. The qualified patients underwent basic examination consisting of the following elements: AMDP scale (the estimation of psychic and somatic condition), Global Scale of Dementia, Hachinski scale, Blessed scale, Folsteins scale (MMS), Instrumental Activities of Daily Living, Physical self Maintenance Scale and two methods of the authors: Current Events Card and Prodromal Symptoms Card. On the basis of examinations the following conclusions can be stated:--persons in early stages of dementia differ from those without any symptoms of it by the occurrence of many psychopathological symptoms--not only connected with the cognitive sphere;--in the period preceding the development of dementia the frequency of occurrence of some symptoms is different according to etiology of the process (Alzheimer or vasogenic);--the applied clinical scales differ significantly in their value for the diagnosis and the estimation of intensification of dementia processes. PMID:9920996

  9. Lipid peroxidation may not be important in an early stage of alcohol-induced liver injury

    SciTech Connect

    Inomata, T.; Rao, G.A.; Tsukamoto, H.

    1986-03-01

    Role of lipid peroxidation (LP) in alcoholic liver injury (ALI) is still controversial. The authors have previously described a rat model which produced the sequential injury from alcoholic fatty liver to liver necrosis and fibrosis. In the present study, the authors have examined the degree of LP and GSH/GSSG ratio in the liver to investigate whether the LP can be identified in an early stage of progressive ALI. Six pairs of male Wistar rats were continuously infused intragastrically for 30 days with a high fat diet (25% total calories) plus either ethanol or isocaloric amount of dextrose. Following intoxication, the content of diene conjugates in mitochondrial and microsomal lipids as well as the liver GSH/GSSG ratio were determined by the diene difference spectrum and fluorometry, respectively. The UV absorption at 234nm by mitochondrial lipid from alcoholic rats (0.668 +/- 0.023 OD/mg) was significantly (p<0.05) lower than that of controls (0.977 +/- 0.102 OD/mg). The microsomal lipid, however, exhibited a similar absorbance in the two groups (0.986 +/- 0.086 vs 1.149 +/- 0.091 OD/mg0. Similarly, no difference in the ratio of GSH/GSSG was found (6.05 +/- 0.27 vs 5.35 +/- 0.44). These results do not support a concept that LP is an important pathogenetic factor for the progression of alcoholic fatty liver to liver necrosis.

  10. Ectomycorrhizin Synthesis and Polypeptide Changes during the Early Stage of Eucalypt Mycorrhiza Development 1

    PubMed Central

    Hilbert, Jean-Louis; Costa, Guy; Martin, Francis

    1991-01-01

    In functioning eucalypt ectomycorrhizas, biochemical alterations are accompanied by a differential accumulation of polypeptides including the synthesis of symbiosis-related proteins (JL Hilbert, Martin FM [1988] New Phytol 110: 339-346). In the present study, protein biosynthesis in the early stages of ectomycorrhiza formation on Eucalyptus globulus subsp. bicostata Kirkp. was examined using compatible and incompatible isolates of the basidiomycete Pisolithus tinctorius (Coker & Couch). Changes in polypeptide composition were observed within hours following contact of the compatible mycelium with the roots, well before the differentiation of typical symbiotic tissues. At this stage, at least seven symbiosis-related proteins (ectomycorrhizins) accumulated in root tissues. In vivo incorporation of [35S]methionine by ectomycorrhizas followed by electrophoresis of the labeled proteins revealed that most of these differences in polypeptide concentrations, including the ectomycorrhizin accumulation, are the result of differential protein biosynthesis rather than posttranslational modifications of the polypeptides. The initial development of eucalypt ectomycorrhizas, therefore, coincides with the synthesis of symbiosis-related proteins and the data presented here provide essential evidence to ascribe a functional developmental role to these proteins. ImagesFigure 2Figure 3Figure 4Figure 5 PMID:16668539

  11. A Report On Eight Early-Stage State And Regional Projects Testing Value-Based Payment

    PubMed Central

    Conrad, Douglas; Grembowski, David; Gibbons, Claire; Marcus-Smith, Miriam; Hernandez, Susan E.; Chang, Judy; Renz, Anne; Lau, Bernard; Cruz, Erin dela

    2014-01-01

    To help contain health care spending and improve the quality of care, practitioners and policy makers are trying to move away from fee-for-service toward value-based payment, which links providers’ reimbursement to the value, rather than the volume, of services delivered. With funding from the Robert Wood Johnson Foundation, eight grantees across the country are designing and implementing value-based payment reform projects. For example, in Salem, Oregon, the Physicians Choice Foundation is testing “Program Oriented Payments,” which include incentives for providers who follow a condition-specific program of care designed to meet goals set jointly by patient and provider. In this article we describe the funding rationale and the specific objectives, strategies, progress, and early stages of implementation of the eight projects. We also share some early lessons and identify prerequisites for success, such as ensuring that providers have broad and timely access to data so they can meet patients’ needs in cost-effective ways. PMID:23650332

  12. Influence of the surface morphology on the early stages of Cu oxidation

    NASA Astrophysics Data System (ADS)

    Luo, Langli; Kang, Yihong; Yang, Judith C.; Zhou, Guangwen

    2012-10-01

    The growth and morphological features of Cu films deposited on NaCl(1 0 0) by e-beam evaporation have been examined to evaluate the effect of various surface morphologies on the initial oxidation of Cu. It is shown that epitaxial Cu films with significantly reduced surface roughness can be achieved by first nucleating Cu seeds at 450 °C that favors epitaxial Cu grains which is followed by subsequent seed growth at 150 °C that favors smooth Cu film. The effect of the variations of the surface morphology of the resulting Cu films by the different growth conditions on the early stages oxidation of Cu films is examined by in situ transmission electron microscopy (TEM) and ex situ atomic force microscopy (AFM). It is shown that the changes in the surface morphologies of the Cu film result in distinct variations in the nucleation density and growth rates of oxide islands. Such correlation between the surface morphology and the initial oxidation behavior of the Cu films provides insights into understanding the microscopic processes of the transient oxidation of metals and for manipulating the initial oxide formation through surface treatments.

  13. Do Hospital Characteristics Influence Cancer-Specific Survival for Early Stage Lung Cancer?

    PubMed Central

    David, Elizabeth A; Chen, Yingjia; Cooke, David T; Perry, Andrew; Canter, Robert J; Cress, Rosemary

    2015-01-01

    Background Quality of oncologic outcomes is of paramount importance in the care of patients with non-small cell lung cancer (NSCLC). We sought to evaluate the relationship of hospital volume for lobectomy on cancer-specific survival in NSCLC patients treated in California, as well as the influence of Committee on Cancer (CoC) accreditation. Methods The California Cancer Registry was queried from 2004–2011 for cases of Stage I NSCLC and 8,345 patients were identified. Statistical analysis was used to determine prognostic factors for cancer-specific survival. Results 7,587 patients were treated surgically. CoC accreditation was not significant for cancer-specific survival, but treatment in high volume centers was associated with longer survival when compared to low and medium volume centers (HR 1.77, 1.474–2.141 and HR 1.23, 1.058–1.438). Conclusions These data suggest that surgical treatment in high volume hospitals is associated with longer cancer-specific survival for early-stage NSCLC, but that CoC accreditation is not. PMID:26193801

  14. Small pelagics in a changing ocean: biological responses of sardine early stages to warming

    PubMed Central

    Faleiro, Filipa; Pimentel, Marta; Pegado, Maria Rita; Bispo, Regina; Lopes, Ana Rita; Diniz, Mário S.; Rosa, Rui

    2016-01-01

    Small pelagic fishes are known to respond rapidly to changes in ocean climate. In this study, we evaluate the effects of future environmental warming (+2°C) during the early ontogeny of the European sardine, Sardina pilchardus. Warming reduced the survival of 30-day-old larvae by half. Length at hatching increased with temperature as expected, but no significant effect was observed on the length and growth at 30 days post-hatching. Warming did not significantly affect the thermal tolerance of sardine larvae, even though the mean lethal temperature increased by 1°C. In the warm conditions, sardine larvae showed signs of thermal stress, indicated by a pronounced increase in larval metabolism (Q10 = 7.9) and a 45% increase in the heat shock response. Lipid peroxidation was not significantly affected by the higher temperature, even though the mean value doubled. Warming did not affect the time larvae spent swimming, but decreased by 36% the frequency of prey attacks. Given the key role of these small pelagics in the trophic dynamics off the Western Iberian upwelling ecosystem, the negative effects of warming on the early stages may have important implications for fish recruitment and ecosystem structure. PMID:27293764

  15. Modeling bacterial attachment to surfaces as an early stage of biofilm development.

    PubMed

    El Moustaid, Fadoua; Eladdadi, Amina; Uys, Lafras

    2013-06-01

    Biofilms are present in all natural, medical and industrial surroundings where bacteria live. Biofilm formation is a key factor in the growth and transport of both beneficial and harmful bacteria. While much is known about the later stages of biofilm formation, less is known about its initiation which is an important first step in the biofilm formation. In this paper, we develop a non-linear system of partial differential equations of Keller-Segel type model in one-dimensional space, which couples the dynamics of bacterial movement to that of the sensing molecules. In this case, bacteria perform a biased random walk towards the sensing molecules. We derive the boundary conditions of the adhesion of bacteria to a surface using zero-Dirichlet boundary conditions, while the equation describing sensing molecules at the interface needed particular conditions to be set. The numerical results show the profile of bacteria within the space and the time evolution of the density within the free-space and on the surface. Testing different parameter values indicate that significant amount of sensing molecules present on the surface leads to a faster bacterial movement toward the surface which is the first step of biofilm initiation. Our work gives rise to results that agree with the biological description of the early stages of biofilm formation. PMID:23906151

  16. Cross-modal re-organization in adults with early stage hearing loss.

    PubMed

    Campbell, Julia; Sharma, Anu

    2014-01-01

    Cortical cross-modal re-organization, or recruitment of auditory cortical areas for visual processing, has been well-documented in deafness. However, the degree of sensory deprivation necessary to induce such cortical plasticity remains unclear. We recorded visual evoked potentials (VEP) using high-density electroencephalography in nine persons with adult-onset mild-moderate hearing loss and eight normal hearing control subjects. Behavioral auditory performance was quantified using a clinical measure of speech perception-in-noise. Relative to normal hearing controls, adults with hearing loss showed significantly larger P1, N1, and P2 VEP amplitudes, decreased N1 latency, and a novel positive component (P2') following the P2 VEP. Current source density reconstruction of VEPs revealed a shift toward ventral stream processing including activation of auditory temporal cortex in hearing-impaired adults. The hearing loss group showed worse than normal speech perception performance in noise, which was strongly correlated with a decrease in the N1 VEP latency. Overall, our findings provide the first evidence that visual cross-modal re-organization not only begins in the early stages of hearing impairment, but may also be an important factor in determining behavioral outcomes for listeners with hearing loss, a finding which demands further investigation.

  17. Proton therapy for early stage prostate cancer: is there a case?

    PubMed

    Chan, Tabitha Y; Tan, Poh Wee; Tang, Johann I

    2016-01-01

    Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT's future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery. PMID:27672328

  18. Developing an inventor support service which performs early stage market and manufacturing evaluations. [Final Report

    SciTech Connect

    Not Available

    1991-10-01

    American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was to establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.

  19. Developing an inventor support service which performs early stage market and manufacturing evaluations. Final report

    SciTech Connect

    Not Available

    1991-10-01

    American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was to establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.

  20. Do Diacritical Marks Play a Role at the Early Stages of Word Recognition in Arabic?

    PubMed Central

    Perea, Manuel; Abu Mallouh, Reem; Mohammed, Ahmed; Khalifa, Batoul; Carreiras, Manuel

    2016-01-01

    A crucial question in the domain of visual word recognition is whether letter similarity plays a role in the early stages of visual word processing. Here we focused on Arabic because in this language there are various groups of letters that share the same basic shape and only differ in the number/location of diacritical points. We conducted a masked priming lexical decision experiment in which a target word was preceded by: (i) an identity prime; (ii) a prime in which the critical letter was replaced by a letter with the same shape that differed in the number of diacritics (e.g., ); or (iii) a prime in which the critical letter was replaced by a letter with different shape (e.g., ). Results showed a sizable advantage of the identity condition over the two substituted-letter priming conditions (i.e., diacritical information is rapidly processed). Thus, diacritical marks play an essential role in the “feature letter” level of models of visual word recognition in Arabic.

  1. User involvement in the early stages of the development of an aircraft warning system.

    PubMed

    Noyes, J M; Starr, A F; Frankish, C R

    1996-01-01

    There is an increasing awareness of the importance and the benefits to be attained from consulting the end-users during system and product development. Although the rationale of utilizing the expertise of end-users in the system development life cycle appears to provide an apparently straightforward, even 'ideal' approach, there are many difficulties associated with eliciting the required knowledge from experts, both general and specific to every user group. Furthermore, many developers do not know how to involve users, or if they do, they do not utilize them to best effect. In the avionics sphere, the wealth of knowledge possessed by line pilots and flight engineers represents a vital information resource for the design of future flight-deck systems. As a specific example, this paper overviews some of the considerations which arose from working with these end-users in the early stages of the development of a warning and diagnostic system for civil aircraft. The end-goal of this particular phase of the work was the generation of guidelines for the design of the interface for the software engineers to use when building the prototype, and the methodological approach taken to achieve this is reported here.

  2. In situ nanomechanical characterization of the early stages of swelling and degradation of a biodegradable polymer.

    PubMed

    Dumitru, A C; Espinosa, F M; Garcia, R; Foschi, G; Tortorella, S; Valle, F; Dallavalle, M; Zerbetto, F; Biscarini, F

    2015-03-12

    The interactions of a biodegradable scaffold with cells or living tissues depend on the time-evolution of the nanoscale properties of the scaffold. We present an in situ quantitative study on the early-stage swelling and degradation of poly(lactic-co-glycolic acid) (PLGA). A novel metrology scheme based on force microscopy measurements of the patterns of PLGA nanostructures is developed to characterize the evolution of topography, volume and nanomechanical properties. The volume and nanoscale roughness show an oscillating behaviour during the first eight days of immersion; at a later stage, we observe a continuous decrease of the volume. The effective Young's modulus exhibits a monotonic decrease from an initial value of about 2.4 GPa down to 9 MPa at day 14. The oscillating behaviour of the volume before the onset of full degradation is explained by a coupled diffusion-swelling mechanism. The appearance of a second maximum in the volume evolution results from the competition between swelling and degradation.

  3. Acousto-spinodal decomposition of compressible polymer solutions: early stage analysis.

    PubMed

    Rasouli, Ghoncheh; Rey, Alejandro D

    2011-05-14

    The structure and dynamics of early stage kinetics of pressure-induced phase separation of compressible polymer solutions via spinodal decomposition is analyzed using a linear Euler-Cahn-Hilliard model and the modified Sanchez Lacombe equation of state. The integrated density wave and Cahn-Hilliard equations combine the kinetic and structural characteristics of spinodal decomposition with density waves arising from pressure-induced couplings. When mass transfer rate is slower that acoustic waves, concentration gradients generate density waves that cycle back into the spinodal decomposition dynamics, resulting in oscillatory demixing. The wave attenuation increases with increasing mass transfer rates eventually leading to nonoscillatory spinodal demixing. The novel aspects of acousto-spinodal decomposition arise from the coexistence of stable oscillatory density dynamics and the unstable monotonic concentration dynamics. Scaling laws for structure and dynamics indicate deviations from incompressible behavior, with a significant slowing down of demixing due to couplings with density waves. Partial structure factors for density and density-concentration reflect the oscillatory nature of acousto-spinodal modes at lower wave vectors, while the single maximum at a constant wave vector reflects the presence of a dominant mode in the linear regime. The computed total structure factor is in qualitative agreement with experimental data for a similar polymer solution. PMID:21568529

  4. User involvement in the early stages of the development of an aircraft warning system.

    PubMed

    Noyes, J M; Starr, A F; Frankish, C R

    1996-01-01

    There is an increasing awareness of the importance and the benefits to be attained from consulting the end-users during system and product development. Although the rationale of utilizing the expertise of end-users in the system development life cycle appears to provide an apparently straightforward, even 'ideal' approach, there are many difficulties associated with eliciting the required knowledge from experts, both general and specific to every user group. Furthermore, many developers do not know how to involve users, or if they do, they do not utilize them to best effect. In the avionics sphere, the wealth of knowledge possessed by line pilots and flight engineers represents a vital information resource for the design of future flight-deck systems. As a specific example, this paper overviews some of the considerations which arose from working with these end-users in the early stages of the development of a warning and diagnostic system for civil aircraft. The end-goal of this particular phase of the work was the generation of guidelines for the design of the interface for the software engineers to use when building the prototype, and the methodological approach taken to achieve this is reported here. PMID:11541759

  5. Coping with early stage breast cancer: examining the influence of personality traits and interpersonal closeness.

    PubMed

    Saita, Emanuela; Acquati, Chiara; Kayser, Karen

    2015-01-01

    The study examines the influence of personality traits and close relationships on the coping style of women with breast cancer. A sample of 72 Italian patients receiving treatment for early stage breast cancer was recruited. Participants completed questionnaires measuring personality traits (Interpersonal Adaptation Questionnaire), interpersonal closeness (Inclusion of the Other in the Self Scale), and adjustment to cancer (Mini-Mental Adjustment to Cancer Scale). We hypothesized that diverse personality traits and degrees of closeness contribute to determine the coping styles shown by participants. Multiple regression analyses were conducted for each of the five coping styles (Helplessness/Hopelessness, Anxious Preoccupation, Avoidance, Fatalism, and Fighting Spirit) using personality traits and interpersonal closeness variables (Strength of Support Relations, and Number of Support Relations) as predictors. Women who rated high on assertiveness and social anxiety were more likely to utilize active coping strategies (Fighting Spirit). Perceived strength of relationships was predictive of using an active coping style while the number of supportive relationships did not correlate with any of the coping styles. Implications for assessment of breast cancer patients at risk for negative adaptation to the illness and the development of psychosocial interventions are discussed. PMID:25699003

  6. Stereotactic radiotherapy for early stage non-small cell lung cancer

    PubMed Central

    Badellino, Serena; Filippi, Andrea Riccardo

    2015-01-01

    Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice. PMID:26157674

  7. Affective systems induce formal thought disorder in early-stage psychosis.

    PubMed

    Minor, Kyle S; Marggraf, Matthew P; Davis, Beshaun J; Mehdiyoun, Nicole F; Breier, Alan

    2016-05-01

    Although formal thought disorder (FTD) has been described since early conceptualizations of psychosis, its underlying mechanisms are unclear. Evidence suggests FTD may be influenced by affective and cognitive systems; however, few have examined these relationships-with none focusing on early-stage psychosis (EP). In this study, positive FTD and speech production were measured in sex- and race-matched EP (n = 19) and healthy control (n = 19) groups by assessing "reactivity"-a change in experimental compared with baseline conditions-across baseline, affective, and cognitive conditions. Relationships with functioning were also examined within each group. Three key findings emerged: (a) the EP group displayed large differences in positive FTD and speech production, (b) those with EP exhibited affective reactivity for positive FTD, and (c) positive FTD and affective reactivity were linked with poor real-world functioning in EP and these relationships did not considerably change when controlling for positive symptom (e.g., delusions, hallucinations) severity. Our findings provide preliminary evidence that affective, but not cognitive, systems play a critical role in positive FTD. Affective reactivity, in particular, may aid in predicting those with EP who go on to develop serious social impairments. Future work should focus on whether affective systems differentially influence those at separate points on the psychosis-spectrum in an effort to establish evidence-based treatments for FTD. (PsycINFO Database Record PMID:26999283

  8. Effects of cryopreservation of Phaseolus vulgaris L. seeds on early stages of germination.

    PubMed

    Cejas, Inaudis; Vives, Karel; Laudat, Taletha; González-Olmedo, Justo; Engelmann, Florent; Martínez-Montero, Marcos Edel; Lorenzo, José Carlos

    2012-11-01

    In this work, we studied the effects of cryopreservation on various parameters of early stages of germination of Phaseolus vulgaris seeds (0, 7 and 14 days). Percentages of germination, fresh mass of different plant parts, levels of chlorophyll pigments (a, b, total), malondialdehyde, other aldehydes, phenolics (cell wall-linked, free, and total) and protein were determined. No phenotypic changes were observed visually in seedlings recovered from cryopreserved seeds. However, several significant effects of seed liquid nitrogen exposure were recorded at the biochemical level. There was a significant negative effect of cryopreservation on shoot protein content, which decreased from 3.11 mg g(-1) fresh weight for non-cryopreserved controls to 0.44 mg g(-1) fresh shoot weight for cryopreserved seeds. On the other hand, cryopreservation significantly increased levels of other aldehydes than malondialdehyde in shoots at day 7, from 56.47 μmol g(-1) for non-cryopreserved controls to 253.19 μmol g(-1) fresh shoot weight for cryopreserved samples. Liquid nitrogen exposure significantly reduced phenolics contents (free, cell-wall linked, total) in roots at day 7 after onset of germination. In general, roots were more affected by cryostorage compared with other plant parts, while leaves were the least affected. The effects of seed cryopreservation seem to decline progressively along with seedling growth.

  9. Biogeochemical Changes at Early Stage After the Closure of Radioactive Waste Geological Repository in South Korea

    SciTech Connect

    Choung, Sungwook; Um, Wooyong; Choi, Seho; Francis, Arokiasamy J.; Kim, Sungpyo; Park, Jin beak; Kim, Suk-Hoon

    2014-09-01

    Permanent disposal of low- and intermediate-level radioactive wastes in the subterranean environment has been the preferred method of many countries, including Korea. A safety issue after the closure of a geological repository is that biodegradation of organic materials due to microbial activities generates gases that lead to overpressure of the waste containers in the repository and its disintegration with the release of radionuclides. As part of an ongoing large-scale in situ experiment using organic wastes and groundwater to simulate geological radioactive waste repository conditions, we investigated the geochemical alteration and microbial activities at an early stage (~63 days) intended to be representative of the initial period after repository closure. The increased numbers of both aerobes and facultative anaerobes in waste effluents indicate that oxygen content could be the most significant parameter to control biogeochemical conditions at very early periods of reaction (<35 days). Accordingly, the values of dissolved oxygen and redox potential were decreased. The activation of anaerobes after 35 days was supported by the increased concentration to ~50 mg L-1 of ethanol. These results suggest that the biogeochemical conditions were rapidly altered to more reducing and anaerobic conditions within the initial 2 months after repository closure. Although no gases were detected during the study, activated anaerobic microbes will play more important role in gas generation over the long term.

  10. Bringing Clouds into Our Lab! - The Influence of Turbulence on the Early Stage Rain Droplets

    NASA Astrophysics Data System (ADS)

    Yavuz, Mehmet Altug; Kunnen, Rudie; Heijst, Gertjan; Clercx, Herman

    2015-11-01

    We are investigating a droplet-laden flow in an air-filled turbulence chamber, forced by speaker-driven air jets. The speakers are running in a random manner; yet they allow us to control and define the statistics of the turbulence. We study the motion of droplets with tunable size (Stokes numbers ~ 0.13 - 9) in a turbulent flow, mimicking the early stages of raindrop formation. 3D Particle Tracking Velocimetry (PTV) together with Laser Induced Fluorescence (LIF) methods are chosen as the experimental method to track the droplets and collect data for statistical analysis. Thereby it is possible to study the spatial distribution of the droplets in turbulence using the so-called Radial Distribution Function (RDF), a statistical measure to quantify the clustering of particles. Additionally, 3D-PTV technique allows us to measure velocity statistics of the droplets and the influence of the turbulence on droplet trajectories, both individually and collectively. In this contribution, we will present the clustering probability quantified by the RDF for different Stokes numbers. We will explain the physics underlying the influence of turbulence on droplet cluster behavior. This study supported by FOM/NWO Netherlands.

  11. Early Stages in Polymer Crystal Growth for Isotactic Poly-1-Butene: From Nucleation to Network Percolation

    NASA Astrophysics Data System (ADS)

    Arora, Deepak; Winter, Horst

    2010-03-01

    Isothermal crystallization experiments on isotactic poly-1-butene at early stages of spherulite growth provide quantitative information about nucleation density, volume fraction of spherulites and their crystallinity, and the mechanism of connecting into a sample spanning structure. An attempt is made to connect the crystal fraction inside spherulites with the average crystallinity of the entire sample. The crystal fraction inside spherulites is very small initially but increases with time and catches up with the sample crystallinity later on. Experiments include optical microscopy, DSC, SALS, and rheology. Optical microscopy near the fluid-to-solid transition suggests that the transition, as determined by rheology, is not caused by packing/jamming of spherulites but by the formation of a percolating structure. Impingement of pairs of spherulites occurs already much before percolation. This makes it difficult to predict crystal growth and define spherulitic impingement for the whole sample. At percolation, the absolute crystallinity is about 7-8 vol%. This shows that spherulites are mostly amorphous before impingement.

  12. Proton therapy for early stage prostate cancer: is there a case?

    PubMed Central

    Chan, Tabitha Y; Tan, Poh Wee; Tang, Johann I

    2016-01-01

    Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT’s future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery.

  13. Early stage of the electron kinetics in swift heavy ion tracks in dielectrics

    SciTech Connect

    Medvedev, N. A.; Rethfeld, B.; Volkov, A. E.; Shcheblanov, N. S.

    2010-09-15

    A Monte Carlo approach was applied for simulations of the early stage (first tens of femtosecond) of kinetics of the electronic subsystem of silica (SiO{sub 2}) in tracks of swift heavy ions (SHIs) decelerated in the electronic stopping regime. At the first step multiple ionizations of target atoms by a projectile (Ca{sup +19}, E=11.4 MeV/amu) were described that gave the initial spatial distributions of free electrons having different momenta as well as distributions of holes in different atomic shells. Spatial propagation of fast electrons results in secondary ionizations of target atoms as well as in energy transfer to the lattice at times much shorter than the times of atomic oscillations (phonons). The well detected front of excitation in the electronic and ionic subsystems is formed due to this propagation which cannot be described by models based on diffusion mechanisms (e.g., parabolic equations of heat diffusion). At times {approx}10 fs after the projectile passage, about {approx}0.1% of the energy is already transferred to the lattice. About 63% of the energy deposited by the ion is accumulated in holes at these times. Calculated distributions of these holes through the atomic shells are in excellent agreement with the spectroscopy experiments. Comparison with these experiments demonstrated also that relaxation of the electronic subsystem in SHI tracks in solids cannot be described adequately without taking into account intra-atomic and interatomic Auger (Knotek-Feibelman) processes.

