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Sample records for early-stage grade 1-2

  1. Long-term outcome and mortality trends in early-stage, Grade 1-2 follicular lymphoma treated with radiation therapy

    SciTech Connect

    Guadagnolo, Beverly A.; Neuberg, Donna; Ng, Andrea; Mauch, Peter

    2006-03-01

    Purpose: To analyze long-term outcomes and causes of death in patients receiving radiation therapy (RT) for localized, low-grade follicular lymphoma. Methods and Materials: Between 1972 and 2000, 106 patients with Stage I-II, Grade 1-2 follicular lymphoma received RT alone or radiation and chemotherapy (RT/CT). Seventy-four percent had Stage I, and 26% had Stage II disease. Seventy-six percent received RT alone, and 24% received combined RT/CT. Second malignancy rates were compared with an age- and sex-matched population. Results: Median follow-up was 12 years. Median survival time was 19 years. The 5-, 10-, and 15-year overall survival (OS) rates were 93%, 75%, and 62%, respectively. Age {>=}60 was the only significant adverse prognostic factor with respect to OS. There were 35 deaths, 20 of which were attributable to lymphoma. Freedom from treatment failure (FFTF) rates at 5, 10, and 15 years were 72%, 46%, and 39%, respectively. Forty-seven patients (48%) relapsed. Tumor size >3 cm was the only significant adverse factor for FFTF. Observed incidence of second malignancy did not significantly exceed expected incidence. Conclusions: Although patients with early-stage, low-grade follicular lymphoma have long median survival, the leading cause of death remains lymphoma. However, patients receiving RT do not have significantly elevated cumulative incidence of second malignancy.

  2. Effect of Spirogyra neglecta on the early stages of 1, 2-dimethylhydrazine-induced colon carcinogenesis in rats.

    PubMed

    Taya, Sirinya; Thumvijit, Tarika; Chewonarin, Teera; Punvittayagul, Charatda; Wongpoomchai, Rawiwan

    2016-12-06

    This study focused on the chemopreventive effects of Spirogyra neglecta extract (SNE) and dried S. neglecta mixed diet on the early stages of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. Male Wistar rats were injected with DMH to initiate aberrant crypt foci (ACF) formation. In the initiation stage, SNE significantly decreased the number of ACF in the colon of DMH-treated rats. Rats that received a low dose of SNE showed enhanced activity of several detoxifying and antioxidant enzymes. In the postinitiation stage, a low dose of SNE significantly decreased the number of ACF in the colon of DMH-treated rats. It significantly reduced the number of proliferating cell nuclear antigen-positive cells and increased the number of apoptotic cells in colonic crypts. S. neglecta thus inhibited the development of the early stages of DMH-induced colon carcinogenesis in rats by modulation of xenobiotic metabolizing enzymes and inhibition of cell proliferation as well as induction of apoptosis.

  3. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

    PubMed Central

    Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    Objectives This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. Methods The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Results Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Conclusions Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification. PMID:27861522

  4. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk.

    PubMed

    Huang, Bangxing; Cai, Jing; Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification.

  5. Ovarian Conservation and Overall Survival in Young Women With Early-Stage Low-Grade Endometrial Cancer.

    PubMed

    Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D

    2016-10-01

    To characterize contributing factors for ovarian conservation during surgical treatment for endometrial cancer and to examine the association of ovarian conservation on survival of young women with early-stage, low-grade tumors. This was a population-based study using the Surveillance, Epidemiology, and End Results program to identify surgically treated stage I type I (grade 1-2 endometrioid histology) endometrial cancer cases diagnosed between 1983 and 2012 (N=86,005). Multivariable models were used to identify independent factors for ovarian conservation. Survival outcomes and cause of death were examined for women aged younger than 50 with stage I type I endometrial cancer who underwent ovarian conservation (1,242 among 12,860 women [9.7%]). On multivariable analysis, age younger than 50 years, grade 1 endometrioid histology, and tumor size 2.0 cm or less were noted to be independent factors for ovarian conservation (all, P<.001). For 9,110 women aged younger than 50 years with stage I grade 1 tumors, cause-specific survival was similar between ovarian conservation and oophorectomy cases (20-year rates 98.9% compared with 97.7%, P=.31), whereas overall survival was significantly higher in ovarian conservation cases than oophorectomy cases (88.8% compared with 82.0%, P=.011). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.73, 95% confidence interval [CI] 0.54-0.98, P=.036) and was independently associated with a lower cumulative risk of death resulting from cardiovascular disease compared with oophorectomy (20-year rates, 2.3% compared with 3.7%, adjusted hazard ratio 0.40, 95% CI 0.17-0.91, P=.029). Contrary, cause-specific survival (20-year rates 94.6% compared with 96.1%, P=.68) and overall survival (81.0% compared with 80.6%, P=.91) were similar between ovarian conservation and oophorectomy among 3,750 women aged younger than 50 years with stage I grade 2 tumors

  6. Antioxidant response at early stages and low grades of simple coal worker's pneumoconiosis diagnosed by high resolution computed tomography.

    PubMed

    Altin, Remzi; Armutcu, Ferah; Kart, Levent; Gurel, Ahmet; Savranlar, Ahmet; Ozdemir, Hüiseyin

    2004-10-01

    In miners exposed to coal dusts, coal worker's pneumoconiosis (CWP) can occur. The purpose of the present study is to better understand the relations between coal dust exposure and activities of blood plasma antioxidant enzymes, namely, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation end product malondialdehyde (MDA) concentration in coal workers with early and low grade simple CWP diagnosed by high resolution computed tomography (HRCT). Forty-three coal workers who had profusions of 0/1-2/2 according to ILO 1980 chest X-ray (CXR) classification, 43 coal workers without CWP (control group 1) and 44 healthy subjects (control group 2) who were randomly selected from the population register or recruited from the hospital staff were enrolled. Coal workers were reevaluated by HRCT (Hosoda-Shida classification) due to its higher sensitivity than standard CXR. Then, blood plasma SOD and GSH-Px activities and MDA plasma levels were measured. CWP was found positive in 46 of 89 coal workers by HRCT evaluation. Profusion 0 (P0, CWP not present), profusion 1 (P1, early CWP) and profusion 2 (P2, low grade CWP) were found in 43, 23 and 19 of patients found to have CWP by HRCT, respectively. We had no worker with profusion 3 (P3). Complicated CWP was shown in four of 46 patients and thesecases were excluded as the study was restricted to early and low-grade pneumoconiosis. In respect to the plasma levels of MDA and plasma activities of SOD and GSH-Px, statistically significant differences were found between CWP cases and control groups (p < 0.01, p < 0.01, p < 0.001 respectively). Statistical differences were also obtained for the plasma activities of SOD and GSH-Px and levels of MDA in relation to HRCT profusions (p < 0.05). In conclusion, these findings suggest an oxidative stress due to increased free radicals and reactive oxygen metabolite production in early stages and low grades of simple CWP diagnosed by HRCT.

  7. Metabolomic serum profiling detects early-stage high-grade serous ovarian cancer in a mouse model.

    PubMed

    Jones, Christina M; Monge, María Eugenia; Kim, Jaeyeon; Matzuk, Martin M; Fernández, Facundo M

    2015-02-06

    Ovarian cancer is a deadly disease killing more than any other gynecologic cancer. Nonspecific symptoms, combined with a lack of early detection methods, contribute to late diagnosis and low five-year survival rates. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype that results in 90% of ovarian cancer deaths. To investigate metabolic patterns for early detection of this deadly ovarian cancer, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic HGSC observed in women were studied. Using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), serum samples from 14 early-stage tumor (ET) DKO mice and 11 controls were analyzed in depth to screen for metabolic signatures capable of differentiating early-stage HGSC from controls. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for classification. Altered metabolic pathways reflected in that panel included those of fatty acids, bile acids, glycerophospholipids, peptides, and some dietary phytochemicals. These alterations revealed impacts to cellular energy storage and membrane stability, as well as changes in defenses against oxidative stress, shedding new light on the metabolic alterations associated with early ovarian cancer stages.

  8. 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. PMID:27785367

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

    PubMed

    Theelen, Willemijn Sme; 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, J L; van Noesel, Carel J; Bernards, René; van den Heuvel, Michel M

    2016-10-01

    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.

  10. 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

  11. Clinical investigation survival prediction in high-grade gliomas by MRI perfusion before and during early stage of RT

    SciTech Connect

    Cao Yue . E-mail: yuecao@med.umich.edu; Tsien, Christina I.; Nagesh, Vijaya; Junck, Larry; Haken, Randall ten; Ross, Brian D.; Chenevert, Thomas L.; Lawrence, Theodore S.

    2006-03-01

    Purpose: To determine whether cerebral blood volume (CBV) and cerebral blood flow can predict the response of high-grade gliomas to radiotherapy (RT) by taking into account spatial heterogeneity and temporal changes in perfusion. Methods and Materials: Twenty-three patients with high-grade gliomas underwent conformal RT, with magnetic resonance imaging perfusion before and at Weeks 1-2 and 3-4 during RT. Tumor perfusion was classified as high, medium, or low. The prognostic values of pre-RT perfusion and the changes during RT for early prediction of tumor response to RT were evaluated. Results: The fractional high-CBV tumor volume before RT and the fluid-attenuated inversion recovery imaging tumor volume were identified as predictors for survival (p = 0.01). Changes in tumor CBV during the early treatment course also predicted for survival. Better survival was predicted by a decrease in the fractional low-CBV tumor volume at Week 1 of RT vs. before RT, a decrease in the fractional high-CBV tumor volume at Week 3 vs. Week 1 of RT, and a smaller pre-RT fluid-attenuated inversion recovery imaging tumor volume (p = 0.01). Conclusion: Early temporal changes during RT in heterogeneous regions of high and low perfusion in gliomas might predict for different physiologic responses to RT. This might also open the opportunity to identify tumor subvolumes that are radioresistant and might benefit from intensified RT.

  12. Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

    PubMed

    Scrima, Marianna; Zito Marino, Federica; Oliveira, Duarte Mendes; Marinaro, Cinzia; La Mantia, Elvira; Rocco, Gaetano; De Marco, Carmela; Malanga, Donatella; De Rosa, Nicla; Rizzuto, Antonia; Botti, Gerardo; Franco, Renato; Zoppoli, Pietro; Viglietto, Giuseppe

    2017-01-01

    Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease.

  13. Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients

    PubMed Central

    Scrima, Marianna; Zito Marino, Federica; Oliveira, Duarte Mendes; Marinaro, Cinzia; La Mantia, Elvira; Rocco, Gaetano; De Marco, Carmela; Malanga, Donatella; De Rosa, Nicla; Rizzuto, Antonia; Botti, Gerardo; Franco, Renato; Zoppoli, Pietro; Viglietto, Giuseppe

    2017-01-01

    Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease. PMID:28243327

  14. Respective Prognostic Value of Genomic Grade and Histological Proliferation Markers in Early Stage (pN0) Breast Carcinoma

    PubMed Central

    Reyal, Fabien; Bollet, Marc A.; Caly, Martial; Gentien, David; Carpentier, Sabrina; Peyro-Saint-Paul, Hélène; Pierga, Jean-Yves; Cottu, Paul; Dieras, Véronique; Sigal-Zafrani, Brigitte; Vincent-Salomon, Anne; Sastre-Garau, Xavier

    2012-01-01

    Background Genomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score. Methods A series of 163 consecutive breast cancers was retained (pT1–2, pN0, pM0, 10-yr follow-up). GG was computed using MapQuant Dx(R). Results GG was low (GG-1) in 48%, high (GG-3) in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2− tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02). Conclusions In a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i) the relatively close prognostic values of GG and Ki67, (ii) the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii) the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma. PMID:22529987

  15. Early Stage W.H.O. Grade I and II Follicular Lymphoma Treated with Radiation Therapy Alone

    PubMed Central

    Ahmed, Naseer; Owen, Timothy E.; Rubinger, Morel; Williams, Gaynor; Nugent, Zoann; Ahmed, Shahida; Cooke, Andrew

    2013-01-01

    Objectives This retrospective study was undertaken to evaluate the outcome of patients with stage I or II (limited stage), grade I–II follicular non-Hodgkin’s lymphoma (FL) treated with radiation therapy (RT) alone as initial management. Methods Patients with stage I or II and pathologically confirmed WHO grade I or II FL treated initially with RT alone between 1982 and 2008 were identified from a population based cancer registry. Results Forty patients with a mean age 61.3 years at diagnosis were identified. The median follow up was 6.9 years from the end of radiation therapy. Stage was I (n = 26) and II (n = 14). None had B symptoms. The Follicular Lymphoma International Prognostic Index (FLIPI) was low risk in 26 patients and intermediate risk in 5. Doses ranged from 15 Gy to 48 Gy, with a median dose of 35 Gy. All patients achieved a complete clinical response (CR). 5 and 10 year overall survival (OS) was 86% and 59%, progression free survival (PFS) 67% and 54%. Age ≥60 at diagnosis was associated with reduced OS, p = 0.029, but did not affect PFS. No other clinical features including grade or FLIPI were significant for outcomes. Local failure was uncommon occurring in 8% (3/40) although this was 21% (3/14) of all recurrences. Conclusions OS and PFS outcomes for radiation alone in limited stage low grade FL patients from this single institution study are consistent with previously published data. No predictors were prognostic for PFS. A dose of ≤35 Gy may be appropriate. In this highly selected homogeneous group the FLIPI loses discriminating ability. Local control is excellent, and a majority of patients are free of disease after 5 years. PMID:23762303

  16. TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer.

    PubMed

    Chien, Jeremy; Sicotte, Hugues; Fan, Jian-Bing; Humphray, Sean; Cunningham, Julie M; Kalli, Kimberly R; Oberg, Ann L; Hart, Steven N; Li, Ying; Davila, Jaime I; Baheti, Saurabh; Wang, Chen; Dietmann, Sabine; Atkinson, Elizabeth J; Asmann, Yan W; Bell, Debra A; Ota, Takayo; Tarabishy, Yaman; Kuang, Rui; Bibikova, Marina; Cheetham, R Keira; Grocock, Russell J; Swisher, Elizabeth M; Peden, John; Bentley, David; Kocher, Jean-Pierre A; Kaufmann, Scott H; Hartmann, Lynn C; Shridhar, Viji; Goode, Ellen L

    2015-08-18

    To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC.

  17. Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

    PubMed Central

    Risinger, John I.; Allard, Jay; Chandran, Uma; Day, Roger; Chandramouli, Gadisetti V. R.; Miller, Caela; Zahn, Christopher; Oliver, Julie; Litzi, Tracy; Marcus, Charlotte; Dubil, Elizabeth; Byrd, Kevin; Cassablanca, Yovanni; Becich, Michael; Berchuck, Andrew; Darcy, Kathleen M.; Hamilton, Chad A.; Conrads, Thomas P.; Maxwell, G. Larry

    2013-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis. PMID:23785665

  18. Early stage colon cancer.

    PubMed

    Freeman, Hugh James

    2013-12-14

    Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care.

  19. 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

  20. 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

    Kawagoe, Naoyuki; Kano, Osamu; Kijima, Sho; Tanaka, Hideki; Takayanagi, Masaaki; Urita, Yoshihisa

    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.

  1. SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading.

    PubMed

    Pityński, Kazimierz; Banas, Tomasz; Pietrus, Milosz; Milian-Ciesielska, Katarzyna; Ludwin, Artur; Okon, Krzysztof

    2015-01-01

    Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.

  2. 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…

  3. 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),…

  4. 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…

  5. Impact of histology and surgical approach on survival among women with early-stage, high-grade uterine cancer: An NRG Oncology/Gynecologic Oncology Group ancillary analysis ✩

    PubMed Central

    Fader, Amanda N.; Java, James; Tenney, Meaghan; Ricci, Stephanie; Gunderson, Camille C.; Temkin, Sarah M.; Spirtos, Nick; Kushnir, Christina L.; Pearl, Michael L.; Zivanovic, Oliver; Tewari, Krishnansu S.; O'Malley, David; Hartenbach, Ellen M.; Hamilton, Chad A.; Gould, Natalie S.; Mannel, Robert S.; Rodgers, William; Walker, Joan L.

    2016-01-01

    Objectives We sought to analyze the clinicopathologic features, recurrence patterns and survival outcomes of women with high-grade uterine cancer (UC) enrolled on The Gynecologic Oncology Group (GOG) LAP2 trial. Methods This is a post-hoc analysis of LAP-2 patients with grade 3 endometrioid adenocarcinoma (ENDO), uterine serous (USC), clear cell (CC) and carcinosarcoma (CS). Demographics, clinicopathologic features, and recurrence patterns, were compared by histology and surgical approach. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results Of the 2600 patients enrolled in LAP-2, 753 patients had high-grade UC: 350 had ENDO, 289 had USC, 42 had CC and 72 had CS. Compared with the ENDO cohort, those with other high-grade subtypes were older (p < 0.001) and were more likely to have positive peritoneal cytology (p < 0.001), positive lymph nodes (p = 0.05) and higher disease stage on final pathology (p < 0.001). With a median follow-up time of 60 months, compared to patients with ENDO, those with USC, CCC and CS subtypes had higher recurrence rates (p < 0.001), extra-pelvic recurrences (p < 0.001) and poorer PFS (p < 0.001) and OS (p < 0.001). Those diagnosed with USC and CS experienced the worst survival outcomes (p = 0.003). Patterns of recurrence and survival were not different in those staged with LSC vs LAP. On multivariable analysis, age, stage, pelvic washings and Type II histology were independently and adversely associated with survival. Conclusions Women with apparent early-stage, USC and CS histologies have poorer outcomes than women with grade 3 endometrioid adenocarcinoma. Patterns of recurrence and survival were not impacted by surgical approach. PMID:27743738

  6. Outcomes after involved-field radiation therapy (IFRT) with or without rituximab in patients with early-stage low-grade non-Hodgkin lymphoma (NHL) staged with CT and PET.

    PubMed

    Lukens, John N; Nasta, Sunita D; Fram, Brianna; Glatstein, Eli; Plastaras, John P

    2014-02-01

    We evaluated whether staging with positron emission tomography (PET) or treatment with rituximab after involved-field radiation therapy (IFRT) results in an improved progression-free survival (PFS) for early-stage indolent non-Hodgkin lymphoma (NHL). We identified 42 patients with stage I/II low-grade NHL treated with initial IFRT at our institution between 1992 and 2009, who had been staged with computed tomography (CT) or PET. A retrospective analysis was performed to evaluate PFS according to staging by CT or PET, and by receipt of rituximab after IFRT. Overall PFS was 68% and 61% at 5 and 10 years, respectively. There was no significant difference in PFS whether patients were staged by CT (n=17) or by PET (n=25), with 5-year PFS rates of 76% and 60%, respectively. Eleven patients received 4 weekly doses of rituximab after IFRT, with no improvement in 5-year PFS: 46% for rituximab-treated patients versus 72% for patients who were not given rituximab. However, more patients who were given rituximab were stage II. Patients with limited stage indolent NHL staged with either CT or PET and treated with IFRT have favorable PFS compared with historical controls. The administration of 4 weekly doses of rituximab after IFRT did not improve PFS in these patients. The use of rituximab in this setting should be evaluated in a randomized prospective study.

  7. 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)

  8. 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.

  9. DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer

    DTIC Science & Technology

    2015-08-01

    AWARD NUMBER: W81XWH-14-1-0194 TITLE: DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER DNA Copy Number Signature to Predict Recurrence in Early Stage Ovarian Cancer 5b. GRANT NUMBER W81XWH-14-1-0194 5c...tasks Major Task 1: Obtain DNA samples from consortium specimens • Subtask 1 Pathological review of 592 early-stage high-grade ovarian cancer specimens

  10. 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…

  11. 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…

  12. Vowel Diphthongs. Fun with Phonics! Book 10. Grades 1-2.

    ERIC Educational Resources Information Center

    Daniel, Claire

    This book provides hands-on activities for grades 1-2 that make phonics instruction easy and fun for teachers and children in the classroom. The book offers methods for practice, reinforcement, and assessment of phonics skills. A poem is used to introduce the phonics element of this book, vowel diphthongs. The poem is duplicated so children can…

  13. Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

    PubMed

    Herst, J; Crump, M; Baldassarre, F G; MacEachern, J; Sussman, J; Hodgson, D; Cheung, M C

    2017-01-01

    In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: 'Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma'; 'The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival'. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients' point of view. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  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. Food-grade antimicrobials potentiate the antibacterial activity of 1,2-hexanediol.

    PubMed

    Yogiara; Hwang, S J; Park, S; Hwang, J-K; Pan, J-G

    2015-05-01

    Preservative agents determining the shelf life of cosmetic products must have effective antimicrobial activity while meeting safety requirements for topical use. In this study, we determined the antimicrobial activity of 1,2-hexanediol against several Gram-positive and Gram-negative bacteria. Antimicrobial susceptibility tests have shown that 1,2-hexanediol exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria with MICs of 0·5-2% (v/v). The bactericidal concentration of 1,2-hexanediol was ranging from 1 to 2 × MIC as demonstrated by time-kill curve assay. A membrane depolarization assay showed that 1,2-hexanediol disrupted the cytoplasmic membrane potential. A checkerboard assay indicated that the effective concentration of 1,2-hexanediol was reduced up to 0·25-0·5 × MIC when combined with macelignan and octyl gallate against Gram-positive bacteria. However, this combination was not effective against Gram-negative bacteria. A turbidity reduction assay demonstrated that the combination of a high concentration of 1,2-hexanediol with food-grade antimicrobial compounds could trigger lytic activity towards Bacillus cereus cells. The remaining cell turbidity was 24·6 and 22·2% when 2% of 1,2-hexanediol was combined with 8 mg l(-1) octyl gallate or with 32 mg l(-1) macelignan respectively. This study showed that food-grade antimicrobial compounds may be used in combination with 1,2-hexanediol to increase its efficacy as a preservative agent in cosmetics. The antimicrobial activity of 1,2-hexanediol against Gram-positive and Gram-negative bacteria was potentiated with food-grade antimicrobials including xanthorrhizol, macelignan, panduratin A and octyl gallate, which have already been reported to display anti-inflammatory and other beneficial activities related to cosmetics. Therefore, the combination of 1,2-hexanediol and these food-grade antimicrobial agents would have benefits not only for increasing the antimicrobial activity

  16. Stereotactic body radiation therapy for inoperable early stage lung cancer.

    PubMed

    Timmerman, Robert; Paulus, Rebecca; Galvin, James; Michalski, Jeffrey; Straube, William; Bradley, Jeffrey; Fakiris, Achilles; Bezjak, Andrea; Videtic, Gregory; Johnstone, David; Fowler, Jack; Gore, Elizabeth; Choy, Hak

    2010-03-17

    Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management. To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer. Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction x 3 fractions (54 Gy total) with entire treatment lasting between 1(1/2) and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009. The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 34.4 months (range, 4.8-49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval [CI], 84.3%-99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%-96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95% CI, 71.0%-94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%-60.8%) and 55.8% (95% CI, 41.6%-67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6 months to not

  17. Pancreatic neuroendocrine neoplasms at magnetic resonance imaging: comparison between grade 3 and grade 1/2 tumors

    PubMed Central

    Guo, Chuangen; Chen, Xiao; Xiao, Wenbo; Wang, Qidong; Sun, Ke; Wang, Zhongqiu

    2017-01-01

    Background The grading of pancreatic neuroendocrine neoplasms (PanNENs) is associated with the choice of treatment strategy. The aim of this study is to identify the magnetic resonance imaging (MRI) features in differentiating pancreatic neuroendocrine tumors (PanNETs) grade 1/2 (G1/G2) and pancreatic neuroendocrine carcinoma grade 3 (PanNEC G3). Patients and methods A total of 59 patients with histologically proven PanNENs and who underwent pretreatment MRI were retrospectively analyzed. Tumor location, size, boundary, cystic or solid appearance, enhancement degree, pancreatic duct dilatation, metastases and MRI signal were evaluated. Apparent diffusion coefficients (ADCs) were measured on ADC maps. Receiver operating characteristic curve was used to determine the cut off values and the sensitivity and specificity of prediction. Spearman correlation and logistic regression analysis were adopted to identify the association between MRI features and pathological parameters. Results A total of 47 lesions were PanNETs G1/G2 and 12 lesions were PanNEC G3. G1/G2 tumors were more common with well-circumscribed border compared with PanNEC G3. Ill- defined boundary, big size, necrosis, low-moderate enhancement, pancreatic duct dilatation, metastases and high diffusion-weighted imaging (DWI) intensity were more common in PanNEC G3 than in PanNETs G1/G2. The ADC values of PanNEC G3 were also significantly lower compared with the PanNETs G1/G2 and normal pancreatic parenchyma. The cut off value of ADC was 0.95×10−3 mm2/s for differentiating PanNEC G3 from PanNETs G1/G2 with 72.3% sensitivity and 91.6% specificity, respectively. Ki-67 index and mitosis count positively correlated with tumor size, pancreatic duct dilatation and metastases (P<0.05) and negatively correlated with ADC values (P<0.01), respectively. Regression analysis further showed that metastases and ADC value were associated with PanNENs grade. Conclusion Metastases and ADC value may have potential for

  18. Adjuvant chemotherapy for early-stage cervical cancer.

    PubMed

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  19. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  20. 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.

  1. Liquid biopsy in early stage lung cancer

    PubMed Central

    Pérez-Ramírez, Cristina; Robles, Ana I.; Molina, Miguel Ángel; Faus-Dáder, María José; Calleja-Hernández, Miguel Ángel

    2016-01-01

    Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). However, 30% to 80% of these patients will die within 5 yearS of diagnosis. Circulating cell-free DNA (cfDNA) harbors pathologic characteristics of the original tumor, such as gene mutations or epigenetic alterations. Analysis of cfDNA has revolutionized the clinical care of advanced lung cancer patients undergoing targeted therapies. However, the low concentration of cfDNA in the blood of early-stage NSCLC patients has hampered its use for management of early disease. Continuing development of more specific and sensitive techniques for detection and analysis of cfDNA will soon enable its leverage in early stage and, perhaps, even screening settings. Therefore, cfDNA analysis may become a tool used for routine NSCLC diagnosis and for monitoring tumor burden, as well as for identifying hidden residual disease. In this review, we will focus on the current evidence of cfDNA in patients with early-stage NSCLC, new and upcoming approaches to identify circulating-tumor biomarkers, their clinical applications and future directions. PMID:27826533

  2. Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension.

    PubMed

    Cardona-Muñoz, Ernesto G; López-Alvarado, Agustín; Conde-Carmona, Ignacio; Sánchez-Mejorada, Gerardo; Pascoe-González, Sara; Banda-Elizondo, Ramiro G; García-Castillo, Armando; González-Gálvez, Guillermo; Velasco-Sánchez, Raúl G; Vidrio-Velázquez, Maricela; Leiva-Pons, José L; Villeda-Espinosa, Efraín; Guerra-López, Arturo; Esturau-Santalo, Ramón M

    2017-02-10

    To evaluate efficacy and safety of 60mg and 120mg Fimasartan (FMS) alone or combined with 12.5mg hydrochlorothiazide (HCTZ) in Mexican population. Six month, treat-to-target, open study in subjects with grade 1-2 hypertension. Subjects were initially treated with 60mg FMS once daily; on week 8, those with Diastolic Blood Pressure (DBP) <90mmHg continued on the same FMS dose during the rest of the study while those with DBP ≥90mmHg were randomized to either 120mg FMS or 60mg FMS+12.5mg HCTZ once daily. On week 12, randomized subjects with DBP ≥90mmHg received 120mg FMS+12.5mg HCTZ while those achieving target continued with their assigned treatment until the end of the study. FMS 60mg (n=272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3±8.9 (p<0.0001) and 16.0±14.1 (p<0.0001)mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120mg, to FMS 60mg+HCTZ 12.5mg and to FMS 120mg+HCTZ 12.5mg once daily showed significant DBP and SBP reductions with their assigned treatment; At study end, 237/272 subjects (87.1%) achieved DBP<90mmHg and SBP <140mmHg. Most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%) and dizziness (0.7%). Fimasartan is safe and efficacious in Mexican subjects with grade 1-2 essential hypertension. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. 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.