  14. Re-examining the effects of verbal instructional type on early stage motor learning.

    PubMed

    Bobrownicki, Ray; MacPherson, Alan C; Coleman, Simon G S; Collins, Dave; Sproule, John

    2015-12-01

    The present study investigated the differential effects of analogy and explicit instructions on early stage motor learning and movement in a modified high jump task. Participants were randomly assigned to one of three experimental conditions: analogy, explicit light (reduced informational load), or traditional explicit (large informational load). During the two-day learning phase, participants learned a novel high jump technique based on the 'scissors' style using the instructions for their respective conditions. For the single-day testing phase, participants completed both a retention test and task-relevant pressure test, the latter of which featured a rising high-jump-bar pressure manipulation. Although analogy learners demonstrated slightly more efficient technique and reported fewer technical rules on average, the differences between the conditions were not statistically significant. There were, however, significant differences in joint variability with respect to instructional type, as variability was lowest for the analogy condition during both the learning and testing phases, and as a function of block, as joint variability decreased for all conditions during the learning phase. Findings suggest that reducing the informational volume of explicit instructions may mitigate the deleterious effects on performance previously associated with explicit learning in the literature.

  15. Coping with early stage breast cancer: examining the influence of personality traits and interpersonal closeness

    PubMed Central

    Saita, Emanuela; Acquati, Chiara; Kayser, Karen

    2015-01-01

    The study examines the influence of personality traits and close relationships on the coping style of women with breast cancer. A sample of 72 Italian patients receiving treatment for early stage breast cancer was recruited. Participants completed questionnaires measuring personality traits (Interpersonal Adaptation Questionnaire), interpersonal closeness (Inclusion of the Other in the Self Scale), and adjustment to cancer (Mini-Mental Adjustment to Cancer Scale). We hypothesized that diverse personality traits and degrees of closeness contribute to determine the coping styles shown by participants. Multiple regression analyses were conducted for each of the five coping styles (Helplessness/Hopelessness, Anxious Preoccupation, Avoidance, Fatalism, and Fighting Spirit) using personality traits and interpersonal closeness variables (Strength of Support Relations, and Number of Support Relations) as predictors. Women who rated high on assertiveness and social anxiety were more likely to utilize active coping strategies (Fighting Spirit). Perceived strength of relationships was predictive of using an active coping style while the number of supportive relationships did not correlate with any of the coping styles. Implications for assessment of breast cancer patients at risk for negative adaptation to the illness and the development of psychosocial interventions are discussed. PMID:25699003

  16. Discovery of gramine derivatives that inhibit the early stage of EV71 replication in vitro.

    PubMed

    Wei, Yanhong; Shi, Liqiao; Wang, Kaimei; Liu, Manli; Yang, Qingyu; Yang, Ziwen; Ke, Shaoyong

    2014-01-01

    Enterovirus 71 (EV71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for EV71 infections. In this study, the antiviral activity of gramine and 21 gramine derivatives against EV71 was investigated in cell-based assays. Eighteen derivatives displayed some degree of inhibitory effects against EV71, in that they could effectively inhibit virus-induced cytopathic effects (CPEs), but the anti-EV71 activity of the lead compound gramine was not observed. Studies on the preliminary modes of action showed that these compounds functioned by targeting the early stage of the EV71 lifecycle after viral entry, rather than inactivating the virus directly, inhibiting virus adsorption or affecting viral release from the cells. Among these derivatives, one (compound 4s) containing pyridine and benzothiazole units showed the most potency against EV71. Further studies demonstrated that derivative 4s could profoundly inhibit viral RNA replication, protein synthesis, and virus-induced apoptosis in RD cells. These results indicate that derivative 4s might be a feasible therapeutic agent against EV71 infection and that these gramine derivatives may provide promising lead scaffolds for the further design and synthesis of potential antiviral agents.

  17. Norvaline and Norleucine May Have Been More Abundant Protein Components during Early Stages of Cell Evolution

    NASA Astrophysics Data System (ADS)

    Alvarez-Carreño, Claudia; Becerra, Arturo; Lazcano, Antonio

    2013-10-01

    The absence of the hydrophobic norvaline and norleucine in the inventory of protein amino acids is readdressed. The well-documented intracellular accumulation of these two amino acids results from the low-substrate specificity of the branched-chain amino acid biosynthetic enzymes that act over a number of related α-ketoacids. The lack of absolute substrate specificity of leucyl-tRNA synthase leads to a mischarged norvalyl-tRNALeu that evades the translational proofreading activites and produces norvaline-containing proteins, (cf. Apostol et al. J Biol Chem 272:28980-28988, 1997). A similar situation explains the presence of minute but detectable amounts of norleucine in place of methionine. Since with few exceptions both leucine and methionine are rarely found in the catalytic sites of most enzymes, their substitution by norvaline and norleucine, respectively, would have not been strongly hindered in small structurally simple catalytic polypeptides during the early stages of biological evolution. The report that down-shifts of free oxygen lead to high levels of intracellular accumulation of pyruvate and the subsequent biosynthesis of norvaline (Soini et al. Microb Cell Factories 7:30, 2008) demonstrates the biochemical and metabolic consequences of the development of a highly oxidizing environment. The results discussed here also suggest that a broader definition of biomarkers in the search for extraterrestrial life may be required.

  18. Optimization of a novel enzyme treatment process for early-stage processing of sheepskins.

    PubMed

    Lim, Y F; Bronlund, J E; Allsop, T F; Shilton, A N; Edmonds, R L

    2010-01-01

    An enzyme treatment process for early-stage processing of sheepskins has been previously reported by the Leather and Shoe Research Association of New Zealand (LASRA) as an alternative to current industry operations. The newly developed process had marked benefits over conventional processing in terms of a lowered energy usage (73%), processing time (47%) as well as water use (49%), but had been developed as a "proof of principle''. The objective of this work was to develop the process further to a stage ready for adoption by industry. Mass balancing was used to investigate potential modifications for the process based on the understanding developed from a detailed analysis of preliminary design trials. Results showed that a configuration utilising a 2 stage counter-current system for the washing stages and segregation and recycling of enzyme float prior to dilution in the neutralization stage was a significant improvement. Benefits over conventional processing include a reduction of residual TDS by 50% at the washing stages and 70% savings on water use overall. Benefits over the un-optimized LASRA process are reduction of solids in product after enzyme treatment and neutralization stages by 30%, additional water savings of 21%, as well as 10% savings of enzyme usage. PMID:20861557

  19. An Early-Stage Epidemic: A Systematic Review of Correlates of Smoking Among Chinese Women

    PubMed Central

    Gebel, Klaus; Oldenburg, Brian F.; Wan, Xia; Zhong, Xuefeng; Novotny, Thomas E.

    2015-01-01

    Background Despite the historically low smoking prevalence among Chinese women, there is a trend of future increase. Purpose We systematically reviewed the correlates of smoking among Chinese girls and women. Method We conducted a systematic review of literature on correlates of smoking among Chinese women using Medline and China Academic Journals databases. Following the PRISMA statement, two investigators independently searched for literature, identified and reviewed papers, assessed the quality of the papers, and extracted information. The characteristics of studies and correlates of smoking were synthesized separately for youth and adults. Results A total of 15 articles (11 on adults, 4 on youth) met the inclusion criteria. Based on these studies, peer smoking was the most consistent correlate of smoking among Chinese girls. Among Chinese women, partner smoking, job-related stress, and exposure to cigarettes made for women were consistent correlates of smoking. Knowledge of harms and negative attitudes towards smoking were found to be negatively associated with smoking. Conclusion Overall, the evidence base for smoking among Chinese women is limited. Although smoking among Chinese women is still at an early stage, it is becoming more prevalent among specific population subgroups, such as rural-to-urban migrant workers. Although further research is needed, findings from the current study provide a roadmap for research and policy on prevention of smoking among Chinese girls and women. PMID:24222041

  20. Altered Gray Matter Structural Covariance Networks in Early Stages of Alzheimer's Disease.

    PubMed

    Montembeault, Maxime; Rouleau, Isabelle; Provost, Jean-Sébastien; Brambati, Simona Maria

    2016-06-01

    Clinical symptoms observed in Alzheimer's disease (AD) patients may reflect variations within specific large-scale brain networks, modeling AD as a disconnection syndrome. The present magnetic resonance imaging study aims to compare the organization of gray matter structural covariance networks between 109 cognitively unimpaired controls (CTRL) and 109 AD patients positive to beta-amyloid at the early stages of the disease, using voxel-based morphometry. The default-mode network (DMN; medial temporal lobe subsystem) was less extended in AD patients in comparison with CTRL, with a significant decrease in the structural association between the entorhinal cortex and the medial prefrontal and the dorsolateral prefrontal cortices. The DMN (midline core subsystem) was also less extended in AD patients. Trends toward increased structural association were observed in the salience and executive control networks. The observed changes suggest that early disruptions in structural association between heteromodal association cortices and the entorhinal cortex could contribute to an isolation of the hippocampal formation, potentially giving rise to the clinical hallmark of AD, progressive memory impairment. It also provides critical support to the hypothesis that the reduced connectivity within the DMN in early AD is accompanied by an enhancement of connectivity in the salience and executive control networks.

  1. Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation.

    PubMed

    Wolff, Gretchen; Davidson, Sarah J; Wrobel, Jagoda K; Toborek, Michal

    2015-08-01

    Tumor cell extravasation into the brain requires passage through the blood-brain barrier, which is a highly protected microvascular environment fortified with tight junction (TJ) proteins. TJ integrity can be regulated under physiological and pathophysiological conditions. There is evidence that exercise can modulate oxidation status within the brain microvasculature and protect against tumor cell extravasation and metastasis formation. In order to study these events, mature male mice were given access to voluntary exercise on a running wheel (exercise) or access to a locked wheel (sedentary) for five weeks. The average running distance was 9.0 ± 0.2 km/day. Highly metastatic tumor cells (murine Lewis lung carcinoma) were then infused into the brain microvasculature through the internal carotid artery. Analyses were performed at early stage (48 h) and late stage (3 weeks) post tumor cell infusion. Immunohistochemical analysis revealed fewer isolated tumor cells extravasating into the brain at both 48 h and 3 weeks post surgery in exercised mice. Occludin protein levels were reduced in the sedentary tumor group, but maintained in the exercised tumor group at 48 h post tumor cell infusion. These results indicate that voluntary exercise may participate in modulating blood-brain barrier integrity thereby protecting the brain during metastatic progression.

  2. Prehension synergies and hand function in early-stage Parkinson's disease.

    PubMed

    Jo, Hang Jin; Park, Jaebum; Lewis, Mechelle M; Huang, Xuemei; Latash, Mark L

    2015-02-01

    We explored the multi-digit synergies and hand performance in object manipulations and pressing tasks in patients with early-stage Parkinson's disease (PD) and healthy controls. Synergies were defined as inter-trials co-variation patterns among forces/moments produced by individual digits that stabilized a resultant mechanical variable. The subjects performed three main tasks: pressing (steady-state force production followed by a force pulse into the target), prehension (manipulation of a handheld instrumented handle imitating the action of taking a sip from a glass), and functional object manipulation (moving a glass with water as quickly and accurately as possible along a chain of targets). The PD patients were slower compared to controls in all three tasks. Patients showed smaller synergy indices in the pressing and prehension tasks. In the prehension tasks, patients showed elevated grip force at steady states with smaller grip force modulation during the handle motion. PD patients showed smaller feed-forward synergy adjustments in preparation to the quick action in the pressing and (to a smaller degree) prehension tasks. Synergy indices correlated with the time index of performance in the functional glass-with-water task, whereas none of the indices correlated with the Unified PD Rating Scale part III-motor scores. We interpret the results as pointing at an important role of subcortical structures in motor synergies and their feed-forward adjustments to action. PMID:25370346

  3. Social exclusion and early-stage interpersonal perception: selective attention to signs of acceptance.

    PubMed

    Dewall, C Nathan; Maner, Jon K; Rouby, D Aaron

    2009-04-01

    Social exclusion can thwart people's powerful need for social belonging. Whereas prior studies have focused primarily on how social exclusion influences complex and cognitively downstream social outcomes (e.g., memory, overt social judgments and behavior), the current research examined basic, early-in-the-cognitive-stream consequences of exclusion. Across 4 experiments, the threat of exclusion increased selective attention to smiling faces, reflecting an attunement to signs of social acceptance. Compared with nonexcluded participants, participants who experienced the threat of exclusion were faster to identify smiling faces within a "crowd" of discrepant faces (Experiment 1), fixated more of their attention on smiling faces in eye-tracking tasks (Experiments 2 and 3), and were slower to disengage their attention from smiling faces in a visual cueing experiment (Experiment 4). These attentional attunements were specific to positive, social targets. Excluded participants did not show heightened attention to faces conveying social disapproval or to positive nonsocial images. The threat of social exclusion motivates people to connect with sources of acceptance, which is manifested not only in "downstream" choices and behaviors but also at the level of basic, early-stage perceptual processing. PMID:19309198

  4. Cowpea-Meloidogyne incognita interaction: Root proteomic analysis during early stages of nematode infection.

    PubMed

    Villeth, Gabriela R C; Carmo, Lilian S T; Silva, Luciano P; Fontes, Wagner; Grynberg, Priscila; Saraiva, Mario; Brasileiro, Ana C M; Carneiro, Regina M D; Oliveira, José T A; Grossi-de-Sá, Maria F; Mehta, Angela

    2015-05-01

    Cowpea (Vigna unguiculata L. Walp) is an important legume species well adapted to low fertility soils and prolonged drought periods. One of the main problems that cause severe yield losses in cowpea is the root-knot nematode Meloidogyne incognita. The aim of this work was to analyze the differential expression of proteins in the contrasting cultivars of cowpea CE 31 (highly resistant) and CE 109 (slightly resistant) during early stages of M. incognita infection. Cowpea roots were collected at 3, 6, and 9 days after inoculation and used for protein extraction and 2-DE analysis. From a total of 59 differential spots, 37 proteins were identified, mostly involved in plant defense, such as spermidine synthase, patatin, proteasome component, and nitrile-specifier protein. A follow-up study was performed by quantitative RT-PCR analysis of nine selected proteins and the results revealed a very similar upregulation trend between the protein expression profiles and the corresponding transcripts. This study also identified ACT and GAPDH as a good combination of reference genes for quantitative RT-PCR analysis of the pathosystem cowpea/nematode. Additionally, an interactome analysis showed three major pathways affected by nematode infection: proteasome endopeptidase complex, oxidative phosphorylation, and flavonoid biosynthesis. Taken together, the results obtained by proteome, transcriptome, and interactome approaches suggest that oxidative stress, ubiquitination, and glucosinolate degradation may be part of cowpea CE 31 resistance mechanisms in response to nematode infection. PMID:25736976

  5. [Symbiogenesis as a Model for Reconstructing the Early Stages of Genome Evolution].

    PubMed

    Provorov, N A; Tikhonovich, I A; Vorobyov, N I

    2016-02-01

    Symbiogenic evolution, which involves transformations of bacteria into the cellular organelles, is represented as a model for reconstructing the early stages of genome evolution, including the origin of DNA genomes from RNA genomes and the emergence of template processes on the basis of self-replicating molecular complexes in the ancestral metabolic systems. The antiquity of RNA genomes is supported by an increased evolutionary stability of ribosomal protein synthesis (translation) with respect to the DNA-dependent template processes (replication, transcription, recombination, and reparation). This stability is demonstrated by analysis of the deeply reduced genomes of symbiotic bacteria and cellular organelles as well as the "minimal" genomes which are common to phylogenetically diverse organisms. Higher evolutionary conservation of template biosynthetic processes with respect to step processes determining the metabolism and development in cells does not support the hypothesis about emergence ofgenomes within the ancestral cellular metabolic systems which are thought to be of abiogenic origin, instead suggesting dualistic origin of life on Earth. We suppose that the genome-free organelles of some eukaryotes (mitosomes, many hydrogenosomes, and some plastids) represent the products of reversion of symbiotic bacteria into ancestral forms which implemented their basic cellular functions using the informational macromolecules of exogenic origin. In the framework of this hypothesis the eukaryotic cells functioning based on the massive transfer of gene products (RNAs, proteins) from cytosol to organelles may represent the analogs of ancestral biocenoses that possessed integral hereditary systems (metagenomes). PMID:27215028

  6. Proton therapy for early stage prostate cancer: is there a case?

    PubMed Central

    Chan, Tabitha Y; Tan, Poh Wee; Tang, Johann I

    2016-01-01

    Proton-beam therapy (PBT) for prostate cancer has been in used for several decades, with its technique evolving significantly over this period. A growing number of centers now routinely utilize pencil-beam scanning as an advanced technique of PBT. Interest and controversy concerning its use have recently come under scrutiny. While the past decade has produced an assemblage of evidence suggesting that PBT is safe and effective for early stage prostate cancer, it is still unknown whether the theoretical dosimetric advantages of PBT translate into meaningful clinical improvements over routine intensity-modulated radiation therapy, which is commonly used for these patients. Outcomes from early trials using whole courses of PBT have shown mixed results when compared with routine intensity-modulated radiation therapy. Therefore, randomized trials comparing these two techniques should be undertaken, as this would help in defining the role of PBT for this patient group. This article aims to describe the basics of PBT, review the reasons for the growing interest in PBT, review the evidence for PBT, review the controversy surrounding PBT, and inquire about PBT’s future in the treatment of prostate cancer, with attention to its physical properties, comparative clinical and cost-effectiveness, and advances in its delivery. PMID:27672328

  7. Parallel processing of general and specific threat during early stages of perception.

    PubMed

    You, Yuqi; Li, Wen

    2016-03-01

    Differential processing of threat can consummate as early as 100 ms post-stimulus. Moreover, early perception not only differentiates threat from non-threat stimuli but also distinguishes among discrete threat subtypes (e.g. fear, disgust and anger). Combining spatial-frequency-filtered images of fear, disgust and neutral scenes with high-density event-related potentials and intracranial source estimation, we investigated the neural underpinnings of general and specific threat processing in early stages of perception. Conveyed in low spatial frequencies, fear and disgust images evoked convergent visual responses with similarly enhanced N1 potentials and dorsal visual (middle temporal gyrus) cortical activity (relative to neutral cues; peaking at 156 ms). Nevertheless, conveyed in high spatial frequencies, fear and disgust elicited divergent visual responses, with fear enhancing and disgust suppressing P1 potentials and ventral visual (occipital fusiform) cortical activity (peaking at 121 ms). Therefore, general and specific threat processing operates in parallel in early perception, with the ventral visual pathway engaged in specific processing of discrete threats and the dorsal visual pathway in general threat processing. Furthermore, selectively tuned to distinctive spatial-frequency channels and visual pathways, these parallel processes underpin dimensional and categorical threat characterization, promoting efficient threat response. These findings thus lend support to hybrid models of emotion.

  8. Cowpea-Meloidogyne incognita interaction: Root proteomic analysis during early stages of nematode infection.

    PubMed

    Villeth, Gabriela R C; Carmo, Lilian S T; Silva, Luciano P; Fontes, Wagner; Grynberg, Priscila; Saraiva, Mario; Brasileiro, Ana C M; Carneiro, Regina M D; Oliveira, José T A; Grossi-de-Sá, Maria F; Mehta, Angela

    2015-05-01

    Cowpea (Vigna unguiculata L. Walp) is an important legume species well adapted to low fertility soils and prolonged drought periods. One of the main problems that cause severe yield losses in cowpea is the root-knot nematode Meloidogyne incognita. The aim of this work was to analyze the differential expression of proteins in the contrasting cultivars of cowpea CE 31 (highly resistant) and CE 109 (slightly resistant) during early stages of M. incognita infection. Cowpea roots were collected at 3, 6, and 9 days after inoculation and used for protein extraction and 2-DE analysis. From a total of 59 differential spots, 37 proteins were identified, mostly involved in plant defense, such as spermidine synthase, patatin, proteasome component, and nitrile-specifier protein. A follow-up study was performed by quantitative RT-PCR analysis of nine selected proteins and the results revealed a very similar upregulation trend between the protein expression profiles and the corresponding transcripts. This study also identified ACT and GAPDH as a good combination of reference genes for quantitative RT-PCR analysis of the pathosystem cowpea/nematode. Additionally, an interactome analysis showed three major pathways affected by nematode infection: proteasome endopeptidase complex, oxidative phosphorylation, and flavonoid biosynthesis. Taken together, the results obtained by proteome, transcriptome, and interactome approaches suggest that oxidative stress, ubiquitination, and glucosinolate degradation may be part of cowpea CE 31 resistance mechanisms in response to nematode infection.

  9. Norvaline and norleucine may have been more abundant protein components during early stages of cell evolution.

    PubMed

    Alvarez-Carreño, Claudia; Becerra, Arturo; Lazcano, Antonio

    2013-10-01

    The absence of the hydrophobic norvaline and norleucine in the inventory of protein amino acids is readdressed. The well-documented intracellular accumulation of these two amino acids results from the low-substrate specificity of the branched-chain amino acid biosynthetic enzymes that act over a number of related α-ketoacids. The lack of absolute substrate specificity of leucyl-tRNA synthase leads to a mischarged norvalyl-tRNA(Leu) that evades the translational proofreading activities and produces norvaline-containing proteins, (cf. Apostol et al. J Biol Chem 272:28980-28988, 1997). A similar situation explains the presence of minute but detectable amounts of norleucine in place of methionine. Since with few exceptions both leucine and methionine are rarely found in the catalytic sites of most enzymes, their substitution by norvaline and norleucine, respectively, would have not been strongly hindered in small structurally simple catalytic polypeptides during the early stages of biological evolution. The report that down-shifts of free oxygen lead to high levels of intracellular accumulation of pyruvate and the subsequent biosynthesis of norvaline (Soini et al. Microb Cell Factories 7:30, 2008) demonstrates the biochemical and metabolic consequences of the development of a highly oxidizing environment. The results discussed here also suggest that a broader definition of biomarkers in the search for extraterrestrial life may be required. PMID:24013929

  10. Supradiaphragmatic early stage Hodgkin's disease: does mantle radiation therapy still have a role?

    PubMed

    Frezza, G; Barbieri, E; Zinzani, P L; Babini, L; Tura, S

    1996-01-01

    Extended field radiation therapy represents the main therapeutic option in early stage Hodgkin's disease with favorable prognostic features. Its role however has recently been criticized, mainly due to the high incidence of late complications in irradiated tissues. Furthermore, surgical staging, which in the opinion of many is mandatory for proper selection of patients for radiotherapy alone, has a well-known morbidity, and splenectomy has been associated with a high risk of secondary leukemias. Lastly, the failure rate after radiotherapy only is not negligible and second-line treatment is not always successful. A review of our experience and of the recent literature has allowed us to refute these objections. The results of radiotherapy, when properly performed, are highly reliable and have been reproducible in many Institutions. Chemotherapy alone cannot yet be regarded as an alternative to radiotherapy in these patients since data reported on this issue are conflicting. Present knowledge regarding the relationship between clinical features and the risk of occult subdiaphragmatic spread allows patients with localized disease to be selected without surgical staging; the results of radiotherapy in clinically staged patients confirm this statement. Concern for the late effects in irradiated tissues is justified, and future efforts should be directed at reducing the toxicity of this treatment. Associating a short chemotherapy course with low-dose radiotherapy to involved sites could help to achieve this goal.

  11. On the Early Stage Isothermal Oxidation of APS CoNiCrAlY Coatings

    NASA Astrophysics Data System (ADS)

    Di Girolamo, G.; Alfano, M.; Pagnotta, L.; Taurino, A.; Zekonyte, J.; Wood, R. J. K.

    2012-09-01

    The aim of this study is to analyze the evolution of microstructural and room temperature mechanical properties of air plasma sprayed (APS) CoNiCrAlY coatings before and after early stage high-temperature oxidation. To this purpose, selected samples were isothermally heat treated at 1110 °C for different durations. Phase analysis and oxide scale characterization were performed using x-ray diffraction. Morphological and microstructural features of as-sprayed and oxidized CoNiCrAlY coatings were analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. After heat treatment, a duplex oxide scale, composed of an inner α-Al2O3 layer and an outer spinel-type oxide layer, was observed on coating top-surface. The nanoindentation technique was employed to study the evolution of the mechanical properties. An increase in Young's modulus and hardness with increasing the aging time was observed, this effect was mainly addressed to the partial densification of coating microstructure.

  12. Do Diacritical Marks Play a Role at the Early Stages of Word Recognition in Arabic?

    PubMed

    Perea, Manuel; Abu Mallouh, Reem; Mohammed, Ahmed; Khalifa, Batoul; Carreiras, Manuel

    2016-01-01

    A crucial question in the domain of visual word recognition is whether letter similarity plays a role in the early stages of visual word processing. Here we focused on Arabic because in this language there are various groups of letters that share the same basic shape and only differ in the number/location of diacritical points. We conducted a masked priming lexical decision experiment in which a target word was preceded by: (i) an identity prime; (ii) a prime in which the critical letter was replaced by a letter with the same shape that differed in the number of diacritics (e.g., ); or (iii) a prime in which the critical letter was replaced by a letter with different shape (e.g., ). Results showed a sizable advantage of the identity condition over the two substituted-letter priming conditions (i.e., diacritical information is rapidly processed). Thus, diacritical marks play an essential role in the "feature letter" level of models of visual word recognition in Arabic. PMID:27597838

  13. Coping with early stage breast cancer: examining the influence of personality traits and interpersonal closeness.

    PubMed

    Saita, Emanuela; Acquati, Chiara; Kayser, Karen

    2015-01-01

    The study examines the influence of personality traits and close relationships on the coping style of women with breast cancer. A sample of 72 Italian patients receiving treatment for early stage breast cancer was recruited. Participants completed questionnaires measuring personality traits (Interpersonal Adaptation Questionnaire), interpersonal closeness (Inclusion of the Other in the Self Scale), and adjustment to cancer (Mini-Mental Adjustment to Cancer Scale). We hypothesized that diverse personality traits and degrees of closeness contribute to determine the coping styles shown by participants. Multiple regression analyses were conducted for each of the five coping styles (Helplessness/Hopelessness, Anxious Preoccupation, Avoidance, Fatalism, and Fighting Spirit) using personality traits and interpersonal closeness variables (Strength of Support Relations, and Number of Support Relations) as predictors. Women who rated high on assertiveness and social anxiety were more likely to utilize active coping strategies (Fighting Spirit). Perceived strength of relationships was predictive of using an active coping style while the number of supportive relationships did not correlate with any of the coping styles. Implications for assessment of breast cancer patients at risk for negative adaptation to the illness and the development of psychosocial interventions are discussed.

  14. Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

    PubMed Central

    Jin, Jonghwa; Min, Hophil; Kim, Sang Jin; Oh, Sohee; Kim, Kyunggon; Yu, Hyeong Gon; Park, Taesung; Kim, Youngsoo

    2016-01-01

    Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR. PMID:26665153

  15. Fluoride alters type I collagen expression in the early stages of odontogenesis.

    PubMed

    Maciejewska, I; Spodnik, J H; Domaradzka-Pytel, B; Sidor-Kaczmarek, J; Bereznowski, Z

    2006-11-01

    Fluoride alters the expression and post-translational modifications of extracellular matrix proteins in dentin. The aim of our study was to determine the effects of fluoride on type I collagen expression during the early stages of tooth germ development in rats. Pregnant dams were divided into three groups and fed a standard diet. From the fifth day of pregnancy the three groups received tap water with, respectively, trace amounts of fluoride (C), a low fluoride concentration (FL) or and a high fluoride concentration (FH). Changes in type I collagen expression and distribution were evaluated. The expression of type I collagen was restricted to the extracellular spaces of cells of mesenchymal origin. In the youngest animals the most intense immunoreactivity for type I collagen was detected in predentin of the FL group. Although the intensity of immunostaining increased in proportion to the age of the animals, the largest increase in the groups investigated was detected in the FL group. We concluded that a low concentration of fluoride can act as a stimulator of type I collagen deposition in the extracellular matrix of dentin, while high concentrations of fluoride have an opposite effect, acting as an inhibitor of type I collagen formation in dentin.

  16. Atomic structure of Cu-10. 9 at % Be alloys in the early stages of aging

    SciTech Connect

    Koo, Y.M.

    1987-01-01

    Diffuse x-ray scattering was employed to investigate the local atomic structure and static strains in a single crystal of a Cu-10.9 at. % Be alloy in the early stages of aging. In addition to these experiments, neutron elastic and inelastic scattering were obtained to investigate the phonon properties in the as-quenched state of this alloy. In the as-quenched state, there is a nearly regular array of small ellipsoidal Be clusters aligned along <100> directions (This produces the tweed contrast seen in TEM). The density of these clusters is 7.5 x 10/sup 26//m/sup 3/. The diffuse streaks seen in electron diffraction patterns are due largely to thermal diffuse scattering. Phonon-dispersion curves show no large differences from those of pure copper, except at (xi xi xi)/sub T/ zone boundary, where there is softening. This difference may be due to a Kohn anomaly. The elastic anisotropy of this alloy increases considerably with alloying, which probably leads to the plate-like GP zone morphology in subsequent aging treatments. The structure of the GP zones is a mixture of Be-rich single- and multi-layered zones. As aging proceeds, the zones grow in thickness.

  17. Presentation of underglycosylated mucin 1 in pancreatic adenocarcinoma (PDAC) at early stages

    PubMed Central

    Lo, Su-Tang; Pantazopouos, Pamela; Medarova, Zdravka; Moore, Anna

    2016-01-01

    Underglycosylated mucin 1 antigen (uMUC1) is a proven biomarker of cancer progression relevant to many malignancies including pancreatic ductal adenocarcinoma (PDAC). However, while ample evidence exists of the expression of total MUC1, little is known about the abundance of the underglycolsylated form of the antigen and its significance in disease progression. Such knowledge is important because the underglycosylated form of MUC1 is intimately linked to metastatic potential. Here, we investigated the expression uMUC1 at various stages of PDAC including pancreatic intraepithelial neoplasia (PanIN). Immunohistochemical analysis was performed on human tissue microarrays (TMAs) containing PDAC and PanIN using monoclonal antibody specific to uMUC1. uMUC1 expression was analyzed by a traditional pathological scoring system and using automatic imaging analysis software. Our results demonstrated low uMUC1 abundance in PanIN lesions and a transient increase in antigen availability in stage I PDAC, followed by decreased expression in later stages of the disease. An additional finding was that there was intermediate expression of uMUC1 in adjacent normal tissues from PDAC irrespective of the stage. These studies suggest the intriguing possibility that a pro-metastatic uMUC1 expression signature may appear at early stages of PDAC, providing an additional clue about the aggressive nature of pancreatic cancer. PMID:27725904

  18. Reward, motivation, and emotion systems associated with early-stage intense romantic love.

    PubMed

    Aron, Arthur; Fisher, Helen; Mashek, Debra J; Strong, Greg; Li, Haifang; Brown, Lucy L

    2005-07-01

    Early-stage romantic love can induce euphoria, is a cross-cultural phenomenon, and is possibly a developed form of a mammalian drive to pursue preferred mates. It has an important influence on social behaviors that have reproductive and genetic consequences. To determine which reward and motivation systems may be involved, we used functional magnetic resonance imaging and studied 10 women and 7 men who were intensely "in love" from 1 to 17 mo. Participants alternately viewed a photograph of their beloved and a photograph of a familiar individual, interspersed with a distraction-attention task. Group activation specific to the beloved under the two control conditions occurred in dopamine-rich areas associated with mammalian reward and motivation, namely the right ventral tegmental area and the right postero-dorsal body and medial caudate nucleus. Activation in the left ventral tegmental area was correlated with facial attractiveness scores. Activation in the right anteromedial caudate was correlated with questionnaire scores that quantified intensity of romantic passion. In the left insula-putamen-globus pallidus, activation correlated with trait affect intensity. The results suggest that romantic love uses subcortical reward and motivation systems to focus on a specific individual, that limbic cortical regions process individual emotion factors, and that there is localization heterogeneity for reward functions in the human brain. PMID:15928068

  19. Robotic-Assisted Thoracic Surgery for Early-Stage Lung Cancer: A Review.

    PubMed

    Brooks, Paula

    2015-07-01

    This review evaluates the benefits and disadvantages associated with the use of robotic-assisted technology in performing lobectomies in patients with early-stage lung cancer. The author conducted a literature search of Ovid®, MEDLINE®, PubMed®, and CINAHL® for articles published from 2005 to 2013. Search criteria included key terms such as robot, robotic, robotic-assisted lobectomy, and lung cancer. Of 922 articles, the author included a total of 12 research-based published studies in the analysis and incorporated the findings into an evidence table. Results showed that robotic-assisted lobectomies are feasible safe procedures for patients with stage 1A or 1B lung cancer; however, there is a steep learning curve and long-term randomized studies evaluating robotic-assisted lobectomy and conventional posterolateral thoracotomy or video-assisted thoracic lobectomy are needed. For patient safety, perioperative nurses should be aware of the length of time and experience required to perform these procedures, the costs, techniques, benefits, and disadvantages.

  20. Supradiaphragmatic early stage Hodgkin's disease: does mantle radiation therapy still have a role?

    PubMed

    Frezza, G; Barbieri, E; Zinzani, P L; Babini, L; Tura, S

    1996-01-01

    Extended field radiation therapy represents the main therapeutic option in early stage Hodgkin's disease with favorable prognostic features. Its role however has recently been criticized, mainly due to the high incidence of late complications in irradiated tissues. Furthermore, surgical staging, which in the opinion of many is mandatory for proper selection of patients for radiotherapy alone, has a well-known morbidity, and splenectomy has been associated with a high risk of secondary leukemias. Lastly, the failure rate after radiotherapy only is not negligible and second-line treatment is not always successful. A review of our experience and of the recent literature has allowed us to refute these objections. The results of radiotherapy, when properly performed, are highly reliable and have been reproducible in many Institutions. Chemotherapy alone cannot yet be regarded as an alternative to radiotherapy in these patients since data reported on this issue are conflicting. Present knowledge regarding the relationship between clinical features and the risk of occult subdiaphragmatic spread allows patients with localized disease to be selected without surgical staging; the results of radiotherapy in clinically staged patients confirm this statement. Concern for the late effects in irradiated tissues is justified, and future efforts should be directed at reducing the toxicity of this treatment. Associating a short chemotherapy course with low-dose radiotherapy to involved sites could help to achieve this goal. PMID:8641642

  1. Susceptibility of L-FABP-/- mice to oxidative stress in early-stage alcoholic liver.

    PubMed

    Smathers, Rebecca L; Galligan, James J; Shearn, Colin T; Fritz, Kristofer S; Mercer, Kelly; Ronis, Martin; Orlicky, David J; Davidson, Nicholas O; Petersen, Dennis R

    2013-05-01

    Chronic ethanol consumption is a prominent cause of liver disease worldwide. Dysregulation of an important lipid uptake and trafficking gene, liver-fatty acid binding protein (L-FABP), may contribute to alterations in lipid homeostasis during early-stage alcoholic liver. We have reported the detrimental effects of ethanol on the expression of L-FABP and hypothesize this may deleteriously impact metabolic networks regulating fatty acids. Male wild-type (WT) and L-FABP(-/-) mice were fed a modified Lieber-DeCarli liquid diet for six weeks. To assess the response to chronic ethanol ingestion, standard biochemical indicators for alcoholic liver disease (ALD) and oxidative stress were measured. Ethanol ingestion resulted in attenuation of hepatic triglyceride accumulation and elevation of cholesterol in L-FABP(-/-) mice. Lipidomics analysis validated multiple alterations in hepatic lipids resulting from ethanol treatment. Increased immunohistochemical staining for the reactive aldehydes 4-hydroxynonenal and malondialdehyde were observed in WT mice ingesting ethanol; however, L-FABP(-/-) mice displayed prominent protein adducts in liver sections evaluated from pair-fed and ethanol-fed mice. Likewise, alterations in glutathione, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes, and protein carbonyl content all indicated L-FABP(-/-) mice exhibit high sustained oxidative stress in the liver. These data establish that L-FABP is an indirect antioxidant protein essential for sequestering FFA and that its impairment could contribute to in the pathogenesis of ALD.

  2. Proteomic analysis of early-stage embryos: implications for egg quality in hapuku (Polyprion oxygeneios).

    PubMed

    Kohn, Yair Y; Symonds, Jane E; Kleffmann, Torsten; Nakagawa, Shinichi; Lagisz, Malgorzata; Lokman, P Mark

    2015-12-01

    In order to develop biomarkers that may help predict the egg quality of captive hapuku (Polyprion oxygeneios) and provide potential avenues for its manipulation, the present study (1) sequenced the proteome of early-stage embryos using isobaric tag for relative and absolute quantification analysis, and (2) aimed to establish the predictive value of the abundance of identified proteins with regard to egg quality through regression analysis. Egg quality was determined for eight different egg batches by blastomere symmetry scores. In total, 121 proteins were identified and assigned to one of nine major groups according to their function/pathway. A mixed-effects model analysis revealed a decrease in relative protein abundance that correlated with (decreasing) egg quality in one major group (heat-shock proteins). No differences were found in the other protein groups. Linear regression analysis, performed for each identified protein separately, revealed seven proteins that showed a significant decrease in relative abundance with reduced blastomere symmetry: two correlates that have been named in other studies (vitellogenin, heat-shock protein-70) and a further five new candidate proteins (78 kDa glucose-regulated protein, elongation factor-2, GTP-binding nuclear protein Ran, iduronate 2-sulfatase and 6-phosphogluconate dehydrogenase). Notwithstanding issues associated with multiple statistical testing, we conclude that these proteins, and especially iduronate 2-sulfatase and the generic heat-shock protein group, could serve as biomarkers of egg quality in hapuku.

  3. Autophagy during early stages contributes to bovine viral diarrhea virus replication in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Zhang, Hui; Ren, Yan; Guo, Fei; Qiao, Jun; Jia, Bin; Wang, Pengyan; Chen, Chuangfu

    2014-10-01

    Autophagy (or autophagocytosis) is an essential and precise control process by which cells degrade unnecessary or dysfunctional cellular components or organelles in the cytoplasm in response to nutrient depletion, exogenous pathogens, or other stimuli. This process results in the removal of damaged or surplus organelles and macromolecular complexes via a lysosome-dependent mechanism. Bovine viral diarrhea virus (BVDV) is a ssRNA virus of the Flaviviridae family (genus Pestivirus). BVDV infection results in major economic losses due to poor reproductive performance and poor calf performance in cattle herds. In our previous studies, we have shown that BVDV NADL infection significantly increases autophagy in MDBK cells. To further define the interactions between autophagy and BVDV infection, we investigated the effects of autophagy on the replication of BVDV NADL. The findings showed that autophagy was inhibited by treatment with 3-methyladenine (3-MA) or wortmannin and that the knockdown of LC3 and Beclin1 using lentivirus-mediated RNA interference (RNAi) suppressed BVDV NADL replication. In contrast, the findings showed the replication of BVDV NADL was significantly increased by treatment with the autophagy inducer rapamycin within 18 h post-infection (pi). However, the mRNA levels of BVDV NADL 5'UTRs showed a downward trend after 18 h pi, and this effect was reversed by chloroquine treatment. Therefore, we inferred that infection with BVDV NADL increases autophagy, which in turn favors BVDV NADL replication at early stages.

  4. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    SciTech Connect

    Elshaikh, Mohamed A.; Vance, Sean; Suri, Jaipreet S.; Mahan, Meredith; Munkarah, Adnan

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  5. No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

    SciTech Connect

    Stanic, Sinisa; Paulus, Rebecca; Timmerman, Robert D.; Michalski, Jeff M.; Barriger, Robert B.; Bezjak, Andrea; Videtic, Gregory M.M.; Bradley, Jeffrey

    2014-04-01

    Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

  6. Adherence and Persistence With Oral Adjuvant Chemotherapy in Older Women With Early-Stage Breast Cancer in CALGB 49907: Adherence Companion Study 60104

    PubMed Central

    Partridge, Ann H.; Archer, Laura; Kornblith, Alice B.; Gralow, Julie; Grenier, Debjani; Perez, Edith; Wolff, Antonio C.; Wang, Xiaofei; Kastrissios, Helen; Berry, Donald; Hudis, Clifford; Winer, Eric; Muss, Hyman

    2010-01-01

    Purpose Patient adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure adherence among women randomly assigned to capecitabine in a preplanned substudy of a multicenter clinical trial. Patients and Methods Cancer and Leukemia Group B study CALGB 49907 was a randomly assigned trial comparing standard chemotherapy versus oral chemotherapy with capecitabine in patients age 65 years or older with early-stage breast cancer. We used microelectronic monitoring system (MEMS) caps on participants' capecitabine bottles to record pill bottle openings. Capecitabine was given in two divided daily doses for 14 consecutive days of a 21-day cycle for six cycles. Adherence was calculated as the number of doses taken divided by doses expected, taking into account toxicity-related dosing changes. A participant was defined as adherent if 80% or more of expected doses were recorded by MEMS. Results Overall, 161 patients were enrolled. Median age was 71 years (range, 65 to 89 years); 124 patients (83%) persisted with capecitabine to completion of planned protocol therapy. Adherence was 78% across all cycles, and adherence did not vary by cycle (P = .32). Twenty-five percent of participants took fewer than 80% of expected doses and were nonadherent. In a logistic regression model, participants with node-negative disease (P = .01) and mastectomy (P = .01) were more likely to be nonadherent. Adherence was not related to age, tumor stage, or hormone receptor status. Adherence was not significantly associated with relapse-free survival or grade 3 or 4 toxicity. Conclusion Most older women with early-stage breast cancer were adherent to short-term oral chemotherapy in a randomized clinical trial. Age was not associated with adherence. PMID:20368559

  7. United We Stand? The Effects of a Couple-Coping Intervention on Adjustment to Early Stage Breast or Gynecological Cancer

    ERIC Educational Resources Information Center

    Scott, Jennifer L.; Halford, W. Kim; Ward, Bruce G.

    2004-01-01

    Cancer diagnosis affects the psychological well-being of both patients and their partners, and effective coping has been suggested to be a conjoint process of mutual support. Ninety-four married women with early stage cancer and their partners were randomly assigned to couples-based coping training (CanCOPE), individual coping training for the…

  8. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    PubMed

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. PMID:24698029

  9. Education for Older Adults with Early-Stage Dementia: Health Promotion for the Mind, Body, and Spirit

    ERIC Educational Resources Information Center

    Richeson, Nancy E.; Boyne, Sarah; Brady, E. Michael

    2007-01-01

    The purpose of this study was to examine the effects of a 13-week adult education class for older adults with early-stage dementia titled Health Promotion for the Mind, Body, and Spirit. The mixed method research design (N = 14) used a quasiexperimental one-group pretest/posttest and the qualitative methods of focus group and phone interview with…

  10. Selective Attention Deficits Associated with Mild Cognitive Impairment and Early Stage Alzheimer's Disease in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Krinsky-McHale, Sharon J.; Devenny, Darlynne A.; Kittler, Phyllis; Silverman, Wayne

    2008-01-01

    Adults with Down syndrome and early stage Alzheimer's disease showed decline in their ability to selectively attend to stimuli in a multitrial cancellation task. They also showed variability in their performance over the test trials, whereas healthy participants showed stability. These changes in performance were observed approximately 2 years…

  11. "I've Never Seen People Work So Hard!" Teachers' Working Conditions in the Early Stages of School Turnaround

    ERIC Educational Resources Information Center

    Cucchiara, Maia Bloomfield; Rooney, Erin; Robertson-Kraft, Claire

    2015-01-01

    School turnaround--a reform strategy that strives for quick and dramatic transformation of low-performing schools--has gained prominence in recent years. This study uses interviews and focus groups conducted with 86 teachers in 13 schools during the early stages of school turnaround in a large urban district to examine teachers' perceptions of the…

  12. 3D simulations of the early stages of AGN jets: geometry, thermodynamics and backflow

    NASA Astrophysics Data System (ADS)

    Cielo, S.; Antonuccio-Delogu, V.; Macciò, A. V.; Romeo, A. D.; Silk, J.

    2014-04-01

    We investigate the interplay between jets from active galactic nuclei (AGNs) and the surrounding interstellar medium (ISM) through full 3D, high-resolution, adaptive mesh refinement simulations performed with the FLASH code. We follow the jet-ISM system for several Myr in its transition from an early, compact source to an extended one including a large cocoon. During the jet evolution, we identify three major evolutionary stages and we find that, contrary to the prediction of popular theoretical models, none of the simulations shows a self-similar behaviour. We also follow the evolution of the energy budget, and find that the fraction of input power deposited into the ISM (the AGN coupling constant) is of the order of a few per cent during the first few Myr. This is in broad agreement with galaxy formation models employing AGN feedback. However, we find that in these early stages, this energy is deposited only in a small fraction (<1 per cent) of the total ISM volume. Finally, we demonstrate the relevance of backflows arising within the extended cocoon generated by a relativistic AGN jet within the ISM of its host galaxy, previously proposed as a mechanism for self-regulating the gas accretion on to the central object. These backflows tend later to be destabilized by the 3D dynamics, rather than by hydrodynamic (Kelvin-Helmholtz) instabilities. Yet, in the first few hundred thousand years, backflows may create a central accretion region of significant extent, and convey there as much as a few millions of solar masses.

  13. Transcriptome Analysis of the SL221 Cells at the Early Stage during Spodoptera litura Nucleopolyhedrovirus Infection

    PubMed Central

    Yu, Qian; Xiong, Youhua; Liu, Jianliang; Wen, Dongling; Wu, Xiaohui; Yin, Hanqi

    2016-01-01

    Spodoptera litura (S. litura) is one of the most destructive agricultural pests worldwide. There is urgent need for a nuclear polyhedrosis virus that is specific to S. litura. To date, there have been no reports regarding the responses of S. litura cells to early Spodoptera litura nucleopolyhedrovirus (SpltNPV) infection due to the lack of a reference genome and transcriptome for S. litura. In this study, a cell transcriptome from the host S. litura was assembled and used for Illumina strand-specific RNA sequencing (RNA-seq) to generate 99180 unigenes, representing the 18 hour infection cycle. More than 2000 S. litura genes were significant differentially regulated throughout the infection. The levels of viral mRNAs began to increase dramatically at 6 hpi, and this increase continued throughout the remainder of the infection. We focused on the expression of genes related to stress responses, apoptosis, metabolic enzymes and host cell innate immune system. A small subset of genes related to host stress response, especially for 62 ones being able to annotated as enzyme, ligand and receptor genes, were observed to be specifically differentially expressed at 6 hpi. At 18 hpi, 104 unigenes were continuously significantly changing from 0 hpi to 18 hpi, considered to be viral multiplication related genes, including 3 annotated SL221 unigenes and 81 viral genes, such as tetraspanin and iap gene. This information and further studies on the regulation of host gene expression by baculovirus infection at early stage will provide the tools needed to enhance the utility of this virus as an effective insecticide. PMID:26840182

  14. The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

    PubMed Central

    Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Zhao, Hong; Zhao, Zhen; Du, Shiyu; Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.; Wong, Stephen T. C.; Jin, Xin; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H.-F.

    2014-01-01

    Summary Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We further elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human datasets analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases. Significance In advanced stages, breast cancer bone metastases are driven by paracrine crosstalk among cancer cells, osteoblasts, and osteoclasts, which constitute a vicious osteolytic cycle. Current therapies targeting this process limit tumor progression, but do not improve patient survival. On the other hand, bone micrometastases may remain indolent for years before activating the vicious cycle, providing a therapeutic opportunity to prevent macrometastases. Here, we show that bone colonization is initiated in a microenvironment niche exhibiting active osteogenesis. Cancer and osteogenic cells form heterotypic adherens junctions, which enhance mTOR activity and drive early-stage bone colonization prior to osteolysis. These results reveal a strong connection between osteogenesis and micrometastasis and suggest potential therapeutic targets to prevent bone macrometastases. PMID:25600338

  15. Nephelinite lavas at early stage of rift initiation (Hanang volcano, North Tanzanian Divergence)

    NASA Astrophysics Data System (ADS)

    Baudouin, Céline; Parat, Fleurice; Denis, Carole M. M.; Mangasini, Fredrik

    2016-07-01

    North Tanzanian Divergence is the first stage of continental break-up of East African Rift (<6 Ma) and is one of the most concentrated areas of carbonatite magmatism on Earth, with singular Oldoinyo Lengai and Kerimasi volcanoes. Hanang volcano is the southernmost volcano in the North Tanzanian Divergence and the earliest stage of rift initiation. Hanang volcano erupted silica-undersaturated alkaline lavas with zoned clinopyroxene, nepheline, andradite-schorlomite, titanite, apatite, and pyrrhotite. Lavas are low MgO-nephelinite with low Mg# and high silica content (Mg# = 22.4-35.2, SiO2 = 44.2-46.7 wt%, respectively), high incompatible element concentrations (e.g. REE, Ba, Sr) and display Nb-Ta fractionation (Nb/Ta = 36-61). Major elements of whole rock are consistent with magmatic differentiation by fractional crystallization from a parental melt with melilititic composition. Although fractional crystallization occurred at 9-12 km and can be considered as an important process leading to nephelinite magma, the complex zonation of cpx (e.g. abrupt change of Mg#, Nb/Ta, and H2O) and trace element patterns of nephelinites recorded magmatic differentiation involving open system with carbonate-silicate immiscibility and primary melilititic melt replenishment. The low water content of clinopyroxene (3-25 ppm wt. H2O) indicates that at least 0.3 wt% H2O was present at depth during carbonate-rich nephelinite crystallization at 340-640 MPa and 1050-1100 °C. Mg-poor nephelinites from Hanang represent an early stage of the evolution path towards carbonatitic magmatism as observed in Oldoinyo Lengai. Paragenesis and geochemistry of Hanang nephelinites require the presence of CO2-rich melilititic liquid in the southern part of North Tanzanian Divergence and carbonate-rich melt percolations after deep partial melting of CO2-rich oxidized mantle source.

  16. Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine.

    PubMed

    Steuten, Lotte M G

    2016-01-01

    Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved "upstream" so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bridges between oral health and systems medicine since what happens in oral health affects systems pathophysiology, and vice versa. This article offers a synthesis of the latest trends and approaches in early phase HTA, with a view to near future applications in oral health, systems medicine, and biomarker-guided precision medicine. In brief, this review underscores that demonstrating health outcomes of biomarkers and next-generation diagnostics is particularly challenging because they do not always influence long-term outcomes directly, but rather impact subsequent care processes. Biomarker testing costs are typically less of a barrier to uptake in practice than the biomarker's impact on longer term health outcomes. As a single biomarker or next-generation diagnostic in oral health can inform decisions about numerous downstream diagnosis-treatment combinations, early stage "upstream" HTA is crucial in prioritizing the most valuable diagnostic applications to pursue first. For the vast array of oral health biomarkers currently developed, early HTA is necessary to timely and iteratively assess their comparative effectiveness and anticipate the inevitable questions about value for money from regulators and payers.

  17. Molecular Dynamics of Channelrhodopsin at the Early Stages of Channel Opening.

    PubMed

    Takemoto, Mizuki; Kato, Hideaki E; Koyama, Michio; Ito, Jumpei; Kamiya, Motoshi; Hayashi, Shigehiko; Maturana, Andrés D; Deisseroth, Karl; Ishitani, Ryuichiro; Nureki, Osamu

    2015-01-01

    Channelrhodopsin (ChR) is a light-gated cation channel that responds to blue light. Since ChR can be readily expressed in specific neurons to precisely control their activities by light, it has become a powerful tool in neuroscience. Although the recently solved crystal structure of a chimeric ChR, C1C2, provided the structural basis for ChR, our understanding of the molecular mechanism of ChR still remains limited. Here we performed electrophysiological analyses and all-atom molecular dynamics (MD) simulations, to investigate the importance of the intracellular and central constrictions of the ion conducting pore observed in the crystal structure of C1C2. Our electrophysiological analysis revealed that two glutamate residues, Glu122 and Glu129, in the intracellular and central constrictions, respectively, should be deprotonated in the photocycle. The simulation results suggested that the deprotonation of Glu129 in the central constriction leads to ion leakage in the ground state, and implied that the protonation of Glu129 is important for preventing ion leakage in the ground state. Moreover, we modeled the 13-cis retinal bound; i.e., activated C1C2, and performed MD simulations to investigate the conformational changes in the early stage of the photocycle. Our simulations suggested that retinal photoisomerization induces the conformational change toward channel opening, including the movements of TM6, TM7 and TM2. These insights into the dynamics of the ground states and the early photocycle stages enhance our understanding of the channel function of ChR.