  4. 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

  5. CS-27IDH1/2 MUTATIONS INFLUENCE ZEB1 EXPRESSION IN GRADES II AND III GLIOMAS

    PubMed Central

    Nesvick, Cody; Zhang, Chao; Montgomery, Blake; Lee, Michaela; Yang, Chunzhang; Wang, Herui; Merrill, Marsha; Heiss, John; Ray-Chaudhury, Abhik; Zhuang, Zhengping

    2014-01-01

    Epithelial-mesenchymal transition (EMT) is a cell program that crucially regulates polarity and enhances invasion in normal epithelia and carcinomas. It has been recently demonstrated that EMT-promoting transcription factors (EMT-TFs) also govern cell invasion in glioblastoma, but the role of these proteins in lower-grade gliomas has not yet been investigated. We investigated the impact of EMT-TF expression on overall survival in World Health Organization (WHO) grades II and III gliomas using the National Cancer Institute Repository for Molecular Brain Neoplasis Data (REMBRANDT) and Cancer Genome Atlas Network Lower-Grade Glioma (CGAN LGG) datasets. Surprisingly, while expression of EMT-promoting transcription factors were generally associated with a decrease in overall survival, high ZEB1 expression was associated with an increase in overall survival in both datasets (log-rank test on all grade II and III gliomas: for REMBRANDT, median overall survival (OS) 54.2 months ZEB1-high vs. 19.6 months ZEB1-low, p = 0.0016; for CGAN, median OS 134.3 months ZEB1-high vs. 63.6 months ZEB1-low, p = 0.0038). Mutations in the genes coding for Isocitrate Dehydrogenases 1 and 2 (IDH1/2) are found in 85-90% of grades II and III gliomas and confer a favorable prognosis in these tumors. Using the CGAN LGG dataset, we found that ZEB1 is upregulated in IDH1/2-mutant versus IDH1/2-wild type tumors (unpaired t-test on all grade II and III gliomas: t = 10.292, p < 0.0001). Moreover, IDH1/2-mutant gliomas express lower levels of genes that are suppressed by ZEB1 including MIR200B and MIR200C (unpaired t-test on all grade II and III gliomas: p < 0.0001 for both targets). We further validated these findings in an independent set of 37 grade II and III gliomas using quantitative real-time PCR, Western blot and immunohistochemistry. These findings reveal that ZEB1 not only has an unexpected prognostic significance in grades II and III gliomas but also may play an important role in IDH1/2

  6. Systemic chemotherapy with FOLFOX in metastatic grade 1/2 neuroendocrine cancer

    PubMed Central

    Faure, Marjorie; Niccoli, Patricia; Autret, Aurelie; Cavaglione, Gerard; Mineur, Laurent; Raoul, Jean-Luc

    2017-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with various clinical presentations and evolution. NETs are often diagnosed at a late stage, when they are already metastatic. Treatment is currently based on traditional chemotherapies, such as streptozocin, with serious side effects. The favorable toxicity profile of the combination of 5-fluorouracil with oxaliplatin, together with its significant antitumor activity in several gastrointestinal malignancies, led to the evaluation of its efficacy and tolerability in patients with advanced grade 1/2 (G1/G2) NETs. The endpoints of the study were tumor response (according to the Response Evaluation Criteria in Solid Tumors 1.1), overall survival (OS), progression-free survival (PFS) and symptom improvement. From January, 2013 to January, 2015, during our Regional Multidisciplinary Tumor Board dedicated to NETs (RENATEN network), FOLFOX was recommended for the treatment of metastatic NETs as first-line therapy or after failure of other therapies. The inclusion criteria were metastatic, well-differentiated G1/G2 NETs, progressing within the last 3 months. Cases with previous antitumor therapy were allowed. The patients received modified FOLFOX-6 and were assessed every 3 months by computed tomography or magnetic resonance imaging examinations. A total of 31 patients were included. The median follow-up was 20 months [95% confidence interval (CI): 15–27]. Nine patients (29%) exhibited a partial response, and 13 (41%) achieved stable disease; the disease control rate was 70%. A total of 9 patients exhibited disease progression. The control rate was 78% for pancreatic and 65% for extrapancreatic NETs. The median OS was not reached; the 1- and 2-year OS rates were 89 and 70%, respectively (Fig. 1). No significant difference in OS was observed between the <5 and 5–20% Ki-67 subgroups (P=0.41) (Fig. 2A) or according to primary tumor location (P=0.71) (Fig. 2B). The median PFS was 14.1 months (95

  7. An Ungraded Primary Level Science Program, Levels One Through Three (Grades 1-2-3).

    ERIC Educational Resources Information Center

    Dickinson Public Schools, ND. Instructional Media Center.

    This curriculum guide is intended for use in an ungraded science program encompassing grades one, two and three in public elementary schools in southwestern North Dakota. Five major units in the biological, physical and earth sciences and in health education are included. In each unit major concepts to be studied are stated. For each concept,…

  8. Career Awareness Education: Social Studies, Grades 1-2, 3-5.

    ERIC Educational Resources Information Center

    Fort Worth Public Schools, TX.

    A supplement to the textbook, "The Social Sciences Concepts and Values" (Harcourt Brace and World), the elementary grades curriculum guide incorporates career education into the social sciences with emphasis on career awareness and the world of work and the development of attitudes toward the dignity and satisfaction of work. The guide…

  9. Early stages of arthrospore maturation in Streptomyces.

    PubMed Central

    Manzanal, M B; Hardisson, C

    1978-01-01

    In the sporogenesis of Streptomyces, two basic stages can be considered: sporulation septum synthesis and arthrospore maturation. Most of the information about the ultrastructural changes accompanying the sporogenesis refer to the first stage of the process, but nothing has been published about the evolution of the sporulation septum during maturation. In a previous paper, proposed three basic types of sporulation septum formation in Streptomyces. Our ultrastructural study on the evolution of the sporulation septum during the early stages of arthrospore maturation in seven species of Streptomyces indicates correlation between the sporulation septum type and its evolution during the arthrospore maturation. In types I and II the material of the annuli was incorporated into the lateral walls of the arthrospore, whereas in types II and III the deposits were lysed during the maturation. Only in type III was the arthrospore wall synthesized de novo. In type I there was total integration and in type II there was partial integration of the septum into the arthrospore wall. Images PMID:618842

  10. Integrative Protein-Based Prognostic Model for Early Stage Endometrioid Endometrial Cancer

    PubMed Central

    Yang, Ji-Yeon; Werner, Henrica M.J.; Li, Jie; Westin, Shannon N.; Lu, Yiling; Halle, Mari K.; Trovik, Jone; Salvesen, Helga B.; Mills, Gordon B.; Liang, Han

    2015-01-01

    Purpose Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. Experimental Design We employed two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. Results Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test p-value = 0.565 for disease stage, 0.567 for tumor grade, 1.3×10−4 for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Conclusions Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies. PMID:26224872

  11. Nationwide trends in mastectomy for early-stage breast cancer.

    PubMed

    Kummerow, Kristy L; Du, Liping; Penson, David F; Shyr, Yu; Hooks, Mary A

    2015-01-01

    Accredited breast centers in the United States are measured on performance of breast conservation surgery (BCS) in the majority of women with early-stage breast cancer. Prior research in regional and limited national cohorts suggests a recent shift toward increasing performance of mastectomy in patients eligible for BCS. To examine whether mastectomy rates in patients eligible for BCS are increasing over time nationwide, and are associated with coincident increases in breast reconstruction and bilateral mastectomy for unilateral disease. We performed a retrospective cohort study of temporal trends in performance of mastectomy for early-stage breast cancer using multivariable logistic regression modeling to adjust for pertinent covariates and interactions. We studied more than 1.2 million adult women treated at centers accredited by the American Cancer Society and the American College of Surgeons Commission on Cancer from January 1, 1998, to December 31, 2011, using the National Cancer Data Base. Year of breast cancer diagnosis. Proportion of women with early-stage breast cancer who underwent mastectomy. Secondary outcome measures include temporal trends in breast reconstruction and bilateral mastectomy for unilateral disease. A total of 35.5% of the study cohort underwent mastectomy. The adjusted odds of mastectomy in BCS-eligible women increased 34% during the most recent 8 years of the cohort, with an odds ratio of 1.34 (95% CI, 1.31-1.38) in 2011 relative to 2003. Rates of increase were greatest in women with clinically node-negative disease (odds ratio, 1.38; 95% CI, 1.34-1.41) and in situ disease (odds ratio, 2.05; 95% CI, 1.95-2.15). In women undergoing mastectomy, rates of breast reconstruction increased from 11.6% in 1998 to 36.4% in 2011 (P < .001 for trend). Rates of bilateral mastectomy for unilateral disease increased from 1.9% in 1998 to 11.2% in 2011 (P < .001). In the past decade, there have been marked trends toward higher proportions of BCS

  12. Virtual exploration of early stage atherosclerosis.

    PubMed

    Olivares, Andy L; González Ballester, Miguel A; Noailly, Jérôme

    2016-12-15

    Biological mechanisms contributing to atherogenesis are multiple and complex. The early stage of atherosclerosis (AS) is characterized by the accumulation of low-density lipoprotein (LDL) droplets, leading to the creation of foam cells (FC). To address the difficulty to explore the dynamics of interactions that controls this process, this study aimed to develop a model of agents and infer on the most influential cell- and molecule-related parameters. FC started to accumulate after six to eight months of simulated hypercholesterolemia. A sensitivity analysis revealed the strong influence of LDL oxidation rate on the risk of FC creation, which was exploited to model the antioxidant effect of statins. Combined with an empirical simulation of the drug ability to decrease the level of LDL, the virtual statins treatment led to reductions of oxidized LDL levels similar to reductions measured in vivo. An Open source software was used to develop the agent-based model of early AS. Two different concentrations of LDL agents were imposed in the intima layer to simulate healthy and hypercholesterolemia groups of 'virtual patients'. The interactions programmed between molecules and cells were based on experiments and models reported in the literature. A factorial sensitivity analysis explored the respective effects of the less documented model parameters as (i) agent migration speed, (ii) LDL oxidation rate and (iii) concentration of autoantibody agents. Finally, the response of the model to known perturbations was assessed by introducing statins agents, able to reduce the oxidation rate of LDL agents and the LDL boundary concentrations. jerome.noailly@upf.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Driving behaviors in early stage dementia: a study using in-vehicle technology.

    PubMed

    Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

    2012-11-01

    According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. 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

  15. Mean diffusivity discriminates between prostate cancer with grade group 1&2 and grade groups equal to or greater than 3.

    PubMed

    Nezzo, M; Di Trani, M G; Caporale, A; Miano, R; Mauriello, A; Bove, P; Capuani, S; Manenti, G

    2016-10-01

    To test the potential ability of mean diffusivity (MD) and fractional anisotropy (FA) in discriminating between PCa of grade group (GG) 1&2, and GGs≥3. Diffusion Tensor Imaging (DTI) experiments at 3T in a cohort of 38 patients with PCa (fifty lesions in total) were performed, by using different diffusion weights (b values) up to 2500s/mm(2). Gleason score (GS) and GG data were correlated with DTI parameters (MD and FA) estimated in PCa. The relation between DTI measures and GS was tested by the linear correlation analysis (Pearson's coefficient). One-way analysis of variance to check the statistical significance of the difference between GG 1&2 and GGs 3, 4, 5, ≥3 was used. Results were reported for each of the three b-values ranges: 0-800s/mm(2), 0-1500s/mm(2), 0-2500s/mm(2). A negative correlation was found between MD and GS. The highest linear correlation was observed when the fit was performed with data acquired in the b-values range 0-2500s/mm(2). MD values were significantly different between GG 1&2 and GG=3 and between GG 1&2 and GG ≥3. Moreover this difference is better defined when high b values (higher than b=800s/mm(2)) are used. The specificity, sensitivity and accuracy in the discrimination between GG 1&2 and GG=3 were: 90%, 66.7% and 82.4%, respectively when MD was estimated in the b-values range 0-2500s/mm(2) while these values were 85%, 58.3% and 78.4% when MD was estimated in the b-values range 0-800s/mm(2). Conversely FA did not discriminate between GG 1&2 and GG ≥3, at any investigated b-values range. This study suggests that MD estimation in PCa, obtained from DTI acquired at high b-values, can contribute to the diagnosis and grading of prostate cancer while FA is not a useful parameter for this purpose. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. 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

  17. Early stages of irradiation induced dislocations in urania

    NASA Astrophysics Data System (ADS)

    Chartier, A.; Onofri, C.; Van Brutzel, L.; Sabathier, C.; Dorosh, O.; Jagielski, J.

    2016-10-01

    The early stages of nucleation and growth of dislocations by irradiation in urania is clarified based on the combination of experiments and atomistic calculations. It is established that irradiation induced dislocations follow a five stage process: (i) point defects are first created by irradiation, (ii) they aggregate into clusters, (iii) from which nucleate Frank loops, (iv) which transform into unfaulted loops via Shockley that in turn grow, and (v) finally reorganize into forest dislocations. Stages (i)-(iii) participate in the lattice expansion while the onset of lattice contraction starts with stage (iv), i.e., when unfaulted loops nucleate. Irradiation induced dislocations operate in the spontaneous recombination regime, to be opposed to the thermal diffusion regime. Body of arguments collaborates to this statement, the main one is the comparison between characteristic distances estimated from the dose rate (Vat/(K0×τ ) ) 1/3 and from the diffusion coefficient (D×τ ) 1/2 . Such a comparison identifies materials under irradiation as belonging either into the recombination regime or not.

  18. US: A Cultural Mosaic Program. Groups: Alike and Different. A Social Studies Unit for Level 2 (Grades 2, 1-2, 1-2-3).

    ERIC Educational Resources Information Center

    Martinez, Jimmie; And Others

    This curriculum guide emphasizes a multicultural approach to the teaching of social studies in grades one through three. The guide is organized around three principal objectives. The first objective is for children to describe how cultural heritage is transmitted through the recognition of special days. Lesson plans presented under this objective…

  19. 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

  20. Increasing national mastectomy rates for the treatment of early stage breast cancer.

    PubMed

    Mahmood, Usama; Hanlon, Alexandra L; Koshy, Matthew; Buras, Robert; Chumsri, Saranya; Tkaczuk, Katherine H; Cheston, Sally B; Regine, William F; Feigenberg, Steven J

    2013-05-01

    To study national trends in the mastectomy rate for treatment of early stage breast cancer. We analyzed data from the Surveillance, Epidemiology, and End Results database, including 256,081 women diagnosed with T1-2 N0-3 M0 breast cancer from 2000 to 2008. We evaluated therapeutic mastectomy rates by the year of diagnosis and performed a multivariable logistic regression analyses to determine predictors of mastectomy as the treatment choice. The proportion of women treated with mastectomy decreased from 40.1 to 35.6 % between 2000 and 2005. Subsequently, the mastectomy rate increased to 38.4 % in 2008 (p < 0.0001). Simple logistic regression models demonstrated that mastectomy rates between 2005 and 2008 were moderated by age (p < 0.0001), marital status (p = 0.0230), and geographic location (p < 0.0001). Multivariate logistic regression analysis found that age, race, marital status, geographic location, involvement of multiple regions of the breast, lobular histology, increasing T stage, lymph node positivity, increasing grade, and negative hormone receptor status were independent predictors of mastectomy. Additionally, multivariate analysis confirmed that women diagnosed in 2008 were more likely to undergo mastectomy than women diagnosed in 2005 (odds ratio 1.17, 95 % confidence interval 1.13 to 1.21, p < 0.0001). There is evidence of a reversal in the previously declining national mastectomy rates, with the mastectomy rate reaching a nadir in 2005 and subsequently rising. Further follow-up to confirm this trend and investigation to determine the underlying cause of this trend and its effect on outcomes may be warranted.

  1. Weight loss in the early stage of progressive supranuclear palsy.

    PubMed

    Tsuge, Ayako; Kaneko, Satoshi; Wate, Reika; Oki, Mitsuaki; Nagashima, Masato; Asayama, Shinya; Nakamura, Masataka; Fujita, Kengo; Saito, Akemi; Takenouchi, Norihiro; Kusaka, Hirofumi

    2017-02-01

    To clarify whether weight change in patients with Parkinson's disease (PD) or progressive supranuclear palsy (PSP) is caused by the disease itself or secondarily by other factors. We conducted a retrospective analysis of 51 patients with PD and 14 patients with PSP, especially during the early stage of their diseases. All patients were independent in terms of their activities of daily living and did not have any feeding difficulty. The body mass index measured within 3 years after the disease onset did not show a significant difference between the two diseases. However, the subsequent weight was stable in patients with PD and significantly decreased in patients with PSP. Weight loss begins in the early stage of PSP, whereas dopaminergic treatment may contribute to keep weight in the early stage of PD through reduction of energy expenditure and/or improvement in appetite.

  2. Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

    PubMed

    Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

    2016-12-29

    The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH4/H2S/H2O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

  3. [Objective assessment of school-time physical activity of a grade 1-2 junior school students in Beijing].

    PubMed

    Li, Hongjuan; Li, Xin; Wang, Yan; Wang, Zhengzhen; Wang, Juan; Chen, Yinkang

    2013-07-01

    To quantify the physical activity (PA) level during school time, especially in PE class, among Beijing junior school students. 81 healthy adolescents (37 boys and 44 girls) aged 11-15 were recruited from grade 1-2 of a junior school, and a hip-worn ActiGraph GT3X + accelerometer was used to measure students' PA. Accelerometer-determined steps, moderate-and vigorous-intensity PA (MVPA), vigorous-intensity PA (VPA) and MET-mins at school time and physical education (PE) class were assessed. During school time, girls spent (47.2 +/- 16.0) mins performing, and boys (67.3 +/- 20.5) mins per day (P < 0.01). Boys also had more steps per day, VPA time and MVPA MET-min than girls (P < 0.001). In PE class, boys spent 53.6% +/- 10.2% of time in MVPA, as compared to girls' 35.2% +/- 7.2%. Boys with normal BMI had the highest VPA time during PE than other groups (P < 0.05). No significant BMI group differences in PA level were found in girls. PA in school time was objectively qualified in Beijing junior school students. Girls were less active than boys. PE class provided a major portion of the VPA time and MVPA MET-min in school time PA for boys and girls. Boys with normal BMI had the highest PA level during PE classes.

  4. 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.

  5. 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.

  6. Use and duration of chemotherapy and its impact on survival in early-stage ovarian cancer.

    PubMed

    Dinkelspiel, Helen E; Tergas, Ana I; Zimmerman, Lilli A; Burke, William M; Hou, June Y; Chen, Ling; Hillyer, Grace; Neugut, Alfred I; Hershman, Dawn L; Wright, Jason D

    2015-05-01

    Although 5-year survival for early-stage ovarian cancer is favorable, prognosis at recurrence is poor, necessitating appropriate initial management. We examined the patterns of care and the impact of the duration of chemotherapy on survival for women with early-stage ovarian cancer. We used the SEER-Medicare database to identify women ≥ 65 years of age with stage I ovarian cancer diagnosed from 1992 to 2009. Patients were categorized as low-risk (non-clear cell histology, stage IA or IB, grade 1 or 2) or high-risk (clear cell histology, grade 3, or stage IC). We used multivariable logistic regression models to determine predictors of chemotherapy use and duration and Cox proportional hazards models to evaluate the effect of chemotherapy use and duration on survival. We identified 1394 patients. Among low-risk patients, 32.9% received adjuvant chemotherapy and the use of chemotherapy increased with time. Among high-risk patients, 71.9% received adjuvant chemotherapy; 44.2% had ≤ 3 months of treatment, and 55.8% had > 3 months of treatment. Older patients were less likely to receive chemotherapy, while those with higher stage and grade were more likely to receive chemotherapy (P<0.05 for all). Among high-risk patients, the duration of chemotherapy did not impact overall (HR=0.93, 95% CI, 0.67-1.27) or cancer specific (HR=0.93; 95% CI, 0.61-1.42) survival. Among early-stage ovarian cancer patients, practice patterns are widely divergent. Extended duration chemotherapy does not appear to impact survival for women with high-risk disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The importance of adjuvant chemotherapy and pelvic radiotherapy in high-risk early stage endometrial carcinoma.

    PubMed

    Jutzi, Leah; Hoskins, Paul; Lim, Peter; Aquino-Parsons, Christina; Tinker, Anna; Kwon, Janice S

    2013-12-01

    To determine the impact of a policy change in which women with high-risk early stage endometrioid endometrial cancer (EEC) received adjuvant chemoradiotherapy. This is a population-based retrospective cohort study of British Columbia Cancer Registry patients diagnosed from 2008 to 2012 with high-risk early stage EEC, who received adjuvant chemoradiotherapy after primary surgery. High-risk early stage was defined as the presence of two or more high-risk uterine factors: grade 3 tumor, more than 50% myometrial invasion, and/or cervical stromal involvement. Adjuvant therapy consisted of 3 or 4 cycles of carboplatin and paclitaxel chemotherapy, followed by pelvic radiotherapy. Sites and rate of recurrence were compared to a historical cohort diagnosed from 2005 to 2008 in which none of the patients received adjuvant chemoradiotherapy. Five-year progression-free and overall survival rates were calculated. The study includes 55 patients. All patients except for 2 received at least 3 cycles of chemotherapy. All patients received pelvic radiotherapy except for 2 who received brachytherapy only. Median follow-up was 27 months (7-56 months). Four patients (7.3%) recurred, including three with distant recurrence only and one with both a pelvic and paraaortic nodal recurrence. The historical cohort had a 29.4% recurrence rate, and therefore the hazard ratio for recurrence was 0.27 (95% CI 0.02-4.11). Five-year progression-free and overall survival rates were 88.6% and 97.3%, respectively. Patients with high-risk early stage endometrial carcinoma treated with adjuvant chemoradiotherapy have a low rate of recurrence compared to those not receiving such therapy. © 2013.

  8. 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.

  9. 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

  10. 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

  11. [The conservative treatment of early-stage benign prostatic hypertrophy].

    PubMed

    Kumanov, Kh; Stoianova, V; Lilov, A; Kaloianov, D

    1993-01-01

    After outlining the methods currently used in benign prostate hyperplasia (BPH) treatment, data defining some etiological aspects of the disease are briefly analyzed. Initial experience had with the treatment of early stage BPH using Permixon--a drug exerting effect on alpha-2 reductase--is described. The results in a series of twenty-seven patients presenting BPH are encouraging.

  12. 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…

  13. 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.

  14. Signatures of unfolding in the early stages of protein denaturation

    NASA Astrophysics Data System (ADS)

    Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

    2012-04-01

    A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

  15. 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

  16. 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

  17. 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.

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

    PubMed

    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

    2015-03-19

    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.

  19. TCM tongue diagnosis index of early-stage breast cancer.

    PubMed

    Lo, Lun-Chien; Cheng, Tsung-Lin; Chen, Yi-Jing; Natsagdorj, Sainbuyan; Chiang, John Y

    2015-10-01

    This paper investigates discriminating tongue features to distinguish between early stage breast cancer (BC) patients and non-breast cancer individuals through non-invasive traditional Chinese medicine (TCM) tongue diagnosis. The tongue features for 67 patients with 0 and 1 stages of BC, and 70 non-breast cancer individuals are extracted by the automatic tongue diagnosis system (ATDS). A total of nine tongue features, namely, tongue color, tongue quality, tongue fissure, tongue fur, red dot, ecchymosis, tooth mark, saliva, and tongue shape are identified for each tongue. Features extracted are further sub-divided according to the areas located, i.e., spleen-stomach, liver-gall-left, liver-gall-right, kidney, and heart-lung areas. This study focuses on deriving significant tongue features (p<0.05) to discriminate early-stage BC patients from non-breast cancer individuals. The Mann-Whitney test shows that the amount of tongue fur (p=0.024), maximum covering area of tongue fur (p=0.009), thin tongue fur (p=0.009), the average area of red dot (p=0.049), the maximum area of red dot (p=0.009), red dot in the spleen-stomach area (p=0.000), and red dot in the heart-lung area (p=0.000) demonstrate significant differences. The data collected are further classified into two groups. The training group consists of 57 early-stage BC patients and 60 non-breast cancer individuals, while the testing group is composed of 10 early-stage BC patients and 10 non-breast cancer individuals. The logistic regression by utilizing these 7 tongue features with significant differences in Mann-Whitney test as factors is performed. In order to reduce the number of tongue features employed in prediction, tongue features with the least amount of significant difference, namely, maximum area of red dot and average area of red dot, are removed progressively. The tongue features of the testing group are employed in the aforementioned three models to test the power of significant tongue features

  20. In vivo kinematics of early-stage osteoarthritic knees during pivot and squat activities.

    PubMed

    Matsuki, Keisuke; Matsuki, Kei O; Kenmoku, Tomonori; Yamaguchi, Satoshi; Sasho, Takahisa; Banks, Scott A

    2017-08-04

    Kinematic changes have been shown to accompany severe knee osteoarthritis, but no studies have analyzed early-stage osteoarthritic knee kinematics in the transverse plane during functional activities. The purpose of this study was to analyze kinematics of early-stage osteoarthritic knees using model registration techniques. Fifteen early-stage osteoarthritic knees from eight females with a mean age of 52 years old (range, 43-57years old) were involved in this study. A radiologist confirmed with plain radiographs that knees had Kellgren-Lawrence grade-1 or -2 arthritic changes. Fluoroscopic images of squat and pivot activities were recorded for each subject. Three-dimensional surface models of the distal femur and proximal tibia were created from CT images, and anatomic coordinate systems were embedded in each model. The three-dimensional position and orientation of the femur and the tibia were determined using model-image registration techniques, and tibial anteroposterior translation and internal/external rotation relative to the femur were calculated. The contact points of the medial and lateral femoral condyle were also computed. Compared to healthy knees, osteoarthritic knees showed lateral contact points that were significantly shifted anteriorly in both pivot (P<0.001) and squat (P=0.001) activities and greater tibial external rotation in pivot activity (P=0.007). The medial contact point location was similar to healthy knees, but the amount of anteroposterior translation was smaller (P<0.001). These kinematic changes might change stress distributions in the medial compartment during weight-bearing activities. The changes in kinematics possibly have some influence on initiation or progression of knee osteoarthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2011-07-08

    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-κB and TNF-α 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 suggest that genistein supplementation reduces oxidative stress by increasing antioxidant capacity and modulating proinflammatory cytokine expression during the early stage of wound healing. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Inflammation in the early stages of neurodegenerative pathology

    PubMed Central

    Khandelwal, Preeti J.; Herman, Alexander M.; Moussa, Charbel E-H

    2011-01-01

    Inflammation is secondary to protein accumulation in neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis. Emerging evidence indicate sustained inflammatory responses, involving microglia and astrocytes in animal models of neurodegeneration. It is unknown whether inflammation is beneficial or detrimental to disease progression and how inflammatory responses are induced within the CNS. Persistence of an inflammatory stimulus or failure to resolve sustained inflammation can result in pathology, thus, mechanisms that counteract inflammation are indispensable. Here we review studies on inflammation mediated by innate and adaptive immunity in the early stages of neurodegeneration and highlight important areas for future investigation. PMID:21820744

  3. Intraoperative radiation therapy delivered prior to lumpectomy for early-stage breast cancer: a single institution study

    PubMed Central

    Yu, Wei; Lin, Zhi; Ju, Zhong-Jian; Li, Xi-Ru; Zhang, Yan-Jun; Kong, Qing-Long; Gong, Han-Shun; Wang, Jian-Dong; Ma, Lin

    2015-01-01

    Objective: To evaluate the safety, cosmesis, and clinical outcome of intraoperative electron radiation therapy (IOERT) delivered prior to lumpectomy for early-stage breast cancer. Methods: From December 2008 to March 2012, 75 breast cancer patients (ages 34-66 years) were treated with IOERT during breast conservative surgery. IOERT was delivered using a mobile linear accelerator. Suitable energy and applicator size were chosen to ensure coverage of the tumor with anterior and posterior margins of 1 cm and lateral margins of 2 cm. Patients with sentinel node metastases or younger than 40 years received 8 Gy as boost followed by post-operative external beam radiation therapy of 50 Gy/25F; the others had 15 Gy, prescribed to the 90% isodose depth. Adjuvant treatment consisted of chemotherapy (55 patients), hormonal therapy (59 patients), or combined chemotherapy and hormonal therapy (41 patients). The safety, cosmesis, and short-term outcome were evaluated. Results: Median follow-up was 54 months (range: 30-66 months). Two (2.7%) patients developed post-surgical hematoma. Six (8.0%) patients developed mild breast fibrosis. Eight (10.7%) patients suffered from local pain. One (1.2%) patient experienced a post-operative infection. Sixteen (21.3%) patients developed Grade 1 pulmonary fibrosis. Forty-three (57.3%) patients had an excellent cosmetic result and 23 (30.7%) had a good cosmetic result. Three patients had an ipsilateral breast recurrence, with an actual 3-year local recurrence rate of 4.0%. One patient had an ipsilateral axillary recurrence, resulting in a 3-year regional recurrence rate of 1.3%. No distant metastases or deaths were observed. The 3-year disease free survival was 94.6%. Conclusions: Intraoperative electron radiation therapy delivered prior to lumpectomy is safe and feasible for selected patients with early-stage breast cancer. Early side effects, cosmesis and short-term efficacy are acceptable, but a longer follow-up is needed for evaluation of

  4. Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management.

    PubMed

    Nwanodi, Oroma

    2017-07-08

    Globally, endometrial cancer is the sixth leading cause of female cancer-related deaths. Non-atypical endometrial hyperplasia (EH), has a lifetime progression rate to endometrial cancer ranging from less than 5%, if simple without atypia, to 40%, if complex with atypia. Site specific, long-acting intrauterine devices (IUDs) provide fertility sparing, progestin-based EH medical management. It is unclear which IUD is most beneficial, or if progesterone sensitizing metformin offers improved outcomes. For resolution, PubMed searches for "Mirena" or "Metformin," "treatment," "endometrial hyperplasia," or "stage 1 endometrial cancer," were performed, yielding 33 articles. Of these, 19 articles were included. The 60 mg high-dose frameless IUD/20 mcg levonorgestrel has achieved sustained regression of Grade 3 endometrial intraepithelial neoplasia for 14 years. Case series on early stage endometrial cancer (EC) treatment with IUDs have 75% or greater regression rates. For simple through complex EH with atypia, the 52 mg-IUD/10-20 mcg-LNG-14t has achieved 100% complete regression in 6-months. Clearly, IUDs have an outcome advantage over oral progestins. However, studies on metformin for EH, and of progestins or metformin for early stage EC management are underpowered, with inadequate dose ranges to achieve significant differences in, or optimal outcomes for, the treatment modalities. Therefore, outcomes from the feMMe trial for the 52 mg-IUD/10-20 mcg-LNG-14t and metformin will fill a gap in the literature.

  5. Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas.

    PubMed

    Takano, Shingo; Ishikawa, Eiichi; Sakamoto, Noriaki; Matsuda, Masahide; Akutsu, Hiroyoshi; Noguchi, Masayuki; Kato, Yukinari; Yamamoto, Tetsuya; Matsumura, Akira

    2016-04-01

    The molecular subgrouping of diffuse gliomas was recently found to stratify patients into prognostically distinct groups better than histological classification. Among several molecular parameters, the key molecules for the subtype diagnosis of diffuse gliomas are IDH mutation, 1p/19q co-deletion, and ATRX mutation; 1p/19q co-deletion is undetectable by immunohistochemistry, but is mutually exclusive with ATRX and p53 mutation in IDH mutant gliomas. Therefore, we applied ATRX and p53 immunohistochemistry instead of 1p/19q co-deletion analysis. The prognostic value of immunohistochemical diagnosis for Grade III gliomas was subsequently investigated. Then, the same immunohistochmical diagnostic approach was expanded for the evaluation of Grade II and IV diffuse glioma prognosis. The results indicate immunohistochemical analysis including IDH1/2, ATRX, p53, and Ki-67 index is valuable for the classification of diffuse gliomas, which is useful for the evaluation of prognosis, especially Grade III gliomas and lower-grade gliomas (i.e., Grade II and III).