  18. Modeling TGF-β in Early Stages of Cancer Tissue Dynamics

    PubMed Central

    Ascolani, Gianluca; Liò, Pietro

    2014-01-01

    Recent works have highlighted a double role for the Transforming Growth Factor (-): it inhibits cancer in healthy cells and potentiates tumor progression during late stage of tumorigenicity, respectively; therefore it has been termed the “Jekyll and Hyde” of cancer or, alternatively, an “excellent servant but a bad master”. It remains unclear how this molecule could have the two opposite behaviours. In this work, we propose a - multi scale mathematical model at molecular, cellular and tissue scales. The multi scalar behaviours of the - are described by three coupled models built up together which can approximatively be related to distinct microscopic, mesoscopic, and macroscopic scales, respectively. We first model the dynamics of - at the single-cell level by taking into account the intracellular and extracellular balance and the autocrine and paracrine behaviour of -. Then we use the average estimates of the - from the first model to understand its dynamics in a model of duct breast tissue. Although the cellular model and the tissue model describe phenomena at different time scales, their cumulative dynamics explain the changes in the role of - in the progression from healthy to pre-tumoral to cancer. We estimate various parameters by using available gene expression datasets. Despite the fact that our model does not describe an explicit tissue geometry, it provides quantitative inference on the stage and progression of breast cancer tissue invasion that could be compared with epidemiological data in literature. Finally in the last model, we investigated the invasion of breast cancer cells in the bone niches and the subsequent disregulation of bone remodeling processes. The bone model provides an effective description of the bone dynamics in healthy and early stages cancer conditions and offers an evolutionary ecological perspective of the dynamics of the competition between cancer and healthy cells. PMID:24586338

  19. Molecular Simulation Study of the Early Stages of Formation of Bioinspired Mesoporous Silica Materials.

    PubMed

    Centi, Alessia; Jorge, Miguel

    2016-07-19

    The use of bioinspired templates, such as polyamines and polypeptides, could lead to significant improvements in the synthesis conditions under which mesoporous materials are traditionally produced, removing the need for strong pH as well as high temperature or pressure. In this work, we perform atomistic molecular dynamics simulations of 1,12-diaminododecane surfactants, in water and in the presence of silica monomers, to investigate the early stages of synthesis of one of the first examples of bioinspired silica materials. Different surfactant concentrations and pH were considered, clarifying the influence of the charge state of the molecules on the self-assembly process. We show that the amphiphilic amines form stable lamellar structures at equilibrium in the range from intermediate to high pH values. In a later stage, when silica species are added to the system, our results reveal that, in the same range of pH, silicates strongly adsorb around these aggregates at the interface with water. This causes a considerable modification of the curvature of the layer, which suggests a tendency for the system to evolve from a lamellar phase to the formation of vesicle structures. Furthermore, we show that silica monomers are able to penetrate the layer spontaneously when defects are created as a result of surfactants' head-to-head repulsion. These findings are in agreement with experimental observations and support the pillaring mechanism postulated for this class of materials. However, our simulations indicate that the aggregation process is driven by charge matching between surfactant heads and silica monomers rather than by hydrogen bond interactions between neutral species, as had been previously hypothesized. PMID:27340948

  20. Mechanistic reappraisal of early stage photochemistry in the light-driven enzyme protochlorophyllide oxidoreductase.

    PubMed

    Heyes, Derren J; Hardman, Samantha J O; Mansell, David; Gardiner, John M; Scrutton, Nigel S

    2012-01-01

    The light-driven enzyme protochlorophyllide oxidoreductase (POR) catalyzes the reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide). This reaction is a key step in the biosynthesis of chlorophyll. Ultrafast photochemical processes within the Pchlide molecule are required for catalysis and previous studies have suggested that a short-lived excited-state species, known as I675*, is the first catalytic intermediate in the reaction and is essential for capturing excitation energy to drive subsequent hydride and proton transfers. The chemical nature of the I675* excited state species and its role in catalysis are not known. Here, we report time-resolved pump-probe spectroscopy measurements to study the involvement of the I675* intermediate in POR photochemistry. We show that I675* is not unique to the POR-catalyzed photoreduction of Pchlide as it is also formed in the absence of the POR enzyme. The I675* species is only produced in samples that contain both Pchlide substrate and Chlide product and its formation is dependent on the pump excitation wavelength. The rate of formation and the quantum yield is maximized in 50∶50 mixtures of the two pigments (Pchlide and Chlide) and is caused by direct energy transfer between Pchlide and neighboring Chlide molecules, which is inhibited in the polar solvent methanol. Consequently, we have re-evaluated the mechanism for early stage photochemistry in the light-driven reduction of Pchlide and propose that I675* represents an excited state species formed in Pchlide-Chlide dimers, possibly an excimer. Contrary to previous reports, we conclude that this excited state species has no direct mechanistic relevance to the POR-catalyzed reduction of Pchlide.

  1. Alveolar bone remodeling in the early stage of experimental apical periodontitis in the rat mandible.

    PubMed

    Yamaga, M; Iwaku, M; Ozawa, H

    1992-05-01

    Apical periodontitis was surgically induced in the mandibular first molar of rats and chronological changes in the periapical bone tissue were observed by histochemistry and electron microscopy. On the second postoperative day (Day 2), tartrateresistant acid phosphatase (TRACPase)-positive cells emerged on the bone surface facing the inferior alveolar nerve, whereas alkaline phosphatase (ALPase)-positive cells proliferated on the bone marrow surface of the mandibular canal wall. On Day 3, the active resorption of the mandibular canal wall appeared on the surface facing the inferior alveolar nerve. The bone of the upper wall of the canal was completely resorbed. On Day 4, however, numerous ALPase-positive cells emerged over the bone surface facing the inferior alveolar nerve intermingled with TRACPase-positive cells. On Day 5, repair of the upper wall of the mandibular canal by new bone progressed. Bone formation was also observed on the bone surface facing the inferior alveolar nerve. On Day 6, the upper wall of the mandibular canal was remodeled by the new bone, whereas TRACPase-positive cells had already migrated over the bone surface in the vicinity of ALPase-positive cells. From Days 2 to 5, active trabecular bone formation continued in the bone marrow cavity close to the mandibular canal, while TRACPase-positive cells were found only on Day 6. These demonstrate that inflammatory stimuli activate bone formation coupled with bone resorption, as well as direct trabecular bone formation without a bone resorption phase. A rapid bone turnover in the early stage of apical periodontitis is also suggested. We conclude that bone defects in apical periodontitis are not the result of sole bone resorption but rather, active bone remodeling. PMID:1497944

  2. Investigating the early stages of mineral precipitation by potentiometric titration and analytical ultracentrifugation.

    PubMed

    Kellermeier, Matthias; Cölfen, Helmut; Gebauer, Denis

    2013-01-01

    Despite the importance of crystallization for various areas of research, our understanding of the early stages of the mineral precipitation from solution and of the actual mechanism of nucleation is still rather limited. Indeed, detailed insights into the processes underlying nucleation may enable a systematic development of novel strategies for controlling mineralization, which is highly relevant for fields ranging from materials chemistry to medicine. In this work, we describe experimental aspects of a quantitative assay, which relies on pH titrations combined with in situ metal ion potentiometry and conductivity measurements. The assay has originally been designed to study the crystallization of calcium carbonate, one of the most abundant biominerals. However, the developed procedures can also be readily applied to any compound containing cations for which ion-selective electrodes are available. Besides the possibility to quantitatively assess ion association prior to nucleation and to directly determine thermodynamic solubility products of precipitated phases, the main advantage of the crystallization assay is the unambiguous identification of the different stages of precipitation (i.e., prenucleation, nucleation, and early postnucleation) and the characterization of the multiple effects of additives. Furthermore, the experiments permit targeted access to distinct precursor species and intermediate stages, which thus can be analyzed by additional methods such as cryo-electron microscopy or analytical ultracentrifugation (AUC). Regarding ion association in solution, AUC detects entities significantly larger than simple ion pairs, so-called prenucleation clusters. Sedimentation coefficient values and distributions obtained for the calcium carbonate system are discussed in light of recent insights into the structural nature of prenucleation clusters.

  3. Prognosis for Mammographically Occult, Early-Stage Breast Cancer Patients Treated With Breast-Conservation Therapy

    SciTech Connect

    Yang, Tzu-I. J.; Yang Qifeng; Haffty, Bruce G.; Moran, Meena S.

    2010-01-15

    Purpose: To compare mammographically occult (MamOcc) and mammographically positive (MamPos) early-stage breast cancer patients treated with breast-conservation therapy (BCT), to analyze differences between the two cohorts. Methods and Materials: Our two cohorts consisted of 214 MamOcc and 2168 MamPos patients treated with BCT. Chart reviews were conducted to assess mammogram reports and method of detection. All clinical-pathologic and outcome parameters were analyzed to detect differences between the two cohorts. Results: Median follow-up was 7 years. There were no differences in final margins, T stage, nodal status, estrogen/progesterone receptor status, or 'triple-negative' status. Significant differences included younger age at diagnosis (p < 0.0001), more positive family history (p = 0.0033), less HER-2+ disease (p = 0.0294), and 1{sup o} histology (p < 0.0001). At 10 years, the differences in overall survival, cause-specific survival, and distant relapse between the two groups did not differ significantly. The MamOcc cohort had more breast relapses (15% vs. 8%; p = 0.0357), but on multivariate analysis this difference was not significant (hazard ratio 1.0, 95% confidence interval 0.993-1.007, p = 0.9296). Breast relapses were mammographically occult in 32% of the MamOcc and 12% of the MamPos cohorts (p = 0.0136). Conclusions: Although our study suggests that there are clinical-pathologic variations for the MamOcc cohort vs. MamPos patients that may ultimately affect management, breast relapse after BCT was not significantly different. Breast recurrences were more often mammographically occult in the MamOcc cohort; consideration should be given to closer follow-up and alternative imaging strategies (ultrasound, breast MRI) for routine posttreatment examination. To our knowledge, this represents the largest series addressing the prognostic significance of MamOcc cancers treated with BCT.

  4. Novel approaches to improve prostate cancer diagnosis and management in early-stage disease.

    PubMed

    Marberger, Michael; Barentsz, Jelle; Emberton, Mark; Hugosson, Jonas; Loeb, Stacy; Klotz, Laurence; Koch, Michael; Shariat, Shahrokh F; Vickers, Andrew

    2012-03-01

    The reported incidence of prostate cancer has risen since the implementation of screening. It is felt that the introduction of widespread prostate-specific antigen testing is responsible for most patients with prostate cancer now being diagnosed with asymptomatic, clinically localised disease. Diagnosis at this stage is associated with significantly improved treatment outcomes and longer life expectancy. Although there is evidence that screening has reduced prostate cancer mortality, there is a risk of over-diagnosis and over-treatment of early state prostate cancers, including clinically insignificant and indolent cancers. Active surveillance and focal therapy have been advocated as potential management options for some patients. However, these approaches face several challenges. Biopsy sampling errors together with less than optimal imaging of tumours can lead to difficulties in selecting suitable low-risk patients for these options.  To overcome these challenges, novel approaches to the staging and monitoring of patients with early prostate cancer are being developed. These include new imaging techniques, such as multi-parametric magnetic resonance imaging, and the development of new biomarkers and biopsy-based methods. These techniques aim to assess the potential of a specific tumour to be aggressive, and to improve patient outcomes. The aim of the present paper is to summarise presentations and debates at the third annual Interactive Genitourinary Cancer Conference concerning the use of population-based screening methods and the roles of active surveillance and focal therapy as prostate cancer treatments. The application of novel imaging biopsy-based methods and biomarkers in early-stage prostate cancer will also be explored.

  5. Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease

    SciTech Connect

    Lehericy, S.; Baulac, M.; Chiras, J.; Pierot, L.; Martin, N.; Pillon, B.; Deweer, B.; Dubois, B.; Marsault, C.

    1994-05-01

    To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status {ge} 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. For patients with a minimental status score of 21 or greater, atrophy was significant for the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease. 46 refs., 8 figs., 2 tabs.

  6. What do we know about the initiation and early stages of brittle faulting in crystalline rocks?

    NASA Astrophysics Data System (ADS)

    Crider, J. G.

    2011-12-01

    The styles of initiation and subsequent growth of faults control fault length-slip scaling, the internal structure of fault zones, and fault-rock properties, influencing seismogenic behavior and fluid flow along the faults. Observations by many researchers over the last several decades have illustrated that faults in the upper crust initiate on pre-existing (inherited) or precursory (early-formed) structures and grow by the mechanical interaction and linkage of these structures. These pre-existing and precursory structures are typically mode I fractures (joints, veins, dikes) but may also be semi-brittle shear zones (such as deformation bands in porous sandstone). Research in the granitic outcrops of the central Sierra Nevada (California) has provided significant insight into the geometry and fundamental mechanics of the early stages of fault development. This work has shown that faults in plutonic rocks initiate on pre-existing or precursory joints or dikes and that the discontinuous nature of early mode I fractures has a strong influence on the subsequent development of the fault zone. In basalt, we have similarly observed the important influence of preexisting joints, and, at a broader scale, precursory, semi-brittle shear zones in the form of fault-tip monoclines. In metamorphic rocks, foliation appears to control the initial development of faults, influencing fault orientation, or enabling precursory structures such as kink bands. Kink bands, like deformation bands in porous sandstone, accommodate only small strains before locking, but then become strong inclusions in the material, serving to localize brittle fractures. The quasi-static mechanics of isotropic, isothermal linear-elastic materials in two and three dimensions provides first order understanding of controls on interaction and linkage of early structures, including the concentration of stresses and local stress reorientation. Fruitful research directions important to faulting in crystalline rock

  7. Oxidative reactions during early stages of beer brewing studied by electron spin resonance and spin trapping.

    PubMed

    Frederiksen, Anne M; Festersen, Rikke M; Andersen, Mogens L

    2008-09-24

    An electron spin resonance (ESR)-based method was used for evaluating the levels of radical formation during mashing and in sweet wort. The method included the addition of 5% (v/v) ethanol together with the spin trap alpha-4-pyridyl(1-oxide)- N- tert-butylnitrone (POBN) to wort, followed by monitoring the rate of formation of POBN spin adducts during aerobic heating of the wort. The presence of ethanol makes the spin trapping method more selective and sensitive for the detection of highly reactive radicals such as hydroxyl and alkoxyl radicals. Samples of wort that were collected during the early stages of the mashing process gave higher rates of spin adduct formation than wort samples collected during the later stages. The lower oxidative stability of the early wort samples was confirmed by measuring the rate of oxygen consumption during heating of the wort. The addition of Fe(II) to the wort samples increased the rate of spin adduct formation, whereas the addition of Fe(II) during the mashing had no effect on the oxidative stability of the wort samples. Analysis of the iron content in the sweet wort samples demonstrated that iron added during the mashing had no effect on the iron level in the wort. The moderate temperatures during the early steps of mashing allow the endogenous malt enzymes to be active. The potential antioxidative effects of different redox-active enzymes during mashing were tested by measuring the rate of spin adduct formation in samples of wort. Surprisingly, a high catalase dosage caused a significant, 20% reduction of the initial rate of radical formation, whereas superoxide dismutase had no effect on the oxidation rates. This suggests that hydrogen peroxide and superoxide are not the only intermediates that play a role in the oxidative reactions occurring during aerobic oxidation of sweet wort.

  8. Slowing progression of early stages of AD with alternative therapies: a feasibility study.

    PubMed

    Lu, Der-Fa; Hart, Laura K; Lutgendorf, Susan K; Oh, Hyunkyoung; Schilling, Margo

    2013-01-01

    This pilot study identified the feasibility and efficacy of the effect of combining healing touch (HT) and body talk cortices (BTC) on the progression of Alzheimer's disease (AD). Both HT and BTC elicit the relaxation response and support cognitive function from two different perspectives. A two-group, repeated measures design was used. Subjects (n = 22), 65 or older with early stage (less than four) AD, residing in the community (n = 2) or in care agencies (n = 20), were assigned to either the HT-BTC group (n = 12) or the control group (n = 10) randomized by residence. The treatment group received, 6 months of weekly HT and performed the BTC technique daily. The usual medical regimen for all subjects was continued. The control group had no additional interventions. Both groups were assessed at baseline, 3 and 6 months. The groups did not differ significantly at baseline on cognitive reserve, age, gender, and ethnicity, nor on the outcome variables (cognitive function, mood, & depression). Adherence (76%) to the BTC protocol, the major feasibility problem, related to memory deficits. Significant interactions occurred regarding cognitive function and mood. Significant improvements in cognitive function (p = .008), mood (p = .001), and depression (p = .028) were observed in the treatment group which is not the usual course of AD. A decline in cognitive function occurred in the control group typical of AD's usual course. Although the number of subjects in this pilot study was small, and there were feasibility challenges with recruitment and adherence, important trends were noted suggesting areas for future study.

  9. Early Stage Biomineralization in the Periostracum of the ‘Living Fossil’ Bivalve Neotrigonia

    PubMed Central

    Checa, Antonio G.; Salas, Carmen; Harper, Elizabeth M.; Bueno-Pérez, Juan de Dios

    2014-01-01

    A detailed investigation of the shell formation of the palaeoheterodont ‘living fossil’ Neotrigonia concentrated on the timing and manufacture of the calcified ‘bosses’ which stud the outside of all trigonioid bivalves (extant and fossil) has been conducted. Electron microscopy and optical microscopy revealed that Neotrigonia spp. have a spiral-shaped periostracal groove. The periostracum itself is secreted by the basal cell, as a thin dark pellicle, becoming progressively transformed into a thin dark layer by additions of secretions from the internal outer mantle fold. Later, intense secretion of the internal surface of the outer mantle fold forms a translucent layer, which becomes transformed by tanning into a dark layer. The initiation of calcified bosses occurred at a very early stage of periostracum formation, deep within the periostracal groove immediately below the initialmost dark layer. At this stage, they consist of a series of polycyclically twinned crystals. The bosses grow as the periostracum traverse through the periostracal groove, in coordination with the thickening of the dark periostracal layer and until, upon reaching the mantle edge, they impinge upon each other and become transformed into large prisms separated by dark periostracal walls. In conclusion, the initial bosses and the external part of the prismatic layer are fully intraperiostracal. With later growth, the prisms transform into fibrous aggregates, although the details of the process are unknown. This reinforces the relationships with other groups that have the ability to form intraperiostracal calcifications, for example the unionoids with which the trigonioids form the clade Paleoheterodonta. The presence of similar structures in anomalodesmatans and other euheterodonts raises the question of whether this indicates a relationship or represents a convergence. The identification of very early calcification within an organic sheet has interesting implications for our

  10. Hypofractionation with no boost after breast conservation in early-stage breast cancer patients.

    PubMed

    Arcadipane, Francesca; Franco, Pierfrancesco; De Colle, Chiara; Rondi, Nadia; Di Muzio, Jacopo; Pelle, Emanuela; Martini, Stefania; Ala, Ada; Airoldi, Mario; Donadio, Michela; De Sanctis, Corrado; Castellano, Isabella; Ragona, Riccardo; Ricardi, Umberto

    2016-10-01

    The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6-124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good-excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity. PMID:27573380

  11. S-nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

    PubMed Central

    Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B.; Ravindra, Kodihalli C.; Wishnok, John S.; Tsai, Li-Huei; Tannenbaum, Steven R.

    2016-01-01

    Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein’s function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25–inducible mouse model of Alzheimer’s disease-like neurodegeneration. The approach—SNOTRAP (SNO trapping by triaryl phosphine)—is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer’s disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration. PMID:27035958

  12. Early stage biomineralization in the periostracum of the 'living fossil' bivalve Neotrigonia.

    PubMed

    Checa, Antonio G; Salas, Carmen; Harper, Elizabeth M; Bueno-Pérez, Juan de Dios

    2014-01-01

    A detailed investigation of the shell formation of the palaeoheterodont 'living fossil' Neotrigonia concentrated on the timing and manufacture of the calcified 'bosses' which stud the outside of all trigonioid bivalves (extant and fossil) has been conducted. Electron microscopy and optical microscopy revealed that Neotrigonia spp. have a spiral-shaped periostracal groove. The periostracum itself is secreted by the basal cell, as a thin dark pellicle, becoming progressively transformed into a thin dark layer by additions of secretions from the internal outer mantle fold. Later, intense secretion of the internal surface of the outer mantle fold forms a translucent layer, which becomes transformed by tanning into a dark layer. The initiation of calcified bosses occurred at a very early stage of periostracum formation, deep within the periostracal groove immediately below the initialmost dark layer. At this stage, they consist of a series of polycyclically twinned crystals. The bosses grow as the periostracum traverse through the periostracal groove, in coordination with the thickening of the dark periostracal layer and until, upon reaching the mantle edge, they impinge upon each other and become transformed into large prisms separated by dark periostracal walls. In conclusion, the initial bosses and the external part of the prismatic layer are fully intraperiostracal. With later growth, the prisms transform into fibrous aggregates, although the details of the process are unknown. This reinforces the relationships with other groups that have the ability to form intraperiostracal calcifications, for example the unionoids with which the trigonioids form the clade Paleoheterodonta. The presence of similar structures in anomalodesmatans and other euheterodonts raises the question of whether this indicates a relationship or represents a convergence. The identification of very early calcification within an organic sheet has interesting implications for our understanding of

  13. Early Stage Health Technology Assessment for Precision Biomarkers in Oral Health and Systems Medicine.

    PubMed

    Steuten, Lotte M G

    2016-01-01

    Health technology assessment (HTA) is a crucial science that influences the responsible and evidence-based transition of new discoveries from laboratory to applications in the clinic and society. HTA has recently moved "upstream" so as to assess technologies from their onset at their discovery, design, or planning phase. Biomarker research is relatively recent in oral health, but growing rapidly with investments made to advance dentistry and oral health and importantly, to build effective bridges between oral health and systems medicine since what happens in oral health affects systems pathophysiology, and vice versa. This article offers a synthesis of the latest trends and approaches in early phase HTA, with a view to near future applications in oral health, systems medicine, and biomarker-guided precision medicine. In brief, this review underscores that demonstrating health outcomes of biomarkers and next-generation diagnostics is particularly challenging because they do not always influence long-term outcomes directly, but rather impact subsequent care processes. Biomarker testing costs are typically less of a barrier to uptake in practice than the biomarker's impact on longer term health outcomes. As a single biomarker or next-generation diagnostic in oral health can inform decisions about numerous downstream diagnosis-treatment combinations, early stage "upstream" HTA is crucial in prioritizing the most valuable diagnostic applications to pursue first. For the vast array of oral health biomarkers currently developed, early HTA is necessary to timely and iteratively assess their comparative effectiveness and anticipate the inevitable questions about value for money from regulators and payers. PMID:26760958

  14. The Early Stages of Formation of a Solar System Dust Band

    NASA Astrophysics Data System (ADS)

    Espy, Ashley J.; Dermott, S. F.; Kehoe, T. J. J.

    2009-09-01

    A solar system dust band is formed as the dust released in the catastrophic disruption of an asteroid in the main belt decays under the effects of radiation forces and is sculpted by gravitational perturbations. There are currently known to be at least three full dust band pairs (Low et al., 1984) and these have been associated with several-million-year-old asteroidal disruptions (Dermott et al., 2002; Nesvorny et al., 2003; 2008). A method of coadding the IRAS data set to increase the signal-to-noise ratio revealed the existence of an additional, very faint, partially-formed dust band at 17 degrees inclination (Espy et al., 2009), likely a confirmation of the M/N pair suggested by Sykes (1988). Partial dust bands represent a very early stage of the dynamical evolution of the dust released in the catastrophic disruption of a parent asteroid. We build a model of the formation of this partial band, in order to determine the main dynamical mechanisms controlling dust band formation. Comparison of this model to the coadded IRAS observations also allows us to put strong constraints on the node, semi-major axis, inclination and age of the source body, as well as the cross-sectional area and size-distribution of dust in the band. Because of the young age of partial dust bands, typically much less than a million years old, collisions have not yet begun to play an important role and the size-distribution is closer to that created in the original disruption. Additionally, less of the dust produced in the disruption has been lost to removal by P-R drag than in the older, fully-formed dust bands. These factors imply that partial dust bands provide important information about the dust originally produced in the catastrophic disruption of an asteroid.

  15. Laser phototherapy improves early stage of cutaneous wound healing of rats under hyperlipidic diet.

    PubMed

    Uzêda-E-Silva, Virgínia Dias; Rodriguez, Tania Tavares; Rocha, Isadora Almeida Rios; Xavier, Flávia Calo Aquino; Dos Santos, Jean Nunes; Cury, Patrícia Ramos; Ramalho, Luciana Maria Pedreira

    2016-09-01

    The aim of this study was to evaluate the influence of laser photobiomodulation in cutaneous healing of rats under a hyperlipidic diet. Forty-eight Wistar Albinus rats, weaned, received standard diet (SD) or hyperlipidic diet (HD) for 20 weeks. The groups were divided into SD rats and HD rats, SD-irradiated rats (LSD), and HD-irradiated rats (LHD). Standard cutaneous wound (1 cm(2)) was created on the dorsum of each rat. The irradiation started immediately after surgery and every 48 h for 7 or 14 days (λ660 nm, 40 mW, 6 J/cm(2), ϕ 0,04 cm(2), CW), when they were killed under deep anesthesia. The specimens were removed, routinely processed, stained with hematoxylin/eosin (H/E), and evaluated by light microscopy. Rats fed with hyperlipidic diet had greater intensity in the inflammatory process and prolonged hyperemia. At day 7, the intensity of inflammation was reduced in LSD and LHD groups when compared to their control groups, SD (p = 0.002) and HD (p = 0.02). There was an increase in fibroblast proliferation and collagen deposition, especially in the LHD group. At day 14, the HD group presented more intensive hyperemia than the SD group. It can be concluded that the hyperlipidic diet modified the inflammation pattern in wound healing and that laser light has a positive biomodulative effect on the healing process only in early stages. PMID:27412288

  16. Abnormal visual experience during development alters the early stages of visual-tactile integration.

    PubMed

    Niechwiej-Szwedo, Ewa; Chin, Jessica; Wolfe, Paul J; Popovich, Christina; Staines, W Richard

    2016-05-01

    Visual experience during the critical periods in early postnatal life is necessary for the normal development of the visual system. Disruption of visual input during this period results in amblyopia, which is associated with reduced activation of the striate and extrastriate cortices. It is well known that visual input converges with other sensory signals and exerts a significant influence on cortical processing in multiple association areas. Recent work in healthy adults has also shown that task-relevant visual input can modulate neural excitability at very early stages of information processing in the primary somatosensory cortex. Here we used electroencephalography to investigate visual-tactile interactions in adults with abnormal binocular vision due to amblyopia and strabismus. Results showed three main findings. First, in comparison to a visually normal control group, participants with abnormal vision had a significantly lower amplitude of the P50 somatosensory event related potential (ERP) when visual and tactile stimuli were presented concurrently. Second, the amplitude of the P100 somatosensory ERP was significantly greater in participants with abnormal vision. These results indicate that task relevant visual input does not significantly influence the excitability of the primary somatosensory cortex, instead, the excitability of the secondary somatosensory cortex is increased. Third, participants with abnormal vision had a higher amplitude of the P1 visual ERP when a tactile stimulus was presented concurrently. Importantly, these results were not modulated by viewing condition, which indicates that the impact of amblyopia on crossmodal interactions is not simply related to the reduced visual acuity as it was evident when viewing with the unaffected eye and binocularly. These results indicate that the consequences of abnormal visual experience on neurophysiological processing extend beyond the primary and secondary visual areas to other modality

  17. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab.

    PubMed

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2(+)) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2(+) breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2(+) breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. PMID:26937204

  18. S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration.

    PubMed

    Seneviratne, Uthpala; Nott, Alexi; Bhat, Vadiraja B; Ravindra, Kodihalli C; Wishnok, John S; Tsai, Li-Huei; Tannenbaum, Steven R

    2016-04-12

    Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein's function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25-inducible mouse model of Alzheimer's disease-like neurodegeneration. The approach-SNOTRAP (SNO trapping by triaryl phosphine)-is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer's disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration.