  6. Delayed Presentation of Ureteropelvic Junction Obstruction and Loss of Renal Function After Initially Mild (SFU Grade 1-2) Hydronephrosis.

    PubMed

    Bowen, Diana K; Yerkes, Elizabeth B; Lindgren, Bruce W; Gong, Edward M; Faasse, Mark A

    2015-07-01

    We report 4 pediatric cases of ureteropelvic junction obstruction involving delayed progression of initially mild postnatal hydronephrosis. All 4 children became symptomatic; however, 3 already had a substantial decrement of ipsilateral kidney function by the time of diagnosis. Two of these 3 patients had previous renal scintigraphy demonstrating normal differential function. We caution that counseling regarding hydronephrosis should emphasize the importance of prompt re-evaluation for any symptoms potentially referable to delayed presentation of ureteropelvic junction obstruction, irrespective of initial hydronephrosis grade. Future studies are needed to determine the optimal follow-up regimen for conservative management of hydronephrosis.

  7. 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

  8. 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.

  9. Oral propranolol in early stages of retinopathy of prematurity.

    PubMed

    Bancalari, Aldo; Schade, Ricardo; Muñoz, Tomás; Lazcano, Carolina; Parada, Rodrigo; Peña, Rubén

    2016-07-01

    To assess the effect of oral propranolol on the progression of early stages of retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants. We analyzed VLBW infants with ROP (stages 2-3, zones II-III). Newborns received oral propranolol (0.5 mg/kg/dose q8h), and were monitored throughout the treatment period for possible side effects. Propranolol was administered until regression of ROP. A historic control group of patients with equivalent ROP was used. We compared characteristics of both groups and the progression of retinopathy. Forty-seven newborns were included, 20 in the propranolol group and 27 in the control group. There were no significant differences in gestational age, birthweight or gender. The mean duration of treatment with propranolol was 58.2±17.6 days. Most patients started treatment with stage 2 disease (65.0%), and had zone III involvement (55.0%). In the treated group, 90.0% (18/20) of patients did not require intervention with laser or bevacizumab, compared to 51.8% in the control group (P<0.005). No cases of bradycardia, hypotension or hypoglycemia were observed. Oral propranolol in early stages of ROP could prevent disease progression and reduce the need for invasive rescue therapy with laser or bevacizumab. No significant side effects were reported.

  10. 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

  11. Early stage of nanodroplet impact on solid wall

    NASA Astrophysics Data System (ADS)

    Kobayashi, Kazumichi; Konno, Kazuki; Yaguchi, Hisao; Fujii, Hiroyuki; Sanada, Toshiyuki; Watanabe, Masao

    2016-03-01

    In this study, we investigated nanodroplet spreading at the early stage after the impact using molecular dynamics simulations by changing the magnitude of the intermolecular force between the liquid and wall molecules. We showed that the droplet deformation after the impact greatly depends on the intermolecular force. The temporal evolution of the spreading diameters was measured by the cylindrical control volume for several molecular layers in the vicinity of the wall. At the early stage of the nanodroplet impact, the normalized spreading radius of the droplet is proportional to the square root of the normalized time, t ˆ . This result is understood by the geometrical consideration presented by Rioboo et al. ["Time evolution of liquid drop impact onto solid, dry surfaces," Exp. Fluids 33, 112-124 (2002)]. In addition, we found that as the intermolecular force between the liquid and wall becomes stronger, the normalized spreading diameter of the first molecular layer on the wall remains less dependent on the impact velocity. Furthermore, the time evolution of the droplet spreading changes from √{ t ˆ } to log t ˆ with time.

  12. Understanding early-stage dune development: morphodynamics of aeolian protodunes

    NASA Astrophysics Data System (ADS)

    Baddock, Matthew; Wiggs, Giles; Nield, Joanna

    2016-04-01

    For such a fundamental aspect of bedform development, the initiation and early-stage growth of sand dunes remain poorly understood. Protodunes are bedforms within the continuum of early-stage depositional aeolian features that exist between flat sand patches and small dunes. As transitory bedforms with the potential to develop into dunes, the detailed study of protodune morphodynamics can provide significant insights into nascent dune development. As part of a multi-annual study investigating bedform change through repeat morphological surveys of bedforms with differing maturity, measurements of near-surface airflow and sand transport were conducted over a protodune in a small Namibian barchan dune field. The protodune was approximately 85 m in length and 1 m high, and was without a slipface. Data show that over the course of a week, patterns of airflow and transport flux variation were linked with accretion at the crest, and erosion of the leeside edge showing an increase in protodune height, and providing evidence of the dune's vertical development. Surveys reveal the longer term evolution of the protodune, in the context of changes exhibited by nearby, fully developed barchan dunes, and long term monitoring of wind regime at the site.

  13. Neural changes underlying early stages of L2 vocabulary acquisition.

    PubMed

    Pu, He; Holcomb, Phillip J; Midgley, Katherine J

    2016-11-01

    Research has shown neural changes following second language (L2) acquisition after weeks or months of instruction. But are such changes detectable even earlier than previously shown? The present study examines the electrophysiological changes underlying the earliest stages of second language vocabulary acquisition by recording event-related potentials (ERPs) within the first week of learning. Adult native English speakers with no previous Spanish experience completed less than four hours of Spanish vocabulary training, with pre- and post-training ERPs recorded to a backward translation task. Results indicate that beginning L2 learners show rapid neural changes following learning, manifested in changes to the N400 - an ERP component sensitive to lexicosemantic processing and degree of L2 proficiency. Specifically, learners in early stages of L2 acquisition show growth in N400 amplitude to L2 words following learning as well as a backward translation N400 priming effect that was absent pre-training. These results were shown within days of minimal L2 training, suggesting that the neural changes captured during adult second language acquisition are more rapid than previously shown. Such findings are consistent with models of early stages of bilingualism in adult learners of L2 (e.g. Kroll and Stewart's RHM) and reinforce the use of ERP measures to assess L2 learning.

  14. Early stage of Superradiance from Bose-Einstein condensates

    NASA Astrophysics Data System (ADS)

    Buchmann, Lukas

    2011-05-01

    We investigate the dynamics of matter and optical waves at the early stage of superradiant Rayleigh scattering from Bose-Einstein condensates, an instance of four-wave-mixing of matter and optical waves. Our analysis is within a spatially dependent model which treats the matter-waves as well as the optical end-fire modes quantum mechanically and is capable of providing analytic solutions for the operators of interest. In particular, we study the statistical properties of the outgoing scattered light which provide insight into the rich internal dynamics of the system at this early stage. Furthermore, we investigate coherence properties of pairs of counter propagating atomic sidemodes produced during the process. It is shown that these clouds exhibit long-range spatial coherence and strong nonclassical density cross-correlations due to entanglement between the clouds. These findings make this scheme a promising candidate for the production of highly directional nonclassically correlated atomic pulses. Our prediction of number difference squeezing between the clouds was observed in another instance of a four-wave mixing process using metastable helium. Work performed at IESL-FORTH in Crete, Greece

  15. Sensorimotor Cortical Neuroplasticity in the Early Stage of Bell's Palsy

    PubMed Central

    Dai, Minhui; Xuan, Lihua; Cao, Zhijian; Zhou, Sisi; Lang, Courtney; Lv, Kun

    2017-01-01

    Neuroplasticity is a common phenomenon in the human brain following nerve injury. It is defined as the brain's ability to reorganize by creating new neural pathways in order to adapt to change. Here, we use task-related and resting-state fMRI to investigate neuroplasticity in the primary sensory (S1) and motor cortex (M1) in patients with acute Bell's palsy (BP). We found that the period directly following the onset of BP (less than 14 days) is associated with significant decreases in regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF), and intrinsic connectivity contrast (ICC) values in the contralateral S1/M1 and in ReHo and ICC values in the ipsilateral S1/M1, compared to healthy controls. The regions with decreased ReHo, fALFF, and ICC values were in both the face and hand region of S1/M1 as indicated by resting-state fMRI but not task-related fMRI. Our results suggest that the early stages of BP are associated with functional neuroplasticity in both the face and hand regions of S1/M1 and that resting-state functional fMRI may be a sensitive tool to detect these early stages of plasticity in patient populations. PMID:28299208

  16. Expression of midkine in the early stage of carcinogenesis in human colorectal cancer

    PubMed Central

    Ye, C; Qi, M; Fan, Q-W; Ito, K; Akiyama, S; Kasai, Y; Matsuyama, M; Muramatsu, T; Kadomatsu, K

    1999-01-01

    It has been suggested that a heparin-binding growth factor, midkine (MK), plays an important role incarcinogenesis because of its frequent overexpression in various malignant tumours. To clarify whether or not MK contributes to theearly stage of carcinogenesis, we examined the status of MK mRNA in 20 adenomas with moderate- and severe-grade dysplasia, 28carcinomas and 28 corresponding normal tissues, by means of Northern blotting. The MK expression level was significantly moreelevated in adenomas than in normal tissues P< 0.001, unpaired Student's t -test). A difference wasalso observed between carcinomas and the corresponding normal tissues P< 0.04, paired Student's t-test). Moreover, MK immunostaining was positive in the adenomas with moderate- and severe-grade dysplasia and in the carcinomas,but not in mild-grade dysplasia or in normal tissues. These findings were in line with those on Western blotting. In three patientswith both adenomas with moderate- or severe-grade dysplasia and carcinomas, elevated MK expression was observed in the neoplasticlesions. This is the first report of the association of elevated MK expression with the early stage of carcinogenesis in humans. © 1999 Cancer Research Campaign PMID:10408712

  17. 13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early Stage SBICs. (a) Reserve requirement. If you are an Early Stage SBIC with outstanding Leverage, for...

  18. 13 CFR 107.1180 - Required distributions to SBA by Early Stage SBICs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1180 Required distributions to SBA by Early Stage SBICs. (a) Distribution requirement. If you are an Early Stage SBIC with outstanding Leverage, you...

  19. 13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early Stage SBICs. (a) Reserve requirement. If you are an Early Stage SBIC with outstanding Leverage, for...

  20. 13 CFR 107.1180 - Required distributions to SBA by Early Stage SBICs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1180 Required distributions to SBA by Early Stage SBICs. (a) Distribution requirement. If you are an Early Stage SBIC with outstanding Leverage, you...

  1. Early-stage esophageal squamous cell carcinoma treated with californium-252 neutron brachytherapy: clinical report on 16 cases.

    PubMed

    Liu, Huiming; Wang, Qifeng; Jia, Xitang; Liu, Bo; Wang, C-K Chris

    2013-01-01

    Californium-252 (²⁵²Cf) neutron brachytherapy is a form of high linear energy transfer radiotherapy, which has proven effective when used in combination with external beam radiotherapy to treat intracavitary cancers of the cervix, colon/rectum and esophagus. No study has been reported for treatment of intracavitary cancers with neutron brachytherapy alone. The aim of the study was to observe and analyze the long-term curative effects and complications for early stage thoracic esophageal cancer patients treated with neutron brachytherapy alone. From December 2001 to August 2006, 16 patients of early stage squamous cell carcinoma underwent neutron brachytherapy. The total radiation dose to the reference point was 20-28 Gy-eq in 5 to 7 fractions with 4 Gy-eq/fraction. The 1-, 3-, and 5-year follow-up rates were 100%. The 2-, 3-, 4-, and 5-year survival rates were 100%, 87.5%, 87.5%, and 75%, respectively. The early complication rates for grades 1 and 2 radiation esophagitis were 75% and 25%, respectively. The late complication rates for grades 0 and 1 (according to the RTOG/EORTC standard) were 87.5% and 12.5%, respectively. Barium esophagography after treatments confirmed that the complete response rate was 100%. Fourteen patients were confirmed by endoscopy to have either normal mucosa or inflammation change. Neutron brachytherapy alone was an effective and safe treatment for early stage esophageal squamous cell cancer.

  2. Evaluation of activity and effectiveness of occupational therapy in stroke patients at the early stage of rehabilitation.

    PubMed

    Petruseviciene, Daiva; Krisciūnas, Aleksandras

    2008-01-01

    In Lithuania, the stroke is not only medical, but social issue as well, since only 20% of patients suffering from stroke remain active at work. Yearly stroke incidence in Lithuania is 7000-8000 cases. The most common outcome of stroke is unilateral paralysis (hemiplegia) followed by disorders of coordination, balance, and movements. Due to dysfunctions of movements, self-care, cognition, behavior, and communication, some part of stroke patients remains disabled. They need assistance and care provided by other people. Occupational therapy, which is part of rehabilitation of patients after stroke, is directed to independence training. There are scarce data related to effectiveness of occupational therapy depending on motor, cognitive, and psychosocial dysfunctions. Goals of study were to estimate effectiveness of occupational therapy at the early stage of rehabilitation depending on type of stroke, localization of brain injury, grade of lesion, age, and gender, to identify factors influencing effectiveness of occupational therapy, and to estimate their positive predictive value. The study included 106 patients at the early stage of rehabilitation, who were admitted to Department of Neurorehabilitation after stabilization of clinical condition from Departments of Neurology and Neurosurgery (mean duration of 14+/-2 days after stroke). The program of occupational therapy was not fulfilled by 6 patients: 2 patients were transferred to Nursing Hospital due to severe condition, and 4 patients were discharged prematurely and continued rehabilitation in outpatient setting. Hence, study population consisted of 100 subjects (47 men and 53 women) who were diagnosed with stroke (ischemic or hemorrhagic). Patient's functional status and disorders of activities were evaluated using Barthel Index and Functional Independence Measure. Complexes of occupational therapy were adjusted according to examination of patient's disorders of activities, age, grade of lesion, other diseases

  3. 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

  4. Evaluation of treatment outcomes of early-stage endometrial cancer radiotherapy: a single center experience.

    PubMed

    Demiral, S; Beyzadeoglu, M; Sager, O; Dincoglan, F; Uysal, B; Gamsiz, H; Akin, M; Turker, T; Dirican, B

    2014-01-01

    Postoperative adjuvant radiotherapy (RT) in the management of early stage endometrial cancer (EC) is still controversial. Here we report our institutional experience with patients who received postoperative RT for stage I-II EC over a period of 35 years and assess potential predictors of local recurrence (LR), distant metastasis (DM), and overall survival (OS). A total of 188 patients undergoing postoperative RT for stage IA-II EC between 1977 and 2012 were evaluated. Some 96 received median 46 Gy whole pelvic radiotherapy (WPRT) (range: 40-60 Gy), 37 were given WPRT with vaginal cuff therapy (VCT), and 55 received only VCT either with brachytherapy (BT) or stereotactic body radiotherapy (SBRT). Chemotherapy was given to 5 patients with uterine papillary serous carcinoma (UPSC). Logistic regression analysis was used to assess the effect of clinicopathological factors on LR, DM, and OS. Median follow-up time was 11 years (range: 1-35 years). At the time of analysis, 34 patients were not alive. Of the 15 patients with LR, 7 (46.7%) recurred in the vaginal stump, 5 (33.3%) in the pelvic region, and 3 (20%) in the paraaortic nodal region, while 12 had distant metastasis. UPSC histology (p=0.027), sole VCT (p=0.041), high histologic grade (p=0.034), and age≥71 (p=0.04) were poor prognostic factors on univariate analysis. In our patients receiving radiotherapy for early-stage EC, grade III disease and age≥71 were associated with shorter OS whereas UPSC histology was an independent predictor for both LR and DM.

  5. Prognostic Value of Tumor Budding in Early-Stage Cervical Adenocarcinomas

    PubMed

    Satabongkoch, Nopporn; Khunamornpong, Surapan; Pongsuvareeyakul, Tip; Settakorn, Jongkolnee; Sukpan, Kornkanok; Soongkhaw, Aungsumalee; intaraphet, Suthida; Suprasert, Prapaporn; Siriaunkgul, Sumalee

    2017-06-25

    Background: Tumor budding has recently been reported as an independent adverse prognostic factor for colorectal adenocarcinomas and other types of carcinoma in the digestive tract. This study aimed to evaluate the prognostic value of tumor budding in patients with early-stage cervical adenocarcinomas and any associations with other clinical and pathological features. Methods: Histological slides of patients with early-stage (IB-IIA) usual-type endocervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection, without preoperative chemotherapy, between January 2006 and December 2012 were reviewed. Tumor budding was evaluated in routinely-stained sections and defined as detached single cells or clusters of fewer than 5 cells in a tumor invasive front and was stratified based on the number of bud counts in 10-high-power fields as low (<15 buds) and high (≥15 buds). Correlations between tumor bud count and other clinical and pathological variables including follow-up outcomes were assessed. Results: Of 129 patients, a high tumor bud count was observed in 15 (11.6%), positively associated with histologic grade 3 (p<0.001), invasive pattern C (Silva System) (p=0.004), lymph node metastasis (p=0.008), stage IB2-IIA (p=0.016), and tumor size >2 cm (p=0.036). Kaplan-Meyer analysis showed a significant decrease in both disease-free survival and cancer-specific survival for patients with a high tumor bud count (p=0.027 and 0.031, respectively). On multivariate analysis, histologic grade 3 was the only independent predictor for decreased disease-free survival (p=0.004) and cancer-specific survival (p=0.003). Conclusions: A high tumor budding count based on assessment of routinely-stained sections was found to be associated with decreased disease-free and cancer-specific survival in patients with early-stage cervical adenocarcinomas. However, it was not found to be an independent prognostic predictor in this study. Creative Commons Attribution

  6. Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development

    PubMed Central

    Murray, Jessica R.; Stanciauskas, Monika E.; Aralere, Tejas S.; Saha, Margaret S.

    2014-01-01

    The zebra finch (Taeniopygiaguttata) has become an increasingly important model organism in many areas of research including toxicology1,2, behavior3, and memory and learning4,5,6. As the only songbird with a sequenced genome, the zebra finch has great potential for use in developmental studies; however, the early stages of zebra finch development have not been well studied. Lack of research in zebra finch development can be attributed to the difficulty of dissecting the small egg and embryo. The following dissection method minimizes embryonic tissue damage, which allows for investigation of morphology and gene expression at all stages of embryonic development. This permits both bright field and fluorescence quality imaging of embryos, use in molecular procedures such as in situ hybridization (ISH), cell proliferation assays, and RNA extraction for quantitative assays such as quantitative real-time PCR (qtRT-PCR). This technique allows investigators to study early stages of development that were previously difficult to access. PMID:24999108

  7. Contingency Table Browser − prediction of early stage protein structure

    PubMed Central

    Kalinowska, Barbara; Krzykalski, Artur; Roterman, Irena

    2015-01-01

    The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table − this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them − analysis of specific protein sequences from the point of view of their structural ambiguity. PMID:26664034

  8. SBRT in operable early stage lung cancer patients.

    PubMed

    Roesch, Johannes; Andratschke, Nicolaus; Guckenberger, Matthias

    2014-08-01

    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.

  9. 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

  10. Contingency Table Browser - prediction of early stage protein structure.

    PubMed

    Kalinowska, Barbara; Krzykalski, Artur; Roterman, Irena

    2015-01-01

    The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table - this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them - analysis of specific protein sequences from the point of view of their structural ambiguity.

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. 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)

  13. Does the type of surgery for early-stage endometrial cancer affect the rate of reported lymphovascular space invasion in final pathology specimens?

    PubMed

    Momeni, Mazdak; Kolev, Valentin; Cardenas-Goicoechea, Joel; Getrajdman, Joelle; Fishman, David; Chuang, Linus; Kalir, Tamara; Rahaman, Jamal; Zakashansky, Konstantin

    2013-01-01

    /25 (44.0%) of patients treated with LAVH had positive LVSI compared with 10/31 (32.3%) of patients receiving TAH (P = .53). The stage I cancer patients were further subdivided into histological grades 1, 2, and 3, and LVSI was not significantly different between TAH and LAVH groups per grade of cancer. We found no differences between TAH and LAVH in early-stage endometrial cancer (stage IA and IB), with respect to the presence of positive peritoneal washings. In early-stage endometrial cancer (stage IA and IB), there were no differences between TAH and LAVH in the final pathologic report of LVSI. The use of an intrauterine manipulator for LAVH was not associated with an increased detection of LVSI. Copyright © 2013 Mosby, Inc. All rights reserved.

  14. 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.

  15. Cytokines, Fatigue, and Cutaneous Erythema in Early Stage Breast Cancer Patients Receiving Adjuvant Radiation Therapy

    PubMed Central

    De Sanctis, Vitaliana; Visco, Vincenzo; Muni, Roberta; Campanella, Barbara; Valeriani, Maurizio; Minniti, Giuseppe; Osti, Mattia F.; Amanti, Claudio; Pellegrini, Patrizia; Brunetti, Serena; Costantini, Anna; Alfò, Marco; Torrisi, Maria Rosaria; Marchetti, Paolo; Enrici, Riccardo Maurizi

    2014-01-01

    We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels. PMID:24800238

  16. Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

    PubMed

    De Sanctis, Vitaliana; Agolli, Linda; Visco, Vincenzo; Monaco, Flavia; Muni, Roberta; Spagnoli, Alessandra; Campanella, Barbara; Valeriani, Maurizio; Minniti, Giuseppe; Osti, Mattia F; Amanti, Claudio; Pellegrini, Patrizia; Brunetti, Serena; Costantini, Anna; Alfò, Marco; Torrisi, Maria Rosaria; Marchetti, Paolo; Enrici, Riccardo Maurizi

    2014-01-01

    We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

  17. Diffusion tensor imaging can detect the early stages of cartilage damage: a comparison study.

    PubMed

    Ukai, Taku; Sato, Masato; Yamashita, Tomohiro; Imai, Yutaka; Mitani, Genya; Takagaki, Tomonori; Serigano, Kenji; Mochida, Joji

    2015-02-21

    In the present study, we measured damaged areas of cartilage with diffusion tensor (DT) imaging and T2 mapping, and investigated the extent to which cartilage damage could be determined using these techniques. Forty-one patients underwent arthroscopic knee surgery for osteoarthritis of the knee, a meniscus injury, or an anterior cruciate ligament injury. Preoperative magnetic resonance imaging of the knee was performed, including T2 mapping and diffusion tensor imaging. The presence of cartilage injury involving the medial and lateral femoral condyles and tibia plateau was assessed during surgery using the Outerbridge scale. The ADC, T2 values and fractional anisotropy of areas of cartilage injury were then retrospectively analysed. The ADC results identified significant differences between Outerbridge grades 0 and 2 (P = 0.041); 0 and 3 (P < 0.001); 1 and 2 (P = 0.045); 1 and 3 (P < 0.001); and 2 and 3 (P = 0.028). The FA results identified significant differences between grades 0 and 1 (P < 0.001); 0 and 2 (P < 0.001); and 0 and 3 (P < 0.001). T2 mapping identified significant differences between Outerbridge grades 0 and 2 (P = 0.032); 0 and 3 (P < 0.001); 1 and 3 (P < 0.001); and 2 and 3 (P < 0.001). Both the T2 mapping (R(2) = 0.7883) and the ADC (R(2) = 0.9184) correlated significantly with the Outerbridge grade. The FA (R(2) = 0.6616) correlated slightly with the Outerbridge grade. T2 mapping can be useful for detecting moderate or severe cartilage damage, and the ADC can be used to detect early stage cartilage damage. The FA can also distinguish normal from damaged cartilage.

  18. 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

  19. Life satisfaction of women in early stages of fertility treatment.

    PubMed

    Ben Shlomo, Shirley; Pascal, Mor; Taubman Ben-Ari, Orit; Azuri, Yoseph; Horowtz, Eran

    2017-01-01

    As many women perceive motherhood to be a central component of identity that enhances life satisfaction, difficulties conceiving may lead to stress. This study examined women in the early stages of fertility treatment to ascertain the relations of perceived stress, cognitive appraisal, and self-mastery to the life satisfaction of women embarking on fertility treatment and whether the associations were the same for women who were already mothers versus those who were not. Women were recruited for the study over a period of 18 months, from January 2013 to June 2014. The final sample was composed of 145 women; of these, 67 had 1 or 2 children and 78 had no children. No significant differences were found in perceived stress and life satisfaction between women with and without children. However, in the sample as a whole, higher levels of self-mastery and lower levels of stress were associated with greater life satisfaction. Moreover, the associations between self-mastery and cognitive appraisals of threat and self-efficacy were mediated by perceived stress. The findings highlight the importance of developing interventions at fertility clinics that begin at the very first point of contact to promote the psychological well-being of women being treated for infertility.

  20. Treatment of early-stage Hodgkin lymphoma.

    PubMed

    Engert, Andreas; Raemaekers, John

    2016-07-01

    Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed.

  1. Endoscopic mucosal resection of early stage colon neuroendocrine carcinoma

    PubMed Central

    Yamasaki, Yasushi; Uedo, Noriya; Ishihara, Ryu; Tomita, Yasuhiko

    2015-01-01

    Early stage colorectal neuroendocrine carcinoma is rare. A small colon tumour was found in a 56-year-old man during diagnostic colonoscopy performed after a positive faecal occult blood test, and he was referred for treatment. A slightly reddish superficial elevated lesion with a shallow depression 10 mm in size was found in the transverse colon. Magnifying narrow-band imaging revealed disrupted irregular microvessels and the absence of a surface pattern in the depressed area. En bloc endoscopic mucosal resection (EMR) of the tumour was undertaken. The tumour was positive for chromogranin A and synaptophysin, and had a mitotic rate of >20/10 high-power fields and a Ki-67 proliferative index of >50%; it was diagnosed as a neuroendocrine carcinoma. The tumour minimally invaded the submucosa (300 μm) without lymphovascular involvement. The patient was followed up carefully, and at 1 year after EMR, no recurrence was found using colonoscopy and CT scans. PMID:25737221

  2. Nanoparticles target early-stage breast cancer metastasis in vivo.

    PubMed

    Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

    2017-10-27

    Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

  3. 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.

  4. Isolation and transplantation of sturgeon early-stage germ cells.

    PubMed

    Pšenička, Martin; Saito, Taiju; Linhartová, Zuzana; Gazo, Ievgeniia

    2015-04-01

    We report, for the first time, a series of baseline techniques comprising isolation and transplantation of female and male early-stage germ cells in sturgeon to generate a germline chimera as a potential tool for surrogate reproduction and gene banking. Cells were dissociated from testis, characterized by mostly spermatogonia, and from ovary, exclusively comprising oogonia and previtellogenic oocytes, of Acipenser baerii, using 0.3% trypsin (2 hours, 23 °C) dissolved in PBS, isotonic with blood plasma. The dissociated germ cells were sorted by Percoll gradient centrifugation followed by immunolabeling with germ cell-specific vasa antibody DDX4, while 10% to 30% Percoll solution contained 79.4% and 70.8% labeled testicular and ovarian cells. Sorted germ cells were transplanted into a cavity close to a presumptive genital ridge of newly hatched heterospecific Acipenser ruthenus larvae with fluorescein isothiocyanate-labeled endogenous primordial germ cells. The transplanted germ cells were randomly distributed in the body cavity through 30-day posttransplantation (dpt). Subsequently, the cells were organized into genital ridges 50 dpt and proliferated 90 dpt. The number of both transplanted and endogenous germ cells significantly increased from 18.1, 22.2, and 29.1 (30 dpt) to 108.5, 90.8, and 118.5 (90 dpt) in ovarian, testicular, and endogenous germ cells, respectively (P < 0.05). The efficiency of transplantation was 60% (counted 90 dpt). Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Affective motives for smoking among early stage smokers.

    PubMed

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

    2014-10-01

    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. 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). 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. Results are consistent with our understanding of dependence and provide further support for 3 common measures of nicotine dependence among early stage smokers. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  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. Longitudinal trajectories of awareness in early-stage dementia.

    PubMed

    Clare, Linda; Nelis, Sharon M; Martyr, Anthony; Whitaker, Christopher J; Marková, Ivana S; Roth, Ilona; Woods, Robert T; Morris, Robin G

    2012-01-01

    Although it is often assumed that awareness decreases as dementia severity increases, there is limited evidence regarding changes in awareness over time. We examined awareness in 101 individuals with early-stage dementia (PwD) and their carers; 66 were reassessed after 12 months and 51 were seen again at 20 months. Awareness was assessed in relation to memory, everyday activities, and socio-emotional functioning using discrepancies between PwD and carer ratings on parallel questionnaires. PwD completed neuropsychological tests and measures of mood and quality of life. Carers completed measures of mood and stress. At initial assessment, discrepancies were greatest for activities of daily living, moderate for memory, and least pronounced for socio-emotional functioning. Discrepancy scores did not change over time. PwD self-ratings indicated perceived poorer functioning in everyday activities over time, but no change for memory and socio-emotional functioning. Carer ratings indicated perceived decline in everyday activities and socio-emotional functioning, but no change for memory. PwD declined in neuropsychological functioning, but self-ratings of depression, anxiety, and quality of life remained stable over time. Carer mood and stress levels also remained stable. At least in the earlier stages of dementia, it should not be assumed that awareness will inevitably decrease as dementia progresses.

  8. Caregiver burden and coping in early-stage Alzheimer disease.

    PubMed

    Zucchella, Chiara; Bartolo, Michelangelo; Pasotti, Chiara; Chiapella, Laura; Sinforiani, Elena

    2012-01-01

    This study was set out to describe caregiver-perceived burden and coping in early-stage Alzheimer disease (AD). A total of 163 consecutive pairs of patients with AD and their principal caregivers were initially recruited. The caregivers completed the Caregiver Burden Inventory (CBI) and the Coping Orientations to Problems Experienced scale, and also provided sociodemographic information; the patients with AD were assessed by means of the Mini Mental State Examination and the Neuropsychiatric Inventory. Data from 126 patient-caregiver pairs were analyzed. The caregivers (mean age 56.11±12.37 y) were mainly women (76%); 64% were the patient's offspring; 39% lived with the patient. From the CBI data, it emerged that caregivers perceived loss of personal time (objective burden, 33%) and the feeling of missing out on opportunities (developmental burden, 25%) as their main stressors. Total CBI score was negatively correlated with Mini Mental State Examination (P=0.005). As regards coping strategies, the caregivers predominantly used problem-oriented strategies associated with a positive attitude. The use of dysfunctional strategies was predictive of caregiver burden. It is important to be aware that avoidance and dysfunctional coping strategies predispose caregivers of patients with AD to higher level of distress, whereas successful caregiving seems to be based on the use of problem-oriented strategies early in the disease when solutions are still available.