  19. Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab

    PubMed Central

    Gollamudi, Jahnavi; Parvani, Jenny G; Schiemann, William P; Vinayak, Shaveta

    2016-01-01

    Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. PMID:26937204

  20. Economic Impact of Gene Expression Profiling in Patients with Early-Stage Breast Cancer in France

    PubMed Central

    Katz, Gregory; Romano, Olivier; Foa, Cyril; Vataire, Anne-Lise; Chantelard, Jean-Victor; Hervé, Robert; Barletta, Hugues; Durieux, Axel; Martin, Jean-Pierre; Salmon, Rémy

    2015-01-01

    Background and Aims The heterogeneous nature of breast cancer can make decisions on adjuvant chemotherapy following surgical resection challenging. Oncotype DX is a validated gene expression profiling test that predicts the likelihood of adjuvant chemotherapy benefit in early-stage breast cancer. The aim of this study is to determine the costs of chemotherapy in private hospitals in France, and evaluate the cost-effectiveness of Oncotype DX from national insurance and societal perspectives. Methods A multicenter study was conducted in seven French private hospitals, capturing retrospective data from 106 patient files. Cost estimates were used in conjunction with a published Markov model to assess the cost-effectiveness of using Oncotype DX to inform chemotherapy decision making versus standard care. Sensitivity analyses were performed. Results The cost of adjuvant chemotherapy in private hospitals was estimated at EUR 8,218 per patient from a national insurance perspective and EUR 10,305 from a societal perspective. Cost-effectiveness analysis indicated that introducing Oncotype DX improved life expectancy (+0.18 years) and quality-adjusted life expectancy (+0.17 QALYs) versus standard care. Oncotype DX was found cost-effective from a national insurance perspective (EUR 2,134 per QALY gained) and cost saving from a societal perspective versus standard care. Inclusion of lost productivity costs in the modeling analysis meant that costs for eligible patients undergoing Oncotype DX testing were on average EUR 602 lower than costs for those receiving standard care. Conclusions As Oncotype DX was found both cost and life-saving from a societal perspective, the test was considered to be dominant to standard care. However, the delay in coverage has the potential to erode the quality of the French healthcare system, thus depriving patients of technologies that could improve clinical outcomes and allow healthcare professionals to better allocate hospital resources to

  1. Early-Stage Induction of SWI/SNF Mutations during Esophageal Squamous Cell Carcinogenesis.

    PubMed

    Nakazato, Hidetsugu; Takeshima, Hideyuki; Kishino, Takayoshi; Kubo, Emi; Hattori, Naoko; Nakajima, Takeshi; Yamashita, Satoshi; Igaki, Hiroyasu; Tachimori, Yuji; Kuniyoshi, Yukio; Ushijima, Toshikazu

    2016-01-01

    The SWI/SNF chromatin remodeling complex is frequently inactivated by somatic mutations of its various components in various types of cancers, and also by aberrant DNA methylation. However, its somatic mutations and aberrant methylation in esophageal squamous cell carcinomas (ESCCs) have not been fully analyzed. In this study, we aimed to clarify in ESCC, what components of the SWI/SNF complex have somatic mutations and aberrant methylation, and when somatic mutations of the SWI/SNF complex occur. Deep sequencing of components of the SWI/SNF complex using a bench-top next generation sequencer revealed that eight of 92 ESCCs (8.7%) had 11 somatic mutations of 7 genes, ARID1A, ARID2, ATRX, PBRM1, SMARCA4, SMARCAL1, and SMARCC1. The SMARCA4 mutations were located in the Forkhead (85Ser>Leu) and SNF2 family N-terminal (882Glu>Lys) domains. The PBRM1 mutations were located in a bromodomain (80Asn>Ser) and an HMG-box domain (1,377Glu>Lys). For most mutations, their mutant allele frequency was 31-77% (mean 61%) of the fraction of cancer cells in the same samples, indicating that most of the cancer cells in individual ESCC samples had the SWI/SNF mutations on one allele, when present. In addition, a BeadChip array analysis revealed that a component of the SWI/SNF complex, ACTL6B, had aberrant methylation at its promoter CpG island in 18 of 52 ESCCs (34.6%). These results showed that genetic and epigenetic alterations of the SWI/SNF complex are present in ESCCs, and suggested that genetic alterations are induced at an early stage of esophageal squamous cell carcinogenesis.

  2. Radiotherapy treatment of early stage prostate cancer with IMRT and protons: a treatment planning comparison

    PubMed Central

    Trofimov, Alexei; Nguyen, Paul L.; Coen, John J.; Doppke, Karen P.; Schneider, Robert J.; Adams, Judith A.; Bortfeld, Thomas R.; Zietman, Anthony L.; DeLaney, Thomas F.; Shipley, William U.

    2009-01-01

    Purpose To compare intensity-modulated photon radiotherapy (IMRT) with 3D-conformal proton therapy (3D-CPT) for early stage prostate cancer, and explore the potential utility of intensity-modulated proton therapy (IMPT). Methods Ten patients were planned with both 3D-CPT (2 parallel-opposed lateral fields) and IMRT (7 equally spaced coplanar fields). Prescribed dose was 79.2 Gy (or cobalt Gray-equivalent, CGE for protons) to the prostate gland. Dose-volume histograms, dose conformity, and equivalent uniform dose (EUD) were compared. Additionally, plans were optimized for 3D-CPT with non-standard beam configuration, and for IMPT assuming delivery with beam scanning. Results At least 98% of the PTV received the prescription dose. IMRT plans yielded better dose conformity to the target, while proton plans achieved higher dose homogeneity, and better sparing of rectum and bladder in the range below 30 Gy/CGE. Bladder volumes receiving over 70 Gy/CGE (V70) were reduced, on average, by 34% with IMRT vs. 3D-CPT, while rectal V70 were equivalent. EUD from 3D-CPT and IMRT plans were indistinguishable within uncertainties, for both bladder and rectum. With the use of small-angle lateral-oblique fields in 3D-CPT and IMPT, the rectal V70 was reduced by up to 35% compared to the standard lateral configuration, while the bladder V70 increased by less than 10%. Conclusions In the range over 60 Gy/CGE, IMRT achieved significantly better sparing of the bladder, while rectal sparing was similar with 3D-CPT and IMRT. Dose to healthy tissues in the range below 50% of the target prescription was substantially lower with proton therapy. PMID:17513063

  3. Early stages of neural crest ontogeny: formation and regulation of cell delamination.

    PubMed

    Kalcheim, Chaya; Burstyn-Cohen, Tal

    2005-01-01

    Long standing research of the Neural Crest embodies the most fundamental questions of Developmental Biology. Understanding the mechanisms responsible for specification, delamination, migration and phenotypic differentiation of this highly diversifying group of progenitors has been a challenge for many researchers over the years and continues to attract newcomers into the field. Only a few leaps were more significant than the discovery and successful exploitation of the quail-chick model by Nicole Le Douarin and colleagues from the Institute of Embryology at Nogent-sur-Marne. The accurate fate mapping of the neural crest performed at virtually all axial levels was followed by the determination of its developmental potentialities as initially analysed at a population level and then followed by many other significant findings. Altogether, these results paved the way to innumerable questions which brought us from an organismic view to mechanistic approaches. Among them, elucidation of functions played by identified genes is now rapidly underway. Emerging results lead the way back to an integrated understanding of the nature of interactions between the developing neural crest and neighbouring structures. The Nogent Institute thus performed an authentic "tour de force" in bringing the Neural Crest to the forefront of Developmental Biology. The present review is dedicated to the pivotal contributions of Nicole Le Douarin and her collaborators and to unforgettable memories that one of the authors bears from the time spent in the Nogent Institute. We summarize here recent advances in our understanding of early stages of crest ontogeny that comprise specification of epithelial progenitors to a neural crest fate and the onset of neural crest migration. Particular emphasis is given to signaling by BMP and Wnt molecules, to the role of the cell cycle in generating cell movement and to possible interactions between both mechanisms.

  4. Dissecting host factors that regulate the early stages of tuberculosis infection.

    PubMed

    Agrawal, Neha; Bhattacharyya, Chandrika; Mukherjee, Ankur; Ullah, Ubaid; Pandit, Bhaswati; Rao, Kanury V S; Majumder, Partha P

    2016-09-01

    Incomplete understanding of mechanisms involved in the host-pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days. Production of cytokines and chemokines in culture supernatants was monitored at various times, and the resulting temporal profiles were examined for possible correlations with either granuloma formation, or bacterial growth. While a positive association of TNF-α and IFN-γ secretion levels with extent of granuloma formation could clearly be identified, we were, however, unable to detect any statistically significant relationship between any cytokine/chemokine and bacterial growth. Examination of specific host cellular biochemical pathways revealed that either modulation of neutral lipid homeostasis through inhibition of the Gi-protein coupled receptor GPR109A, or regulation of host metabolic pathways through addition of vitamin D, provided a more effective means of controlling infection. A subsequent genotypic analysis for a select subset of genes belonging to pathways known to be significant for TB pathology revealed associations of polymorphisms with cytokine secretions and bacterial growth independently. Collectively therefore, the present study supports that key metabolic pathways of the host cell, rather than levels of relevant cytokines/chemokines might be more critical for regulating the intracellular mycobacterial load, in the context of granuloma formation. PMID:27553417

  5. Survival and Quality of Life After Stereotactic or 3D-Conformal Radiotherapy for Inoperable Early-Stage Lung Cancer

    SciTech Connect

    Widder, Joachim; Postmus, Douwe; Ubbels, Jan F.; Wiegman, Erwin M.; Langendijk, Johannes A.

    2011-11-15

    Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or three-dimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment. Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate. Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p < 0.01). 3D-CRT conferred a subhazard ratio for LC of 5.0 (95% CI: 1.7-14.7; p < 0.01) compared with SABR. GQOL and PF were stable after SABR (p = 0.21 and p = 0.62, respectively). Dyspnea increased after SABR by 3.2 out of 100 points (95% CI: 1.0-5.3; p < 0.01), which is clinically insignificant. At 1 year, PF decreased by an excess of 8.7 out of 100 points (95% CI: 2.8-14.7; p < 0.01) after 3D-CRT compared with SABR. Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRT approaching clinical significance already at 1 year.

  6. The Carbon_h-factor: predicting individuals' research impact at early stages of their career.

    PubMed

    Carbon, Claus-Christian

    2011-01-01

    Assessing an individual's research impact on the basis of a transparent algorithm is an important task for evaluation and comparison purposes. Besides simple but also inaccurate indices such as counting the mere number of publications or the accumulation of overall citations, and highly complex but also overwhelming full-range publication lists in their raw format, Hirsch (2005) introduced a single figure cleverly combining different approaches. The so-called h-index has undoubtedly become the standard in scientometrics of individuals' research impact (note: in the present paper I will always use the term "research impact" to describe the research performance as the logic of the paper is based on the h-index, which quantifies the specific "impact" of, e.g., researchers, but also because the genuine meaning of impact refers to quality as well). As the h-index reflects the number h of papers a researcher has published with at least h citations, the index is inherently positively biased towards senior level researchers. This might sometimes be problematic when predictive tools are needed for assessing young scientists' potential, especially when recruiting early career positions or equipping young scientists' labs. To be compatible with the standard h-index, the proposed index integrates the scientist's research age (Carbon_h-factor) into the h-index, thus reporting the average gain of h-index per year. Comprehensive calculations of the Carbon_h-factor were made for a broad variety of four research-disciplines (economics, neuroscience, physics and psychology) and for researchers performing on three high levels of research impact (substantial, outstanding and epochal) with ten researchers per category. For all research areas and output levels we obtained linear developments of the h-index demonstrating the validity of predicting one's later impact in terms of research impact already at an early stage of their career with the Carbon_h-factor being approx. 0.4, 0.8, and

  7. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism

    PubMed Central

    Peng, Huan; Cui, Jiangkuan; Long, Haibo; Huang, Wenkun; Kong, Lingan; Liu, Shiming; He, Wenting; Hu, Xianqi; Peng, Deliang

    2016-01-01

    the important roles of this gene in the early stages of parasitism. Our combined data suggest that two types of pectate lyases are present in the H. glycines genome and may have different roles during infection. PMID:26930215

  8. Dynamics of early stage nano-oxidation by in situ UHV-TEM

    NASA Astrophysics Data System (ADS)

    Yang, Judith

    2011-03-01

    Environmental stability is one of the most important properties for materials exposed to air. As dimensions of engineered systems approach nanoscale, fundamental understanding of reactions with oxygen at this length scale is critical for environmental stability as well as for processing oxide nanostructures, where surface reactions are commonly utilized. The nanoscale stages of oxidation from the nucleation of the metal oxide to the formation of the thermodynamically stable oxide represent a scientifically challenging and technologically important terra incognito. The kinetics of early stage oxidation of Cu, Cu-Au and Cu-Ni alloys were visualized using in situ ultra-high vacuum transmission electron microscopy (UHV-TEM), where the initial oxidation stages can be observed in real-time under well-controlled surface conditions. We examined the dynamic responses of thin films to variations in thermodynamic variables such as temperature, oxygen pressure, strain, and crystallographic orientation. The kinetics of the nucleation and growth of three-dimensional oxide islands demonstrate that oxygen surface diffusion is the primary mechanism for oxide growth during initial oxidation in dry oxygen, and thus bears a striking resemblance to heteroepitaxy. Compared with the behavior of Cu films, the oxidation of Cu-Au alloys revealed more complexity. For example, the oxidation of (100)-oriented Cu-Au alloys with low Au content at ~ 600 C results in the formation of Cu2O oxide islands with a dendritic morphology and a non-uniform lateral distribution of Au around the islands. For Cu-Ni oxidation, the addition of Ni causes the formation Cu2O and/or NiO where the oxide type(s) and the relative orientation with the film depend on the Ni concentration, oxygen partial pressure and temperature. Evolution of the shape and size of the oxide islands can be quantitatively analyzed and provide fundamental insights into the complex kinetics and energetics of oxidation. Models based on

  9. The Carbon_h-Factor: Predicting Individuals' Research Impact at Early Stages of Their Career

    PubMed Central

    Carbon, Claus-Christian

    2011-01-01

    Assessing an individual's research impact on the basis of a transparent algorithm is an important task for evaluation and comparison purposes. Besides simple but also inaccurate indices such as counting the mere number of publications or the accumulation of overall citations, and highly complex but also overwhelming full-range publication lists in their raw format, Hirsch (2005) introduced a single figure cleverly combining different approaches. The so-called h-index has undoubtedly become the standard in scientometrics of individuals' research impact (note: in the present paper I will always use the term “research impact” to describe the research performance as the logic of the paper is based on the h-index, which quantifies the specific “impact” of, e.g., researchers, but also because the genuine meaning of impact refers to quality as well). As the h-index reflects the number h of papers a researcher has published with at least h citations, the index is inherently positively biased towards senior level researchers. This might sometimes be problematic when predictive tools are needed for assessing young scientists' potential, especially when recruiting early career positions or equipping young scientists' labs. To be compatible with the standard h-index, the proposed index integrates the scientist's research age (Carbon_h-factor) into the h-index, thus reporting the average gain of h-index per year. Comprehensive calculations of the Carbon_h-factor were made for a broad variety of four research-disciplines (economics, neuroscience, physics and psychology) and for researchers performing on three high levels of research impact (substantial, outstanding and epochal) with ten researchers per category. For all research areas and output levels we obtained linear developments of the h-index demonstrating the validity of predicting one's later impact in terms of research impact already at an early stage of their career with the Carbon_h-factor being approx. 0.4, 0

  10. Doppler Ultrasound Detection of Preclinical Changes in Foot Arteries in Early Stage of Type 2 Diabetes

    PubMed Central

    Leoniuk, Jolanta; Łukasiewicz, Adam; Szorc, Małgorzata; Sackiewicz, Izabela; Janica, Jacek; Łebkowska, Urszula

    2014-01-01

    Summary Background There are few reports regarding the changes within the vessels in the initial stage of type 2 diabetes. The aim of this study was to estimate the hemodynamic and morphological parameters in foot arteries in type 2 diabetes subjects and to compare these parameters to those obtained in a control group of healthy volunteers. Material/Methods Ultrasound B-mode, color Doppler and pulse wave Doppler imaging of foot arteries was conducted in 37 diabetic patients and 36 non-diabetic subjects to determine their morphological (total vascular diameter and flow lumen diameter) and functional parameters (spectral analysis). Results In diabetic patients, the overall vascular diameter and wall thickness were statistically significantly larger when compared to the control group in the right dorsalis pedis artery (P=0.01; P=0.001), left dorsalis pedis artery (P=0.007; P=0.006), right posterior tibial artery (P=0.005; P=0.0005), and left posterior tibial artery (P=0.007; P=0.0002). No significant differences were observed in both groups in flow lumen diameters and blood flow parameters (PSV, EDV, PI, RI). In the diabetic group, the level of HbA1c positively correlated with flow resistance index in the right dorsalis pedis artery (r=0.38; P=0.02), right posterior tibial artery (r=0.38; P=0.02) and left posterior tibial artery (r=0.42; P=0.009). The pulsatility index within the dorsalis pedis artery decreased with increased trophic skin changes (r=–0.431, P=0.009). Conclusions In the diabetic group, overall artery diameters larger than and flow lumina comparable to the control group suggest vessel wall thickening occurring in the early stage of diabetes. Doppler flow parameters are comparable in both groups. In the diabetic group, the level of HbA1c positively correlated with flow resistance index and negative correlation was observed between the intensity of trophic skin changes and the pulsatility index. PMID:25202434

  11. Novel Pectate Lyase Genes of Heterodera glycines Play Key Roles in the Early Stage of Parasitism.

    PubMed

    Peng, Huan; Cui, Jiangkuan; Long, Haibo; Huang, Wenkun; Kong, Lingan; Liu, Shiming; He, Wenting; Hu, Xianqi; Peng, Deliang

    2016-01-01

    the important roles of this gene in the early stages of parasitism. Our combined data suggest that two types of pectate lyases are present in the H. glycines genome and may have different roles during infection. PMID:26930215

  12. Breast Cancer Medications and Vision: Effects of Treatments for Early-stage Disease

    PubMed Central

    Eisner, Alvin; Luoh, Shiuh-Wen

    2011-01-01

    This review concerns the effects on vision and the eye of medications prescribed at three phases of treatment for women with early-stage breast cancer (BC): (1) adjuvant cytotoxic chemotherapy, (2) adjuvant endocrine therapy, and (3) symptomatic relief. The most common side effects of cytotoxic chemotherapy are epiphora and ocular surface irritation, which can be caused by any of several different regimens. Most notably, the taxane docetaxel can lead to epiphora by inducing canalicular stenosis. The selective-estrogen-receptor-modulator (SERM) tamoxifen, long the gold-standard adjuvant-endocrine-therapy for women with hormone-receptor-positive BC, increases the risk of posterior subcapsular cataract. Tamoxifen also affects the optic nerve head more often than previously thought, apparently by causing subclinical swelling within the first 2 years of use for women older than ∼50 years. Tamoxifen retinopathy is rare, but it can cause foveal cystoid spaces that are revealed with spectral-domain optical coherence tomography (OCT) and that may increase the risk for macular holes. Tamoxifen often alters the perceived color of flashed lights detected via short-wavelength-sensitive (SWS) cone response isolated psychophysically; these altered perceptions may reflect a neural-response sluggishness that becomes evident at ∼2 years of use. The aromatase inhibitor (AI) anastrozole affects perception similarly, but in an age-dependent manner suggesting that the change of estrogen activity towards lower levels is more important than the low estrogen activity itself. Based on analysis of OCT retinal thickness data, it is likely that anastrozole increases the tractional force between the vitreous and retina. Consequently, AI users, myopic AI users particularly, might be at increased risk for traction-related vision loss. Because bisphosphonates are sometimes prescribed to redress AI-induced bone loss, clinicians should be aware of their potential to cause scleritis and uveitis

  13. Evaluation of Periodontal Parameters in Patients with Early Stage Chronic Lymphocytic Leukemia

    PubMed Central

    Božić, Darko; Rinčić, Goran; Gaćina, Petar; Plančak, Darije

    2016-01-01

    Objective To assess periodontal conditions in patients with early stage CLL and to compare it with the periodontal status of age matched healthy controls and to analyze the relationship between periodontal and hematological parameters in CLL patients. Materials and Methods 60 subjects were examined: 30 patients with CLL Rai 0 (test group) and 30 age-matching healthy individuals (control group). The exclusion criteria were: presence of other systemic disease or condition (e.g. diabetes), history of treatment for periodontitis, use of antibiotics during the last 3 months, use of medications. Socio-demographic data were obtained by means of a questionnaire. Participants with at least 8 teeth underwent a full mouth examination assessing API, PBI, PPD, REC and CAL. Medical data for CLL patients were collected from the patients’ records, while hematological data were obtained from the hemogram. Results Difference between groups was statistically significant for age, number of teeth and frequency of dental checkups (p<0.05). Patients with CLL had significantly higher average values of periodontal indices (API 0.81±0.18; PBI 2.72±0.68; PPD 3.40±0.53; REC 1.95±0.87, CAL 4.37±0.80) compared to the control group (API 0.69±0.15; PBI 1.91±0.45; PPD 2.51±0.40; REC 0.99±0.54; CAL 3.00±0.58). The correlation coefficients between age and periodontal indices showed statistically significance between age and REC (r=0.357; p<0.01), and age and CAL (r=0.295; p<0.05). Age was not statistically significant covariate for CAL (F=2.205; p>0.05), only for REC (F=4.601; p<0.05). After the removal of the statistical effect of age, the difference in REC between CLL and control group remained statistically significant (F=19.732; p<0.01; eta2=0.287). Statistically significant association between periodontal and hematological parameters in CLL patients was not found (p>0.05). Conclusion The results of this study showed that patients with CLL had worse periodontal status compared to

  14. Evaluation of Periodontal Parameters in Patients with Early Stage Chronic Lymphocytic Leukemia

    PubMed Central

    Božić, Darko; Rinčić, Goran; Gaćina, Petar; Plančak, Darije

    2016-01-01

    Objective To assess periodontal conditions in patients with early stage CLL and to compare it with the periodontal status of age matched healthy controls and to analyze the relationship between periodontal and hematological parameters in CLL patients. Materials and Methods 60 subjects were examined: 30 patients with CLL Rai 0 (test group) and 30 age-matching healthy individuals (control group). The exclusion criteria were: presence of other systemic disease or condition (e.g. diabetes), history of treatment for periodontitis, use of antibiotics during the last 3 months, use of medications. Socio-demographic data were obtained by means of a questionnaire. Participants with at least 8 teeth underwent a full mouth examination assessing API, PBI, PPD, REC and CAL. Medical data for CLL patients were collected from the patients’ records, while hematological data were obtained from the hemogram. Results Difference between groups was statistically significant for age, number of teeth and frequency of dental checkups (p<0.05). Patients with CLL had significantly higher average values of periodontal indices (API 0.81±0.18; PBI 2.72±0.68; PPD 3.40±0.53; REC 1.95±0.87, CAL 4.37±0.80) compared to the control group (API 0.69±0.15; PBI 1.91±0.45; PPD 2.51±0.40; REC 0.99±0.54; CAL 3.00±0.58). The correlation coefficients between age and periodontal indices showed statistically significance between age and REC (r=0.357; p<0.01), and age and CAL (r=0.295; p<0.05). Age was not statistically significant covariate for CAL (F=2.205; p>0.05), only for REC (F=4.601; p<0.05). After the removal of the statistical effect of age, the difference in REC between CLL and control group remained statistically significant (F=19.732; p<0.01; eta2=0.287). Statistically significant association between periodontal and hematological parameters in CLL patients was not found (p>0.05). Conclusion The results of this study showed that patients with CLL had worse periodontal status compared to

  15. Reduction in Radiation-Induced Morbidity by Use of an Intercurrent Boost in the Management of Early-Stage Breast Cancer

    SciTech Connect

    Trombetta, Mark; Julian, Thomas B.; Valakh, Vladimir; Greenberg, Larisa; Labban, George; Khalid, Mian K.; Werts, E. Day; Parda, David

    2010-08-01

    Purpose: Electron or photon boost immediately following whole-breast irradiation performed after conservation surgery for early-stage breast cancer is the accepted standard of care. This regimen frequently results in Grade III dermatitis, causing discomfort or treatment interruption. Herein, we compare patients treated with whole-breast irradiation followed by boost compared with a cohort with a planned intercurrent radiation boost. Methods and Materials: The records of 650 consecutive breast cancer patients treated at Allegheny General Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were 327 patients with T1 or T2 tumors treated with external beam radiotherapy postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT). The mean whole breast radiation dose in the conventionally treated group was 5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost. Results: The occurrence of Grade III dermatitis was significantly reduced in the WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%), as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median follow-up of 32 months and 27 months, respectively, no significant difference in local control was identified. Conclusions: Patients treated with intercurrent boost developed less Grade III dermatitis and unplanned treatment interruptions with similar local control.

  16. Dose-Volume Histogram Predictors of Chronic Gastrointestinal Complications After Radical Hysterectomy and Postoperative Concurrent Nedaplatin-Based Chemoradiation Therapy for Early-Stage Cervical Cancer

    SciTech Connect

    Isohashi, Fumiaki; Yoshioka, Yasuo; Mabuchi, Seiji; Konishi, Koji; Koizumi, Masahiko; Takahashi, Yutaka; Ogata, Toshiyuki; Maruoka, Shintaroh; Kimura, Tadashi; Ogawa, Kazuhiko

    2013-03-01

    concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer.

  17. Phosphorylated LIM kinases colocalize with gamma-tubulin in centrosomes during early stages of mitosis.

    PubMed

    Chakrabarti, Ratna; Jones, Jennifer L; Oelschlager, Denise K; Tapia, Tenekua; Tousson, Albert; Grizzle, William E

    2007-12-01

    LIM kinases (LIMK1 and LIMK2) are LIM domain containing serine/threonine kinases that modulate reorganization of actin cytoskeleton through inactivating phosphorylation of cofilin. The Rho family of small GTPases regulates the catalytic activity of LIMK1 and LIMK2 through activating phosphorylation by ROCK or by p21 kinase. Recent studies have suggested that LIMK1 could play a role in modulation of cellular growth by alteration of the cell cycle in breast and prostate tumor cells; however, the direct mitogenic effects of LIMK1 in these tumor cells is yet to be elucidated. Via immunofluorescence, in this study, we show that phosphorylated LIM kinases (pLIMK1/2) are colocalized with gamma-tubulin in the centrosomes during the early mitotic phases of human breast and prostate cancer cells (MDA-MB-231 and DU145); apparent colocalization begins in the centrosomes in prophase. As shown by both bright field (MDA-MB-231) and fluorescent immunohistochemistry (MDA-MB-231 and DU145), pLIMK1/2 does not localize to centrosomes during interphase. By bright field immunohistochemistry, the largest area of the centrosome that is stained with pLIMK1/2 occurs at anaphase. In early telophase, reduced staining of pLIMK1/2 at the spindle poles and concomitant accumulation of pLIMK1/2 at the cleavage furrow begins to occur. In late telophase, loss of staining of pLIMK1/2 and of colocalization with gamma-tubulin occurs at the poles and pLIMK1/2 became further concentrated at the junction between the two daughter cells. Co-immunoprecipitation studies indicated that gamma-tubulin associates with phosphorylated LIMK1 and LIMK2 but not with dephosphorylated LIMK1 or LIMK2. The results suggest that activated LIMK1/2 may associate with gamma-tubulin and play a role in mitotic spindle assembly.