  9. Cytonuclear incompatibility contributes to the early stages of speciation.

    PubMed

    Barnard-Kubow, Karen B; So, Nina; Galloway, Laura F

    2016-12-01

    Genetic incompatibility is a hallmark of speciation. Cytonuclear incompatibilities are proposed to be among the first genetic barriers to arise during speciation. Accordingly, reproductive isolation (RI) within species should be heavily influenced by interactions between the organelle and nuclear genomes. However, there are few clear examples of cytonuclear incompatibility within a species. Here, we show substantial postzygotic RI in first-generation hybrids between differentiated populations of an herbaceous plant (up to 92% reduction in fitness). RI was primarily due to germination and survival, with moderate RI for pollen viability. RI for survival was asymmetric and caused by cytonuclear incompatibility, with the strength of incompatibility linearly related to chloroplast genetic distance. This cytonuclear incompatibility may be the result of a rapidly evolving plastid genome. Substantial asymmetric RI was also found for germination, but was not associated with cytonuclear incompatibility, indicating endosperm or maternal-zygote incompatibilities. These results demonstrate that cytonuclear incompatibility contributes to RI within species, suggesting that initial rates of speciation could be influenced by rates of organelle evolution. However, other genetic incompatibilities are equally important, indicating that even at early stages, speciation can be a complex process involving multiple genes and incompatibilities.

  10. The Early Stages of Groundwater-fed River Bifurcation

    NASA Astrophysics Data System (ADS)

    Yi, R.; Seybold, H. F.; Gibbins, G.; Rothman, D.

    2014-12-01

    Recent work shows, both theoretically and empirically, that river networks fed by subsurface flow bifurcate on average at an angle of 2π/5 [1]. However, the network's existence within a complex natural framework obscures the emergence of this pattern. Fortunately, this ambiguity betrays the presence of processes that have had some effect on the channels during the network's long history. In particular, we concern ourselves with the signature of the third dimension - the topographic relief - on the early stages of channel bifurcation. While, on average, channels grow in a direction dictated by the shape of the groundwater table, we hypothesize that the valley relief plays a crucial role in determining the opening angle and its relaxation to 2π/5 in this regime. A network-wide averaging of several thousand channel bifurcations driven by subsurface flow on the Florida Panhandle reveals that rivers on average branch initially at an angle wider than 2π/5, yet quickly relax to 2π/5 after a few meters. We hypothesize that this initial wide growth direction is governed by the shape of the topography. As these channels form independent valleys, the Laplacian field prevails, yielding an emergent 2π/5 branching angle. Our results therefore suggest that the path-selection of incipient channels fed by subsurface flow is coupled both to the local topography and the surrounding groundwater field. 1. Devauchelle, Olivier, et al. "Ramification of stream networks." Proceedings of the National Academy of Sciences 109.51 (2012): 20832-20836.

  11. 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

  12. Involvement of 15-lipoxygenase in early stages of atherogenesis

    PubMed Central

    1994-01-01

    The arachidonate 15-lipoxygenase which is expressed in atherosclerotic lesions is implicated in the oxidative modification of low density lipoproteins during atherogenesis. To obtain experimental in vivo evidence for this hypothesis, we analyzed the structure of oxygenated lipids isolated from the aorta of rabbits fed with a cholesterol-rich diet for different time periods and compared the pattern of oxygenation products with that isolated from low density lipoproteins treated in vitro with the pure rabbit 15-lipoxygenase and with oxygenated lipids isolated from advanced human atherosclerotic lesions. In early atherosclerotic lesions (12-wk cholesterol feeding), specific lipoxygenase products were detected whose structure was similar to those isolated from lipoxygenase-treated low density lipoproteins. The appearance of these products did coincide with the lipid deposition in the vessel wall. In later stages of atherogenesis (26-wk cholesterol feeding) the degree of oxidative modification of the tissue lipids did increase but the share of specific lipoxygenase products was significantly lower, suggesting an increasing overlay of the specific lipoxygenase products by nonenzymatic lipid peroxidation. In advanced human atherosclerotic lesions, large amounts of oxygenation products were detected whose structure suggests a nonenzymatic origin. These data suggest that the arachidonate 15-lipoxygenase is of pathophysiological importance during the early stages of atherogenesis. In later stages of plaque development nonenzymatic lipid peroxidation becomes more relevant. PMID:8195716

  13. Impact of gross total resection in patients with WHO grade III glioma harboring the IDH 1/2 mutation without the 1p/19q co-deletion.

    PubMed

    Kawaguchi, Tomohiro; Sonoda, Yukihiko; Shibahara, Ichiyo; Saito, Ryuta; Kanamori, Masayuki; Kumabe, Toshihiro; Tominaga, Teiji

    2016-09-01

    The prognosis of patients with WHO grade III gliomas is highly dependent on their genomic status such as the isocitrate dehydrogenase (IDH) 1/2 mutation and1p/19q co-deletion. However, difficulties have been associated with determining which tumors have certain genomic profiles by preoperative radiographical modalities, and the role of surgical resection in achieving better outcomes remains unclear. This retrospective study included 124 consecutive patients with newly diagnosed grade III gliomas. The genomic status of IDH1/2 and 1p/19q was analyzed in these patients. Tumors were then divided into 3 subgroups based on their genomic status; the IDH 1/2 mutation with the 1p/19q co-deletion (1p/19q co-del), the IDH 1/2 mutation without the 1p/19q co-deletion (non-1p/19q co-del), and the IDH 1/2 wild type (IDH wt). Survival times were compared between patients who underwent gross total resection and those who did not (GTR versus non-GTR). The relationships between genomic statuses and MR imaging characteristics such as ring-like or nodular enhancements by gadolinium, and very low intensity on T1-weighted images with blurry enhancements (T1VL) were also examined. Among all patients with grade III gliomas, GTR patients had longer median survival and progression-free times than those of non-GTR patients (undefined versus 87 months, p = 0.097, and 124 versus 34 months, p = 0.059, respectively). No significant differences were observed in survival between GTR and non-GTR patients in the 1p/19q co-del group (p = 0.14), or between GTR and non-GTR patients in the IDH wt group (26 and 27 months, p = 0.29). On the other hand, in non-1p/19q co-del group, survival was significantly longer in GTR patients than in non-GTR patients (undefined versus 77 months, p = 0.005). Radiographically, T1VL was detected in most tumors in the non-1p/19q co-del group (78.2 %), but only 6 (21.4 %) and 17 (41.5 %) tumors in the 1p/19q co-del and IDH wt groups

  14. The physical performance test predicts aerobic capacity sufficient for independence in early-stage Alzheimer disease.

    PubMed

    Vidoni, Eric D; Billinger, Sandra A; Lee, Charesa; Hamilton, Jenna; Burns, Jeffrey M

    2012-01-01

    Early identification of physical impairment related to Alzheimer disease (AD) is increasingly identified as an important aspect of diagnosis and care. Clinically accessible tools for evaluating physical capacity and impairment in AD have been developed but require further characterization for their effective use. To assess the utility of the Physical Performance Test (PPT) for identifying functionally limiting aerobic capacity in older adults with AD and without dementia. Secondary analysis of a dataset of community dwelling older adults, 70 without dementia and 60 with early-stage AD. Participants were administered the PPT and performed a graded maximal exercise test. The clinical utility of 2 versions of the PPT was described by determining sensitivity and specificity to functionally limiting aerobic capacity. The 9-item PPT is predictive of diminished aerobic capacity in older adults with AD. A score of 28 or less indicates likelihood of functionally limiting aerobic capacity that would limit independent function with 67% sensitivity and 67% specificity. The 4-item mini-PPT demonstrates improved capability for identifying impaired functional aerobic capacity with 85% sensitivity and 62% specificity. The PPT was not useful for identifying impaired functional aerobic capacity in older adults without dementia. The PPT, which incorporates basic and instrumental activities of daily living as test items, and the mini-PPT which focuses on basic activities of daily living and simple physical functions, are both clinically useful tool for the evaluation for individuals in the earliest stages of AD and both provide important information about functional performance. The mini-PPT additionally inform the clinician as to whether or not individual with early-stage AD is likely to have insufficient aerobic capacity to perform instrumental daily functions.

  15. A Novel Low Dose Fractionation Regimen for Adjuvant Vaginal Brachytherapy in Early Stage Endometrial Cancer

    PubMed Central

    Townamchai, Kanokpis; Lee, Larissa; Viswanathan, Akila N.

    2012-01-01

    Purpose To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen Methods We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method. Results All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5–76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient. Conclusion Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity. PMID:22850411

  16. Patient education materials about the treatment of early-stage prostate cancer: a critical review.

    PubMed

    Fagerlin, Angela; Rovner, David; Stableford, Sue; Jentoft, Christophir; Wei, John T; Holmes-Rovner, Margaret

    2004-05-04

    To ensure that patients make informed medical decisions, patient education materials must communicate treatment risks and benefits. To survey publicly available patient education materials and assess their suitability to support informed decision making in early-stage prostate cancer. Cross-sectional review of Internet, print, and multimedia sources. University data analysis laboratory. The content of 44 materials that described all standard treatment options was reviewed. Top-rated documents underwent plain-language review. Total score on 54 content items and accuracy, balance, and plain-language evaluation was measured. 502 of 546 patient education materials did not describe all standard treatments (watchful waiting, surgery, radiation, and hormone therapy). Eighty percent of the 44 materials that addressed standard treatments and underwent content review described anatomy, physiology, stage, and grade of cancer. Half of the materials fully described radical prostatectomy and radiation therapy. One third of the materials included risks and benefits of each treatment; none explicitly compared outcomes of all treatments in a single summary. Information was accurate and balanced but did not include key content for informed consent. The search was restricted to publicly available materials and did not include books or materials written in languages other than English. The accuracy, balance, and plain-language reviews were evaluated by 1 reviewer. The criteria reflect the authors' focus on informed decision making. Other aspects of health education may require a different evaluation template. Currently available patient education materials on early-stage prostate cancer treatment do not contain comprehensive information about the risks and benefits of each treatment. To assist patients and physicians in choosing among prostate cancer treatment options, a new generation of materials is needed.

  17. Plasma of argon accelerates murine fibroblast adhesion in early stages of titanium disk colonization.

    PubMed

    Canullo, Luigi; Cassinelli, Clara; Götz, Werner; Tarnow, Dennis

    2013-01-01

    This study was conducted to analyze how a cleaning treatment using plasma of argon would affect fibroblast growth on titanium disks at different time points to determine whether this treatment could enhance soft tissue healing around titanium dental implant abutments. Sixty sterile disks made of machined grade 5 titanium were divided into two groups; 30 disks were left untreated (control) and 30 were cleaned using plasma of argon (test). To simulate clinical conditions during soft tissue healing around titanium abutments, both groups were immersed in a culture of murine fibroblasts (L929) for 2, 8, or 48 hours. After preparation, they were stained using 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) to label the cellular nuclei and fluorescent phalloidin to label the cellular bodies. The nuclei were counted, and cellular bodies were analyzed with fluorescent microscopy and imaging analysis software. Analysis was performed at the three different time points. Fibroblast adhesion for the test group was statistically significantly greater versus the control group at 2 and 8 hours but not at 48 hours. At 2 and 8 hours, the cellular bodies in the test group appeared flatter and more spread out, revealing more advanced cellular adhesion, compared to the cells observed in the control group. At 48 hours, the test and control specimens were nearly indistinguishable. The removal of organic and inorganic contaminants from the surfaces of titanium disks using plasma of argon accelerated fibroblast adhesion in the early stages of colonization (2 to 8 hours). This effect disappeared after 48 hours as a result of saturation. Clinically, abutment cleaning using plasma of argon might positively affect soft tissue healing in early stages.

  18. 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

  19. Characteristics and prognosis of patients with early-stage endometrial cancer who refuse adjuvant radiotherapy.

    PubMed

    Koskas, Martin; Huchon, Cyrille; Amant, Frederic

    2016-06-01

    To investigate the risk factors for refusing adjuvant radiotherapy in patients who have undergone surgery for early-stage endometrial cancer, and to compare their survival rates with patients who have undergone adjuvant radiotherapy. Data from the Surveillance, Epidemiology, and End Results database for patients operated on for histologically-proven early-stage endometrioid endometrial cancer, between 1988 and 2012, were screened. Univariate and multivariate logistic regression analyses tested the associations between refusal of adjuvant radiotherapy and demographic, tumoral, and management characteristics. Overall and cancer-related survival rates were compared between 376 patients who refused adjuvant radiotherapy and 752 patients who received adjuvant radiotherapy, matched for demographics (age, race, year of diagnosis, marital status, region), tumoral (grade, FIGO stage, size), and management (lymphadenectomy performed) criteria. 434 of the 16,014 patients (2.7%) who were proposed adjuvant radiotherapy refused this treatment. Older, widowed, divorced, or separated patients, who were recently diagnosed and managed in the Northern plains or Pacific coast (USA), with limited tumoral extension, were more likely to refuse adjuvant radiotherapy. Five-year cancer-related survival was significantly lower in patients who refused adjuvant radiotherapy (88.9% vs. 95.7%, p<0.001) whereas overall survival did not significantly differ between the two groups (76.4% vs. 83.7%, p=0.23). We have identified the patients' characteristics related to refusal of adjuvant radiotherapy. Refusing adjuvant radiotherapy increased cancer-related death but probably does not reduce overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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.

  1. Does Life Expectancy Affect Treatment of Women Aged 80 and Older with Early Stage Breast Cancers?

    PubMed Central

    Schonberg, Mara A.; Marcantonio, Edward R.; Ngo, Long; Silliman, Rebecca A.; McCarthy, Ellen P.

    2011-01-01

    BACKGROUND Data are needed on how life expectancy affects treatment decisions among women ≥80 years with early stage breast cancer. METHODS We used the linked Surveillance Epidemiology and End Results-Medicare claims dataset from 1992–2005 to identify women aged ≥80 newly diagnosed with lymph node negative, estrogen receptor positive tumors, ≤5 centimeters. To estimate life expectancy, we matched these women to women of similar age, region, and insurance, not diagnosed with breast cancer. We examined 5-year mortality of matched controls by illness burden (measured with the Charlson Comorbidity Index [CCI]) using Kaplan-Meier statistics. We examined treatments received by estimated life expectancy within CCI levels. We further examined factors associated with receipt of radiotherapy after breast conserving surgery (BCS). RESULTS Of 9,932 women, 39.6% underwent mastectomy, 30.4% received BCS plus radiotherapy, and 30.0% received BCS alone. Estimated 5-year mortality was 72% for women with CCIs of 3+, yet 38.0% of these women underwent mastectomy and 22.9% received radiotherapy after BCS. Conversely, estimated 5-year mortality was 36% for women with CCIs of 0 and 26.6% received BCS alone. Age 80–84, urban residence, higher grade, recent diagnosis, mammography use, and low comorbidity, were factors associated with receiving radiotherapy after BCS. Among women with CCIs of 3+ treated with BCS, 36.9% underwent radiotherapy. CONCLUSIONS Many women aged ≥80 with limited life expectancies receive radiotherapy after BCS for treatment of early stage breast cancers while many in excellent health do not. More consideration needs to be given to patient life expectancy when considering breast cancer treatments. KEY WORDS: Breast cancer, older women, treatment, life expectancy, radiation PMID:22368726

  2. Regional Nodal Irradiation in Early-Stage Breast Cancer.

    PubMed

    Whelan, Timothy J; Olivotto, Ivo A; Parulekar, Wendy R; Ackerman, Ida; Chua, Boon H; Nabid, Abdenour; Vallis, Katherine A; White, Julia R; Rousseau, Pierre; Fortin, Andre; Pierce, Lori J; Manchul, Lee; Chafe, Susan; Nolan, Maureen C; Craighead, Peter; Bowen, Julie; McCready, David R; Pritchard, Kathleen I; Gelmon, Karen; Murray, Yvonne; Chapman, Judy-Anne W; Chen, Bingshu E; Levine, Mark N

    2015-07-23

    Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

  3. Regional Nodal Irradiation in Early-Stage Breast Cancer

    PubMed Central

    Whelan, Timothy J.; Olivotto, Ivo A.; Parulekar, Wendy R.; Ackerman, Ida; Chua, Boon H.; Nabid, Abdenour; Vallis, Katherine A.; White, Julia R.; Rousseau, Pierre; Fortin, Andre; Pierce, Lori J.; Manchul, Lee; Chafe, Susan; Nolan, Maureen C.; Craighead, Peter; Bowen, Julie; McCready, David R.; Pritchard, Kathleen I.; Gelmon, Karen; Murray, Yvonne; Chapman, Judy-Anne W.; Chen, Bingshu E.; Levine, Mark N.

    2015-01-01

    BACKGROUND Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. METHODS We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. RESULTS Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P = 0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P = 0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P = 0.01) and lymphedema (8.4% vs. 4.5%, P = 0.001). CONCLUSIONS Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. PMID:26200977

  4. Total laparoscopic hysterectomy in early-stage endometrial cancer using an intrauterine manipulator: is it a bias for frozen section analysis? Case-control study.

    PubMed

    Fanfani, F; Gagliardi, M L; Zannoni, G F; Gallotta, V; Vizzielli, G; Lecca, A; Scambia, G; Fagotti, A

    2011-01-01

    To evaluate whether the systematic use of an intrauterine manipulator influences the accuracy of frozen section analysis in early-stage endometrial cancer. Case-control study (Canadian Task Force classification II-1). Three hundred fourteen consecutive women with early-stage endometrial cancer. Between January 2004 and December 2009, 314 women with early-stage endometrial cancer underwent staging at laparoscopy (case group) or laparotomy (control group). All women in the case group underwent total laparoscopic hysterectomy using an intrauterine manipulator. The positive predictive value of frozen section analysis for myometrial infiltration, histotype, and grade of differentiation was 97.2%, 100%, and 97.2%, respectively. The correct diagnosis rate was of 85.7%. The accuracy of frozen section analysis, rate of correct diagnosis, and rate of tumor vascular invasion did not seem to be significantly modified by systematic use of an intrauterine manipulator for total laparoscopic hysterectomy compared with total abdominal hysterectomy in early-stage endometrial cancer staging. Frozen section analysis of early-stage endometrial cancer is highly accurate, and systematic use of an intrauterine manipulator does not represent a bias for correct evaluation of the specimen. Copyright © 2011 AAGL. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. Reduced-intensity allografting as first transplantation approach in relapsed/refractory grade 1-2 follicular lymphoma provides improved outcomes in long-term survivors

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ahn, Kwang Woo; Carreras, Jeanette; Bachanova, Veronika; Bashey, Asad; Cohen, Jonathon B.; D'Souza, Anita; Freytes, César O.; Gale, Robert Peter; Ganguly, Siddhartha; Hertzberg, Mark S.; Holmberg, Leona A.; Kharfan-Dabaja, Mohamed A.; Klein, Andreas; Ku, Grace H.; Laport, Ginna G.; Lazarus, Hillard M.; Miller, Alan M.; Mussetti, Alberto; Olsson, Richard F.; Slavin, Shimon; Usmani, Saad Z.; Vij, Ravi; Wood, William A.; Maloney, David G.; Sureda, Anna M.; Smith, Sonali M.; Hamadani, Mehdi

    2015-01-01

    Purpose Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. Methods Adult patients with relapsed/refractory grade 1-2 FL undergoing 1st reduced-intensity allo-HCT or 1st autograft during 2000-2012 were evaluated. Results A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger; more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto- vs. allo-HCT groups for non-relapse mortality (NRM) were 5% vs. 26% (p<0.0001); relapse/progression: 54% vs. 20% (p<0.0001); progression-free survival (PFS): 41% vs. 58% (p<0.001) and overall survival (OS): 74% vs. 66% (p=0.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months post-HCT (RR=4.4; p<0.0001), and worse PFS (RR=2.9; p<0.0001) beyond 11 months post HCT. In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.41; p<0.0001), but beyond 24 months with inferior OS (RR=2.2; p=0.006). A landmark analysis of patients alive and progression-free at 2-years post-HCT confirmed these observations, showing no difference in further NRM between both groups, but significantly higher risk of relapse/progression (RR=7.3; p<0.0001) and inferior PFS (RR=3.2; p<0.0001) and OS (RR=2.1; p=0.04) following auto-HCT. The 10-year cumulative incidence of second hematological malignancies following allo- and auto-HCT was 0% and 7%, respectively. Conclusion Auto- and RIC-allo-HCT as 1st transplantation approach can provide durable disease control in grade 1-2 FL patients. Continued disease relapse-risk following auto-HCT translates into improved PFS and OS following allo-HCT, in long-term survivors. PMID:26253007

  7. Dream features in the early stages of Parkinson's disease.

    PubMed

    Bugalho, Paulo; Paiva, Teresa

    2011-11-01

    Few studies have investigated the relation between dream features and cognition in Parkinson's disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients' dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient's dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.

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

    PubMed Central

    Bice, Kinsey; Kroll, Judith F.

    2015-01-01

    Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The co-activation 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 the second language (L2). The present study asked whether L1 change can be detected at early stages of L2 learning and how it is modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials (ERPs) 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 to 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. Additionally, 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 the L2 affects the L1 only when L2 speakers are highly proficient, L2 learning begins to impact the L1 early in the development of L2 skill. PMID:26351964

  9. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    PubMed

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

    Kundu, Prasanta; Dua, Arti

    2013-01-28

    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.

  11. 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.

  12. Taste function in early stage treated and untreated Parkinson's disease.

    PubMed

    Doty, Richard L; Nsoesie, Michael T; Chung, Inna; Osman, Allen; Pawasarat, Ian; Caulfield, Julie; Hurtig, Howard; Silas, Jonathan; Dubroff, Jacob; Duda, John E; Ying, Gui-Shuang; Tekeli, Hakan; Leon-Sarmiento, Fidias E

    2015-03-01

    Since brain stem regions associated with early Parkinson's disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated whole-mouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue. The PD cohort was tested both on and off dopamine-related medications in counterbalanced test sessions. While whole-mouth taste identification test scores for all stimuli were, on average, nominally lower for the PD patients than for the controls, a trend in the opposite direction was noted for the intensity ratings at the lower stimulus concentrations for all stimuli except caffeine. Moreover, regional testing found that PD subjects tended to rate the stimuli, relative to the controls, as more intense on the anterior tongue and less intense on the posterior tongue. No significant associations were evident between taste test scores and UPDRS scores, L-DOPA medication equivalency values, or [(99m)Tc]TRODAT-1 SPECT imaging of dopamine transporter uptake within the striatum and associated regions. Our findings suggest that suprathreshold measures of taste function are influenced by PD and that this disease differentially influences taste function on anterior (CN VII) and posterior (CN IX) tongue regions. Conceivably PD-related damage to CN IX releases central inhibition on CN VII at the level of the brainstem, resulting in enhanced taste intensity on the anterior tongue.

  13. Metabolic syndrome and outcomes following early-stage breast cancer.

    PubMed

    Calip, Gregory S; Malone, Kathleen E; Gralow, Julie R; Stergachis, Andy; Hubbard, Rebecca A; Boudreau, Denise M

    2014-11-01

    The prevalence of risk factors contributing to metabolic syndrome (MetS) is increasing, and numerous components of MetS are associated with increased primary breast cancer (BC) risk. However, less is known about the relationship of MetS to BC outcomes. The aim of this study was to evaluate whether MetS, characterized by increased weight, hypertension, low HDL-cholesterol, high triglycerides, and diabetes or impaired glucose tolerance, is associated with risk of second breast cancer events (SBCE) and BC-specific mortality. Retrospective cohort study of women diagnosed with incident early-stage (I-II) BC between 1990 and 2008, enrolled in an integrated health plan. Outcomes of interest were SBCE, defined as recurrence or second primary BC, and BC-specific mortality. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for time-varying exposure to MetS components while accounting for potential confounders and competing risks. Among 4,216 women in the cohort, 26% had ≥3 MetS components and 13% developed SBCE during median follow-up of 6.3 years. Compared to women with no MetS components, presence of MetS (≥3 components) was associated with increased risk of SBCE (HR = 1.50, 95% CI 1.08-2.07) and BC-specific mortality (HR = 1.65, 95% CI 1.02-2.69). Of the individual components, only increased weight was associated with increased risk of SBCE (HR = 1.26, 95% CI 1.06-1.49). MetS is associated with modestly increased risk of SBCE and BC-specific mortality. Given the growing population of BC survivors, further research in larger and more diverse populations is warranted.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Treatment-associated toxicities reported by patients with early-stage invasive breast cancer.

    PubMed

    Friese, Christopher R; Harrison, Jordan M; Janz, Nancy K; Jagsi, Reshma; Morrow, Monica; Li, Yun; Hamilton, Ann S; Ward, Kevin C; Kurian, Allison W; Katz, Steven J; Hofer, Timothy P

    2017-06-01

    Patient-reported toxicities help to appraise the breast cancer treatment experience. Yet extant data come from clinical trials and health care claims, which may be biased. Using patient surveys, the authors sought to quantify the frequency, severity, and burden of treatment-associated toxicities. Between 2013 and 2014, the iCanCare study surveyed a population-based sample of women residing in Los Angeles County and Georgia with early-stage, invasive breast cancer. The authors assessed the frequency and severity of toxicities; correlated toxicity severity with unscheduled health care use (clinic visits, emergency department visits/hospitalizations) and physical health; and examined patient, tumor, and treatment factors associated with reporting increased toxicity severity. The overall survey response rate was 71%. From the analyzed cohort of 1945 women, 866 (45%) reported at least 1 toxicity that was severe/very severe, 9% reported unscheduled clinic visits for toxicity management, and 5% visited an emergency department or hospital. Factors associated with reporting higher toxicity severity included receipt of chemotherapy (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 2.0-2.5), receipt of both chemotherapy and radiotherapy (OR, 1.3; 95% CI, 1.0-1.7), and Latina ethnicity (OR vs whites: 1.3; 95% CI, 1.1-1.5). A nonsignificant increase in at least 1 severe/very severe toxicity report was observed for bilateral mastectomy recipients (OR, 1.2; 95% CI, 1.0-1.4). Women with early-stage invasive breast cancer report substantial treatment-associated toxicities and related burden. Clinicians should collect toxicity data routinely and offer early intervention. Toxicity differences observed by treatment modality may inform decision making. Cancer 2017;123:1925-1934. © 2017 American Cancer Society. © 2017 American Cancer Society.

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

    PubMed

    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

    2016-04-01

    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). 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. 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 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. 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. © 2016 Associated Professional Sleep Societies, LLC.

  20. 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.

  1. Extent of pelvic lymphadenectomy and use of adjuvant vaginal brachytherapy for early-stage endometrial cancer.

    PubMed

    Matsuo, Koji; Machida, Hiroko; Ragab, Omar M; Takiuchi, Tsuyoshi; Pham, Huyen Q; Roman, Lynda D

    2017-03-01

    To examine trends of adjuvant radiotherapy choice and to examine associations between pelvic lymphadenectomy and radiotherapy choice for women with early-stage endometrial cancer. The Surveillance, Epidemiology, and End Results Program was used to identify surgically treated stage I-II endometrial cancer between 1983 and 2012 (type 1 n=79,474, and type 2 n=25,020). Piecewise linear regression models were used to examine temporal trends of intracavitary brachytherapy (ICBT) and whole pelvic radiotherapy (WPRT) use, pelvic lymphadenectomy rate, and sampled node counts. Multivariable binary logistic regression models were used to identify independent predictors for ICBT use. There was a significant increase in ICBT use and decrease in WPRT use during the study period. ICBT use exceeded WPRT use in 2003 for type 1 stage IA, and in 2007 for type 1 stage IB and type 2 stage IA diseases. In addition, number of sampled pelvic nodes significantly increased over time in type 1-2 stage I-II diseases (mean, 7.0-12.7 in 1988 to 15.2-17.6 in 2012, all P<0.001). On multivariable analysis, extent of sampled pelvic nodes was significantly associated with ICBT use for type 1 cancer: adjusted-odds ratios for 1-10 and >10 nodes versus no lymphadenectomy in stage IA (1.38/2.40), IB (2.75/6.32), and II (1.36/2.91) diseases. Similar trends were observed for type 2 cancer: adjusted-odds ratios for stage IA (1.69/3.73), IB (2.25/5.65), and II (1.36/2.19) diseases. Our results suggest that surgeons and radiation oncologists are evaluating the extent of pelvic lymphadenectomy when counseling women with early-stage endometrial cancer for adjuvant radiotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer.

    PubMed

    Jolly, Shruti; Vargas, Carlos; Kumar, Tushar; Weiner, Sheldon; Brabbins, Donald; Chen, Peter; Floyd, William; Martinez, Alvaro A

    2005-06-01

    Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I-II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively. Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% (n = 2), 2% (n = 3), and 9% (n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB

  3. Consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process.

    PubMed

    Bennett, Cathy; Vakil, Nimish; Bergman, Jacques; Harrison, Rebecca; Odze, Robert; Vieth, Michael; Sanders, Scott; Gay, Laura; Pech, Oliver; Longcroft-Wheaton, Gaius; Romero, Yvonne; Inadomi, John; Tack, Jan; Corley, Douglas A; Manner, Hendrik; Green, Susi; Al Dulaimi, David; Ali, Haythem; Allum, Bill; Anderson, Mark; Curtis, Howard; Falk, Gary; Fennerty, M Brian; Fullarton, Grant; Krishnadath, Kausilia; Meltzer, Stephen J; Armstrong, David; Ganz, Robert; Cengia, Gianpaolo; Going, James J; Goldblum, John; Gordon, Charles; Grabsch, Heike; Haigh, Chris; Hongo, Michio; Johnston, David; Forbes-Young, Ricky; Kay, Elaine; Kaye, Philip; Lerut, Toni; Lovat, Laurence B; Lundell, Lars; Mairs, Philip; Shimoda, Tadakuza; Spechler, Stuart; Sontag, Stephen; Malfertheiner, Peter; Murray, Iain; Nanji, Manoj; Poller, David; Ragunath, Krish; Regula, Jaroslaw; Cestari, Renzo; Shepherd, Neil; Singh, Rajvinder; Stein, Hubert J; Talley, Nicholas J; Galmiche, Jean-Paul; Tham, Tony C K; Watson, Peter; Yerian, Lisa; Rugge, Massimo; Rice, Thomas W; Hart, John; Gittens, Stuart; Hewin, David; Hochberger, Juergen; Kahrilas, Peter; Preston, Sean; Sampliner, Richard; Sharma, Prateek; Stuart, Robert; Wang, Kenneth; Waxman, Irving; Abley, Chris; Loft, Duncan; Penman, Ian; Shaheen, Nicholas J; Chak, Amitabh; Davies, Gareth; Dunn, Lorna; Falck-Ytter, Yngve; Decaestecker, John; Bhandari, Pradeep; Ell, Christian; Griffin, S Michael; Attwood, Stephen; Barr, Hugh; Allen, John; Ferguson, Mark K; Moayyedi, Paul; Jankowski, Janusz A Z

    2012-08-01

    Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett's esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy in early-stage cervical cancer patients with intermediate risk factors

    PubMed Central

    Yu, Hao; Zhang, Linlin; Du, Xuelian; Sheng, Xiugui

    2016-01-01

    Objective To investigate the impact of postoperative adjuvant therapy on survival of patients with intermediate risk early-stage cervical squamous cell carcinoma. Methods A total of 133 consecutive patients with intermediate risk early-stage cervical squamous cell carcinoma treated at Shandong Cancer Hospital and Institute from February 2010 to March 2014 were enrolled in our study. All patients received adjuvant therapy and were subdivided into three groups: pelvic radiotherapy (RT; N=42), adjuvant chemotherapy + intracavitary radiotherapy (CT+ICRT; N=47), or concurrent chemoradiation (CCRT; N=44). Disease-free survival (DFS) and therapeutic complications were evaluated. Results There were no significant differences in DFS for patients treated with RT, CT+ICRT, and CCRT (P>0.05) with 3-year rates of 94.0%, 93.4%, and 97.6%, respectively. Frequencies of grade III–IV acute toxicities were higher in patients treated with CCRT (34.1%) than those treated with RT (9.5%) or CT+ICRT (16.7%; P<0.05), with no significant differences observed between RT and CT+ICRT groups (P>0.05). Grade I–II late toxicities were higher in CCRT (25%), followed by RT (19.0%), and finally, the CT+ICRT group (4.3%; P<0.05); with no significant differences observed between CCRT and RT groups (P>0.05). Conclusion Treatment with CT+ICRT or RT resulted in the equivalent of 3-year DFS compared to CCRT, but fewer therapeutic complications were observed with CT for patients with intermediate risk early-stage cervical squamous cell carcinoma. PMID:27942225

  5. Patterns of CT lung injury and toxicity after stereotactic radiotherapy delivered with helical tomotherapy in early stage medically inoperable NSCLC

    PubMed Central

    Agolli, L; Portalone, L; Migliorino, M R; Lopergolo, M G; Monaco, A; Dognini, J; Pressello, M C; Bracci, S; Donato, V

    2015-01-01

    Objective: To evaluate toxicity and patterns of radiologic lung injury on CT images after hypofractionated image-guided stereotactic body radiotherapy (SBRT) delivered with helical tomotherapy (HT) in medically early stage inoperable non-small-cell lung cancer (NSCLC). Methods: 28 elderly patients (31 lesions) with compromised pulmonary reserve were deemed inoperable and enrolled to undergo SBRT. Patterns of lung injury based on CT appearance were assessed at baseline and during follow up. Acute (6 months or less) and late (more than 6 months) events were classified as radiation pneumonitis and radiation fibrosis (RF), respectively. Results: After a median follow-up of 12 months (range, 4–20 months), 31 and 25 lesions were examined for acute and late injuries, respectively. Among the former group, 25 (80.6%) patients showed no radiological changes. The CT appearance of RF revealed modified conventional, mass-like and scar-like patterns in three, four and three lesions, respectively. No evidence of late lung injury was demonstrated in 15 lesions. Five patients developed clinical pneumonitis (four patients, grade 2 and one patient, grade 3, respectively), and none of whom had CT findings at 3 months post-treatment. No instance of symptomatic RF was detected. The tumour response rate was 84% (complete response + partial response). Local control was 83% at 1 year. Conclusion: Our findings show that HT-SBRT can be considered an effective treatment with a mild toxicity profile in medically inoperable patients with early stage NSCLC. No specific pattern of lung injury was demonstrated. Advances in knowledge: Our study is among the few showing that HT-SBRT represents a safe and effective option in patients with early stage medically inoperable NSCLC, and that it is not associated with a specific pattern of lung injury. PMID:25645106

  6. Consensus Statements for Management of Barrett’s Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

    PubMed Central

    BENNETT, CATHY; VAKIL, NIMISH; BERGMAN, JACQUES; HARRISON, REBECCA; ODZE, ROBERT; VIETH, MICHAEL; SANDERS, SCOTT; GAY, LAURA; PECH, OLIVER; LONGCROFT–WHEATON, GAIUS; ROMERO, YVONNE; INADOMI, JOHN; TACK, JAN; CORLEY, DOUGLAS A.; MANNER, HENDRIK; GREEN, SUSI; DULAIMI, DAVID AL; ALI, HAYTHEM; ALLUM, BILL; ANDERSON, MARK; CURTIS, HOWARD; FALK, GARY; FENNERTY, M. BRIAN; FULLARTON, GRANT; KRISHNADATH, KAUSILIA; MELTZER, STEPHEN J.; ARMSTRONG, DAVID; GANZ, ROBERT; CENGIA, GIANPAOLO; GOING, JAMES J.; GOLDBLUM, JOHN; GORDON, CHARLES; GRABSCH, HEIKE; HAIGH, CHRIS; HONGO, MICHIO; JOHNSTON, DAVID; FORBES–YOUNG, RICKY; KAY, ELAINE; KAYE, PHILIP; LERUT, TONI; LOVAT, LAURENCE B.; LUNDELL, LARS; MAIRS, PHILIP; SHIMODA, TADAKUZA; SPECHLER, STUART; SONTAG, STEPHEN; MALFERTHEINER, PETER; MURRAY, IAIN; NANJI, MANOJ; POLLER, DAVID; RAGUNATH, KRISH; REGULA, JAROSLAW; CESTARI, RENZO; SHEPHERD, NEIL; SINGH, RAJVINDER; STEIN, HUBERT J.; TALLEY, NICHOLAS J.; GALMICHE, JEAN–PAUL; THAM, TONY C. K.; WATSON, PETER; YERIAN, LISA; RUGGE, MASSIMO; RICE, THOMAS W.; HART, JOHN; GITTENS, STUART; HEWIN, DAVID; HOCHBERGER, JUERGEN; KAHRILAS, PETER; PRESTON, SEAN; SAMPLINER, RICHARD; SHARMA, PRATEEK; STUART, ROBERT; WANG, KENNETH; WAXMAN, IRVING; ABLEY, CHRIS; LOFT, DUNCAN; PENMAN, IAN; SHAHEEN, NICHOLAS J.; CHAK, AMITABH; DAVIES, GARETH; DUNN, LORNA; FALCK–YTTER, YNGVE; DECAESTECKER, JOHN; BHANDARI, PRADEEP; ELL, CHRISTIAN; GRIFFIN, S. MICHAEL; ATTWOOD, STEPHEN; BARR, HUGH; ALLEN, JOHN; FERGUSON, MARK K.; MOAYYEDI, PAUL; JANKOWSKI, JANUSZ A. Z.

    2017-01-01

    BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett’s esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. PMID:22537613

  7. Lower limb manual muscle testing in the early stages of Charcot-Marie-Tooth disease type 1A.

    PubMed

    Vinci, Paolo; Serrao, Mariano; Pierelli, Francesco; Sandrini, Giorgio; Santilli, Valter

    2006-01-01

    Charcot-Marie-Tooth disease (CMT) is a genetically and clinically heterogeneous disorder that affects approximately one in 2,500 individuals. CMT 1A, which is due to a duplication in the area containing the PMP-22 gene on chromosome 17, is the most frequent CMT subtype. To date, there is no consensus among authors about which muscles are weakened in the early stages of CMT, even though this knowledge would be crucial for deciding the most appropriate interventions to restore balance between muscles and prevent the development of deformities. The aim of this study was to evaluate the strength of several lower limb muscles in the early stages of CMT 1A. In a series of 45 patients (age 10-72 years; 21 males, 24 females) affected by CMT 1A, we evaluated 83 non-operated lower limbs that corresponded to the two milder stages of a five-level functional classification. The strength of two foot muscles, seven leg muscles, two thigh muscles, and three pelvic girdle muscles was graded using the manual muscle testing techniques of Daniels and Worthingham; the power of the triceps surae was graded, in the prone position, using a 4-level scale of ability to raise the heel from the floor. Muscle strength was determined on the basis of interobserver agreement estimated by kappa statistics between two observers. The flexor hallucis brevis and lumbricals were very weak in all the limbs; the leg muscles were strong in more than 90% of limbs, except the peronei (strong in 83.13%); all the triceps surae were strong in the prone test, but 16.87% were weak in the standing test; all the proximal muscles were strong. In the large majority of patients in the early stages of CMT 1A, the intrinsic foot muscles are very weak and the leg and proximal muscles are strong.

  8. To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

    ERIC Educational Resources Information Center

    Wöhrer, Veronika

    2014-01-01

    Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

  9. To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

    ERIC Educational Resources Information Center

    Wöhrer, Veronika

    2014-01-01

    Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

  10. 77 FR 25042 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... intends to issue commitments for Early Stage debenture leverage only until the end of fiscal year 2016... increasing program risk. In general, at the end of the initial 24 months, an Early Stage SBIC with ``expiring... than the base fee until all debenture leverage has been repaid and no further leverage will be issued...

  11. [Changes in radiotherapy indication for early-stage operated endometrial cancer. Revised staging, predictive factors. Conclusions from our own results].

    PubMed

    Póti, Zsuzsa; Katona, Csilla; Szalai, Tibor; Mayer, Árpád

    2016-07-03

    Optimal postoperative radiotherapy indications for early-stage operated endometrial cancers have drastically changed with the new imaging generation (magnetic resonance imaging, positron emission tomography/computed tomography) and more detailed pathomorphology. The depth and growth of tumor invasion, presence or absence of the lymph node metastases, grading and lymphovascular invasion are the most important factors to predict the progression and to influence the prognosis. In 2016, on the basis of these, the European Gynecologist Oncology and Radiotherapy Society published a report in which they proposed unanimously indications for postoperative radio- and/or radiochemotherapy. The basis of their work was prospective multilevel randomized investigations which could avoid over- or undertreatment hazards. The results obtained by the authors of this article from 164 operated patients in early-stage endometrium carcinoma seem to be acceptable, in spite of the fact that their earlier radiotherapy indication was different and in the pathological description lymphovascular invasion was not included and the grading was not always applied.

  12. [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.

  13. Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia

    PubMed Central

    Pearson, John; Aitchison, Alan; Dixon, Liane; Frizelle, Frank A.; Keenan, Jacqueline I.

    2017-01-01

    Background Enterotoxigenic Bacteroides fragilis (ETBF) is a toxin-producing bacteria thought to possibly promote colorectal carcinogenesis by modulating the mucosal immune response and inducing epithelial cell changes. Here, we aim to examine the association of colonic mucosal colonization with ETBF and the presence of a range of lesions on the colonic neoplastic spectrum. Methods Mucosal tissue from up to four different colonic sites was obtained from a consecutive series of 150 patients referred for colonoscopy. The presence and relative abundance of the B. fragilis toxin gene (bft) in each tissue sample was determined using quantitative PCR, and associations with clinicopathological characteristics were analysed. Findings We found a high concordance of ETBF between different colonic sites (86%). Univariate analysis showed statistically significant associations between ETBF positivity and the presence of low-grade dysplasia (LGD), tubular adenomas (TA), and serrated polyps (P-values of 0.007, 0.027, and 0.007, respectively). A higher relative abundance of ETBF was significantly associated with LGD and TA (P-values of < 0.0001 and 0.025, respectively). Increased ETBF positivity and abundance was also associated with left-sided biopsies, compared to those from the right side of the colon. Conclusion Our results showing association of ETBF positivity and increased abundance with early-stage carcinogenic lesions underlines its importance in the development of colorectal cancer, and we suggest that detection of ETBF may be a potential marker of early colorectal carcinogenesis. PMID:28151975

  14. Increased Endothelial Progenitor Cell Number in Early Stage of Endometrial Cancer.

    PubMed

    Paprocka, Maria; Kieda, Claudine; Kantor, Aneta; Bielawska-Pohl, Aleksandra; Dus, Danuta; Czekanski, Andrzej; Heimrath, Jerzy

    2017-06-01

    It is generally believed that circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) reflect the state of the endothelium, its injury and/or repair possibilities. In different types of cancers, increased numbers of CECs and EPCs were found, suggesting their participation in cancer angiogenesis. The objective of this study was to determine whether, in the blood circulation of women with early endometrial cancer, CEC and EPC levels differ from those of healthy women of similar age. For CEC number evaluation, samples of peripheral blood cells of women with endometrial carcinoma and control subjects were labeled with anti-CD31 and anti-CD45 antibodies; for EPCs, with anti-VEGFR2 (vascular-endothelium growth factor receptor 2)/KDR and anti-CD34 antibodies. The CEC and EPC cells were then quantified by flow cytometry. Endothelial progenitor cell numbers (CD34, VEGFR2/KDR) in the peripheral blood of women with endometrial carcinoma were significantly augmented as compared with those of control healthy women and CEC numbers (CD31, CD45) were similar in both groups. Cancer patients were divided according to the grading into G1 and G2 groups and according to the stage into International Federation of Gynecology and Obstetrics (FIGO) stage IA and FIGO IB groups. Statistically significant augmented EPC numbers were demonstrated only in G1 and FIGO IA patients. These results strongly suggest new vessel formation from recruited endothelial precursors as being involved mainly at the early stages of tumor progression.

  15. Is microsatellite instability (MSI) associated with multiplicity in early stage gastric neoplasias?

    PubMed

    Park, Hong Jun; Kim, Hyun-Soo; Kim, Jae Woo; Park, So Yeun; Kim, Bo Ra; Ryu, Ho Yoel; Lee, Il Young; Lee, Yong Kwan; Cho, Mee Yon

    2013-09-01

    The aim of this study was to investigate the relationship between microsatellite instability (MSI) and clinicopathologic features including multiplicity in early stage gastric neoplasias (ESGN). From November 2004 until September 2009, 372 patients with consecutive resected gastric neoplasias were retrospectively enrolled. The gastric neoplasias were composed of 117 advanced gastric cancers (AGCs) and 255 ESGNs including 31 gastric dysplasias (including low and high grade dysplasia) and 224 early gastric cancers (EGCs). Based on microsatellite markers, high MSI (MSI-H) was observed in 61 cases (16.4%) and low MSI (MSI-L) in 14 cases (3.8%) of 372 cases. There was a positive correlation between the presence of MSI-H and progression of gastric adenoma to gastric tumor. We compared ESGNs with microsatellite stable (MSS; 223 cases, 87.5%) and ESGNs with MSI-H (24 cases, 9.4%). The ESGNs with MSI-H were only associated with older age and female gender. There were no association with Helicobacter pylori infection, intestinal metaplasia, and distal location in contrast with EGCs with MSI-H. Furthermore, multiplicity of ESGNs was not associated with MSI status. The clinicopatholgic features of MSI-H phenotype were different according to the progression of gastric neoplasias from ESGNs to AGCs. ESGNs with MSI-H were only associated with old age, female sex. In addition ESGNs with MSI-H were not associated with an increased risk of multifocal tumors. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  16. Exclusive electron intraoperative radiotherapy in early-stage breast cancer: a monoinstitutional experience.

    PubMed

    Osti, Mattia Falchetto; Carnevale, Alessia; Bracci, Stefano; Amanti, Claudio; Lombardi, Augusto; Maggi, Stefano; DE Sanctis, Vitaliana; Valeriani, Maurizio; Enrici, Riccardo Maurizi

    2013-03-01

    To evaluate the effectiveness of intra-operative radiotherapy (IORT) in breast cancer in terms of local control, esthetic results and disease-free survival. From June 2007 to October 2011, 110 patients with early-stage breast cancer were submitted to quadrantectomy and IORT. A total dose of 21 Gy prescribed at 90-100% isodose was delivered in all cases. Patients were evaluated after surgery for early and late complications. Median follow-up was 27 (range: 2-54) months. In 10 patients (9.1%), breast ultrasound showed liponecrosis. Six patients (5.5%) developed grade 2 fibrosis. Disease-free survival rates at 2 and 3 years were 96.8% and 92.9 %. Three patients (2.7%) developed local recurrence, two patients (1.8%) distant metastasis. Two patients died. The 2- and 3-year overall survival rates were 100% and 97.3%, respectively. IORT could be an appropriate therapeutic alternative in selected patients although it remains investigational; longer follow-up to confirm these results is required.

  17. Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer

    PubMed Central

    Pietrowska, Monika; Marczak, Lukasz; Polanska, Joanna; Behrendt, Katarzyna; Nowicka, Elzbieta; Walaszczyk, Anna; Chmura, Aleksandra; Deja, Regina; Stobiecki, Maciej; Polanski, Andrzej; Tarnawski, Rafal; Widlak, Piotr

    2009-01-01

    Background Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints) detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions) that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity). Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0.0003) increased level of

  18. Involved-Field, Low-Dose Chemoradiotherapy for Early-Stage Anal Carcinoma

    SciTech Connect

    Hatfield, Paul; Cooper, Rachel; Sebag-Montefiore, David

    2008-02-01

    Purpose: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. Methods and Materials: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m{sup 2} on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m{sup 2}/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that were excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. Results: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. Conclusion: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.

  19. Esophagectomy as a Treatment Consideration for Early-Stage Esophageal Cancer and High-Grade Dysplasia.

    PubMed

    McLaren, Patrick J; Dolan, James P

    2016-10-01

    In recent years, a number of endoluminal procedures such as endoscopic resection and thermal ablation have emerged as less invasive treatment options for early esophageal cancer. These therapies have demonstrated excellent oncologic outcomes for dysplasia as well as intramucosal cancers. However, few studies have directly compared long-term outcomes of endoscopic therapy versus traditional esophagectomy. Current esophagectomy techniques now deliver consistently good outcomes in the hands of experienced surgeons at high volume centers, and this option should be considered an important treatment consideration for early esophageal cancer. Under current recommendations, esophagectomy should be considered for tumors invading the submucosa, tumors with high-risk pathologic features, bulky tumors, multinodular tumors, tumors within a long segment of Barrett's esophagus, and tumors adjacent to a hiatal hernia. Likewise, individual patient factors and comorbidities must also be considered when determining the best treatment for a patient with early esophageal cancer. The risk of missing metastatic disease or recurrence that is associated with endoscopic treatment must be weighed against the surgical risks of esophagectomy. With these considerations in mind, the aim of this article is to review the current guidelines and literature that explore the role of esophagectomy for early esophageal malignancy in the era of endoscopic therapies.

  20. A risk scoring system to determine recurrence in early-stage type 1 endometrial cancer: a French multicentre study.

    PubMed

    Bendifallah, Sofiane; Canlorbe, Geoffroy; Huguet, Florence; Coutant, Charles; Hudry, Delphine; Graesslin, Olivier; Raimond, Emilie; Touboul, Cyril; Collinet, Pierre; Bleu, Géraldine; Daraï, Emile; Ballester, Marcos

    2014-12-01

    To develop a risk scoring system (RSS) to determine recurrence in women with early-stage type 1 endometrial cancer (EC). Data of 396 women with early-stage type 1 EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from multicentre database (training set). A risk model for predicting recurrence was developed and internally validated with the bootstrap technique. The RSS was externally validated using data from an independent population. Overall, the recurrence rate was 12.1 %. The median follow-up and initial time to recurrence were 34 (range 1-152) and 26 (range 1-151) months, respectively. Recurrence was associated with five variables: age ≥60 years, histological grade III, primary tumor diameter >2 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores. A total score of 6.5 points corresponded to the optimal threshold of the RSS. For women with a score <6.5 or ≥6.5, the recurrence rates were 8.4 % (30/357) and 48.7 % (19/39) in the training set, respectively. At this threshold, the diagnostic accuracy of the RSS was 87 %. Areas under the curve of the receiver-operating characteristics for predicting recurrence at internal and external validation were 0.74 [95 % confidence interval (CI) 0.71-0.77] and 0.82 (95 % CI 79-85), respectively. This RSS identified two subsets of women with low and high risk of recurrence among women with early-stage type 1 EC. It could be helpful to better define indications for nodal staging and adjuvant therapy.

  1. Mastectomy trends for early-stage breast cancer: a report from the EUSOMA multi-institutional European database.

    PubMed

    Garcia-Etienne, Carlos A; Tomatis, Mariano; Heil, Joerg; Friedrichs, Kay; Kreienberg, Rolf; Denk, Andreas; Kiechle, Marion; Lorenz-Salehi, Fatemeh; Kimmig, Rainer; Emons, Günter; Danaei, Mahmoud; Heyl, Volker; Heindrichs, Uwe; Rageth, Christoph J; Janni, Wolfgang; Marotti, Lorenza; del Turco, Marco Rosselli; Ponti, Antonio

    2012-09-01

    Recent single-institution reports have shown increased mastectomy rates during the last decade. Further studies aiming to determine if these reports could be reflecting a national trend in the United States of America (US) have shown conflicting results. We report these trends from a multi-institutional European database. Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified patients with newly diagnosed unilateral early-stage breast cancer (stages 0, I or II) to examine rates and trends in surgical treatment. A total of 15,369 early-stage breast cancer cases underwent surgery in 13 Breast Units from 2003 to 2010. Breast conservation was successful in 11,263 cases (73.3%). Adjusted trend by year showed a statistically significant decrease in mastectomy rates from 2005 to 2010 (p = 0.003) with a progressive reduction of 4.24% per year. A multivariate model showed a statistically significant association of the following factors with mastectomy: age < 40 or ≥ 70 years, pTis, pT1mi, positive axillary nodes, lobular histology, tumour grade II and III, negative progesterone receptors and multiple lesions. Our study demonstrates that a high proportion of patients with newly diagnosed unilateral early-stage breast cancer from the eusomaDB underwent breast-conserving surgery. It also shows a significant trend of decreasing mastectomy rates from 2005 to 2010. Moreover, our study suggests mastectomy rates in the population from the eusomaDB are lower than those reported in the US. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Evaluating Use Characteristics for the Oncotype Dx 21-Gene Recurrence Score and Concordance With Chemotherapy Use in Early-Stage Breast Cancer

    PubMed Central

    Chen, Clara; Dhanda, Rahul; Tseng, Wan-Yu; Forsyth, Michael; Patt, Debra A.

    2013-01-01

    Purpose: Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups. Methods: Patients with ESBC with documented estrogen receptor–positive, lymph node–negative, human epidermal growth factor receptor 2–negative tumors registered within McKesson Specialty Health's iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed. Results: The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age ≤ 45, 46-55, 56-65, 66-75, and ≥ 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and ≥ 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2, and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups. Conclusion: Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use. PMID:23942918

  3. Definitive Treatment of Early-Stage Non-Small Cell Lung Cancer with Stereotactic Ablative Body Radiotherapy in a Community Cancer Center Setting.

    PubMed

    Heal, Cory; Ding, William; Lamond, John; Wong, Michael; Lanciano, Rachelle; Su, Stacy; Yang, Jun; Feng, Jing; Arrigo, Stephen; Markiewicz, Deborah; Hanlon, Alexandra; Brady, Luther

    2015-01-01

    Stereotactic ablative body radiotherapy (SABR) provides a superior non-small cell lung cancer (NSCLC) treatment option when compared to conventional radiotherapy for patients deemed inoperable or refusing surgery. This study retrospectively analyzed the rates of tumor control and toxicity following SABR treatment (Cyberknife system) of primary early-stage NSCLC in a community setting. One hundred patients were treated between 2007 and 2011. Patients with T3-4 or N1-3 disease, metastasis, recurrent local disease, or a non-lung primary were excluded from analysis. All patients had biopsy proven disease. Staging included CT or fluorodeoxyglucose-positron emission tomography scan. Median dose was 54 Gy (45-60); 18 Gy (10-20) per fraction. Median planned target volume expansion was 8 mm (2-10). Median BED was 151.2. Tumors were tracked via Synchrony, X-Sight Lung, or X-Sight Spine. Patients were evaluated for local control, overall survival (OS), and toxicity. All local failures were determined by evaluating post treatment PET/CT. With a median follow up of 27.5 months, the 1-, 2-, and 3-year local control rates were 100, 93.55, and 84.33%, respectively. Median survival was 2.29 years; actuarial 3-year survival was 37.20%. Grade-3 toxicity was observed in 2% of patients (pneumonia within 2 months of treatment, n = 1; chronic pneumonitis requiring hospital admission, n = 1). No patients demonstrated toxicity above Grade-3. Multivariate analysis did not show T-stage as an independent predictor of OS, though it did trend toward significance. In a community-center setting, definitive treatment of NSCLC with SABR for non-surgical candidates and those who choose to forego surgery result in excellent and comparable rates of local control and toxicity compared to published series from large academic centers.

  4. 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.

  5. Primary treatment options for high risk/medically inoperable early stage NSCLC patients

    PubMed Central

    Jones, Guy C.; Kehrer, Jason D.; Kahn, Jenna; Koneru, Bobby N.; Narayan, Ram; Thomas, Tarita O.; Camphausen, Kevin; Mehta, Minesh P; Kaushal, Aradhana

    2015-01-01

    Lung cancer is among the most common cancers worldwide, and the leading cause of cancer death in both men and women. For patients with early stage (AJCC T1-2, N0) non-small cell lung cancer the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, medical comorbities often present in patients with lung cancer, may preclude the option of surgical resection . In such cases, a number of minimal to non-invasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages including patient convenience, treatment in an outpatient setting, and acceptable toxicities including reduced impact on lung function and a modest risk of post-procedure chest wall pain. This manuscript seeks to provide a comprehensive review of the literature including reported outcomes, complications and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy and stereotactic body radiation therapy. PMID:26027433

  6. 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.

  7. Early-stage Massive Star Formation near the Galactic Center: Sgr C

    NASA Astrophysics Data System (ADS)

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

    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 H2 and Brackett γ emission alongside a previously detected compact radio source. We calculate the cores' joint mass to be ~103 M ⊙, with column densities of 1-2 × 1024 cm-2. We show the host molecular cloud to hold ~105 M ⊙ 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.

  8. Preoperative [18]fluorodeoxyglucose-positron emission tomography/computed tomography in early stage breast cancer: Rates of distant metastases.

    PubMed

    Vinh-Hung, Vincent; Everaert, Hendrik; Farid, Karim; Djassemi, Navid; Baudin-Veronique, Jacqueline; Bougas, Stefanos; Michailovich, Yuriy; Joachim-Contaret, Clarisse; Cécilia-Joseph, Elsa; Verschraegen, Claire; Nguyen, Nam P

    2017-07-28

    To investigate rates of distant metastases (DM) detected with [18]fluorodeoxyglucose-positron emission tomography/computed tomography ((18)FDG-PET/CT) in early stage invasive breast cancer. We searched the English language literature databases of PubMed, EMBASE, ISI Web of Knowledge, Web of Science and Google Scholar, for publications on DM detected in patients who had (18)FDG-PET/CT scans as part of the staging for early stages of breast cancer (stage I and II), prior to or immediately following surgery. Reports published between 2011 and 2017 were considered. The systematic review was conducted according to the PRISMA guidelines. Among the 18 total studies included in the analysis, the risk of DM ranged from 0% to 8.3% and 0% to 12.9% for stage I and II invasive breast cancer, respectively. Among the patients with clinical stage II, the rate of occult metastases diagnosed by (18)FDG-PET/CT was 7.2% (range, 0%-19.6%) for stage IIA and 15.8% (range, 0%-40.8%) for stage IIB. In young patients (< 40-year-old), (18)FDG-PET/CT demonstrated a higher prevalence of DM at the time of diagnosis for those with aggressive histology (i.e., triple-negative receptors and poorly differentiated grade). Young patients with poorly differentiated tumors and stage IIB triple-negative breast cancer may benefit from (18)FDG-PET/CT at initial staging to detect occult DM prior to surgery.

  9. 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.

  10. 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.

  11. Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR

    PubMed Central

    Raynor, Michael P; Stephenson, Sally-Anne; Pittman, Kenneth B; Walsh, David CA; Henderson, Michael A; Dobrovic, Alexander

    2009-01-01

    Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients. PMID:19500345

  12. 77 FR 74908 - Small Business Investment Companies-Early Stage SBICs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-18

    ... addressing barriers to success for entrepreneurs and small businesses. II. Management Assessment... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Small Business Investment Companies--Early Stage SBICs AGENCY: U.S. Small Business...

  13. 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.

  14. 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. |

  15. New NIA Booklet By and For People With Early-Stage Alzheimer's Disease

    MedlinePlus

    ... Booklet By and For People With Early-Stage Alzheimer's Disease Past Issues / Fall 2007 Table of Contents For ... you have a family member or friends with Alzheimer's disease? Are you wondering what they're going through ...

  16. An actuarial approach to comparing early stage and late stage lung cancer mortality and survival.

    PubMed

    Goldberg, Sara W; Mulshine, James L; Hagstrom, Dale; Pyenson, Bruce S

    2010-02-01

    Comparing the mortality characteristics of different cohorts is an essential process in the life insurance industry. Pseudodisease, lead-time bias, and length bias, which are critical to determining the value of cancer screening, have close analogues in life insurance company management, including the temporal impact of underwriting. Ratios of all-cause mortality rates for cancer cohorts relative to standard population mortality rates can provide insights into early stage and late stage mortality differences, differences by age, sex, race, and histology, and allow modeling of biases associated with early stage detection or screening protocols. The Surveillance, Epidemiology and End Results (SEER) data set has characteristics that allow efficient application of actuarial techniques. We show the mortality burden associated with treated early stage lung cancer and that identifying all lung cancers at early stage could reduce US lung cancer deaths by over 70,000 per year.