  18. Adaptation to Early-Stage Nonfluent/Agrammatic Variant Primary Progressive Aphasia: A First-Person Account.

    PubMed

    Douglas, Joanne T

    2014-06-01

    Primary progressive aphasia (PPA) is a young-onset neurodegenerative disorder characterized by declining language ability. The nonfluent/agrammatic variant of PPA (PPA-G) has the core features of agrammatism in language production and effortful, halting speech. As with other frontotemporal spectrum disorders, there is currently no cure for PPA, nor is it possible to slow the course of progression. The primary goal of treatment is therefore palliative in nature. However, there is a paucity of published information about strategies to make meaningful improvements to the quality of life of people with PPA, particularly in the early stages of the disease where any benefit could most be appreciated by the affected person. This report describes a range of strategies and adaptations designed to improve the quality of life of a person with early-stage PPA-G, based on my experience under the care of a multidisciplinary medical team.

  19. Radiotherapy for Early-Stage Hodgkin's Lymphoma: A 21st Century Perspective and Review of Multiple Randomized Clinical Trials

    SciTech Connect

    Bar Ad, Voichita Paltiel, Ora; Glatstein, Eli

    2008-12-01

    The treatment of Hodgkin's lymphoma has improved dramatically over the past decades. Over the last half century, Hodgkin's lymphoma has become one of the most curable cancers of adulthood. More than 90% of the patients with localized stages of the disease can be cured with modern treatment strategies. Long-term toxicities are now the major concern for survivors of early-stage disease. Contemporary therapeutic approaches for Hodgkin's lymphoma attempt to preserve the high cure rate achieved, while reducing treatment-related acute and late toxicities. The aim of this review is to re-examine the historical and the current role of radiotherapy for early-stage Hodgkin's lymphoma, given the latest evidence of an increasing role of chemotherapy for the treatment of this malignancy. The literature search was performed in PubMed Plus. Studies on children were excluded.

  20. Spectroscopic Analysis of Stimulated Raman Scattering in the Early Stage of Laser-Induced Breakdown in Water

    NASA Astrophysics Data System (ADS)

    Yui, Hiroharu; Yoneda, Yoshinori; Kitamori, Takehiko; Sawada, Tsuguo

    1999-05-01

    We have investigated laser-induced breakdown (LIB) in water by measuring stimulated Raman scattering (SRS) induced in the early stage of the LIB phenomenon. The SRS is emitted before the breakdown plasma continuum emission becomes dominant and lasts about 80 picoseconds. The time-resolved spectra of the SRS indicate that ice VII structure is formed partially and inhomogeneously in the focal volume of the exciting beam on a picosecond time scale. The mechanism of the SRS inducement is also discussed.

  1. The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

    PubMed Central

    Kostakoglu, Lale

    2014-01-01

    Given the excellent survival rates for early-stage Hodgkin lymphoma (HL), the young age of many patients, and concerns regarding acute and late treatment-related toxicities, there is a desire to have a predictive tool that enables therapy to be tailored toward the individual patient. Early (or interim) 18F-fluorodeoxyglucose positron emission tomography with computerized tomography (FDG-PET/CT), as a test of tumor sensitivity to ongoing/planned therapy, has been shown to be prognostic for survival in HL. Based on results of interim FDG-PET/CT, therapy may be subsequently modified through minimization or via intensification for low- and high-risk patient populations, respectively (ie, response-adapted therapy). Important data have been generated to standardize the interpretability and reproducibility of interim FDG-PET/CT (eg, the Deauville 5-point system), and observational and noncontrolled prospective studies have produced evidence supporting the hypothesis that response-adapted therapy may potentially serve as a predictive tool. Furthermore, results from noninferiority phase 3 clinical trials randomizing early-stage HL patients with negative interim FDG-PET/CT to combined modality therapy versus chemotherapy alone have been reported. The current collective findings from these randomized early-stage HL studies have shown that acute relapse rates are lower with combined modality therapy, even in patients with negative interim FDG-PET/CT. Additional randomized response-adapted studies are ongoing and novel FDG-PET/CT applications involving quantitative techniques and innovative imaging modalities are being investigated to identify more robust imaging biomarkers. Treatment of early-stage HL remains a clinical management choice for physicians and patients to make with consideration of acute and long-term outcomes. PMID:25428223

  2. Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson's disease.

    PubMed

    Yin, Sheng-Ming; Zhao, Dan; Yu, De-Qin; Li, Sheng-Long; An, Dong; Peng, Yan; Xu, Hong; Sun, Yi-Ping; Wang, Dong-Mei; Zhao, Jie; Zhang, Wan-Qin

    2014-12-25

    Neuroprotective effect of scorpion venom on Parkinson's disease (PD) has already been reported. The present study was aimed to investigate whether scorpion venom heat resistant peptide (SVHRP) could attenuate ultrastructural abnormalities in mitochondria and oxidative stress in midbrain neurons of early-stage PD model. The early-stage PD model was established by injecting 6-hydroxydopamine (6-OHDA) (20 μg/3 μL normal saline with 0.1% ascorbic acid) into the striatum of Sprague Dawley (SD) rats unilaterally. The rats were intraperitoneally administered with SVHRP (0.05 mg/kg per day) or vehicle (saline) for 1 week. Two weeks after 6-OHDA treatment, the rats received behavior tests for validation of model. Three weeks after 6-OHDA injection, the immunoreactivity of dopaminergic neurons were detected by immunohistochemistry staining, and the ultrastructure of neuronal mitochondria in midbrain was observed by electron microscope. In the meantime, the activities of monoamine oxidase-B (MAO-B), superoxide dismutase (SOD) and content of malondialdehyde (MDA) in the mitochondria of the midbrain neurons, as well as the inhibitory ability of hydroxyl free radical and the antioxidant ability in the serum, were measured by corresponding kits. The results showed that 6-OHDA reduced the optical density of dopaminergic neurons, induced damage of mitochondrial ultrastructure of midbrain neurons, decreased SOD activity, increased MAO-B activity and MDA content, and reduced the antioxidant ability of the serum. SVHRP significantly reversed the previous harmful effects of 6-OHDA in early-stage PD model. These findings indicate that SVHRP may contribute to neuroprotection by preventing biochemical and ultrastructure damage changes which occur during early-stage PD. PMID:25516514

  3. Partial-Breast Irradiation Versus Whole-Breast Irradiation for Early-Stage Breast Cancer: A Cost-Effectiveness Analysis

    SciTech Connect

    Sher, David J.; Wittenberg, Eve; Suh, W. Warren; Taghian, Alphonse G.; Punglia, Rinaa S.

    2009-06-01

    Purpose: Accelerated partial-breast irradiation (PBI) is a new treatment paradigm for patients with early-stage breast cancer. Although PBI may lead to greater local recurrence rates, it may be cost-effective because of better tolerability and lower cost. We aim to determine the incremental cost-effectiveness of PBI compared with whole-breast radiation therapy (WBRT) for estrogen receptor-positive postmenopausal women treated for early-stage breast cancer. Methods and Materials: We developed a Markov model to describe health states in the 15 years after radiotherapy for early-stage breast cancer. External beam (EB) and MammoSite (MS) PBI were considered and assumed to be equally effective, but carried different costs. Patients received tamoxifen, but not chemotherapy. Utilities, recurrence risks, and costs were adapted from the literature; the baseline utility for no disease after radiotherapy was set at 0.92. Probabilistic sensitivity analyses were performed to model uncertainty in the PBI hazard ratio, recurrence pattern, and patient utilities. Costs (in 2004 US dollars) and quality-adjusted life-years were discounted at 3%/y. Results: The incremental cost-effectiveness ratio for WBRT compared with EB-PBI was $630,000/quality-adjusted life-year; WBRT strongly dominated MS-PBI. One-way sensitivity analysis found that results were sensitive to PBI hazard ratio, recurrence pattern, baseline recurrence risk, and no evidence of disease PBI utility values. Probabilistic sensitivity showed that EB-PBI was the most cost-effective technique over a wide range of assumptions and societal willingness-to-pay values. Conclusions: EB-PBI was the most cost-effective strategy for postmenopausal women with early-stage breast cancer. Unless the quality of life after MS-PBI proves to be superior, it is unlikely to be cost-effective.

  4. White Matter Integrity and Reaction Time Intraindividual Variability in Healthy Aging and Early-Stage Alzheimer Disease

    PubMed Central

    Jackson, Jonathan D.; Balota, David A.; Duchek, Janet M.; Head, Denise

    2011-01-01

    Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the RT distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging. PMID:22172547

  5. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

    PubMed Central

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

  6. [Current Status of Stereotactic Ablative Radiotherapy (SABR) for Early-stage 
Non-small Cell Lung Cancer].

    PubMed

    Shi, Anhui; Zhu, Guangying

    2016-06-20

    High level evidence from randomized studies comparing stereotactic ablative radiotherapy (SABR) to surgery is lacking. Although the results of pooled analysis of two randomized trials for STARS and ROSEL showed that SABR is better tolerated and might lead to better overall survival than surgery for operable clinical stage I non-small cell lung cancer (NSCLC), SABR, however, is only recommended as a preferred treatment option for early stage NSCLC patients who cannot or will not undergo surgery. We, therefore, are waiting for the results of the ongoing randomized studies [Veterans affairs lung cancer surgery or stereotactic radiotherapy in the US (VALOR) and the SABRTooth study in the United Kingdom (SABRTooths)]. Many retrospective and case control studies showed that SABR is safe and effective (local control rate higher than 90%, 5 years survival rate reached 70%), but there are considerable variations in the definitions and staging of lung cancer, operability determination, and surgical approaches to operable lung cancer (open vs video-assisted). Therefore, it is difficult to compare the superiority of radiotherapy and surgery in the treatment of early staged lung cancer. Most studies demonstrated that the efficacy of the two modalities for early staged lung cancer is equivalent; however, due to the limited data, the conclusions from those studies are difficult to be evidence based. Therefore, the controversies will be focusing on the safety and invasiveness of the two treatment modalities. This article will review the ongoing debate in light of these goals. PMID:27335303

  7. Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats

    PubMed Central

    Dai, Die; Gao, Yiqiao; Chen, Jiaqing; Huang, Yin; Zhang, Zunjian; Xu, Fengguo

    2016-01-01

    Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production and eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has been widely reported. In our study we observed that two thirds of the rats (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking the dynamic metabolic change in survival and non-survival rats in the early stage may reveal new system information to understand the inter-individual variation in response to LPS. As the time-resolved datasets are very complex and no single method can elucidate the problem clearly and comprehensively, the static and dynamic metabolomics methods were employed in combination as cross-validation. Intriguingly, some common results have been observed. Lipids were the main different metabolites between survival and non-survival rats in pre-dose serum and in the early stage of infection with LPS. The LPS treatment led to S-adenosly-methionine and total cysteine individual difference in early stage, and subsequent significant perturbations in energy metabolism and oxidative stress. Furthermore, cytokine profiles were analyzed to identify potential biological associations between cytokines and specific metabolites. Our collective findings may provide some heuristic guidance for elucidating the underlying mechanism of individual difference in LPS-mediated disease. PMID:27695004

  8. Treatment of Early Stage Endometrial Cancer by Transumbilical Laparoendoscopic Single-Site Surgery Versus Traditional Laparoscopic Surgery

    PubMed Central

    Cai, Hui-hua; Liu, Mu-biao; He, Yuan-li

    2016-01-01

    Abstract To compare the outcomes of transumbilical laparoendoscopic single-site surgery (TU-LESS) versus traditional laparoscopic surgery (TLS) for early stage endometrial cancer (EC). We retrospectively reviewed the medical records of patients with early stage EC who were surgically treated by TU-LESS or TLS between 2011 and 2014 in a tertiary care teaching hospital. We identified 18 EC patients who underwent TU-LESS. Propensity score matching was used to match this group with 18 EC patients who underwent TLS. All patients underwent laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy by TU-LESS or TLS without conversion to laparoscopy or laparotomy. Number of pelvic lymph nodes retrieved, operative time and estimated blood loss were comparable between 2 groups. Satisfaction values of the cosmetic outcome evaluated by the patient at day 30 after surgery were significantly higher in TU-LESS group than that in TLS group (9.6 ± 0.8 vs 7.5 ± 0.7, P < 0.001), while there was no statistical difference in postoperative complications within 30 days after surgery, postoperative hospital stay, and hospital cost. For the surgical management of early stage EC, TU-LESS may be a feasible alternative approach to TLS, with comparable short-term surgical outcomes and superior cosmetic outcome. Future large-scale prospective studies are needed to identify these benefits. PMID:27057851

  9. The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

    PubMed

    Fleming, Jonathan J

    2015-02-01

    A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas.

  10. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy.

    PubMed

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

  11. Upregulation of MAGEA4 correlates with poor prognosis in patients with early stage of esophageal squamous cell carcinoma

    PubMed Central

    Tang, Wei-Wei; Liu, Zi-Hao; Yang, Tong-Xin; Wang, Han-Jin; Cao, Xiu-Feng

    2016-01-01

    Esophageal cancer is a common type of cancer in the People’s Republic of China. Many genes have been reported to be linked with it. Melanoma antigen gene family A (MAGEA) genes are frequently highly expressed in various types of carcinoma. However, the specific role of MAGEA gene expression in esophageal squamous cell carcinoma (ESCC) still remains unclear. MAGEA4 is a member of MAGEA genes. We aimed to investigate the expression and prognosis of MAGEA4 expression in ESCC. MAGEA4 messenger RNA expression levels of 120 pairs of tumor and nontumor tissues of patients with ESCC were measured by quantitative real-time polymerase chain reaction. The results showed that MAGEA4 messenger RNA was significantly elevated in tumor tissues of patients with ESCC compared to nontumor ones. In addition, overexpression of MAGEA4 messenger RNA was significantly correlated with poorer overall survival (P=0.018) in early stage of patients with ESCC (I–IIA). In conclusion, MAGEA4 played an important role in the early stage of ESCC and overexpression of MAGEA4 was expected to become a potential prognostic marker for patients with early stage of ESCC. PMID:27478386

  12. The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

    PubMed

    Fleming, Jonathan J

    2015-02-01

    A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas. PMID:25646107

  13. Representation of Sound Objects within Early-Stage Auditory Areas: A Repetition Effect Study Using 7T fMRI.

    PubMed

    Da Costa, Sandra; Bourquin, Nathalie M-P; Knebel, Jean-François; Saenz, Melissa; van der Zwaag, Wietske; Clarke, Stephanie

    2015-01-01

    Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl's gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds. PMID:25938430

  14. Representation of Sound Objects within Early-Stage Auditory Areas: A Repetition Effect Study Using 7T fMRI

    PubMed Central

    Da Costa, Sandra; Bourquin, Nathalie M.-P.; Knebel, Jean-François; Saenz, Melissa; van der Zwaag, Wietske; Clarke, Stephanie

    2015-01-01

    Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl’s gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds. PMID:25938430

  15. Parkinson's Disease and Cognitive-Motor Dual-Task: Is Motor Prioritization Possible in the Early Stages of the Disease?

    PubMed

    Fernandes, Ângela; Sousa, Andreia S P; Rocha, Nuno; Tavares, João Manuel R S

    2016-01-01

    The authors aimed to compare the postural phase of gait initiation under single-task (gait initiation) and dual-task (gait initiation plus Stroop test) conditions in healthy subjects and in subjects with Parkinson's disease (PD) in the early stages (Hoehn and Yahr scale < 3). The postural phase of gait initiation was assessed through the centre of pressure in single and dual task in 10 healthy subjects and 9 with PD. The analysis indicated that in the early stages of PD, an additional cognitive task did not affect the displacement of the gait initiation. No significant effects occurred between the groups and within-subjects (p > .05). Also, no interaction was found between the groups and the conditions (single- and dual-task). Differences were found in the duration of the mediolateral postural phase (p = .003), which was higher in PD subjects than in healthy subjects. The findings suggest that subjects in the early stages of PD prioritize gait initiation, as their motor performance was similar to that of healthy subjects. PMID:27159414

  16. Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients.

    PubMed

    Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi

    2016-06-15

    Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall. PMID:27145228

  17. Ergospirometry and Echocardiography in Early Stage of Heart Failure with Preserved Ejection Fraction and in Healthy Individuals

    PubMed Central

    Garcia, Eduardo Lima; Menezes, Márcio Garcia; Stefani, Charles de Moraes; Danzmann, Luiz Cláudio; Torres, Marco Antonio Rodrigues

    2015-01-01

    Background Heart failure with preserved ejection fraction is a syndrome characterized by changes in diastolic function; it is more prevalent among the elderly, women, and individuals with systemic hypertension (SH) and diabetes mellitus. However, in its early stages, there are no signs of congestion and it is identified in tests by adverse remodeling, decreased exercise capacity and diastolic dysfunction. Objective To compare doppler, echocardiographic (Echo), and cardiopulmonary exercise test (CPET) variables - ergospirometry variables - between two population samples: one of individuals in the early stage of this syndrome, and the other of healthy individuals. Methods Twenty eight outpatients diagnosed with heart failure according to Framingham’s criteria, ejection fraction > 50% and diastolic dysfunction according to the european society of cardiology (ESC), and 24 healthy individuals underwent Echo and CPET. Results The group of patients showed indexed atrial volume and left ventricular mass as well as E/E’ and ILAV/A´ ratios significantly higher, in addition to a significant reduction in peak oxygen consumption and increased VE/VCO2 slope, even having similar left ventricular sizes in comparison to those of the sample of healthy individuals. Conclusion There are significant differences between the structural and functional variables analyzed by Echo and CPET when comparing two population samples: one of patients in the early stage of heart failure with ejection fraction greater than or equal to 50% and another of healthy individuals. PMID:26247247

  18. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer

    PubMed Central

    Schettino, Clorinda; Bareschino, Maria Anna; Rossi, Antonio; Maione, Paolo; Castaldo, Vincenzo; Mazzeo, Nicole; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Palazzolo, Giovanni; Ciardiello, Fortunato; Gridelli, Cesare

    2009-01-01

    Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection – in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease. PMID:21789109

  19. The potential role of bevacizumab in early stages and locally advanced non-small cell lung cancer.

    PubMed

    Schettino, Clorinda; Bareschino, Maria Anna; Rossi, Antonio; Maione, Paolo; Castaldo, Vincenzo; Mazzeo, Nicole; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Palazzolo, Giovanni; Ciardiello, Fortunato; Gridelli, Cesare

    2009-07-01

    Improving outcomes for early-stage non-small cell lung cancer (NSCLC) is a major research area considering that a significant percentage of such patients develop recurrent disease within 5 years of complete lung resection. Adjuvant chemotherapy prolongs survival, with an absolute improvement in 5-year overall survival of about 5% with drawbacks such as treatment toxicity. Approximately, one third of patients with newly diagnosed NSCLC have locally advanced disease not amenable for surgical resection - in this setting of patients concurrent chemoradiation is the standard of therapy. However, the treatment of locally advanced NSCLC is still controversial and clinical outcomes are disappointing, and so new approaches are required to improve the clinical benefit in this setting of patients. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessels formation and permeability, and tumor VEGF overexpression in patients with early stage lung cancer has been associated with worse relapse free and overall survival. Several agents have been developed that inhibit VEGF or its receptor signalling system. Bevacizumab is the first recombinant humanized monoclonal antibody binding VEGF to demonstrate clinical benefit or rather a survival prolongation in combination with chemotherapy in the treatment of non-squamous advanced NSCLC patients. These positive results led to a large number of clinical trials to evaluate bevacizumab in combination with other targeted agents in advanced disease, and to define the role of this agent in early stage NSCLC such as the impact of bevacizumab integration in chemoradiotherapy strategy for locally advanced disease.

  20. Filling the Gap for Early-Stage Breast Cancer Follow-Up: An Overview for Primary Care Providers.

    PubMed

    Bond-Bero, Stacy

    2016-01-01

    Earlier detection and newer treatments now make breast cancer highly survivable, and breast cancer survivors are the largest female cancer survivor group in the United States. With earlier detection, more women are being diagnosed with early-stage breast cancer and need follow-up care. With the increasing number of breast cancer survivors, there is a projected shortage in the workforce of oncology specialists to care for these women. The American Society of Clinical Oncology recommends that breast cancer follow-up care can be provided by an oncologist or primary care provider, as long as the primary care provider has spoken to the oncologist about appropriate follow-up care. Several studies have shown that primary care providers and oncologists have comparable outcomes for follow-up care of women with early-stage breast cancer. The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) are considered the gold standard for breast cancer treatment and follow-up. These guidelines are clear and straightforward. Using knowledge of the NCCN Guidelines, primary care providers can fill the gap for follow-up care of women with early-stage breast cancer.

  1. Representation of Sound Objects within Early-Stage Auditory Areas: A Repetition Effect Study Using 7T fMRI.

    PubMed

    Da Costa, Sandra; Bourquin, Nathalie M-P; Knebel, Jean-François; Saenz, Melissa; van der Zwaag, Wietske; Clarke, Stephanie

    2015-01-01

    Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl's gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds.

  2. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients.

    PubMed

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-03-01

    GFR: 0.634, P = 0.823).Plasma uromodulin serves as a robust biomarker for kidney function and uniquely allows the identification of early stages of CKD. As a marker of tubular secretion it might represent remaining nephron mass and therefore intrinsic "kidney function" rather than just glomerular filtration, the latter only being of limited value to represent kidney function as a whole. It therefore gives substantial information on the renal situation in addition to glomerular filtration and potentially solves the problem of creatinine-blind range of CKD, in which kidney impairment often remains undetected. PMID:26962815

  3. Reciprocal Vegetation-Flow Feedbacks Driving Early-Stage Landscape Evolution in a Restored Wet Meadow

    NASA Astrophysics Data System (ADS)

    Larsen, L.; Merritts, D. J.; Walter, R. C.; Watts, D.

    2013-12-01

    Just as taxonomic classification has improved understanding in biology, ecogeomorphologists would benefit from a functional classification of biota based on the biophysical feedbacks that they engage in. Early stages of landscape development following disturbance provide a unique opportunity to delineate and understand these feedback processes, as the diversity in functional morphotypes (a.k.a. 'ecomorphs,' to expand on a concept from terrestrial ecology) is high and the potential for self-organization of landscape pattern strong. We used the opportunity of a stream restoration that reset its floodplain to 'initial conditions' to perform a suite of biophysical measurements designed to delineate the classes of feedback that influence landscape evolution in distinct ways. The Big Spring Run restoration (Lancaster, PA), completed in November 2011, involved removal of 15,000 t of legacy sediment from the valley bottom to expose a Holocene hydric layer and reestablish wet meadow hydrology and biota. By performing repeat biogeomorphic surveys within a study grid, we tested the hypothesis that distinct ecomorphs determine the persistence and location of channel and microtopographic features. The qualitatively distinct patch types surveyed included carpet-forming mat vegetation, tussock-forming vegetation, sparsely vegetated mudflats, benthic algal mats, mixed herbaceous communities, grasses, and clonal emergent vegetation. Within each sampling location, changes in vegetation community architecture, grain size distribution, critical shear stress for sediment entrainment, and topography were monitored over time, and flow resistance was measured. An overbank flow event that completely filled the floodplain provided an additional opportunity to measure vegetation-flow-sediment interactions. Once emergent vegetation was bent over by flow, vegetation had a negligible influence on flow velocity--in contrast to most other wetlands--but continued to shelter the bed from sediment

  4. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    = 0.811, and eGFR: 0.634, P = 0.823). Plasma uromodulin serves as a robust biomarker for kidney function and uniquely allows the identification of early stages of CKD. As a marker of tubular secretion it might represent remaining nephron mass and therefore intrinsic “kidney function” rather than just glomerular filtration, the latter only being of limited value to represent kidney function as a whole. It therefore gives substantial information on the renal situation in addition to glomerular filtration and potentially solves the problem of creatinine-blind range of CKD, in which kidney impairment often remains undetected. PMID:26962815

  5. Locoregional Failure in Early-Stage Breast Cancer Patients Treated With Radical Mastectomy and Adjuvant Systemic Therapy: Which Patients Benefit From Postmastectomy Irradiation?

    SciTech Connect

    Trovo, Marco; Durofil, Elena; Polesel, Jerry; Roncadin, Mario; Perin, Tiziana; Mileto, Mario; Piccoli, Erica; Quitadamo, Daniela; Massarut, Samuele; Carbone, Antonino; Trovo, Mauro G.

    2012-06-01

    Purpose: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). Methods and Materials: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. Results: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. Conclusions: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.

  6. Impacts of Early-Stage Drinking Water Treatment on Cyanobacterial Toxin Release and Degradation

    EPA Science Inventory

    This presentation summarizes the impact of potassium permanganate application to suspensions of intact, toxin-producing cyanobacterial cells at pH 7 and 9, oxidant doses of 1, 2.5 and 5 mg/L, turbidities of 0.1, 5 and 20 NTU, and powdered activated carbon doses of 0 and 10 mg/L

  7. 7 CFR 810.1404 - Grades and grade requirements for sorghum.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Grades and grade requirements for sorghum. 810.1404... OFFICIAL UNITED STATES STANDARDS FOR GRAIN United States Standards for Sorghum >grades and Grade Requirements § 810.1404 Grades and grade requirements for sorghum. Grading factors Grades U.S. Nos. 1 1 2 3...

  8. 7 CFR 810.1404 - Grades and grade requirements for sorghum.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Grades and grade requirements for sorghum. 810.1404... OFFICIAL UNITED STATES STANDARDS FOR GRAIN United States Standards for Sorghum Grades and Grade Requirements § 810.1404 Grades and grade requirements for sorghum. Grading factors Grades U.S. Nos. 1 1 2 3...

  9. 7 CFR 810.1404 - Grades and grade requirements for sorghum.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Grades and grade requirements for sorghum. 810.1404... OFFICIAL UNITED STATES STANDARDS FOR GRAIN United States Standards for Sorghum Grades and Grade Requirements § 810.1404 Grades and grade requirements for sorghum. Grading factors Grades U.S. Nos. 1 1 2 3...

  10. 7 CFR 810.1404 - Grades and grade requirements for sorghum.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Grades and grade requirements for sorghum. 810.1404... OFFICIAL UNITED STATES STANDARDS FOR GRAIN United States Standards for Sorghum Grades and Grade Requirements § 810.1404 Grades and grade requirements for sorghum. Grading factors Grades U.S. Nos. 1 1 2 3...