  17. 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.

  18. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

    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. For some time, the national lab’s Nanotechno

  19. Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR

    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. For some time, the national lab’s Nanotechno

  20. 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.

  1. 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.

  2. Tumour budding evaluated in biopsy specimens is a useful predictor of prognosis in patients with cN0 early stage oral squamous cell carcinoma.

    PubMed

    Seki, Mai; Sano, Takaaki; Yokoo, Satoshi; Oyama, Tetsunari

    2017-05-01

    Oral squamous cell carcinoma (OSCC) prognosis depends upon lymph node metastasis (LNM). We have reported recently that tumour budding is a good predictive factor for LNM in squamous cell carcinoma (SCC) of the tongue and floor of the mouth (FOM). Our aim was to evaluate whether tumour budding is a good prognostic factor in OSCC. We examined conventional histopathological assessment and a new factor, tumour budding, in 209 cases of OSCC in incisional biopsy specimens. The relationship of tumour budding with LNM and prognosis was studied. The budding score was evaluated using immunostaining for pan-cytokeratin in all biopsies specimens; the number of budding foci was counted using a ×20 objective lens. Significant factors using univariate analysis (P < 0.05) in association with LNM were the budding score (intermediate or high score ≥3; high score ≥5), tumour grade (2 and 3), tumour depth (≥5 mm), infiltrative pattern (INF), lymphatic invasion and vessel invasion. In multivariate analysis, the budding score, INF and lymphatic invasion were found to be independent risk factors for LNM; in particular, budding score concerning relapse-free survival was statistically significant among patients with T1/2 stage and cN0 cancer using the Kaplan-Meier method and the log-rank test. The assessment of tumour budding is effective in predicting prognosis in cN0 early stage OSCC. In T1/2 stage and cN0 cancer, prophylactic neck dissection to prevent LNM should be considered when the tumour budding score regarding pre-operative biopsy specimens is intermediate or high. © 2016 John Wiley & Sons Ltd.

  3. Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy Alone

    SciTech Connect

    Su Shengfa; Han Fei; Zhao Chong; Chen Chunyan; Xiao Weiwei; Li Jiaxin; Lu Taixiang

    2012-01-01

    Purpose: Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. Methods and Materials: Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. Results: At a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. Conclusions: IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively

  4. Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

    PubMed

    Bogani, Giorgio; Tagliabue, Elena; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Casarin, Jvan; Chiappa, Valentina; Dondi, Giulia; Leone Roberti Maggiore, Umberto; Scaffa, Cono; Borghi, Chiara; Montanelli, Luca; Lorusso, Domenica; Raspagliesi, Francesco

    2017-08-02

    To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (p<0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Do Deregulated Cas Proteins Induce Genomic Instability in Early-Stage Ovarian Cancer

    DTIC Science & Technology

    2006-12-01

    Genomic Instability in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR: Erica A. Golemis, Ph.D. CONTRACTING...ORGANIZATION: Institute for Cancer Research Philadelphia PA 19111-2434 REPORT DATE: December 2006 TYPE OF REPORT...SUBTITLE Do Deregulated Cas Proteins Induce Genomic Instability in Early-Stage Ovarian 5a. CONTRACT NUMBER Cancer 5b. GRANT NUMBER W81XWH-06-1-0073

  6. Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2013-10-01

    0521 TITLE: Identification of a genomic signature predicting for recurrence in early stage ovarian cancer PRINCIPAL INVESTIGATOR: Michael...Identification of a genomic signature predicting for recurrence in early stage ovarian 5b. GRANT NUMBER cancer 5c. PROGRAM ELEMENT NUMBER 6...obtained IRB approval for using these cancer FFPE samples to identify molecular features that distinguish recurrent and non-recurrent tumors through RNA

  7. Shipboard Electrical System Modeling for Early-Stage Design Space Exploration

    DTIC Science & Technology

    2013-04-01

    Shipboard Electrical System Modeling for Early -Stage Design Space Exploration Aaron M. Cramer, Hanling Chen Department of Electrical and Computer...Department United States Naval Academy Annapolis, MD, USA Email: zivi@usna.edu Abstract—In early -stage design exploration, it has been found that...involved the use of linear programming to model the action of the power system [6]. In this approach, the mechanical dynamics associated with prime movers

  8. Early Stage Expansion and Time-Resolved Spectral Emission of Laser-Induced Plasma from Polymer

    DTIC Science & Technology

    2009-01-01

    thus its interaction with ambient air. These influences can significantly alter spectral emission of the plasma. For organic samples especially...to the analysis of organic materials. In this paper, we report observations of early stage expansion and interaction with ambient air of the plasma...ablation interaction is absent. Subsequent to the early stage expansion, we observe for each studied ablation regime, spectral emission from CN, a typical

  9. Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2014-10-01

    RNAseq of 400 training specimens (Months 12-18) 2. Import raw data into public databases (Months 12-18) 3. Generate preliminary gene signature through...This included sequencing a sample test of 10 tumors and comparing the sequencing results of these early stage samples with publicly available RNAseq ...addressed and fulfill an important unmet need. KEYWORDS: Early Stage Ovarian Cancer, genomic predictive signature, recurrence, RNAseq Research

  10. Fertility sparing surgery in early stage epithelial ovarian cancer.

    PubMed

    Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

    2014-10-01

    Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group.

  11. 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.

  12. 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. © 2012 The British Psychological Society.

  13. Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

    SciTech Connect

    Calais, G.; Le Floch, O.; Chauvet, B.; Reynaud-Bougnoux, A.; Bougnoux, P. )

    1989-12-01

    In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor.

  14. Cytological Study of Grade 3 Endometrioid Adenocarcinoma of Endometrial Origin: Cytoarchitecture and Features of Cell Clusters Assessed With Endometrial Brushing Cytology--Focusing on a comparison with endometrioid adenocarcinoma Grade 1, 2.

    PubMed

    Matsui, Naruaki; Kajiwara, Hiroshi; Morishita, Akihiro; Tsukada, Hitomi; Nakazawa, Kazumi; Miyazawa, Masaki; Mikami, Mikio; Nakamura, Naoya; Sato, Shinkichi

    2015-06-20

    Aim of study was to clarify the cytological characteristics of grade 3 endometrioid adenocarcinoma of endometrial origin (G3 EA) by endometrial brushing cytology. The subjects were 11 patients in whom G3 EA was diagnosed by review of preoperative cytological specimens obtained at our hospital and related institutions between 2000 and 2010. These patients were investigated with respect to the preoperative cytological diagnosis, background changes, cell cluster patterns, and individual cellular findings. Background changes were classified as inflammatory or tumorous, while cell clusters were classified as overlapping cell cluster, sheet-like cell cluster, clump of high dense gland, papillary, or other cell cluster. Cellular findings were investigated by comparing the incidence of squamous and clear cell metaplasia, the nuclear rounding rate, and the nuclear area with the findings in a control group (35 patients with G1-2 EA). Background changes were classified as inflammatory in 63.6% and necrotic in 36.4%. The cell clusters were classified as overlapping cell cluster in 44.8%, cell cluster in 21.7%, clump of high dense gland in 10.0%, papillary in 4.0%, and other cell cluster in 19.5%. The incidence of squamous and clear cell metaplasia was 27.2% and 18.1%, respectively. The mean nuclear rounding rate was 0.97, and the mean nuclear area was 55.98 µm2. Investigation of the cytoarchitecture of G3 EA with endometrial brushing cytology revealed overlapping cell cluster and tumor cells of a relatively uniform size. These findings suggest that it is necessary to recognize that there are differences between the cytological findings of G3 EA and the usual features of G1-2 EA.

  15. Accelerated versus conventional radiation fractionation in early stage carcinoma larynx.

    PubMed

    Alam, M S; Perween, R; Siddiqui, S A

    2016-01-01

    In our study, we have treated cases of early glottic carcinoma by two different dose-fractionation schedules in relation to overall treatment time. This is an analysis of 29 patients with invasive, previously untreated T1and T2squamous cell carcinoma of true vocal cord that was treated by radical radiation therapy. All patients were treated with a continuous course of radiation therapy with once-daily fractionation. All the patients were treated 5 days a week from Monday to Friday. The fractionation regime was either: (1) 62.5 Gy/25fractions/5 weeks at 2.5 Gy fractions (Regimen 1), (2) 70 Gy/35 fractions/7 weeks at 2 Gy/fraction (Regimen 2). Regimen 1 included 15/29 patients (51.72%) and Regimen 2 included 14/29 patients (48.27%). Patients were evaluated for: (1) Locoregional control, (2) acute and late radiation toxicities, (3) quality of voice. There was no significant difference in terms of locoregional control rate, acute and late radiation toxicities in both groups. Voice quality during and after radiation was comparable in both arms. Use of high dose per fraction schedule with shorter duration of treatment results in comparable local control as well as the quality of voice to the protracted course of radiotherapy without increase in treatment-related toxicities. Shorter overall treatment time can be of great advantage in terms of time, cost, comfort, and acceptability by the patients.

  16. 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.

  17. 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

  18. Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study

    SciTech Connect

    Cai Ling; Stauder, Michael C.; Zhang Yujing; Poortmans, Philip; Li Yexiong; Constantinou, Nicolaos; Thariat, Juliette; Kadish, Sidney P.; Nguyen, Tan Dat; Kirova, Youlia M.; Ghadjar, Pirus; Weber, Damien C.; Bertran, Victoria Tuset; Ozsahin, Mahmut; Mirimanoff, Rene-Olivier

    2012-05-01

    Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score {<=}1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

  19. Impact of age-adjusted Charlson comorbidity score on outcomes for patients with early-stage endometrial cancer.

    PubMed

    Robbins, Jared R; Gayar, Omar H; Zaki, Mark; Mahan, Meredith; Buekers, Thomas; Elshaikh, Mohamed A

    2013-12-01

    To determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer. After IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I-II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0-1 (n=204), 2-3 (n=293) and >3 (n=174). Kaplan-Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint. After a median follow-up of 85 months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0-1; 81.7%, 95.3%, and 89.8% for AAC 2-3: and 56%, 88.2%, and 84.9% for AAC>3 (p<0.0001, p=0.005 and p=0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not. Comorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma. © 2013.

  20. Fluorescence Visualization-Guided Surgery for Early-Stage Oral Cancer.

    PubMed

    Poh, Catherine F; Anderson, Donald W; Durham, J Scott; Chen, Jiahua; Berean, Kenneth W; MacAulay, Calum E; Rosin, Miriam P

    2016-03-01

    reduction in the 3-year local recurrence rate, from 40.6% (26 of 64 patients) to 6.5% (6 of 92 patients) (P < .001). Among the 90 patients with high-grade lesions, the 62 patients in the FV group showed a reduction in local recurrence rate from 11 of 28 patients (39.3%) to 5 of 62 patients (8.1%) (P < .001). The data also indicated that, compared with conventional surgery, the FV-guided approach for squamous cell carcinoma was associated with less regional failure (14 of 92 patients [15.2%] vs 16 of 64 [25.0%]; P = .08) and death (12 of 92 patients [13.0%] vs 13 of 64 [20.3%]; P = .22), although these differences were not statistically significant. In this study, the use of FV as part of the surgical margin decision process significantly reduced the rate of local recurrence in preinvasive high-grade and early-stage oral cancers. An ongoing multicenter, phase 3, randomized surgical trial has completed accrual, and the data will be used to validate the results of this study.

  1. Current developments in the treatment of early-stage classical Hodgkin lymphoma.

    PubMed

    Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

    2016-09-01

    After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

  2. [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.

  3. Efficient harvesting methods for early-stage snake and turtle embryos.

    PubMed

    Matsubara, Yoshiyuki; Kuroiwa, Atsushi; Suzuki, Takayuki

    2016-04-01

    Reptile development is an intriguing research target for understating the unique morphogenesis of reptiles as well as the evolution of vertebrates. However, there are numerous difficulties associated with studying development in reptiles. The number of available reptile eggs is usually quite limited. In addition, the reptile embryo is tightly adhered to the eggshell, making it a challenge to isolate reptile embryos intact. Furthermore, there have been few reports describing efficient procedures for isolating intact embryos especially prior to pharyngula stage. Thus, the aim of this review is to present efficient procedures for obtaining early-stage reptilian embryos intact. We first describe the method for isolating early-stage embryos of the Japanese striped snake. This is the first detailed method for obtaining embryos prior to oviposition in oviparous snake species. Second, we describe an efficient strategy for isolating early-stage embryos of the soft-shelled turtle. © 2016 Japanese Society of Developmental Biologists.

  4. The Memory Club: Providing support to persons with early-stage dementia and their care partners.

    PubMed

    Gaugler, Joseph E; Gallagher-Winker, Karen; Kehrberg, Kathy; Lunde, Angela M; Marsolek, Connie M; Ringham, Kathryn; Thompson, Gerise; Barclay, Michelle

    2011-05-01

    There is a growing emphasis on delivering services for persons with early-stage dementia (ie, ''persons with memory loss,'' or PWMLs) and their family members (care partners). The goal of this evaluation was to determine whether participation in the Memory Club, a 10- to 13-session joint support group, would result in decreased distress, enhanced preparation for care, and improved feelings of confidence managing the challenges of early-stage dementia. The single group, pre-/post-test evaluation included 63 PWMLs and 61 care partners who participated in three Memory Club sites in Minnesota. Paired T-test results found that care partners reported significant (P < .05) increases in preparation activities, feelings of preparation, and confidence in managing memory loss. The results suggest that the Memory Club can fill an important gap in early-stage dementia care by offering care partners the opportunity to plan, prepare, and increase coping skills in the face of early dementia progression.

  5. Using Spirituality to Cope with Early Stage Alzheimer’s disease

    PubMed Central

    Grando, Victoria T.

    2010-01-01

    Alzheimer’s disease (AD) robs persons living with this disease of their independence and self-esteem, which can lead to depression, anxiety, and loneliness. Understanding how people with early stage AD cope is a critical step to enhance their adaptive abilities and ultimately improve their quality of life. This qualitative study describes how individuals with early stage AD use spirituality to cope with the losses of self-esteem, independence, and social interaction that they face. The purposive sample for this focused ethnography study consisted of 15 participants living at home in central Arkansas. Holding onto faith, seeking reassurance and hope, and staying connected were the global themes. Personal faith, prayer, connection to church, and family support enhanced the ability for people with early stage AD to keep a positive attitude as they face living with Alzheimer’s. PMID:19282270

  6. 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.

  7. Identification of Early-Stage Alzheimer's Disease Using Sulcal Morphology and Other Common Neuroimaging Indices

    PubMed Central

    Cai, Kunpeng; Xu, Hong; Guan, Hao; Zhu, Wanlin; Jiang, Jiyang; Cui, Yue; Zhang, Jicong; Liu, Tao; Wen, Wei

    2017-01-01

    Identifying Alzheimer’s disease (AD) at its early stage is of major interest in AD research. Previous studies have suggested that abnormalities in regional sulcal width and global sulcal index (g-SI) are characteristics of patients with early-stage AD. In this study, we investigated sulcal width and three other common neuroimaging morphological measures (cortical thickness, cortical volume, and subcortical volume) to identify early-stage AD. These measures were evaluated in 150 participants, including 75 normal controls (NC) and 75 patients with early-stage AD. The global sulcal index (g-SI) and the width of five individual sulci (the superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure) were extracted from 3D T1-weighted images. The discriminative performances of the other three traditional neuroimaging morphological measures were also examined. Information Gain (IG) was used to select a subset of features to provide significant information for separating NC and early-stage AD subjects. Based on the four modalities of the individual measures, i.e., sulcal measures, cortical thickness, cortical volume, subcortical volume, and combinations of these individual measures, three types of classifiers (Naïve Bayes, Logistic Regression and Support Vector Machine) were applied to compare the classification performances. We observed that sulcal measures were either superior than or equal to the other measures used for classification. Specifically, the g-SI and the width of the Sylvian fissure were two of the most sensitive sulcal measures and could be useful neuroanatomical markers for detecting early-stage AD. There were no significant differences between the three classifiers that we tested when using the same neuroanatomical features. PMID:28129351

  8. Is Older Age a Real Adverse Prognostic Factor in Women With Early-Stage Endometrial Carcinoma? A Matched Analysis.

    PubMed

    Haley, Laura; Burmeister, Charlotte; Buekers, Thomas; Elshaikh, Mohamed A

    2017-03-01

    The aim of this study was to evaluate if older age alone negatively impacts survival endpoints in women with early-stage uterine endometrioid carcinoma (EC), or its reported prognostic impact is due to an interaction with other well-known adverse factors using matched-analysis methodology. We identified 1254 patients with International Federation of Gynecology and Obstetrics stage I-II EC who underwent hysterectomy at our institution. We created 2 matched groups based on International Federation of Gynecology and Obstetrics stage, tumor grade, lymph node dissection status, and the type of adjuvant management. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were calculated. A total 297 women 70 years or older were matched with 297 women younger than 70 years. The 2 groups were well balanced except for age and higher body mass index in younger patients. There were no significant difference between older and younger patients in regard to 5-year RFS (85% vs 87%; P = 0.52) or DSS (93% for both groups with P = 0.77). Five-year OS was shorter in older patients (76% vs 88% with P < 0.001). On multivariate analysis for RFS and DSS, high tumor grade and the presence of lymphovascular space invasion (LVSI) were the only 2 predictors of shorter RFS and DSS (P = 0.01 and P = 0.02, and P = 0.01 and P = 0.01, respectively). Tumor grade and LVSI also were predictors of shorter OS. Our study suggests that when older patients with EC are matched with younger patients based on tumor stage, grade, and adjuvant management the prognostic impact of old age disappears. High tumor grade and LVSI remained as independent predictors of survival endpoints.

  9. Aurintricarboxylic Acid Inhibits the Early Stage of Vaccinia Virus Replication by Targeting both Cellular and Viral Factors▿

    PubMed Central

    Myskiw, Chad; Deschambault, Yvon; Jefferies, Kristel; He, Runtao; Cao, Jingxin

    2007-01-01

    Aurintricarboxylic acid (ATA) has been shown to inhibit the replication of viruses from several different families, including human immunodeficiency virus, vesicular stomatitis virus, and the coronavirus causing severe acute respiratory syndrome. This study characterizes the inhibitory effect of ATA on vaccinia virus replication in HeLa, Huh7, and AD293 cells. Vaccinia virus replication is significantly abrogated upon ATA treatment, which is associated with the inhibition of early viral gene transcription. This inhibitory effect may be attributed to two findings. First, ATA blocks the phosphorylation of extracellular signal-regulated kinase 1/2, an event shown to be essential for vaccinia virus replication. Second, ATA inhibits the phosphatase activity of the viral enzyme H1L, which is required to initiate viral transcription. Thus, ATA inhibits vaccinia virus replication by targeting both cellular and viral factors essential for the early stage of replication. PMID:17192307

  10. Minimally Invasive Surgery for Early-Stage Lung Cancer: From Innovation to Standard of Care.

    PubMed

    White, Abby; Swanson, Scott J

    2016-11-15

    The era of minimally invasive surgery for lung cancer follows decades of research; the collection and interpretation of countless qualitative and quantitative data points; and tireless efforts by a few pioneering thoracic surgeons who believed they could deliver a safe and oncologically sound operation with less tissue trauma, an improved physiologic profile, and fewer complications than traditional open surgery. This review highlights those efforts and the role of minimally invasive surgery for early-stage lung cancer in light of evolving technology, the emerging understanding of the biology of early-stage lung cancer, and lung cancer screening.

  11. Highly-accurate metabolomic detection of early-stage ovarian cancer

    PubMed Central

    Gaul, David A.; Mezencev, Roman; Long, Tran Q.; Jones, Christina M.; Benigno, Benedict B.; Gray, Alexander; Fernández, Facundo M.; McDonald, John F.

    2015-01-01

    High performance mass spectrometry was employed to interrogate the serum metabolome of early-stage ovarian cancer (OC) patients and age-matched control women. The resulting spectral features were used to establish a linear support vector machine (SVM) model of sixteen diagnostic metabolites that are able to identify early-stage OC with 100% accuracy in our patient cohort. The results provide evidence for the importance of lipid and fatty acid metabolism in OC and serve as the foundation of a clinically significant diagnostic test. PMID:26573008

  12. CSMP Mathematics for the Upper Primary Grades, Part IV, Student Materials: Worksheets; Galaxy of Problems 1, 2, 3, 4; Fishing for Numbers, Part IV; To Picture; Subtraction Problems.

    ERIC Educational Resources Information Center

    CEMREL, Inc., St. Ann, MO.

    These are some of the individual materials needed by students using the Comprehensive School Mathematics Program for the Upper Primary Grades, Part IV. The book of "Worksheets" contains materials that are labeled with the same letter and number as the lessons with which they are to be used. The four "Galaxy of Problems"…

  13. Classification, Seriation, and Counting in Grades 1, 2, and 3 as Two-Year Longitudinal Predictors for Low Achieving in Numerical Facility and Arithmetical Achievement?

    ERIC Educational Resources Information Center

    Desoete, Annemie; Stock, Pieter; Schepens, Annemie; Baeyens, Dieter; Roeyers, Herbert

    2009-01-01

    Previous research stresses the importance of seriation, classification, and counting abilities that should be assessed in kindergarten, when looking for crucial predictors of mathematical learning disabilities in Grade 1. This study examines (n = 158) two-year-long predictive relationships between children's seriation, classification, procedural…

  14. 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.

  15. [Clinicopathologic characteristics and risk factors for lung metastasis after radical hysterectomy in early-stage cervical cancer].

    PubMed

    Zheng, Aiwen; Chen, Yaqing; Fang, Jing; Zhang, Yingli

    2015-03-01

    To discuss the clinicopathologic characteristics and risk factors for lung metastasis of early-stage cervical cancer after radical hysterectomy. The complete clinicopathologic data of patients with lung metastasis of cervical cancer after radical surgery from January 2008 to December 2013 admitted in Zhejiang Cancer Hospital were retrospectively analyzed by univariate and multivariate analysis. (1) There were 38 cases of early cervical cancer suffered from lung metastasis after radical hysterectomy during the period. The median age at diagnosis of cervical cancer was 46 years, the average lung metastasis time was 13 months after operation, 50.0% (19/38) cases occurred in the first year. Thirty-one cases were squamous cell carcinoma and 7 cases were non-squamous cell carcinoma. (2) Univariate analysis showed that age, clinical stage, manner of tumor growth, tumor grade, perineuronal invasion, para-aortic lymph node metastasis were not significant effect on postoperative lung metastasis (all P>0.05). But tumor size, histologic types, depth of stromal invasion, uterine body infiltration, lympho-vascular space invasion,pelvic lymph node metastasis, positive margin and abnormal tumor markers were significantly correlated with postoperative lung metastasis (all P<0.05). Multivariate analysis showed that only tumor size, histologic types and pelvic lymph node metastasis were independent risk factors for lung metastasis of cervical cancer (P<0.05). Patients of early-stage cervical cancer with lung metastasis mostly occurs within 1 year after radical hysterectomy. Local large tumor lesions (tumor size >4 cm), non-squamous cell carcinoma and pelvic lymph node metastasis were more likely to have lung metastasis.

  16. Preoperative [18]fluorodeoxyglucose-positron emission tomography/computed tomography in early stage breast cancer: Rates of distant metastases

    PubMed Central

    Vinh-Hung, Vincent; Everaert, Hendrik; Farid, Karim; Djassemi, Navid; Baudin-Veronique, Jacqueline; Bougas, Stefanos; Michailovich, Yuriy; Joachim-Contaret, Clarisse; Cécilia-Joseph, Elsa; Verschraegen, Claire; Nguyen, Nam P

    2017-01-01

    AIM To investigate rates of distant metastases (DM) detected with [18]fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) in early stage invasive breast cancer. METHODS We searched the English language literature databases of PubMed, EMBASE, ISI Web of Knowledge, Web of Science and Google Scholar, for publications on DM detected in patients who had 18FDG-PET/CT scans as part of the staging for early stages of breast cancer (stage I and II), prior to or immediately following surgery. Reports published between 2011 and 2017 were considered. The systematic review was conducted according to the PRISMA guidelines. RESULTS Among the 18 total studies included in the analysis, the risk of DM ranged from 0% to 8.3% and 0% to 12.9% for stage I and II invasive breast cancer, respectively. Among the patients with clinical stage II, the rate of occult metastases diagnosed by 18FDG-PET/CT was 7.2% (range, 0%-19.6%) for stage IIA and 15.8% (range, 0%-40.8%) for stage IIB. In young patients (< 40-year-old), 18FDG-PET/CT demonstrated a higher prevalence of DM at the time of diagnosis for those with aggressive histology (i.e., triple-negative receptors and poorly differentiated grade). CONCLUSION Young patients with poorly differentiated tumors and stage IIB triple-negative breast cancer may benefit from 18FDG-PET/CT at initial staging to detect occult DM prior to surgery. PMID:28794827

  17. 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.

  18. Methylation of BRCA1 promoter region is associated with unfavorable prognosis in women with early-stage breast cancer.

    PubMed

    Hsu, Nicholas C; Huang, Ya-Fang; Yokoyama, Kazunari K; Chu, Pei-Yi; Chen, Fang-Ming; Hou, Ming-Feng

    2013-01-01

    BRCA1-associated breast cancers are associated with particular features such as early onset, poor histological differentiation, and hormone receptor negativity. Previous studies conducted in Taiwanese population showed that the mutation of BRCA1 gene does not play a significant role in the occurrence of breast cancer. The present study explored methylation of BRCA1 promoter and its relationship to clinical features and outcome in Taiwanese breast cancer patients. Tumor specimens from a cohort of 139 early-stage breast cancer patients were obtained during surgery before adjuvant treatment for DNA extraction. Methylation of BRCA1 promoter region was determined by methylation-specific PCR and the results were related to clinical features and outcome of patients using statistical analysis. Methylation of the BRCA1 promoter was detected in 78 (56%) of the 139 tumors. Chi-square analysis indicated that BRCA1 promoter methylation correlated significantly with triple-negative (ER-/PR-/HER2-) status of breast cancer patients (p = 0.041). The Kaplan-Meier method showed that BRCA1 promoter methylation was significantly associated with poor overall survival (p = 0.026) and disease-free survival (p = 0.001). Multivariate analysis which incorporated variables of patients' age, tumor size, grade, and lymph node metastasis revealed that BRCA1 promoter methylation was associated with overall survival (p = 0.027; hazard ratio, 16.38) and disease-free survival (p = 0.003; hazard ratio, 12.19) [corrected].Our findings underscore the clinical relevance of the methylation of BRCA1 promoter in Taiwanese patients with early-stage breast cancer.

  19. Significance of uterine corpus tumor invasion in early-stage cervical cancer.

    PubMed

    Matsuo, K; Machida, H; Blake, E A; Takiuchi, T; Mikami, M; Roman, L D

    2017-04-01

    To examine characteristics and survival outcomes of women with surgically-treated cervical cancer exhibiting uterine corpus tumor invasion. We utilized The Surveillance, Epidemiology, and End Results Program to identify cervical cancer patients who underwent hysterectomy between 1973 and 2003. Logistic regression models were used to identify risk factors for uterine corpus tumor invasion on multivariable analysis. Association of uterine corpus tumor invasion and cause-specific survival (CSS) from cervical cancer was examined with Cox proportional hazard regression models on multivariable analysis. We identified 837 (4.9%) cases of uterine corpus invasion and 16,237 (95.1%) cases of non-invasion. Median follow-up time was 14.0 years. There were 1642 deaths due to cervical cancer. Uterine corpus invasion was independently associated with older age, non-squamous histology, high-grade tumors, large tumor size, and nodal metastasis on multivariable analysis (all, P < 0.001). On univariable analysis, uterine corpus tumor invasion was significantly associated with decreased CSS compared to the non-invasion (5-year rates, 79.0% versus 94.5%, P < 0.001). After controlling for other significant prognostic factors, uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.45, 95% confidence interval 1.21-1.74). Among stage T1b cases (n = 6730), uterine corpus tumor invasion remained an independent prognostic factor for decreased CSS (adjusted-hazard ratio 1.95, 95%CI 1.47-2.60). Uterine corpus tumor invasion was significantly associated with decreased CSS in stage T1b1 disease (74.5% versus 90.7%, P < 0.001) and in stage T1b2 disease (67.0% versus 79.5%, P = 0.01). Uterine corpus tumor invasion is an independent prognostic factor for decreased survival of women with early-stage cervical cancer. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical

  20. A novel highly potent trivalent TGF-β receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands

    PubMed Central

    Qin, Tai; Barron, Lindsey; Xia, Lu; Huang, Haojie; Villarreal, Maria M.; Zwaagstra, John; Collins, Cathy; Yang, Junhua; Zwieb, Christian; Kodali, Ravindra; Hinck, Cynthia S.; Kim, Sun Kyung; Reddick, Robert L.; Shu, Chang; O’Connor-McCourt, Maureen D.; Hinck, Andrew P.; Sun, Lu-Zhe

    2016-01-01

    The effects of transforming growth factor beta (TGF-β) signaling on prostate tumorigenesis has been shown to be strongly dependent on the stage of development, with TGF-β functioning as a tumor suppressor in early stages of disease and as a promoter in later stages. To study in further detail the paradoxical tumor-suppressive and tumor-promoting roles of the TGF-β pathway, we investigated the effect of systemic treatment with a TGF-β inhibitor on early stages of prostate tumorigenesis. To ensure effective inhibition, we developed and employed a novel trivalent TGF-β receptor trap, RER, comprised of domains derived from the TGF-β type II and type III receptors. This trap was shown to completely block TβRII binding, to antagonize TGF-β1 and TGF-β3 signaling in cultured epithelial cells at low picomolar concentrations, and it showed equal or better anti-TGF-β activities than a pan TGF-β neutralizing antibody and a TGF-β receptor I kinase inhibitor in various prostate cancer cell lines. Systemic administration of RER inhibited prostate tumor cell proliferation as indicated by reduced Ki67 positive cells and invasion potential of tumor cells in high grade prostatic intraepithelial neoplasia (PIN) lesions in the prostate glands of Pten conditional null mice. These results provide evidence that TGF-β acts as a promoter rather than a suppressor in the relatively early stages of this spontaneous prostate tumorigenesis model. Thus, inhibition of TGF-β signaling in early stages of prostate cancer may be a novel therapeutic strategy to inhibit the progression as well as the metastatic potential in patients with prostate cancer. PMID:27863384

  1. A novel highly potent trivalent TGF-β receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands.

    PubMed

    Qin, Tai; Barron, Lindsey; Xia, Lu; Huang, Haojie; Villarreal, Maria M; Zwaagstra, John; Collins, Cathy; Yang, Junhua; Zwieb, Christian; Kodali, Ravindra; Hinck, Cynthia S; Kim, Sun Kyung; Reddick, Robert L; Shu, Chang; O'Connor-McCourt, Maureen D; Hinck, Andrew P; Sun, Lu-Zhe

    2016-12-27

    The effects of transforming growth factor beta (TGF-β) signaling on prostate tumorigenesis has been shown to be strongly dependent on the stage of development, with TGF-β functioning as a tumor suppressor in early stages of disease and as a promoter in later stages. To study in further detail the paradoxical tumor-suppressive and tumor-promoting roles of the TGF-β pathway, we investigated the effect of systemic treatment with a TGF-β inhibitor on early stages of prostate tumorigenesis. To ensure effective inhibition, we developed and employed a novel trivalent TGF-β receptor trap, RER, comprised of domains derived from the TGF-β type II and type III receptors. This trap was shown to completely block TβRII binding, to antagonize TGF-β1 and TGF-β3 signaling in cultured epithelial cells at low picomolar concentrations, and it showed equal or better anti-TGF-β activities than a pan TGF-β neutralizing antibody and a TGF-β receptor I kinase inhibitor in various prostate cancer cell lines. Systemic administration of RER inhibited prostate tumor cell proliferation as indicated by reduced Ki67 positive cells and invasion potential of tumor cells in high grade prostatic intraepithelial neoplasia (PIN) lesions in the prostate glands of Pten conditional null mice. These results provide evidence that TGF-β acts as a promoter rather than a suppressor in the relatively early stages of this spontaneous prostate tumorigenesis model. Thus, inhibition of TGF-β signaling in early stages of prostate cancer may be a novel therapeutic strategy to inhibit the progression as well as the metastatic potential in patients with prostate cancer.