  11. 7 CFR 810.1404 - Grades and grade requirements for sorghum.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Grades and grade requirements for sorghum. 810.1404... OFFICIAL UNITED STATES STANDARDS FOR GRAIN United States Standards for Sorghum Grades and Grade Requirements § 810.1404 Grades and grade requirements for sorghum. Grading factors Grades U.S. Nos. 1 1 2 3...

  12. Cosmetic Outcomes for Accelerated Partial Breast Irradiation Before Surgical Excision of Early-Stage Breast Cancer Using Single-Dose Intraoperative Radiotherapy

    SciTech Connect

    Kimple, Randall J.; Klauber-DeMore, Nancy; Kuzmiak, Cherie M.; Pavic, Dag; Lian, Jun; Livasy, Chad A.; Esler, Laura; Moore, Dominic T.; Sartor, Carolyn I.; Ollila, David W.

    2011-02-01

    Purpose: Determine cosmetic outcome and toxicity profile of intraoperative radiation delivered before tumor excision for patients with early-stage breast cancer. Methods and Materials: Patients age 48 or older with ultrasound-visible invasive ductal cancers <3 cm and clinically negative lymph nodes were eligible for treatment on this institutional review board-approved Phase II clinical trial. Treatment planning ultrasound was used to select an electron energy and cone size sufficient to cover the tumor plus a 1.5- to 2.0-cm circumferential margin laterally and a 1-cm-deep margin with the 90% isodose line. The dose was prescribed to a nominal 15 Gy and delivered using a Mobetron electron irradiator before tumor excision by segmental mastectomy. Physician- and patient-assessed cosmetic outcome and patient satisfaction were determined by questionnaire. Results: From March 2003 to July 2007, 71 patients were treated with intraoperative radiation therapy. Of those, 56 patients were evaluable, with a median follow-up of 3.1 years (minimum 1 year). Physician and patient assessment of cosmesis was 'good or excellent' (Radiation Therapy Oncology Group cosmesis scale) in 45/56 (80%) and 32/42 (76%) of all patients, respectively. Eleven patients who received additional whole breast radiation had similar rates of good or excellent cosmesis: 40/48 (83%) and 29/36 (81%), respectively). Grade 1 or 2 acute toxicities were seen in 4/71 (6%) patients. No Grade 3 or 4 toxicities or serious adverse events have been seen. Conclusion: Intraoperative radiotherapy delivered to an in situ tumor is feasible with acceptable acute tolerance. Patient and physician assessment of the cosmetic outcome is good to excellent.

  13. Phase 2 Trial of Accelerated, Hypofractionated Whole-Breast Irradiation of 39 Gy in 13 Fractions Followed by a Tumor Bed Boost Sequentially Delivering 9 Gy in 3 Fractions in Early-Stage Breast Cancer

    SciTech Connect

    Kim, Ja Young; Jung, So-Youn; Lee, Seeyoun; Kang, Han-Sung; Lee, Eun Sook; Park, In Hae; Lee, Keun Seok; Ro, Jungsil; Lee, Nam Kwon; Shin, Kyung Hwan

    2013-12-01

    Purpose: To report a phase 2 trial of accelerated, hypofractionated whole-breast irradiation (AH-WBI) delivered as a daily dose of 3 Gy to the whole breast followed by a tumor bed boost. Methods and Materials: Two hundred seventy-six patients diagnosed with breast cancer (pT1-2 and pN0-1a) who had undergone breast-conserving surgery in which the operative margins were negative were treated with AH-WBI delivered as 39 Gy in 13 fractions of 3 Gy to the whole breast once daily over 5 consecutive working days, and 9 Gy in 3 sequential fractions of 3 Gy to a lumpectomy cavity, all within 3.2 weeks. Results: After a median follow-up period of 57 months (range: 27-75 months), the rate of 5-year locoregional recurrence was 1.4% (n=4), whereas that of disease-free survival was 97.4%. No grade 3 skin toxicity was reported during the follow-up period. Qualitative physician cosmetic assessments of good or excellent were noted in 82% of the patients at 2 months after the completion of AH-WBI. The global cosmetic outcome did not worsen over time, and a good or excellent cosmetic outcome was reported in 82% of the patients at 3 years. The mean pretreatment percentage breast retraction assessment was 12.00 (95% confidence interval [CI]: 11.14-12.86). The mean value of percentage breast retraction assessment increased to 13.99 (95% CI: 12.17-15.96) after 1 year and decreased to 13.54 (95% CI: 11.84-15.46) after 3 years but was not significant (P>.05). Conclusions: AH-WBI consisting of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions can be delivered with excellent disease control and tolerable skin toxicity in patients with early-stage breast cancer after breast-conserving surgery.

  14. Early stages of wind wave and drift current generation under non-stationary wind conditions.

    NASA Astrophysics Data System (ADS)

    Robles-Diaz, Lucia; Ocampo-Torres, Francisco J.; Branger, Hubert

    2016-04-01

    Generation and amplification mechanisms of ocean waves are well understood under constant wind speed or limited fetch conditions. Under these situations, the momentum and energy transfers from air to water are also quite well known. However during the wind field evolution over the ocean, we may observe sometime high wind acceleration/deceleration situations (e.g. Mexican Tehuano or Mediterranean Mistral wind systems). The evolution of wave systems under these conditions is not well understood. The purpose of these laboratory experiments is to better understand the early stages of water-waves and surface-drift currents under non-stationary wind conditions and to determine the balance between transfers creating waves and surface currents during non-equilibrium situations. The experiments were conducted in the Institut Pythéas wind-wave facility in Marseille-France. The wave tank is 40 m long, 2.7 m wide and 1 m deep. The air section is 50 m long, 3 m wide and 1.8 m height. We used 11 different resistive wave-gauges located along the tank. The momentum fluxes in the air column were estimated from single and X hot-film anemometer measurements. The sampling frequency for wind velocity and surface displacement measurements was 256 Hz. Water-current measurements were performed with a profiling velocimeter. This device measures the first 3.5 cm of the water column with a frequency rate of 100Hz. During the experiments, the wind intensity was abruptly modified with a constant acceleration and deceleration over time. We observed that wind drag coefficient values for accelerated wind periods are lower than the ones reported in previous studies for constant wind speed (Large and Pond 1981; Ocampo-Torres et al. 2010; Smith 1980; Yelland and Taylor 1996). This is probably because the turbulent boundary layer is not completely developed during the increasing-wind sequence. As it was reported in some theoretical studies (Miles 1957; Phillips 1957; Kahma and Donelan 1988), we

  15. Early stages of wind wave and drift current generation under non-stationary wind conditions.

    NASA Astrophysics Data System (ADS)

    Robles-Diaz, Lucia; Ocampo-Torres, Francisco J.; Branger, Hubert

    2016-04-01

    Generation and amplification mechanisms of ocean waves are well understood under constant wind speed or limited fetch conditions. Under these situations, the momentum and energy transfers from air to water are also quite well known. However during the wind field evolution over the ocean, we may observe sometime high wind acceleration/deceleration situations (e.g. Mexican Tehuano or Mediterranean Mistral wind systems). The evolution of wave systems under these conditions is not well understood. The purpose of these laboratory experiments is to better understand the early stages of water-waves and surface-drift currents under non-stationary wind conditions and to determine the balance between transfers creating waves and surface currents during non-equilibrium situations. The experiments were conducted in the Institut Pythéas wind-wave facility in Marseille-France. The wave tank is 40 m long, 2.7 m wide and 1 m deep. The air section is 50 m long, 3 m wide and 1.8 m height. We used 11 different resistive wave-gauges located along the tank. The momentum fluxes in the air column were estimated from single and X hot-film anemometer measurements. The sampling frequency for wind velocity and surface displacement measurements was 256 Hz. Water-current measurements were performed with a profiling velocimeter. This device measures the first 3.5 cm of the water column with a frequency rate of 100Hz. During the experiments, the wind intensity was abruptly modified with a constant acceleration and deceleration over time. We observed that wind drag coefficient values for accelerated wind periods are lower than the ones reported in previous studies for constant wind speed (Large and Pond 1981; Ocampo-Torres et al. 2010; Smith 1980; Yelland and Taylor 1996). This is probably because the turbulent boundary layer is not completely developed during the increasing-wind sequence. As it was reported in some theoretical studies (Miles 1957; Phillips 1957; Kahma and Donelan 1988), we

  16. Mild Toxicity and Favorable Prognosis of High-Dose and Extended Involved-Field Intensity-Modulated Radiotherapy for Patients With Early-Stage Nasal NK/T-Cell Lymphoma

    SciTech Connect

    Wang Hua; Li Yexiong; Wang Weihu; Jin Jing; Dai Jianrong; Wang Shulian; Liu Yueping; Song Yongwen; Wang Zhaoyang; Liu Qingfeng; Fang Hui; Qi Shunan; Liu Xinfan; Yu Zihao

    2012-03-01

    Purpose: The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. Methods and Materials: Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survival were calculated using the Kaplan-Meier method. Results: The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. Conclusions: High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients.

  17. Prognostic significance of circulating laminin gamma2 for early-stage non-small-cell lung cancer

    PubMed Central

    Teng, Yu; Wang, Zitong; Ma, Li; Zhang, Lina; Guo, Yinan; Gu, Meng; Wang, Ziyu; Wang, Yue; Yue, Wentao

    2016-01-01

    Background Laminin gamma2 (Ln-γ2) chain, a distinctive subunit of heterotrimeric laminin-332, is frequently upregulated in carcinomas and is of great importance in cell migration and invasion. Despite this, the status of circulating Ln-γ2 in lung cancer patients is still uncertain. Patients and methods In this retrospective study, serum samples from 538 all-stage (stages I–IV) patients with non-small-cell lung cancer (NSCLC) and 94 age-matched healthy volunteers were investigated by enzyme-linked immunosorbent assay. Data were statistically analyzed in combination with clinicopathological information. Results Circulating Ln-γ2 was markedly increased in NSCLC, even in stage I cases (P<0.01), reflecting the progression of lung cancer. Survival analysis on 370 eligible patients indicated that serum Ln-γ2-negative patients survived much longer compared with Ln-γ2-positive individuals (P=0.028), and it was especially the case for stage I (P<0.001), stage T1 (P=0.001), and stage N0 patients (P=0.038), all of whom represented early-stage cases. For the advanced patients, however, overall survivals were not significantly different among stages II–IV (P=0.830), stages T2–T4 (P=0.575), stages N1–N3 (P=0.669), and stage M1 (P=0.849). Cox analysis subsequently defined serum Ln-γ2 as an independent prognostic indicator of NSCLC, particularly for early-stage patients. Furthermore, we demonstrated the association of serum Ln-γ2 with smoking behavior, but its association with tumor progression and early prognostic significance were not altered in the nonsmoking cohort. Conclusion Our study demonstrated that elevation of circulating Ln-γ2 was an early-emerging event in NSCLC and was significantly associated with poor prognosis in NSCLC, especially for early-stage cases. PMID:27462170

  18. Contribution of mammary epithelial cells to the immune response during early stages of a bacterial infection to Staphylococcus aureus

    PubMed Central

    2014-01-01

    To differentiate between the contribution of mammary epithelial cells (MEC) and infiltrating immune cells to gene expression profiles of mammary tissue during early stage mastitis, we investigated in goats the in vivo transcriptional response of MEC to an experimental intra mammary infection (IMI) with Staphylococcus aureus, using a non-invasive RNA sampling method from milk fat globules (MFG). Microarrays were used to record gene expression patterns during the first 24 hours post-infection (hpi). This approach was combined with laser capture microdissection of MEC from frozen slides of mammary tissue to analyze some relevant genes at 30 hpi. During the early stages post-inoculation, MEC play an important role in the recruitment and activation of inflammatory cells through the IL-8 signalling pathway and initiate a sharp induction of innate immune genes predominantly associated with the pro-inflammatory response. At 30 hpi, MEC express genes encoding different acute phase proteins, including SAA3, SERPINA1 and PTX3 and factors, such as S100A12, that contribute directly to fighting the infection. No significant change in the expression of genes encoding caseins was observed until 24 hpi, thus validating our experimental model to study early stages of infection before the occurrence of tissue damage, since the milk synthesis function is still operative. This is to our knowledge the first report showing in vivo, in goats, how MEC orchestrate the innate immune response to an IMI challenge with S. aureus. Moreover, the non-invasive sampling method of mammary representative RNA from MFG provides a valuable tool to easily follow the dynamics of gene expression in MEC to search for sensitive biomarkers in milk for early detection of mastitis and therefore, to successfully improve the treatment and thus animal welfare. PMID:24521038

  19. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    SciTech Connect

    Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai; Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M.; Bentzen, Søren M.

    2013-10-01

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.

  20. Identification of c-Yes expression in the nuclei of hepatocellular carcinoma cells: involvement in the early stages of hepatocarcinogenesis.

    PubMed

    Nonomura, Takako; Masaki, Tsutomu; Morishita, Asahiro; Jian, Gong; Uchida, Naohito; Himoto, Takashi; Izuishi, Kunihiko; Iwama, Hisakazu; Yoshiji, Hitoshi; Watanabe, Seishiro; Kurokohchi, Kazutaka; Kuriyama, Shigeki

    2007-01-01

    It is thought that the subcellular distribution of Src-family tyrosine kinases, including c-Yes binding to the cellular membrane, is membranous and/or cytoplasmic. c-Yes protein tyrosine kinase is known to be related to malignant transformation. However, the expression patterns of c-Yes in hepatocellular carcinoma (HCC) remains unknown. In the present study, we report that c-Yes is expressed not only in the membrane and cytoplasm, but also in the nuclei of cancer cells in some human HCC tissues and in a human HCC cell line. We examined the expression and localization of c-Yes in human HCC cell lines (HLE, HLF, PLC/PRF/5 and Hep 3B) by Western blotting and immunohistochemical analyses; we also examined the expression of c-Yes by immunohistochemistry and Western blotting in the tissues of various liver diseases, including 39 samples from HCC patients. We used an antibody array to detect proteins that bind to nuclear c-Yes in PLC/PRF/5 cell line. c-Yes was found to be expressed in the membranes and cytoplasm of HLE, HLF and Hep 3B HCC cells; it was also detected in the nuclei in addition to the membranes and cytoplasm of PLC/PRF/5 HCC cells. HCC with nuclear c-Yes was detected in 5 of 39 cases (13.0%), and nuclear c-Yes expression was not detected in normal, chronic hepatitis or cirrhotic livers. All HCCs with nuclear c-Yes expression were well-differentiated, small tumors at the early stages. In the PLC/PRF/5 cell line, the nuclear localization of c-Yes with cyclin-dependent kinase 1 was confirmed by a protein antibody array. In conclusion, nuclear c-Yes expression was found in cancer cells at the early stages of hepatocarcinogenesis, suggesting that nucleus-located c-Yes may be a useful marker to detect early-stage HCC.

  1. Transient elevation of amygdala alpha 2 adrenergic receptor binding sites during the early stages of amygdala kindling.

    PubMed

    Chen, M J; Vigil, A; Savage, D D; Weiss, G K

    1990-03-01

    Enhanced noradrenergic neurotransmission retards but does not prevent the development of kindling. We previously reported that locus coeruleus (LC) alpha 2 adrenergic receptor binding sites are transiently elevated during the early stages of kindling development. Since the firing activity of LC noradrenergic neurons is partially regulated via an alpha 2 receptor-mediated recurrent inhibition, the transient elevation in LC alpha 2 receptors could decrease LC activity and consequently facilitate the development of kindling. Transient elevation of alpha 2 receptor binding sites during early stages of kindling may also occur on noradrenergic axon terminals projecting to forebrain sites. Using in vitro neurotransmitter autoradiography techniques, we investigated this hypothesis by measuring specific [3H]idazoxan binding in 5 different areas of rat forebrain at 2 different stages of kindling development. After 2 class 1 kindled seizures, specific [3H]idazoxan binding was elevated significantly in the amygdala, but not in other forebrain regions. No differences in specific [3H]idazoxan binding were observed in any of the 5 brain regions in rats kindled to a single class 5 kindled motor seizure. Saturation of binding experiments indicated that the increase in amygdala [3H]idazoxan binding, following 2 class 1 kindled motor seizures, was due to an increase in the total number of alpha 2 receptor binding sites without a change in the affinity of the binding sites for [3H]idazoxan. Thus, the transient increase in alpha 2 receptors that occurs in the LC in the early stages of kindling also occurs in the forebrain region in which the kindled seizure originates.

  2. Intermolecular interactions at early stage of protein/detergent particle association induced by salt/polyethylene glycol mixtures.

    PubMed

    Odahara, Takayuki; Odahara, Koji

    2016-04-01

    Mixtures of neutral salts and polyethylene glycol are used for various purposes in biological studies. Although the effects of each component of the mixtures are theoretically well investigated, comprehension of their integrated effects remains insufficient. In this work, their roles and effects as a precipitant were clarified by studying dependence of precipitation curves on salt concentration for integral membrane protein/detergent particles of different physicochemical properties. The dependence of precipitation curves was reasonably related to intermolecular interactions among relevant molecules such as protein, detergent and polyethylene glycol by considering their physicochemical properties. The obtained relationships are useful as basic information to learn the early stage of biological macromolecular associations.

  3. Characteristics of Diffusion in the Corticospinal Tract of Patients with Early Stage of Schizophrenia: Diffusion Tensor Magnetic Resonance Imaging.

    PubMed

    Ublinskii, M V; Semenova, N A; Lukovkina, O V; Sidorin, S V; Lebedeva, I S; Kaleda, V G; Barkhatova, A N; Akhadov, T A

    2015-05-01

    Specific features of diffusion in the cerebral corticospinal tract of patients with early stages of schizophrenia were studied using methods of diffusion tensor magnetic-resonance imaging and magnetic resonance spectroscopy. A decrease in the coefficient of fractional anisotropy in the posterior limb of the internal capsule and an increase in diffusion coefficient in the radiate crown and motor cortex were observed. The results reflect different mechanisms of changes in water diffusion in various areas of the corticospinal tract: changes in nerve fiber microstructure in the internal capsule of the left hemisphere and a decrease in their density in the motor cortex and radiate crown.

  4. Knowledge-based compact disease models identify new molecular players contributing to early-stage Alzheimer’s disease

    PubMed Central

    2013-01-01

    Background High-throughput profiling of human tissues typically yield as results the gene lists comprised of a mix of relevant molecular entities with multiple false positives that obstruct the translation of such results into mechanistic hypotheses. From general probabilistic considerations, gene lists distilled for the mechanistically relevant components can be far more useful for subsequent experimental design or data interpretation. Results The input candidate gene lists were processed into different tiers of evidence consistency established by enrichment analysis across subsets of the same experiments and across different experiments and platforms. The cut-offs were established empirically through ontological and semantic enrichment; resultant shortened gene list was re-expanded by Ingenuity Pathway Assistant tool. The resulting sub-networks provided the basis for generating mechanistic hypotheses that were partially validated by literature search. This approach differs from previous consistency-based studies in that the cut-off on the Receiver Operating Characteristic of the true-false separation process is optimized by flexible selection of the consistency building procedure. The gene list distilled by this analytic technique and its network representation were termed Compact Disease Model (CDM). Here we present the CDM signature for the study of early-stage Alzheimer’s disease. The integrated analysis of this gene signature allowed us to identify the protein traffic vesicles as prominent players in the pathogenesis of Alzheimer’s. Considering the distances and complexity of protein trafficking in neurons, it is plausible that spontaneous protein misfolding along with a shortage of growth stimulation result in neurodegeneration. Several potentially overlapping scenarios of early-stage Alzheimer pathogenesis have been discussed, with an emphasis on the protective effects of AT-1 mediated antihypertensive response on cytoskeleton remodeling, along with

  5. Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease

    PubMed Central

    Stępień, Mariusz; Stępień, Anna; Wlazeł, Rafał Nikodem; Paradowski, Marek; Banach, Maciej; Rysz, Magdalena; Rysz, Jacek

    2013-01-01

    Background The aim of this study was to estimate obesity parameters: waist circumference (WC), waist-to-hip ratio (WHR), weight-to-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI), and serum adipokines (leptin, adiponectin, resistin) and their associations with estimated glomerular filtration rate (eGFR), serum creatinine, and microalbuminuria (MA) in patients with early stages of CKD and in non-CKD obese patients. Material/Methods 67 non-diabetic obese (BMI ≥30 mg/kg2) out-clinic patients (25 males, 42 females), aged from 36.5 to 64 years were divided into 2 groups: Group A (n=15) – patients with early stages of CKD (eGFR between 30 and 60 ml/min/1.73 m2 or with MA >20 mg/l in morning urine sample independently from GFR) and Group B – patients without chronic CKD (n=52). Results In Group A compared to Group B, BAI and leptin were higher (42.2±7.1 vs. 37.5±7.0; p<0.05 and 51.8±26.7 ng/mL vs. 35.3±24.9 ng/mL; p<0.05; respectively) and negative correlations occurred between eGFR and BAI (r=−0.709; p=0.003), leptin (r=−0.68; p=0.005), and resistin (r=−0.528; p<0.05). In Group B, negative correlations occurred between creatinine and VAI (r=−0.332; p<0.05), BAI (r=−0.619; p<0.0001), leptin (r=−0.676; p<0.0001), and adiponectin (r=−0.423; p=0.002), and between eGFR and resistin (r=−0.276; p<0.05). Conclusions BAI may be a valuable obesity parameter as a predictor of early stages of CKD in patients with obesity. Leptin may be an important pathogenic factor in obese patients with early stages of CKD. Resistin is associated with eGFR in obese patients, independently of CKD. PMID:24280776

  6. Early stage of material movements in eutectic SnPb solder joint undergoing current stressing at 150{degree}C.

    SciTech Connect

    Ho, C. E.; Lee, A.; Subramanian, K. N.; Liu, W.; Michigan State Univ.

    2007-07-10

    X-ray fluorescence spectroscopy was used to study movements of Sn and Pb in the eutectic SnPb solder joint undergoing electromigration with a current density of 10{sup 4} A/cm{sup 2} at 150 C. During early stages of current stressing, Sn moves toward the anode faster than Pb. However, on continued application of current stressing, both Sn and Pb will continue to accumulate at the anode. Such accumulation of conductive species facilitates the formation of hillock with associated valley near the cathode.

  7. Assessment and classification of early-stage multiple sclerosis with inertial sensors: comparison against clinical measures of disease state.

    PubMed

    Greene, Barry R; Rutledge, Stephanie; McGurgan, Iain; McGuigan, Christopher; OConnell, Karen; Caulfield, Brian; Tubridy, Niall

    2015-07-01

    A cross-sectional study on patients with early-stage multiple sclerosis (MS) was conducted to examine the reliability of manual and automatic mobility measures derived from shank-mounted inertial sensors during the Timed Up and Go (TUG) test, compared to control subjects. Furthermore, we aimed to determine if disease status [as measured by the Multiple Sclerosis Impact Scale (MSIS-20) and the Expanded Disability Status Score (EDSS)] can be explained by measurements obtained using inertial sensors. We also aimed to determine if patients with early-stage MS could be automatically distinguished from healthy controls subjects, using inertial parameters recorded during the TUG test. The mobility of 38 patients (aged 25-65 years, 14 M, 24 F), diagnosed with relapsing-remitting MS and 33 healthy controls (14 M, 19 F, age 50-65), was assessed using the TUG test, while patients wore inertial sensors on each shank. Reliability analysis showed that 36 of 53 mobility parameters obtained during the TUG showed excellent intrasession reliability, while nine of 53 showed moderate reliability. This compared favorably with the reliability of the mobility parameters in healthy controls. Exploratory regression models of the EDSS and MSIS-20 scales were derived, using mobility parameters and an elastic net procedure in order to determine which mobility parameters influence disease state. A cross-validated elastic net regularized regression model for MSIS-20 yielded a mean square error (MSE) of 1.1 with 10 degrees of freedom (DoF). Similarly, an elastic net regularized regression model for EDSS yielded a cross-validated MSE of 1.3 with 10 DoF. Classification results show that the mobility parameters of participants with early-stage MS could be distinguished from controls with 96.90% accuracy. Results suggest that mobility parameters derived from MS patients while completing the TUG test are reliable, are associated with disease state in MS, and may have utility in screening for early-stage

  8. The softening of human bladder cancer cells happens at an early stage of the malignancy process.

    PubMed

    Ramos, Jorge R; Pabijan, Joanna; Garcia, Ricardo; Lekka, Malgorzata

    2014-01-01

    Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young's modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force. PMID:24778971

  9. The softening of human bladder cancer cells happens at an early stage of the malignancy process

    PubMed Central

    Ramos, Jorge R; Pabijan, Joanna

    2014-01-01

    Summary Various studies have demonstrated that alterations in the deformability of cancerous cells are strongly linked to the actin cytoskeleton. By using atomic force microscopy (AFM), it is possible to determine such changes in a quantitative way in order to distinguish cancerous from non-malignant cells. In the work presented here, the elastic properties of human bladder cells were determined by means of AFM. The measurements show that non-malignant bladder HCV29 cells are stiffer (higher Young’s modulus) than cancerous cells (HTB-9, HT1376, and T24 cell lines). However, independently of the histological grade of the studied bladder cancer cells, all cancerous cells possess a similar level of the deformability of about a few kilopascals, significantly lower than non-malignant cells. This underlines the diagnostic character of stiffness that can be used as a biomarker of bladder cancer. Similar stiffness levels, observed for cancerous cells, cannot be fully explained by the organization of the actin cytoskeleton since it is different in all malignant cells. Our results underline that it is neither the spatial organization of the actin filaments nor the presence of stress fibers, but the overall density and their 3D-organization in a probing volume play the dominant role in controlling the elastic response of the cancerous cell to an external force. PMID:24778971

  10. Time Course of Mild Arm Lymphedema After Breast Conservation Treatment for Early-Stage Breast Cancer

    SciTech Connect

    Bar Ad, Voichita; Cheville, Andrea; Solin, Lawrence J.; Dutta, Pinaki; Both, Stefan; Harris, Eleanor

    2010-01-15

    Purpose: Arm lymphedema is a potential consequence of the treatment for breast carcinoma. The objective of this retrospective study was to characterize the progression of mild arm lymphedema after breast conservation treatment for breast cancer. Methods and Materials: The study cohort was drawn from 1,713 consecutive Stage I or II breast cancer patients who underwent breast conservation therapy, including axillary staging followed by radiation. Arm lymphedema was documented in 266 (16%) of 1,713 patients. One hundred nine patients, 6% of the overall group and 40% of the patients with arm lymphedema, presented with mild arm lymphedema, defined as a difference of 2 cm or less between the measured circumferences of the affected and unaffected arms. Results: Among the 109 patients with mild arm lymphedema at the time of arm lymphedema diagnosis, the rate of freedom from progression to more severe lymphedema was 79% at 1 year, 66% at 3 years, and 52% at 5 years. The patients who were morbidly obese, had positive axillary lymph nodes, or received supraclavicular irradiation at the time of breast cancer treatment were at higher risk of progression from mild arm lymphedema to more severe edema. Conclusions: Mild arm lymphedema, generally considered to be a minor complication after breast conservation treatment for breast cancer, was associated with a risk of progression to a more severe grade of arm lymphedema in a substantial fraction of patients.