  2. 13 CFR 107.1182 - Valuation requirements for Early Stage SBICs based on Capital Impairment Percentage.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1182 Valuation... designated by SBA. Conditional Commitments by SBA To Reserve Leverage for a Licensee...

  3. 13 CFR 107.1182 - Valuation requirements for Early Stage SBICs based on Capital Impairment Percentage.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Special Rules for Leverage Issued by An Early Stage Sbic § 107.1182 Valuation... designated by SBA. Conditional Commitments by SBA To Reserve Leverage for a Licensee...

  4. 76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage SBICs; Public Webinars AGENCY: U.S. Small Business Administration. ACTION: Notice of public Webinars. SUMMARY: The U.S. Small Business Administration (SBA) announces that it is holding a series of public Webinars regarding its...

  5. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  6. Alternatives to Mechanical Drills for the Early Stages of Language Practice in Foreign Language Textbooks

    ERIC Educational Resources Information Center

    Aski, Janice M.

    2005-01-01

    There is a growing body of research indicating that mechanical drills do not facilitate the development of explicit or implicit knowledge. This study identifies the inadequate aspects of mechanical drills and offers alternative activities for the early stages of language practice, whose formats and features comply with recent research in the…

  7. Communication in the Early Stage of Language Development in Children with CHARGE Syndrome

    ERIC Educational Resources Information Center

    Peltokorpi, Sini; Huttunen, Kerttu

    2008-01-01

    CHARGE syndrome is characterized by multiple physical abnormalities, and impaired vision and hearing. In this pilot study, communication in the early stage of language development in three one- to eight-year-old children with CHARGE syndrome was explored using video recorded free-play interaction sessions and a parental questionnaire. The children…

  8. Association Between Increased Vascular Density and Loss of Protective RAS in Early-stage NPDR

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2016-01-01

    Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The renin-angiotensin system (RAS) is implicated in the pathogenesis of DR and in the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population that is instrumental in vascular repair.

  9. 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…

  10. 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…

  11. 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)…

  12. 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.

  13. Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer

    USDA-ARS?s Scientific Manuscript database

    Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...

  14. 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…

  15. Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

    PubMed

    Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

    2012-12-01

    Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. 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,…

  17. Communication in the Early Stage of Language Development in Children with CHARGE Syndrome

    ERIC Educational Resources Information Center

    Peltokorpi, Sini; Huttunen, Kerttu

    2008-01-01

    CHARGE syndrome is characterized by multiple physical abnormalities, and impaired vision and hearing. In this pilot study, communication in the early stage of language development in three one- to eight-year-old children with CHARGE syndrome was explored using video recorded free-play interaction sessions and a parental questionnaire. The children…

  18. Arthroscopic core decompression of the lunate in early stage Kienbock disease of the lunate.

    PubMed

    Bain, Gregory I; Smith, Michael L; Watts, Adam C

    2011-03-01

    Since the first description of Kienbock disease in 1910, the etiology and treatment have remained controversial topics. Core decompression is an accepted treatment option in early-stage avascular necrosis of the femoral head, and more recently the humeral head. This paper reports the technique of arthroscopic fluoroscopically guided core decompression of the lunate with 6-year results.

  19. 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…

  20. 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…

  1. Endoscopic submucosal dissection with the pulley method for early-stage gastric cancer (with video).

    PubMed

    Li, Chung-Hsien; Chen, Peng-Jen; Chu, Heng-Cheng; Huang, Tien-Yu; Shih, Yu-Lueng; Chang, Wei-Kuo; Hsieh, Tsai-Yuan

    2011-01-01

    Using EMR techniques, physicians frequently remove tumors >15 mm by piecemeal resection, which is associated with an increased rate of disease recurrence and difficulty in histologically evaluating the specimen. Endoscopic submucosal dissection (ESD) of early-stage gastric cancer improves the rate of successful en bloc resection, but it is associated with more complications, such as bleeding and perforation, than conventional EMR. To describe a simple technique that uses the pulley method to facilitate ESD procedures in the excision of large early-stage gastric cancers. Case series. Tertiary medical center in Taiwan. Eleven patients with early-stage gastric cancers or adenomas >20 mm underwent ESD. The pulley method with standard clips and dental floss was used to provide traction to improve visualization of the dissection plane during ESD. Proportion with complete en bloc resection. En bloc resection of the lesion was achieved in 11 patients. No perforation or emergent surgery was noted. One endoscopist performed all procedures, and only 11 patients were studied in an uncontrolled manner. The pulley method seems to facilitate en bloc ESD of early-stage gastric cancers >20 mm. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  2. 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,…

  3. 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…

  4. Transvaginal Sonography Versus Cystoscopy for Detecting Urinary Bladder Invasion in Early Stage Cervical Cancer

    PubMed Central

    Zutshi, Vijay; Garg, Anju; Batra, Swaraj

    2017-01-01

    Introduction Cervical cancer is a major cause of mortality from cancer among women. In it’s early stage pre operative staging with cystoscopy is a standard procedure for the detection of urinary bladder involvement. Aim The present study was conducted with the aim to compare the efficacy of Transvaginal Sonography (TVS) and cystoscopy in diagnosing bladder involvement in early stage cervical cancer patients by confirming it intraoperatively and further by histopathologic examination. Materials and Methods A prospective partially blinded study was conducted between March 2006 and September 2008 on 30 patients with early stage cervical cancer (Stage I and IIa) who were planned to undergo radical hysterectomy. Pre operatively, these patients underwent both TVS and cystoscopy to diagnose bladder involvement. Presence or absence of bladder involvement was then confirmed intra operatively and by histopathologic examination. Results In all the 30 patients studied, no bladder involvement was seen on cystoscopy where as TVS showed bladder involvement in three patients. Involvement of the bladder in these three patients was confirmed intra operatively and by histopathologic examination. Thus, in our study, TVS was 100% sensitive in detecting bladder involvement. Conclusion TVS is highly sensitive in diagnosing bladder involvement in early stage cervical cancer and could potentially detect cases missed with a cystoscopy.

  5. 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…

  6. 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…

  7. Treatment of Early-Stage Pressure Ulcers by Using Autologous Adipose Tissue Grafts

    PubMed Central

    Marangi, Giovanni Francesco; Pallara, Tiziano; Cagli, Barbara; Schena, Emiliano; Giurazza, Francesco; Faiella, Elio; Zobel, Bruno Beomonte; Persichetti, Paolo

    2014-01-01

    Assessing pressure ulcers (PUs) in early stages allows patients to receive safer treatment. Up to now, in addition to clinical evaluation, ultrasonography seems to be the most suitable technique to achieve this goal. Several treatments are applied to prevent ulcer progression but none of them is totally effective. Furthermore, the in-depth knowledge of fat regenerative properties has led to a wide use of it. With this study the authors aim at introducing a new approach to cure and prevent the worsening of early-stage PUs by using fat grafts. The authors selected 42 patients who showed clinical and ultrasonographic evidence of early-stage PUs. Values of skin thickness, fascial integrity, and subcutaneous vascularity were recorded both on the PU area and the healthy trochanteric one, used as control region. Fat grafting was performed on all patients. At three months, abnormal ultrasonographic findings, such as reduction of cutaneous and subcutaneous thickness, discontinuous fascia, and decrease in subcutaneous vascularity, all were modified with respect to almost all the corresponding parameters of the control region. Results highlight that the use of fat grafts proved to be an effective treatment for early-stage PUs, especially in the care of neurological and chronic bedridden patients. PMID:24818019

  8. ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma

    PubMed Central

    Murata, Yoshihiko; Minami, Yuko; Iwakawa, Reika; Yokota, Jun; Usui, Shingo; Tsuta, Koji; Shiraishi, Kouya; Sakashita, Shingo; Satomi, Kaishi; Iijima, Tatsuo; Noguchi, Masayuki

    2014-01-01

    Genetic abnormality in early-stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array-comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real-time genomic PCR and immunohistochemistry. The results were then verified using another set of early-stage adenocarcinomas. Array-comparative genomic hybridization indicated frequent amplification at chromosome 3q26. Of the seven genes located in this region, we focused on the epithelial cell transforming sequence 2 (ECT2) oncogene, as ECT2 amplification was detected only in invasive adenocarcinoma, and not in in situ carcinoma. Quantitative PCR and immunohistochemistry analyses also detected overexpression of ECT2 in invasive adenocarcinoma, and this was correlated with both the Ki-67 labeling index and mitotic index. In addition, it was associated with disease-free survival and overall survival of patients with lung adenocarcinoma. These results were verified using another set of early-stage adenocarcinomas resected at another hospital. Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma. PMID:24484057

  9. 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…

  10. Alternatives to Mechanical Drills for the Early Stages of Language Practice in Foreign Language Textbooks

    ERIC Educational Resources Information Center

    Aski, Janice M.

    2005-01-01

    There is a growing body of research indicating that mechanical drills do not facilitate the development of explicit or implicit knowledge. This study identifies the inadequate aspects of mechanical drills and offers alternative activities for the early stages of language practice, whose formats and features comply with recent research in the…

  11. Photons from the early stages of relativistic heavy-ion collisions

    NASA Astrophysics Data System (ADS)

    Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Peng, G. X.; Greco, V.

    2017-07-01

    We present results about photon-production in relativistic heavy-ion collisions. The main novelty of our study is the calculation of the contribution of the early-stage photons to the photon spectrum. The initial stage is modeled by an ensemble of classical gluon fields which decay to a quark-gluon plasma via the Schwinger mechanism, and the evolution of the system is studied by coupling classical field equations to relativistic kinetic theory; photon production is then computed by including the pertinent collision processes into the collision integral. We find that the contribution of the early-stage photons to the direct photon spectrum is substantial for pT≈2 GeV and higher, the exact value depending on the collision energy; therefore, we identify this part of the photon spectrum as the sign of the early stage. Moreover, the amount of photons produced during the early stage is not negligible with respect to those produced by a thermalized quark-gluon plasma: We support the idea that there is no dark age in relativistic heavy-ion collisions.

  12. Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer.

    PubMed

    Wei, Xiao-li; Qiu, Miao-zhen; Lin, Huan-xin; Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis) or patients with proximal gastric cancer (P=0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis). Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

  13. Familiarity and Emotional Expression Influence an Early Stage of Face Processing: An Electrophysiological Study

    ERIC Educational Resources Information Center

    Caharel, Stephanie; Courtay, Nolwenn; Bernard, Christian; Lalonde, Robert; Rebai, Mohamed

    2005-01-01

    Recent data indicate that the familiarity and the emotional expression of faces occur at an early stage of information processing. The goal of the present study was to determine whether these two aspects interact at the structural encoding stage as reflected by the N170 component of event-related potentials in tasks requiring the subjects either…

  14. 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)…

  15. The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases

    PubMed Central

    Braicu, Elena Iona; Sehouli, Jalid; Tauber, Rudolf; Blanchard, Véronique

    2014-01-01

    Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation. PMID:25183900

  16. 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…

  17. Lung stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer in the very elderly (≥80years old): Extremely safe and effective.

    PubMed

    Kreinbrink, Paul; Blumenfeld, Philip; Tolekidis, George; Sen, Neilayan; Sher, David; Marwaha, Gaurav

    2017-09-01

    Stereotactic body radiotherapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) is the standard of care in medically inoperable patients. In very elderly patients, previous studies have shown SBRT to offer excellent local control, though with higher toxicities than in younger populations. We report our institutional experience using SBRT in the definitive management of NSCLC in patients ≥80years old. Using an IRB-approved registry of 158 patients treated with definitive-intent lung SBRT for early-stage NSCLC at our institution between 2010 and 2016, 31 consecutively treated patients ≥80years of age were identified. CTCAEv4 scales were prospectively recorded during follow-ups and utilized for toxicity assessments. Kaplan-Meier estimates were utilized for survival analyses. For the 31 patients (with 34 lesions) included, median age was 83 (R: 80-93), median ECOG performance status was 2 (R: 0-3), and median follow-up was 15.8months (R: 3.1-48.3). Median PTV size was 24.0cm(3) (R: 5.83-62.1cm(3)). Median prescription dose was 54Gy in 3 fractions (R: 50-60Gy in 3-8 fractions). Local control was 100% at 1year and 92.3% at 2years. Median survival was 29.1months. There were no grade 2-5 toxicities. Grade 1 toxicities included: fatigue in 5 patients (16.1%), asymptomatic (radiographic) pneumonitis in 12 (38.7%), and dyspnea in 2 (6.5%). Lung SBRT with a BED of ≥100Gy10 for very elderly patients with NSCLC is extremely safe and effective, with inordinately low toxicity rates (zero grade 2-5 toxicities). With stringent dosimetric parameters and planning guidelines, patients ≥80years remain excellent candidates for full-dose SBRT. SBRT for early-stage NSCLC is the accepted standard of care in medically inoperable patients, though in many very elderly patients, dose is either de-intensified or withheld for concern of toxicity in the setting of advanced age and competing risks. In this study of our very elderly (≥80years old) early-stage NSCLC patients, we

  18. 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.

  19. On the early stages of wind wave under non-stationary wind conditions.

    NASA Astrophysics Data System (ADS)

    Robles-Diaz, Lucia; Ocampo-Torres, Francisco J.; Branger, Hubert

    2017-04-01

    Most efforts in the study of the generation and evolution of wind waves have been conducted under constant wind. The balance of the transfer of different properties has been studied mainly for situations where the wave has already reached the equilibrium with the constant wind conditions. The purpose of these experiments is to study the early stages of the generation of waves under non-stationary wind conditions and to determine a balance in the exchange at the air-water interface for non-equilibrium wind conditions. A total of 16 experiments with a characteristic acceleration and deceleration rate of wind speed were conducted in a large wind-wave facility of Institut Pythéas (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. The momentum fluxes were estimated from hot wire anemometry at station 7. Also, the free surface displacement was measured along the channel tank at 11 stations where resistance wires were installed, except at stations 1, 2, and 7 where capacitance wires were installed. The sampling frequency for wind velocity and surface displacement measurements was 256 Hz. During experiments the wind intensity was abruptly increased with a constant acceleration rate over time, reaching a constant maximum intensity of 13 m/s. This constant velocity remains some time until the intensity is again reduced suddenly. We observed that wind drag coefficient values are higher for the experiments that present the lower acceleration rate; some field data from previous studies is presented for reference (Large and Pond 1981; Ocampo-Torres et al. 2011; Smith 1980; Yelland and Taylor 1996). The empirical grow curves show that in the experiments with lower acceleration, the wave field is more developed, showing higher dimensional energy and lower dimensional peak frequency. In the evolution of the spectral wave energy, there is first high frequency energy saturation, followed by a downshift of

  20. Ovarian Conservation and Overall Survival in Young Women With Early-Stage Cervical Cancer.

    PubMed

    Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D

    2017-01-01

    To identify predictors of ovarian conservation at hysterectomy and to examine the association of ovarian conservation and survival of young women with early-stage cervical cancer. This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program to identify hysterectomy-based surgically treated patients with stage I cervical cancer diagnosed between 1983 and 2012 (N=16,511). Multivariable models were used to identify independent factors associated with ovarian conservation. Among the subgroup of 9,419 women younger than 50 years of age with stage I disease, survival outcomes and causes of death were examined for 3,908 (41.5%) women who underwent ovarian conservation at hysterectomy without radiotherapy. On multivariable analysis, age younger than 50 years, stage IA disease, and squamous histology were independent factors associated with ovarian conservation (all, P<.001). Among 5,526 women younger than 50 years of age with stage IA disease who underwent hysterectomy without radiotherapy, overall survival was significantly higher in patients undergoing ovarian conservation than in those undergoing oophorectomy (20-year rate, 93.5% compared with 86.8%, P<.001); cervical cancer-specific survival was similar between the patients who underwent ovarian conservation and those who underwent oophorectomy (98.8% compared with 97.8%, P=.12). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.63, 95% confidence interval [CI] 0.49-0.82, P=.001) and was independently associated with lower cumulative risks of death resulting from cardiovascular disease (20-year cumulative rate, 1.2% compared with 3.3%, adjusted hazard ratio 0.47, 95% CI 0.26-0.86, P=.014) and other chronic disease (0.5% compared with 1.4%, adjusted hazard ratio 0.24, 95% CI 0.09-0.65, P=.005) compared with oophorectomy. Both cervical cancer-specific survival (20-year rate, 93.1% compared

  1. 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

  2. Usability of tablet computers by people with early-stage dementia.

    PubMed

    Lim, Fabian S; Wallace, Tim; Luszcz, Mary A; Reynolds, Karen J

    2013-01-01

    Tablet computers are generally associated with an intuitive interface. The adoption and use of tablet computers within the early-stage dementia context could potentially assist in daily living and provide users with a source for leisure activities and social networking. As dementia mainly affects the older adult population, it is expected that many people with dementia and even their carers do not use tablet computers as part of their everyday living. This paper explores the usability of tablet computers within the early-stage dementia context as a source of leisure for people with dementia. The main advantage of the use of tablet computers in this manner is to provide carers some reprieve from the constant care and attention often required in caring for people with dementia. Seven-day in-home trials were conducted to determine whether people with early-stage dementia were -capable of using a tablet computer independently. Twenty-one people with early-stage dementia and carer dyads participated in the trial. Feedback was gathered through questionnaires from both the person with dementia and their carer regarding the use of a tablet computer as part of their everyday living. Approximately half the participants with dementia were able to engage with and use the tablet computer independently, which proved to be helpful to their carers. No significant traits were observed to help identify those who were less likely to use a tablet computer. Carer relief was quantified by the amount of time participants with dementia spent using the device without supervision. The results and feedback from the trial provide significant insights to introducing new technology within the early-stage dementia context. Users' needs must be considered on a case-by-case basis to successfully facilitate the uptake of tablet computers in the dementia context. The trial has provided sufficient justification to further explore more uses of tablet computers in the dementia context, and not just for

  3. There were no differences in serum HBV DNA level between HBeAg-positive and HBeAg-negative chronic hepatitis B with same liver histological necroinflammation grade but differences among grades 1, 2, 3 and 4 apportioned by the same hepatic parenchyma cell volume.

    PubMed

    Ke, W-M; Xie, S-B; Li, X-J; Zhang, S-Q; Lai, J; Ye, Y-N; Gao, Z-L; Chen, P-J

    2011-09-01

    Hepatitis B virus (HBV) DNA levels and liver histological necroinflammation grades are correlated with the antiviral efficacy. It is necessary to clarify the relationship between HBV replication levels apportioned by the same hepatic parenchyma cell volume and severity of liver histological necroinflammation grades in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B. The serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume were compared between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4, respectively. There were no differences in the serum HBV DNA levels between HBeAg-positive and HBeAg-negative chronic hepatitis B as well as among liver histological necroinflammation grades 1, 2, 3 and 4. However, there were differences in the serum HBV DNA levels apportioned by the same hepatic parenchyma cell volume among liver histological necroinflammation grades 1, 2, 3 and 4 in both HBeAg-positive and HBeAg-negative chronic hepatitis B, respectively. There were no differences in HBV DNA levels with the same liver histological necroinflammation grade activated by HBV wild-type and variant strains. After the differences in hepatic parenchyma cell volume for HBV replication of the same liver histological necroinflammation grade accompanied by different hepatic fibrosis stages were adjusted, the serum HBV DNA level apportioned by the same hepatic parenchyma cell volume was correlated with the severity of liver histological necroinflammation grade. © 2011 Blackwell Publishing Ltd.

  4. Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.

    PubMed

    Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko; Choi, Noah C; Chan, Shen; Gomez, Daniel; O'Reilly, Michael; Jeter, Melenda; Gillin, Michael; Zhu, Xiaorong; Zhang, Xiaodong; Mohan, Radhe; Swisher, Stephen; Hahn, Stephen; Cox, James D

    2017-02-01

    The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Variations in Receipt of Curative-Intent Surgery for Early-Stage Non-Small Cell Lung Cancer (NSCLC) by State.

    PubMed

    Sineshaw, Helmneh M; Wu, Xiao-Cheng; Flanders, W Dana; Osarogiagbon, Raymond Uyiosa; Jemal, Ahmedin

    2016-06-01

    Previous studies reported racial and socioeconomic disparities in receipt of curative-intent surgery for early-stage non-small cell lung cancer (NSCLC) in the United States. We examined variation in receipt of surgery and whether the racial disparity varies by state. Patients in whom stage I or II NSCLC was diagnosed from 2007 to 2011 were identified from 38 state and the District of Columbia population-based cancer registries compiled by the North American Association of Central Cancer Registries. Percentage of patients receiving curative-intent surgery was calculated for each registry. Adjusted risk ratios were generated by using modified Poisson regression to control for sociodemographic (e.g., age, sex, race, insurance) and clinical (e.g., grade, stage) factors. Non-Hispanic (NH) whites and Massachusetts were used as references for comparisons because they had the lowest uninsured rates. In all registries combined, 66.4% of patients with early-stage NSCLC (73,475 of 110,711) received curative-intent surgery. Receipt of curative-intent surgery for early-stage NSCLC varied substantially by state, ranging from 52.2% to 56.1% in Wyoming, Louisiana, and New Mexico to 75.2% to 77.2% in Massachusetts, New Jersey, and Utah. In a multivariable analysis, the likelihood of receiving curative-intent surgery was significantly lower in all but nine states/registries compared with Massachusetts, ranging from 7% lower in California to 25% lower in Wyoming. Receipt of curative-intent surgery for early-stage NSCLC was lower for NH blacks than for NH whites in every state, although statistically significant in Florida and Texas. Receipt of curative-intent surgery for early-stage NSCLC varies substantially across states in the United States, with northeastern states generally showing the highest rates. Further, receipt of treatment appeared to be lower in NH blacks than in NH whites in every state, although statistically significant in Florida and Texas. Copyright © 2016

  6. Early stages of development of the Taenia solium metacestode in pigs.

    PubMed

    Garrido, Gerardo Salas; de Aluja, Aline S; Casas, Fernando Constantino

    2007-04-01

    In order to identify the early stages of Taenia solium metacestodes, 12 pigs were each fed 100,000 viable eggs and later killed and necropsied at different times after infection. Hematoxylin-eosin (HE) and immunohistochemical techniques (IHCs) were used to identify onchospheres and cysticerci in different tissues. At 2 days postinfection (dpi) structures compatible with onchospheres were found in the lumen of the small intestine, and in the mesenteric blood vessels and lymph nodes. At 4 dpi, these same structures were observed in the small intestine, the liver, and skeletal muscles. Between 6 and 39 dpi, they were found only in skeletal muscles. Between 2 and 6 dpi the postonchospheres were circular and oval shaped and measured between 6 and 34 x 27 microm. From 14 to 39 dpi, well-developed metacestodes 550 x 750 microm were observed. IHCs support the identification of early stages of T. solium.

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

    DOE PAGES

    Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; ...

    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

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

    SciTech Connect

    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 with 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.

  9. [Application of peloidotherapy at the early stage of rehabilitation after cerebral ischemic stroke].

    PubMed

    Gorbunov, F E; Penionzhkevich, D Iu; Kotenko, E P

    2010-01-01

    The objective of the present study was to evaluate clinical efficiency of peloidotherapy in the early reconvalescence period following cerebral ischemic stroke. A rationale for the application of peloidotherapy is presented based on the results of follow-up of 60 patients (26 men and 34 women) aged from 43 to 70 years at the early stage of recovery (within 10 weeks and more after stroke). Special attention was given to clinical dynamics of the post-stroke condition and the influence of peloidotherapy on the mechanisms underlying formation of cerebral hemodynamic effects, adaptive changes in the functional systems of hemostasis and microcirculation, and development of pathophysiological cascade of metabolic processes in the brain. All therapeutic procedures were fairly well tolerated by the patients. Neither allergic reactions nor other adverse effects of the treatment were documented which testifies to the safety of peloidotherapy at the early stage of rehabilitation after cerebral ischemic stroke.

  10. Social network effects of nonlifesaving early-stage breast cancer detection on mammography rates.

    PubMed

    Nowak, Sarah A; Parker, Andrew M

    2014-12-01

    We estimated the effect of anecdotes of early-stage, screen-detected cancer for which screening was not lifesaving on the demand for mammography. 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. 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. 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.

  11. Early Stages of De Novo Designed Beta-Hairpin Peptide Self-Assembly

    NASA Astrophysics Data System (ADS)

    Yucel, Tuna; Schneider, Joel P.; Pochan, Darrin J.

    2007-03-01

    In aqueous solution, MAX 1 peptide is unfolded and does not self-assemble. The peptide intramolecularly folds into a beta-hairpin when the electrostatic interactions between charged residues are screened through increasing the ionic strength at neutral pH. Beta-hairpin molecules supramolecularly assemble via hydrophobic collapse and hydrogen bonding into a 3-D hydrogel network. By combining the results of CD, cryo-TEM, DLS, and oscillatory rheology, we understand that the self-assembly proceeds by nucleation of monodisperse (3 nm wide) beta-sheet fibrils, which elongate, branch and cross-link to form clusters of fibrils. Assembly kinetics at this early stage indicates power law growth with assembly time. Eventually, clusters of fibrils interpenetrate to form a percolated network, as evidenced by the increasing network rigidity. The early stage assembly process will be discussed and compared to published gelation models.

  12. 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.

  13. Impact of early stage non-equilibrium dynamics on photon production in relativistic heavy ion collisions

    NASA Astrophysics Data System (ADS)

    Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Greco, V.

    2017-04-01

    In this study we discuss our results on the spectrum of photons emitted from the quark-gluon plasma produced in heavy ion collisions at RHIC energies. Simulating the space-time evolution of the fireball by solving the relativistic Boltzmann transport equation and including two-particle scattering processes with photon emission allows us to make a first step in the description of thermal photons from the QGP as well as of those produced in the pre-equilibrium stage. Indeed, we consider not only a standard Glauber initial condition but also a model in which quarks and gluons are produced in the very early stage through the Schwinger mechanism by the decay of an initial color-electric field. In the latter approach relativistic kinetic equations are coupled in a self-consistent way to field equations. We aim at spotting the impact of early stage non-equilibrium dynamics on the photon production.

  14. 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.

  15. 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

  16. Analysis of Turbulent flow in early stages of atherosclerosis of coronary artery

    NASA Astrophysics Data System (ADS)

    Bhaganagar, Kiran

    2005-11-01

    During the early stages of atherosclerotic heart disease, fatty material accumulates in the coronary artery resulting in development of streaks of plaque and creating high levels of turbulence, and with significantly modified flow parameters. Diagnostic measures performed during this early stage may not show any evidence of coronary artery disease, because the lumen of the coronary artery has not decreased in caliber. These streaks do not obstruct the flow of blood but alter the flow characteristics, even at this preclinical stage. This talk presents the preliminary results for the analysis of turbulent flow characteristics for a range of atherosclerotic plaque configurations in the left main coronary artery. For this purpose a CAD/medical imaging based direct-simulation (DNS) tool has been developed. The Navier-stokes equations are solved in the vertical vorticity-velocity formulation. The plaque is introduced using immersed body technique. The geometric acquisition of the artery geometry and plaque morphology is obtained using CAD based commercial software.

  17. Emotional enhancement of perceptual priming is preserved in aging and early-stage Alzheimer's disease.

    PubMed

    LaBar, Kevin S; Torpey, Dana C; Cook, Craig A; Johnson, Stephanie R; Warren, Lauren H; Burke, James R; Welsh-Bohmer, Kathleen A

    2005-01-01

    Perceptual priming for emotionally-negative and neutral scenes was tested in early-stage Alzheimer's disease (AD) patients and healthy younger, middle-aged and older adults. In the study phase, participants rated the scenes for their arousal properties. In the test phase, studied and novel scenes were initially presented subliminally, and the exposure duration was gradually increased until a valence categorization was made. The difference in exposure duration required to categorize novel versus studied items was the dependent measure of priming. Aversive content increased the magnitude of priming, an effect that was preserved in healthy aging and AD. Results from an immediate recognition memory test showed that the priming effects could not be attributable to enhanced explicit memory for the aversive scenes. These findings implicate a dissociation between the modulatory effect of emotion across implicit and explicit forms of memory in aging and early-stage AD.