  11. Gender Differences In Social And Developmental Factors Affecting Puerto Rican Adolescents During The Early Stage

    PubMed Central

    Figueroa-Cosme, Wanda I.; Miranda, Christine; Fernandez, Diana M.; Maysonet, Johanna; Ramon, Raul O.

    2011-01-01

    Background Adolescence is associated with risky behaviors related with social and developmental factors. Objectives were to describe social and developmental factors affecting Puerto Rican early adolescent by gender and type of school at study entry. Methods Cross-sectional study design. The study group was composed by 168 seventh grade adolescents from private and public schools. Descriptive and non-parametric comparisons were performed. Results Significance differences among proportions for gender by type of school were found in the following variables: self-esteem and HIV/AIDS attitudes in public school and peer pressure and sensation seeking in private school Discussion Our study revealed that public school adolescents are characterized by males with higher self-esteem and less attitude for HIV/AIDS, while in private school the males has more peer pressure and seeking sensation than females. Future studies could analyze factors related with changes in developmental factors, this step is important to evaluate the effectiveness of ASUMA interventions. PMID:23875519

  12. Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

    NASA Astrophysics Data System (ADS)

    Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

    2015-03-01

    With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

  13. Intensity-Modulated Radiotherapy-Based Stereotactic Body Radiotherapy for Medically Inoperable Early-Stage Lung Cancer: Excellent Local Control

    SciTech Connect

    Videtic, Gregory M.M.; Stephans, Kevin; Reddy, Chandana; Gajdos, Stephen; Kolar, Matthew; Clouser, Edward; Djemil, Toufik

    2010-06-01

    Purpose: To validate the use of stereotactic body radiotherapy (SBRT) using intensity-modulated radiotherapy (IMRT) beams for medically inoperable Stage I lung cancer. Methods and Materials: From February 2004 to November 2006, a total of 26 patients with 28 lesions received SBRT using a Novalis/BrainLAB system. Immobilization involved a Bodyfix vacuum cushion. A weighted abdominal belt limited respiratory excursion. Computed tomographic simulation images were acquired at rest, full inhalation, and full exhalation and were merged to generate an internal gross tumor volume (ITV). Dose was prescribed to cover the planning target volume (PTV), defined as PTV = ITV + 3-5 mm set-up margin. Heterogeneity corrections were used. Delivery of 50 Gy in five sequential fractions typically used seven nonopposing, noncoplanar beams. Image-guided target verification was provided by BrainLAB-ExacTrac. Results: Among the 26 patients, the mean age was 74 years (range, 49-88 years). Of the patients, 50% were male and 50% female. The median Karnofsky performance status was 70 (range, 40-100). The median follow-up was 30.9 months (range, 10.4-51.4 months). Tissue diagnosis was contraindicated in seven patients (26.9%). There were 22 T1 (78.6%) and six T2 (21.4%) tumors. The median conformality index was 1.38 (range, 1.12-1.8). The median heterogeneity index was 1.08 (range, 1.04-1.2). One patient (3.6%) developed acute Grade 3 dyspnea and one patient developed late Grade 2 chest wall pain. Actuarial local control and overall survival at 3 years were 94.4% and 52%, respectively. Conclusions: Use of IMRT-based delivery of SBRT using restriction of tumor motion in medically inoperable lung cancer demonstrates excellent local control and favorable survival.

  14. High-Energy Extracorporeal Shock Wave for Early Stage Osteonecrosis of the Femoral Head: A Single-Center Case Series.

    PubMed

    Gao, Fuqiang; Sun, Wei; Li, Zirong; Guo, Wanshou; Wang, Weiguo; Cheng, Liming; Wang, Bailiang

    2015-01-01

    Our retrospective study assessed the effects of treatment of early stage ONFH with extracorporeal shock wave therapy. 335 patients (528 hips) were treated with shockwave therapy in our institution. Each patient underwent two sessions. The hips were divided into two groups according to whether the lateral pillar of the femoral head (LPFH) was preserved: LPFH and non-LPFH groups. Patients were followed up at 3, 6, and 12 months after the treatment. Most of the patients (83.9% hips) demonstrated pain reduction and improved mobility of the treated joint (visual analogue scale score, P = 0.00006; Harris hip score, P = 0.00091). During the follow-up period, 16 hips failed following femoral head collapse and required hip arthroplasty (2 hips in LPFH group and 14 hips in non-LPFH group). The lesion size decreased after ESWT. However, the differences were statistically not significant (LPFH group, P = 0.091; non-LPFH group, P = 0.087). A significant reduction in bone marrow edema was observed after treatment (LPFH group, P = 0.007; non-LPFH group, P = 0.016). High-energy extracorporeal shock wave therapy resulted in considerable improvement in early stage ONFH, which can effectively relieve pain and improve the function of the hip.

  15. Study of early stages of amyloid Aβ13-23 formation using molecular dynamics simulation in implicit environments.

    PubMed

    Bajda, Marek; Filipek, Slawomir

    2015-06-01

    β-amyloid aggregation and formation of senile plaques is one of the hallmarks of Alzheimer's disease (AD). It leads to degeneration of neurons and decline of cognitive functions. The most aggregative and toxic form of β-amyloid is Aβ1-42 but in experiments, the shorter forms able to form aggregates are also used. The early stages of amyloid formation are of special interest due to the influence of this peptide on progression of AD. Here, we employed nine helices of undecapeptide Aβ13-23 and studied progress of amyloid formation using 500ns molecular dynamics simulation and implicit membrane environment. The small β-sheets emerged very early during simulation as separated two-strand structures and a presence of the membrane facilitated this process. Later, the larger β-sheets were formed. However, the ninth helix which did not form paired structure stayed unchanged till the end of MD simulation. Paired helix-helix interactions seemed to be a driving force of β-sheet formation at early stages of amyloid formation. Contrary, the specific interactions between α-helix and β-sheet can be very stable and be stabilized by the membrane.

  16. Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

    PubMed Central

    Chen, Ke-Zhong; Lou, Feng; Yang, Fan; Zhang, Jing-Bo; Ye, Hua; Chen, Wei; Guan, Tian; Zhao, Ming-Yu; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F.; Chen, Si-Yi; Wang, Jun

    2016-01-01

    Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC. PMID:27555497

  17. Nicotinamide inhibits the early stage of carcinogen-induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growth.

    PubMed

    Park, Soo Young; Lee, Kyoung Bun; Lee, Min-Jae; Bae, Suk-Chul; Jang, Ja-June

    2012-03-01

    Hepatocellular carcinoma (HCC) can cause severe complications, resulting in a high incidence of recurrence after treatment of the primary tumor. Recently, we have shown that nicotinamide effectively inhibits the growth and progression of bladder tumors by up-regulating RUNX3 and p300 expression. Therefore, in this study, the efficacy and inhibitory mechanisms of nicotinamide against HCC were investigated in mice and HCC cell lines, respectively. To evaluate the inhibitory effects of nicotinamide on HCC development, mice were injected with diethylnitrosamine (DEN) and simultaneously treated with 1% nicotinamide. Also, the effect of nicotinamide on human HCC cell lines was assessed by measuring caspase activity, cell proliferation, and DNA content using immunoblot analysis and reverse-transcriptase polymerase chain reaction. It was found that nicotinamide significantly inhibited the development of pre-neoplastic lesions (foci and adenomas) during the early stages of HCC. Furthermore, nicotinamide inhibited cell proliferation and induced mitochondria-mediated apoptosis in HCC cell lines. It also increased the expression of p21, and the expression and acetylation of p53. These results strongly suggest that nicotinamide inhibits the progression of early-stage HCC and may contribute to the induction of apoptosis and the inhibition of proliferation of HCC cells. Taken together, the results of this study indicate that nicotinamide is a potential chemopreventive agent, i.e., it may prevent the progression of early HCC development and/or the recurrence of HCC after primary treatment.

  18. A positron study on the microstructural evolution of Al-Li based alloys in the early stages of plastic deformation

    SciTech Connect

    Diego, N. de; Rio, J. del; Romero, R.; Somoza, A. |

    1997-11-01

    The formation of voids by coalescence of microvoids initiated at precipitates has been proposed to explain the fracture mechanisms in alloys containing a large number of second phase particles whereas in binary Al-Li alloys with shearable particles the brittleness could be linked with the grain boundary fracture. Most of the microstructure studies of Al-Li alloys have been performed by deforming to fracture; however, little is known about the processes and mechanisms involved in the early stages of plastic deformation. Butler et al. have studied a quaternary Al-Li alloy and have found that there is a critical effective strain to cause voiding, which is about 0.06 and 0.1% for the aged and for the solution treated material respectively. It is very well established that positrons are very sensitive to vacancy-like defects. With the aim of clarifying the behavior of Al-Li based alloys in the very early stages of deformation, and detecting the eventual formation of microvoids, the authors have studied the response of the positron lifetime parameters to the degrees of deformation in age-hardenable Al-Li based alloys plastically deformed under tensile stress.

  19. A Decade of Comparative Dose Planning Studies for Early-Stage Hodgkin Lymphoma: What Can We Learn?

    SciTech Connect

    Maraldo, Maja V.; Specht, Lena

    2014-12-01

    During the past 4 decades, the treatment of Hodgkin lymphoma has changed dramatically, and combined modality treatment is now considered the standard of care for patients with early-stage disease. However, the risk of late effects has led to concerns regarding the use of radiation therapy, especially in young patients with a long life expectancy. In this study, we review the current evidence for modern radiation therapy planning and delivery techniques in the treatment of early-stage Hodgkin lymphoma with a focus on a reduced delivered dose, a reduced irradiated volume, and a more conformal dose distribution. Although studies are difficult to compare because of differences in field technique, prescribed dose, target volumes, patient population, and reported dosimetric and plan evaluation parameters, modern radiation therapy significantly reduces exposure to normal tissues and thereby the estimated risk of late effects. However, there is no such thing as a single best modern delivery technique when multiple organs at risk are considered simultaneously because of the heterogeneity in patient anatomy and disease location, and the choice of radiation therapy technique should be made individually for each patient.

  20. Effects of Shiga toxin type 2 on maternal and fetal status in rats in the early stage of pregnancy.

    PubMed

    Sacerdoti, Flavia; Amaral, María M; Zotta, Elsa; Franchi, Ana M; Ibarra, Cristina

    2014-01-01

    Shiga toxin type 2 (Stx2), a toxin secreted by Shiga toxin-producing Escherichia coli (STEC), could be one of the causes of maternal and fetal morbimortality not yet investigated. In this study, we examined the effects of Stx2 in rats in the early stage of pregnancy. Sprague-Dawley pregnant rats were intraperitoneally (i.p.) injected with sublethal doses of Stx2, 0.25 and 0.5 ng Stx2/g of body weight (bwt), at day 8 of gestation (early postimplantation period of gestation). Maternal weight loss and food and water intake were analyzed after Stx2 injection. Another group of rats were euthanized and uteri were collected at different times to evaluate fetal status. Immunolocalization of Stx2 in uterus and maternal kidneys was analyzed by immunohistochemistry. The presence of Stx2 receptor (globotriaosylceramide, Gb3) in the uteroplacental unit was observed by thin layer chromatography (TLC). Sublethal doses of Stx2 in rats caused maternal weight loss and pregnancy loss. Stx2 and Gb3 receptor were localized in decidual tissues. Stx2 was also immunolocalized in renal tissues. Our results demonstrate that Stx2 leads to pregnancy loss and maternal morbidity in rats in the early stage of pregnancy. This study highlights the possibility of human pregnancy loss and maternal morbidity mediated by Stx2.

  1. Genome-Scale Transcriptomic Insights into Early-Stage Fruit Development in Woodland Strawberry Fragaria vesca[C][W

    PubMed Central

    Kang, Chunying; Darwish, Omar; Geretz, Aviva; Shahan, Rachel; Alkharouf, Nadim; Liu, Zhongchi

    2013-01-01

    Fragaria vesca, a diploid woodland strawberry with a small and sequenced genome, is an excellent model for studying fruit development. The strawberry fruit is unique in that the edible flesh is actually enlarged receptacle tissue. The true fruit are the numerous dry achenes dotting the receptacle’s surface. Auxin produced from the achene is essential for the receptacle fruit set, a paradigm for studying crosstalk between hormone signaling and development. To investigate the molecular mechanism underlying strawberry fruit set, next-generation sequencing was employed to profile early-stage fruit development with five fruit tissue types and five developmental stages from floral anthesis to enlarged fruits. This two-dimensional data set provides a systems-level view of molecular events with precise spatial and temporal resolution. The data suggest that the endosperm and seed coat may play a more prominent role than the embryo in auxin and gibberellin biosynthesis for fruit set. A model is proposed to illustrate how hormonal signals produced in the endosperm and seed coat coordinate seed, ovary wall, and receptacle fruit development. The comprehensive fruit transcriptome data set provides a wealth of genomic resources for the strawberry and Rosaceae communities as well as unprecedented molecular insight into fruit set and early stage fruit development. PMID:23898027

  2. Involvement of the T-box transcription factor Brachyury in early-stage embryonic mouse salivary gland.

    PubMed

    Hayashi, Kouhei; Ikari, Tatsuya; Sugiyama, Goro; Sugiura, Tsuyoshi; Ohyama, Yukiko; Kumamaru, Wataru; Shirasuna, Kanemitsu; Mori, Yoshihide

    2016-09-01

    The mouse submandibular gland (SMG) is important organ for embryonic development, and branching morphogenesis is regulated by many molecules containing transcription factors. Real-time reverse transcriptase polymerase chain reaction revealed that the expression of Brachyury increased in the SMG and peaked between E12.5-E13.5, concomitant with the early stage of branching morphogenesis. The expression of Brachyury in SMG rudiments between E12.5-E13.5 was confirmed by western blotting. In addition, fibronectin and Btbd7 (regulated by fibronectin), which are both essential for cleft formation, were expressed strongly during the same period. The Sox2 and Wnt3a, which regulate cell growth, were also expressed strongly during E12.5-E13.5. On the other hand, cleft formation and branching morphogenesis was suppressed by knockdown of Brachyury gene, suggesting that Brachyury plays a central role in regulating cell growth and cleft formation in early-stage embryonic mouse salivary gland development. PMID:27369076

  3. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  4. BEST: a novel computational approach for comparing gene expression patterns from early stages of Drosophila melanogaster development.

    PubMed

    Kumar, Sudhir; Jayaraman, Karthik; Panchanathan, Sethuraman; Gurunathan, Rajalakshmi; Marti-Subirana, Ana; Newfeld, Stuart J

    2002-12-01

    Embryonic gene expression patterns are an indispensable part of modern developmental biology. Currently, investigators must visually inspect numerous images containing embryonic expression patterns to identify spatially similar patterns for inferring potential genetic interactions. The lack of a computational approach to identify pattern similarities is an impediment to advancement in developmental biology research because of the rapidly increasing amount of available embryonic gene expression data. Therefore, we have developed computational approaches to automate the comparison of gene expression patterns contained in images of early stage Drosophila melanogaster embryos (prior to the beginning of germ-band elongation); similarities and differences in gene expression patterns in these early stages have extensive developmental effects. Here we describe a basic expression search tool (BEST) to retrieve best matching expression patterns for a given query expression pattern and a computational device for gene interaction inference using gene expression pattern images and information on the associated genotypes and probes. Analysis of a prototype collection of Drosophila gene expression pattern images is presented to demonstrate the utility of these methods in identifying biologically meaningful matches and inferring gene interactions by direct image content analysis. In particular, the use of BEST searches for gene expression patterns is akin to that of BLAST searches for finding similar sequences. These computational developmental biology methodologies are likely to make the great wealth of embryonic gene expression pattern data easily accessible and to accelerate the discovery of developmental networks.

  5. [Effects of the association of sulbutiamine with an acetylcholinesterase inhibitor in early stage and moderate Alzheimer disease].

    PubMed

    Ollat, H; Laurent, B; Bakchine, S; Michel, B-F; Touchon, J; Dubois, B

    2007-01-01

    The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs. PMID:17675917

  6. Transmissible Plasmid Containing Salmonella enterica Heidelberg Isolates Modulate Cytokine Production During Early Stage of Interaction with Intestinal Epithelial Cells.

    PubMed

    Gokulan, Kuppan; Khare, Sangeeta; Williams, Katherine; Foley, Steven L

    2016-08-01

    The variation in cytokine production during bacterial invasion of human intestinal epithelial cells (IECs) is a contributing factor for progression of the infection. A few Salmonella enterica Heidelberg strains isolated from poultry products harbor transmissible plasmids (TPs), including those that encode a type-IV secretion system. Earlier, we showed that these TPs are responsible for increased virulence during infection. This study examines the potential role of these TPs in cytokine production in IECs. This study showed that S. Heidelberg strains containing TPs (we refer as virulent strains) caused decreased interleukin (IL)-10 production in IECs after 1 h infection. The virulent strains induced a high level of tumor necrosis factor-α production under identical conditions. The virulent strains of S. Heidelberg also altered the production of IL-2, IL-17, and granulocyte macrophage colony-stimulating factor compared to an avirulent strain. As a part of infection, bacteria cross the epithelial barrier and encounter intestinal macrophages. Hence, we examined the cytotoxic mechanism of strains of S. Heidelberg in macrophages. Scanning electron microscopy showed cell necrosis occurs during the early stage of infection. In conclusion, virulent S. Heidelberg strains were able to modify the host cytokine profile during the early stages of infection and also caused necrosis in macrophages.

  7. State of the art in surgery for early stage NSCLC-does the number of resected lymph nodes matter?

    PubMed

    Vielva, Laura Romero; Jaen, Manuel Wong; Alcácer, José A Maestre; Cardona, Mecedes Canela

    2014-04-01

    Surgery is the treatment of choice in patients with early stage NSCLC. However, the results remain poor in these patients. Lymph node involvement is the main prognostic factor in patients with NSCLC, but there is still no clear definition of the number of nodes required to consider a lymphadenectomy as complete. Although there is no defined minimum number of lymph nodes required for a complete lymphadenectomy, there are some recommendations to perform this procedure, published by different scientific societies. Current practice in thoracic surgery regarding lymphadenectomy, differs on some points from the guidelines recommendations, with data regarding patients with no mediastinal assessment between 30-45% according to some of the published data. Different studies have probed the fact that the probability of finding a positive node increases with the number of lymph nodes analyzed. Therefore, a complete lymphadenectomy provides proper staging, which helps to identify the patient's real prognosis. Several nonrandomized studies and retrospective series have shown that survival increases in the group of patients with a higher number of lymph nodes removed. There is no contraindication to performing a complete lymphadenectomy. The increase in survival in patients with a complete lymphadenectomy may be due to more accurate staging. Therefore, complete lymphadenectomy should be mandatory even in early stage patients.

  8. Chloroplast Hsp93 Directly Binds to Transit Peptides at an Early Stage of the Preprotein Import Process.

    PubMed

    Huang, Po-Kai; Chan, Po-Ting; Su, Pai-Hsiang; Chen, Lih-Jen; Li, Hsou-min

    2016-02-01

    Three stromal chaperone ATPases, cpHsc70, Hsp90C, and Hsp93, are present in the chloroplast translocon, but none has been shown to directly bind preproteins in vivo during import, so it remains unclear whether any function as a preprotein-translocating motor and whether they have different functions during the import process. Here, using protein crosslinking followed by ionic detergent solubilization, we show that Hsp93 directly binds to the transit peptides of various preproteins undergoing active import into chloroplasts. Hsp93 also binds to the mature region of a preprotein. A time course study of import, followed by coimmunoprecipitation experiments, confirmed that Hsp93 is present in the same complexes as preproteins at an early stage when preproteins are being processed to the mature size. In contrast, cpHsc70 is present in the same complexes as preproteins at both the early stage and a later stage after the transit peptide has been removed, suggesting that cpHsc70, but not Hsp93, is important in translocating processed mature proteins across the envelope. PMID:26676256

  9. lncRNA profiling in early-stage chronic lymphocytic leukemia identifies transcriptional fingerprints with relevance in clinical outcome.

    PubMed

    Ronchetti, D; Manzoni, M; Agnelli, L; Vinci, C; Fabris, S; Cutrona, G; Matis, S; Colombo, M; Galletti, S; Taiana, E; Recchia, A G; Bossio, S; Gentile, M; Musolino, C; Di Raimondo, F; Grilli, A; Bicciato, S; Cortelezzi, A; Tassone, P; Morabito, F; Ferrarini, M; Neri, A

    2016-01-01

    Long non-coding RNAs (lncRNAs) represent a novel class of functional RNA molecules with an important emerging role in cancer. To elucidate their potential pathogenetic role in chronic lymphocytic leukemia (CLL), a biologically and clinically heterogeneous neoplasia, we investigated lncRNAs expression in a prospective series of 217 early-stage Binet A CLL patients and 26 different subpopulations of normal B-cells, through a custom annotation pipeline of microarray data. Our study identified a 24-lncRNA-signature specifically deregulated in CLL compared with the normal B-cell counterpart. Importantly, this classifier was validated on an independent data set of CLL samples. Belonging to the lncRNA signature characterizing distinct molecular CLL subgroups, we identified lncRNAs recurrently associated with adverse prognostic markers, such as unmutated IGHV status, CD38 expression, 11q and 17p deletions, and NOTCH1 mutations. In addition, correlation analyses predicted a putative lncRNAs interplay with genes and miRNAs expression. Finally, we generated a 2-lncRNA independent risk model, based on lnc-IRF2-3 and lnc-KIAA1755-4 expression, able to distinguish three different prognostic groups in our series of early-stage patients. Overall, our study provides an important resource for future studies on the functions of lncRNAs in CLL, and contributes to the discovery of novel molecular markers with clinical relevance associated with the disease. PMID:27611921

  10. Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT

    SciTech Connect

    Xu, Hanwen; Pirisi, Lucia; Creek, Kim E.

    2015-01-01

    Previous studies in our laboratory discovered that SIX1 mRNA expression increased during in vitro progression of HPV16-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. In this study, we explored the role of Six1 at early stages of HPV16-mediated transformation by overexpressing Six1 in HKc/HPV16. We found that Six1 overexpression in HKc/HPV16 increased cell proliferation and promoted cell migration and invasion by inducing epithelial–mesenchymal transition (EMT). Moreover, the overexpression of Six1 in HKc/HPV16 resulted in resistance to serum and calcium-induced differentiation, which is the hallmark of the HKc/DR phenotype. Activation of MAPK in HKc/HPV16 overexpressing Six1 is linked to resistance to calcium-induced differentiation. In conclusion, this study determined that Six1 overexpression resulted in differentiation resistance and promoted EMT at early stages of HPV16-mediated transformation of human keratinocytes. - Highlights: • Six1 expression increases during HPV16-mediated transformation. • Six1 overexpression causes differentiation resistance in HPV16-immortalized cells. • Six1 overexpression in HPV16-immortalized keratinocytes activates MAPK. • Activation of MAPK promotes EMT and differentiation resistance. • Six1 overexpression reduces Smad-dependent TGF-β signaling.

  11. Telomere length of tumor tissues and survival in patients with early stage non-small cell lung cancer.

    PubMed

    Jeon, Hyo-Sung; Choi, Yi Young; Choi, Jin Eun; Lee, Won Kee; Lee, Eungbae; Yoo, Seung Soo; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2014-04-01

    Telomere shortening leads to genomic instability that drives oncogenesis through the activation of telomerase and the generation of other mutations necessary for tumor progression. This study was conducted to determine the impact of telomere shortening on the survival of patients with early stage non-small cell lung cancer (NSCLC). Relative telomere length in tumor tissues was measured by quantitative polymerase chain reaction in 164 patients with surgically resected NSCLC. The association between telomere length and overall survival (OS) and disease-free survival (DFS) was analyzed. When the patients were categorized into quartiles based on telomere length, those patients with the 1st quartile (shortest) of telomere length had a significantly worse OS and DFS compared to patients with the 2nd to the 4th quartiles of telomere length (adjusted hazard ratio for OS = 2.67, 95% confidence interval = 1.50-4.75, P = 0.001; and adjusted hazard ratio for DFS = 1.92, 95% confidence interval = 1.17-3.14, P = 0.01). An association between telomere length and survival outcome was more pronounced in squamous cell carcinomas than adenocarcinomas (P-value of test for homogeneity for OS and DFS = 0.05 and 0.02, respectively). Telomere length of tumor tissues is an independent prognostic factor in patients with surgically resected early stage NSCLC.

  12. Non-pharmacological Interventions for Adults with Mild Cognitive Impairment and Early Stage Dementia: An Updated Scoping Review

    PubMed Central

    Rodakowski, Juleen; Saghafi, Ester; Butters, Meryl A.; Skidmore, Elizabeth R.

    2015-01-01

    The purpose of this scoping review was to examine the science related to non-pharmacological interventions designed to slow decline for older adults with Mild Cognitive Impairment or early-stage dementia. We reviewed 32 unique randomized controlled trials that employed cognitive training (remediation or compensation approaches), physical exercise, or psychotherapeutic interventions that were published before November 2014. Evidence suggests that cognitive training focused on remediation and physical exercise interventions may promote small improvements in selected cognitive abilities. Cognitive training focused on compensation interventions and selected psychotherapeutic interventions may influence how cognitive changes impact daily living. However, confidence in these findings is limited due methodological limitations. To better assess the value of non-pharmacological interventions for this population, we recommend: 1) adoption of universal criteria for “early stage cognitive decline” among studies, 2) adherence to guidelines for the conceptualization, operationalization, and implementation of complex interventions, 3) consistent characterization of the impact of interventions on daily life, and 3) long-term follow-up of clinical outcomes to assess maintenance and meaningfulness of reported effects over time. PMID:26070444

  13. Investigation of robotic-assisted tilt-table therapy for early-stage spinal cord injury rehabilitation.

    PubMed

    Craven, Colm T D; Gollee, Henrik; Coupaud, Sylvie; Purcell, Mariel A; Allan, David B

    2013-01-01

    Damage to the spinal cord compromises motor function and sensation below the level of injury, resulting in paralysis and progressive secondary health complications. Inactivity and reduced energy requirements result in reduced cardiopulmonary fitness and an increased risk of coronary heart disease and cardiovascular complications. These risks may be minimized through regular physical activity. It is proposed that such activity should begin at the earliest possible time point after injury, before extensive neuromuscular degeneration has occurred. Robotic-assisted tilt-table therapy may be used during early-stage spinal cord injury (SCI) to facilitate stepping training, before orthostatic stability has been achieved. This study investigates whether such a stimulus may be used to maintain pulmonary and coronary health by descri