  18. Early-stage tumor detection using photoacoustic microscopy: a pattern recognition approach

    NASA Astrophysics Data System (ADS)

    Yeh, Chenghung; Wang, Liang; Liang, Jinyang; Zhou, Yong; Hu, Song; Sohn, Rebecca E.; Arbeit, Jeffrey M.; Wang, Lihong V.

    2017-03-01

    We report photoacoustic microscopy (PAM) of arteriovenous (AV) shunts in early stage tumors in vivo, and develop a pattern recognition framework for computerized tumor detection. Here, using a high-resolution photoacoustic microscope, we implement a new blood oxygenation (sO2)-based disease marker induced by the AV shunt effect in tumor angiogenesis. We discovered a striking biological phenomenon: There can be two dramatically different sO2 values in bloodstreams flowing side-by-side in a single vessel. By tracing abnormal sO2 values in the blood vessels, we can identify a tumor region at an early stage. To further automate tumor detection based on our findings, we adopt widely used pattern recognition methods and develop an efficient computerized classification framework. The test result shows over 80% averaged detection accuracy with false positive contributing 18.52% of error test samples on a 50 PAM image dataset.

  19. Early-stage primary signet ring cell carcinoma of the colon.

    PubMed

    Kim, Jae Hyun; Park, Seun Ja; Park, Moo In; Moon, Won; Kim, Sung Eun

    2013-06-28

    Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.

  20. A chart review of patients with early stage mycosis fungoides treated with psoralen plus UVA (PUVA).

    PubMed

    Soung, Jennifer; Muigai, Wangui; Amin, Nilam; Stern, Dana K; Lebwohl, Mark G

    2005-01-01

    PUVA has become a common form of treatment for early stage mycosis fungoides (MF). The purpose of this retrospective study was to review the clinical data of 51 MF patients (96% stage IA or IB) treated with PUVA at the Mt. Sinai MF clinic over the past 20 years. We analyzed the efficacy, safety, and remission duration in patients who were treated with a modified PUVA regimen. Forty-four of 51 patients (86%) achieved complete clinical clearing for all stages after initial PUVA therapy. The mean duration of remission with maintenance treatment was more than 27 months (range: 3 weeks to 130 months). The mean duration of disease from start of first PUVA therapy for all patients was 4.8 years (range: 0.7 to 130 months). PUVA for patients with early-stage MF is a safe and effective therapeutic modality with prolonged disease-free remissions, however, PUVA alone was not adequate for more advanced disease.

  1. Early stages of probable Alzheimer disease are associated with changes in platelet amyloid precursor protein forms.

    PubMed

    Borroni, B; Colciaghi, F; Corsini, P; Akkawi, N; Rozzini, L; Del Zotto, E; Talarico, G; Cattabeni, F; Lenzi, G L; Di Luca, M; Padovani, A

    2002-12-01

    Previous findings demonstrated an altered pattern of amyloid precursor protein (APP) forms in platelets of Alzheimer disease (AD) patients, compared both with healthy control subjects or patients with non-Alzheimer-type dementia. The present study aims to evaluate whether platelet APP form ratio (APPr) is altered in patients with early stage AD. We selected 40 patients with early stage AD and 40 age-matched healthy controls. Compared with controls (mean+/-SD=0.91+/-0.3), mean APPr was decreased in AD (mean+/-SD=0.46+/-0.26, p<0.0001). Sixteen very mild AD patients (clinical dementia rating=0.5), identified among the AD group, showed a significant decrease of APPr values (mean+/-SD=0.50+/-0.3, p<0.0001). These findings indicate that alteration of APP processing in platelets is an early event and suggest that this assay might be of diagnostic value in differentiating mild AD from normal ageing.

  2. Prospective Double-Blind Study of Zidovudine (AZT) in Early Stage HIV infection

    DTIC Science & Technology

    1988-05-01

    FRONT COVER FUNDING NO. 87PP7875 S L. TITLE: Prospective Double-Blind Study of Zidovudine (AZT) in Early Stage HIV Infection PRINCIPAL INVESTIGATOR...Prospective Double-Blind Study of Zidovudine (AZT) in Early State HIV Infection 12. PERSONAL AUTHOR(S) Shannon M. Harrison 13a. TYPE OF REPORT 113b...COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUBGROUP HIV , Zidovudine, Early, Infection 06

  3. Early Stage Breast Cancer in Older Women: Predictions and Outcomes of Therapy

    DTIC Science & Technology

    2000-10-01

    surgery increased , and because women undergoing breast-conserving surgery are more likely to receive inappropriate care. We have now shown that patients...appropriateness of primary therapy for early-stage breast carcinoma and increased use of breast-conserving surgery. Lancet 2000;356:1148-53. 2. Nattinger AB...demographic deterninant of use of breast-conserving surgery despite overall increased adoption. 2000, submitted for publication. 5. Du X. Freeman JL, Warrant

  4. Phase 0 Trial of Itraconazole for Early-Stage Non-Small Cell Lung Cancer

    DTIC Science & Technology

    2015-10-01

    and by targeting the Hedgehog developmental/survival pathway. In this clinical trial, 15 patients with early-stage lung cancer planned for surgical ...Determine the effect of itraconazole pharmacokinetics (PK) on the pharmacodynamic profile of itraconazole. On- treatment serum, tumor tissue, and...itraconazole 600 mg orally daily for 7-10 days followed by repeat skin biopsy, blood sampling, and MRI studies, followed by surgical resection. Baseline

  5. 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.

  6. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  7. 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

  8. Varying postresection lactate dehydrogenase with overall survival of early stage pancreatic cancer patients

    PubMed Central

    Xiao, Yuanyuan; Xie, Zhihui; Shao, Zhenyi; Chen, Wen; Xie, Hua; Qin, Guoyou; Zhao, Naiqing

    2017-01-01

    Abstract Several previously published studies revealed a hazardous role of pretreatment lactate dehydrogenase (LDH) in survival of advanced or metastatic pancreatic cancer (PC) patients. Nevertheless, in early stage PC patients who are eligible for curative resection, the prognostic role of postresection LDH has never been discussed. In this study, we aimed to explore the prognostic significance of varying postresection LDH among early stage PC patients. In total, 80 PC patients who received curative resection were retrospectively selected from a population-based electronic inpatients database which originated from Shanghai, China. A dynamic survival analysis method, counting process approach in combination with the multiple failure-time Cox model, was applied to evaluate the association between postresection LDH and OS. The multiple failure-time Cox model found that age, resection modality, and postresection LDH were significantly associated with OS: an elevated LDH (defined as > 250 U/L) was related to 2.93 (95% CI: 1.26–6.79) folds of death hazard. Further analysis disclosed an identifiable dose–response association between LDH and OS: compared with LDH≤155 U/L, the HRs for 155 U/L < LDH < 196 U/L, and LDH≥196 U/L were 2.07 (95% CI: 0.88–4.88) and 3.15 (95% CI: 1.30–7.59), respectively. Our study results suggest that postresection LDH is a prominent prognostic factor in this group of early stage PC patients. Maintaining normally ranged LDH after resection might bring about survival benefit in early stage PC patients. PMID:28328834

  9. Varying postresection lactate dehydrogenase with overall survival of early stage pancreatic cancer patients: A retrospective study.

    PubMed

    Xiao, Yuanyuan; Xie, Zhihui; Shao, Zhenyi; Chen, Wen; Xie, Hua; Qin, Guoyou; Zhao, Naiqing

    2017-03-01

    Several previously published studies revealed a hazardous role of pretreatment lactate dehydrogenase (LDH) in survival of advanced or metastatic pancreatic cancer (PC) patients. Nevertheless, in early stage PC patients who are eligible for curative resection, the prognostic role of postresection LDH has never been discussed. In this study, we aimed to explore the prognostic significance of varying postresection LDH among early stage PC patients. In total, 80 PC patients who received curative resection were retrospectively selected from a population-based electronic inpatients database which originated from Shanghai, China. A dynamic survival analysis method, counting process approach in combination with the multiple failure-time Cox model, was applied to evaluate the association between postresection LDH and OS. The multiple failure-time Cox model found that age, resection modality, and postresection LDH were significantly associated with OS: an elevated LDH (defined as > 250 U/L) was related to 2.93 (95% CI: 1.26-6.79) folds of death hazard. Further analysis disclosed an identifiable dose-response association between LDH and OS: compared with LDH≤155 U/L, the HRs for 155 U/L < LDH < 196 U/L, and LDH≥196 U/L were 2.07 (95% CI: 0.88-4.88) and 3.15 (95% CI: 1.30-7.59), respectively. Our study results suggest that postresection LDH is a prominent prognostic factor in this group of early stage PC patients. Maintaining normally ranged LDH after resection might bring about survival benefit in early stage PC patients.

  10. Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

    DTIC Science & Technology

    2015-12-01

    clinical data inventory at MGH, 3) micro-dissected and isolated RNA from 110 tumors, and 3) optimized the preparation of cDNA libraries using NuGene WT...Ovation FFPE System V2. Given the fact that RNA sequencing is in its early stage of application, and application of this technology to FFPE tissue is...thus developed a protocol to extract both DNA and RNA from the same samples. Development of a standardized protocol for FFPE ribonucleic acid

  11. SU-F-R-24: Identifying Prognostic Imaging Biomarkers in Early Stage Lung Cancer Using Radiomics

    SciTech Connect

    Zeng, X; Wu, J; Cui, Y; Li, R; Gao, H

    2016-06-15

    Purpose: Patients diagnosed with early stage lung cancer have favorable outcomes when treated with surgery or stereotactic radiotherapy. However, a significant proportion (∼20%) of patients will develop metastatic disease and eventually die of the disease. The purpose of this work is to identify quantitative imaging biomarkers from CT for predicting overall survival in early stage lung cancer. Methods: In this institutional review board-approved HIPPA-compliant retrospective study, we retrospectively analyzed the diagnostic CT scans of 110 patients with early stage lung cancer. Data from 70 patients were used for training/discovery purposes, while those of remaining 40 patients were used for independent validation. We extracted 191 radiomic features, including statistical, histogram, morphological, and texture features. Cox proportional hazard regression model, coupled with the least absolute shrinkage and selection operator (LASSO), was used to predict overall survival based on the radiomic features. Results: The optimal prognostic model included three image features from the Law’s feature and wavelet texture. In the discovery cohort, this model achieved a concordance index or CI=0.67, and it separated the low-risk from high-risk groups in predicting overall survival (hazard ratio=2.72, log-rank p=0.007). In the independent validation cohort, this radiomic signature achieved a CI=0.62, and significantly stratified the low-risk and high-risk groups in terms of overall survival (hazard ratio=2.20, log-rank p=0.042). Conclusion: We identified CT imaging characteristics associated with overall survival in early stage lung cancer. If prospectively validated, this could potentially help identify high-risk patients who might benefit from adjuvant systemic therapy.

  12. 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.

  13. Surgical treatment of early stage breast cancer in elderly: an international comparison.

    PubMed

    Kiderlen, M; Bastiaannet, E; Walsh, P M; Keating, N L; Schrodi, S; Engel, J; van de Water, W; Ess, S M; van Eycken, L; Miranda, A; de Munck, L; van de Velde, C J H; de Craen, A J M; Liefers, G J

    2012-04-01

    Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥ 65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

  14. 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

    2015-07-02

    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.

  15. Factors that influence 12 or more harvested lymph nodes in early-stage colorectal cancer.

    PubMed

    Hsu, Chao-Wen; Lin, Chieh-Hsin; Wang, Jui-Ho; Wang, Hsin-Tai; Ou, Wen-Chieh; King, Tai-Ming

    2009-02-01

    The number of lymph nodes required for accurate staging is a critical component in early-stage (stage A and B) colorectal cancer (CRC). Current guidelines demand at least 12 lymph nodes to be retrieved. Results of previous studies were contradictory in factors, which influenced the number of harvested lymph nodes. This study was designed to determine the factors that influence the number of harvested lymph nodes (> or =12) in early-stage CRC in a single institution. Between 2003 and 2007, data on patients who underwent surgery for early-stage CRC were analyzed retrospectively. Data for a total of 470 patients were collected and all the tumor-bearing specimens were fixed with node identification performed. Several possible factors that influence 12 or more harvested lymph nodes were investigated and classified into four aspects: (1) operating surgeon, (2) examining pathologist, (3) patient (age, sex, and body mass index), and (4) disease (maximal length of tumor, length of specimen, tumor localization, tumor cell differentiation, Dukes stage, type of resection, and type of tumor). A total of 289 patients (61.5%) with 12 or more harvested lymph nodes and 181 patients (38.5%) with < 12 lymph nodes were analyzed. The results demonstrate that within a single institution the maximal length of tumor, tumor localization, and depth of tumor invasion according to Dukes stage were independent influencing factors of 12 or more harvested lymph nodes. Maximal length of tumor was associated with more harvested lymph nodes (P < 0.001). Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes. The number of harvested lymph nodes was highly variable in patients who underwent resection of early-stage CRC. Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes. Therefore, from the viewpoint of the surgeons, disease itself is the most important

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

    PubMed

    Duan, Qianqian; Yang, Xiaohong; Huang, Xianzhi

    2015-07-04

    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.

  17. Systemic Therapy for Early-Stage Breast Cancer: What the Plastic Surgeon Should Know.

    PubMed

    Teven, Chad M; Schmid, Daniel B; Sisco, Mark; Ward, James; Howard, Michael A

    2017-01-01

    Objective: We review the types, indications, and common regimens of systemic forms of therapy offered in early-stage breast cancer. We further detail the mechanism of action, approved uses, major toxicities, and relevance to breast reconstruction of specific agents. Methods: A review of the literature on PubMed and Cochrane databases was undertaken to define the indications and common regimens of systemic therapy in early-stage breast cancer. In addition, literature describing relevant information regarding specific systemic agents was reviewed. Results: The main objectives of systemic therapy, when provided in the perioperative setting, are to reduce the risk for future recurrence and prolong overall survival. Systemic forms of therapy consist of chemotherapy, hormonal therapy, and targeted therapy and are increasingly being offered to women with early-stage breast cancer. Similarly, as more women are diagnosed with disease that is amenable to surgical extirpation, rates of breast reconstruction are on the rise. Many agents have effects that may impact patient safety with respect to breast reconstruction. Conclusions: Increasingly, women with breast cancer receive 1 or more forms of systemic therapy during the course of their treatment. It is therefore of significant importance that plastic surgeons have a clear understanding of the issues surrounding the use of systemic agents.

  18. Systemic Therapy for Early-Stage Breast Cancer: What the Plastic Surgeon Should Know

    PubMed Central

    Teven, Chad M.; Schmid, Daniel B.; Sisco, Mark; Ward, James

    2017-01-01

    Objective: We review the types, indications, and common regimens of systemic forms of therapy offered in early-stage breast cancer. We further detail the mechanism of action, approved uses, major toxicities, and relevance to breast reconstruction of specific agents. Methods: A review of the literature on PubMed and Cochrane databases was undertaken to define the indications and common regimens of systemic therapy in early-stage breast cancer. In addition, literature describing relevant information regarding specific systemic agents was reviewed. Results: The main objectives of systemic therapy, when provided in the perioperative setting, are to reduce the risk for future recurrence and prolong overall survival. Systemic forms of therapy consist of chemotherapy, hormonal therapy, and targeted therapy and are increasingly being offered to women with early-stage breast cancer. Similarly, as more women are diagnosed with disease that is amenable to surgical extirpation, rates of breast reconstruction are on the rise. Many agents have effects that may impact patient safety with respect to breast reconstruction. Conclusions: Increasingly, women with breast cancer receive 1 or more forms of systemic therapy during the course of their treatment. It is therefore of significant importance that plastic surgeons have a clear understanding of the issues surrounding the use of systemic agents. PMID:28293332

  19. Body movements during early stages of chick embryo under intermittent low oxygen environment

    NASA Astrophysics Data System (ADS)

    Moriya, Kenji; Chiba, Yuya; Shimouchi, Akito

    2017-07-01

    We have attempted to elucidate the characteristic pattern of body movements in early stages of chick embryos under intermittent low oxygen incubation environment. In order to achieve this aim, the oxygen control system that can be set arbitrary oxygen concentration was developed. We choose the 18% of O2 concentration and tried to measure the embryonic body movements. As a results, only one chick embryo in the early stages under intermittent 18% O2 environment (the cycle is 18%O2-10min and 21%O2-50min) was successfully recorded and its body movements were analyzed. The characteristic body movements, which are attributed to the instantaneous effect of low oxygen environment, compared with before and after normal O2 condition were not observed. Because the early stage embryos in which the significant organs aside from heart are not formed yet have a strong adaptation to environment changes, short hypoxic condition like a 10 min might not affect instantaneous embryonic physiological changes. Meanwhile, although the cyclic interval of the large body movements becomes short in the normal development, it became long in 18%O2 condition. This result might indicate that intermittent low oxygen condition accumulatively influenced physiological function. Further improvements of accuracy in the oxygen control system and the calculation system of body movements, and further experiments under low oxygen conditions are required in the next step.

  20. Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

    SciTech Connect

    None, None

    2016-03-22

    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 early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly 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 sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.

  1. Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women.

    PubMed

    Obeidat, Rana F

    2015-01-01

    To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers' support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system.

  2. Stereotactic body radiotherapy for early stage lung cancer: History and updated role.

    PubMed

    Ricardi, Umberto; Badellino, Serena; Filippi, Andrea Riccardo

    2015-12-01

    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 over 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. In early stage lung cancer, clinicians are now faced with a decision-making process that should take into account different factors. The need of pathological diagnosis and accurate nodal staging still represents a challenge, as well as the interpretation of radiological findings after SBRT, often confusing du to the difficulties in distinguishing between radiation-induced changes and local relapse. Aim of this review is to summarize and discuss the major studies on SBRT for early stage lung cancer, providing data on its efficacy and toxicity and discussing the still open issues on its role. Quality of life, pulmonary function and risk of secondary cancers are also discussed, as well as future perspectives and current research topics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Tailoring Chemotherapy in Early-Stage Breast Cancer: Based on Tumor Biology or Tumor Burden?

    PubMed

    Ribnikar, Domen; Cardoso, Fatima

    2016-01-01

    The question of whether to offer adjuvant chemotherapy to patients with early-stage breast cancer has always been challenging to answer. It is well known that a substantial proportion of patients with early-stage breast cancer are over treated, especially when staging and hormonal and HER2 receptors are solely taken into consideration. The advances in our knowledge of breast cancer biology and its clinical implications were the basis for the discovery of additional reliable prognostic markers to aid decision making for adjuvant treatment. Gene expression profiling is a molecular tool that more precisely defines the intrinsic characteristics of each individual tumor. The application of this technology has led to the development of gene signatures/profiles with relevant prognostic-and some predictive-value that have become important tools in defining which patients with early-stage breast cancer can be safely spared from chemotherapy. However, the exact clinical utility of these tools will only be determined after the results of two large prospective randomized trials, MINDACT and TailorX, evaluating their role become available. Notwithstanding the existence of these genomic tools, tumor burden (defined as tumor size and nodal status) still has independent prognostic value and must be incorporated in decision making. In addition, these gene signatures have limited predictive value, and new biomarkers and new targets are needed. Therefore close collaboration between clinicians and scientists is crucial. Lastly, issues of cost-effectiveness, reimbursement, and availability are crucial and widely variable around the globe.

  4. Promoting emancipated decision-making for surgical treatment of early stage breast cancer among Jordanian women

    PubMed Central

    Obeidat, Rana F.

    2015-01-01

    To use the critical social theory as a framework to analyze the oppression of Jordanian women with early stage breast cancer in the decision-making process for surgical treatment and suggest strategies to emancipate these women to make free choices. This is a discussion paper utilizing the critical social theory as a framework for analysis. The sexist and paternalistic ideology that characterizes Jordanian society in general and the medical establishment in particular as well as the biomedical ideology are some of the responsible ideologies for the fact that many Jordanian women with early stage breast cancer are denied the right to choose a surgical treatment according to their own preferences and values. The financial and political power of Jordanian medical organizations (e.g., Jordan Medical Council), the weakness of nursing administration in the healthcare system, and the hierarchical organization of Jordanian society, where men are first and women are second, support these oppressing ideologies. Knowledge is a strong tool of power. Jordanian nurses could empower women with early stage breast cancer by enhancing their knowledge regarding their health and the options available for surgical treatment. To successfully emancipate patients, education alone may not be enough; there is also a need for health care providers’ support and unconditional acceptance of choice. To achieve the aim of emancipating women with breast cancer from the oppression inherent in the persistence of mastectomy, Jordanian nurses need to recognize that they should first gain greater power and authority in the healthcare system. PMID:27981122

  5. 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.

  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.

  7. Complexity of resting-state EEG activity in the patients with early-stage Parkinson's disease.

    PubMed

    Yi, Guo-Sheng; Wang, Jiang; Deng, Bin; Wei, Xi-Le

    2017-04-01

    To investigate the abnormal brain activities in the early stage of Parkinson's disease (PD), the electroencephalogram (EEG) signals were recorded with 20 channels from non-dementia PD patients (18 patients, 8 females) and age matched healthy controls (18 subjects, 8 females) during the resting state. Two methods based on the ordinal patterns of the recorded series, i.e., permutation entropy (PE) and order index (OI), were introduced to characterize the complexity of the cortical activities for two groups. It was observed that the resting-state EEG of PD patients showed lower PE and higher OI than healthy controls, which indicated that the early-stage PD caused the reduced complexity of EEG. We further applied two methods to determine the complexity of EEG rhythms in five sub-bands. The results showed that the gamma, beta and alpha rhythms of PD patients were characterized by lower PE and higher OI, i.e., reduced complexity, than healthy subjects. No significant differences were observed in theta or delta rhythms between two groups. The findings suggested that PE and OI were promising methods to detect the abnormal changes in the dynamics of EEG signals associated with early-stage PD. Further, such changes in EEG complexity may be the early markers of the cortical or subcortical dysfunction caused by PD.

  8. Promoting Quality and Evidence-Based Care in Early-Stage Breast Cancer Follow-up

    PubMed Central

    Hayes, Daniel F.; Ramsey, Scott D.; Hortobagyi, Gabriel N.; Barlow, William E.; Gralow, Julie R.

    2014-01-01

    Evidence-based guidelines for long-term follow-up of early-stage breast cancer patients developed by oncology societies in the United States and Europe recommend that breast cancer survivors undergo regular evaluation with history and physical examination, as well as annual mammography. Routine blood tests, circulating tumor markers, and/or surveillance imaging studies beyond mammography are not recommended in the absence of concerning symptoms or physical examination findings because of lack of supportive clinical evidence. Despite these guidelines, studies have shown that 20% to 40% of oncologists assess serum tumor markers as part of routine monitoring of early-stage breast cancer patients. As part of efforts to both address the financial challenges confronting the health-care system and optimize patient outcomes, the American Society of Clinical Oncology’s Cost of Care Task Force identified adherence to breast cancer surveillance guidelines as an opportunity to improve care and reduce cost. However, these recommendations are based on trials done in an era of outdated technology and limited therapeutic options. It is possible that recent improvements in diagnostics and treatments could make earlier detection of recurrent disease important for improving both survival and quality of life outcomes. Research is necessary to further inform optimal breast cancer follow-up strategies, which could impact these recommendations. At this time, outside of well-conducted clinical trials, there is no role for ordering routine serial blood or imaging tests in monitoring for recurrence in early-stage breast cancer patients. PMID:24627271

  9. Reduced fractional anisotropy in early-stage cerebellar variant of multiple system atrophy.

    PubMed

    Oishi, Kenichi; Konishi, Junya; Mori, Susumu; Ishihara, Hiroyuki; Kawamitsu, Hideaki; Fujii, Masahiko; Kanda, Fumio

    2009-04-01

    In patients with the cerebellar variant of multiple system atrophy (MSA-C), reduced fractional anisotropy (FA) has been reported in several brain areas. However, since previous studies have employed predetermined regions of interest (ROI), the brain areas showing the earliest alterations in FA are unknown. The sensitivity of detecting early-stage MSA-C and the time course of the FA reduction are also unknown. The purpose was to address these issues to determine the diagnostic value of FA for early diagnosis. Twenty-one patients with MSA-C were investigated. Voxel-based FA analysis and morphometry were used to detect the differences between early-stage MSA-C and normal controls. An ROI-based FA analysis was also used to clarify the temporal profile. From the early-stage, MSA-C patients exhibited reduced FA and white matter atrophy in the middle cerebellar peduncle, the inferior cerebellar peduncle, and the ventral pons. The FA of these areas decreased rapidly during the first few years after onset, after which a rather gradual reduction occurred. The receiver operating characteristics analysis revealed a high sensitivity and specificity for discriminating early MSA-C from normal controls. FA measurement could potentially be used to make an early diagnosis and monitor progression in MSA-C patients.

  10. The Treatment Effect of Porous Titanium Alloy Rod on the Early Stage Talar Osteonecrosis of Sheep

    PubMed Central

    Zhang, Yong-Quan; Zhang, Zhi-Yong; Guo, Zheng

    2013-01-01

    Osteonecrosis of the talus (ONT) may severely affect the function of the ankle joint. Most orthopedists believe that ONT should be treated at an early stage, but a concise and effective surgical treatment is lacking. In this study, porous titanium alloy rods were prepared and implanted into the tali of sheep with early-stage ONT (IM group). The curative effect of the rods was compared to treatment by core decompression (DC group). No significant differences in bone reconstruction were observed between the two groups at 1 month after intervention. After 3 months, the macroscopic view of gross specimens of the IM group showed ordinary contours, but the specimens of the DC group showed obvious partial bone defects and cartilage degeneration. Quantitative analysis of the reconstructed trabeculae by micro-CT and histological study suggested that the curative effect of the IM group was superior to that of the DC group at 3 months after intervention. These favorable short-term results of the implantation of porous titanium alloy rods into the tali of sheep with early-stage ONT may provide insight into an innovative surgical treatment for ONT. PMID:23516485

  11. Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer

    PubMed Central

    Bender, Catherine M.; Sereika, Susan M.; Brufsky, Adam M.; Ryan, Christopher M.; Vogel, Victor G.; Rastogi, Priya; Cohen, Susan M.; Casillo, Frances E.; Berga, Sarah L.

    2010-01-01

    Objective: Hormones have been implicated as modulators of cognitive functioning. For instance, results of our previous work in women with breast cancer showed that cognitive impairment was more severe and involved more memory domains in those who received adjuvant tamoxifen therapy compared with women who received chemotherapy alone or no adjuvant therapy. Recently aromatase inhibitors such as anastrozole have been used in lieu of tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor–positive, early-stage breast cancer. Plasma estrogen levels are significantly lower in women who receive anastrozole compared with those who receive tamoxifen. We hypothesized, therefore, that anastrozole would have a more profound effect on cognitive function than tamoxifen, a mixed estrogen agonist/antagonist. Design: To test this hypothesis we compared cognitive function in women with early-stage breast cancer who received tamoxifen with those who received anastrozole therapy in a cross-sectional study. We evaluated cognitive function, depression, anxiety, and fatigue in 31 postmenopausal women with early-stage breast cancer who were between the ages of 21 and 65 years and treated with tamoxifen or anastrozole for a minimum of 3 months. Results: The results showed that women who received anastrozole had poorer verbal and visual learning and memory than women who received tamoxifen. Conclusions: Additional, prospective studies are needed to validate and confirm the changes in cognitive function associated with hormone therapy for breast cancer. PMID:17898668

  12. Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

    DOE PAGES

    None, None

    2016-03-22

    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 early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » 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 sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

  13. 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

  14. Implementation of the TMS in the early stages of Parkinson's disease.

    PubMed

    Guekht, A; Selikhova, M; Serkin, G; Gusev, E

    2005-01-01

    47 PD patients were investigated with the single-pulse TMS to find out changes in motor evoked potential and motor conduction related to the stage of minimal motor symptoms and its further deterioration in groups with the different clinical types of the disease. The investigation revealed a markedly longer MEP duration along with the increased number of phases, than in controls, which were bilateral and advanced despite the minimal unilateral motor symptoms. There was also increased MEP amplitude in facilitation, with a higher degree of asymmetry, compared to controls. Patients with predominant rigid clinical forms had the further MEP duration and amplitude increase proportionally to bradikinesia and rigidity in the early stages of the disease. Patients with tremor predominant forms had no further changes in the MEP duration and amplitude, but had their motor CCT decreased in the early stages. Patients with the akinetic form were characterized by the asymmetric increase in the MEP Amplitude in relaxation and motor CCT shortening. Thus, TMS allows us to diagnose early the possible central motor changes secondary to Parkinson's disease, reveals the difference in compensational capacity according to the clinical type of the disease and helps in monitoring of the severity of motor changes in early stages.

  15. Early-stage Alzheimer disease represents increased suicidal risk in relation to later stages.

    PubMed

    Lim, Wee Shiong; Rubin, Eugene H; Coats, Mary; Morris, John C

    2005-01-01

    The level of risk for suicide in individuals with Alzheimer disease (AD) generally is considered to be low. It is important to recognize, however, that suicide can occur in early-stage Alzheimer disease on the background of a distinct high-risk profile. The objective of this report is to describe the clinical profiles of individuals with very mild Alzheimer disease who either attempted or completed suicide. We describe two participants in a longitudinal study of early-stage Alzheimer disease who were in the ninth decade of life and had very mild Alzheimer disease. Consistent with earlier cases reported in the literature, both displayed the following high-risk phenotype predisposing to suicidal risk: male gender, highly educated professional, preserved insight, dysthymic symptoms that did not meet criteria for major depression and post-dated the onset of cognitive decline, and suicidal ideation. Neuropathological examination confirmed histologic Alzheimer disease in both cases. These cases, taken together, emphasize the need for awareness that early-stage Alzheimer disease may present a unique suicidal risk compared with later stages.

  16. Finite element simulation of ultrasonic waves in corroded reinforced concrete for early-stage corrosion detection

    NASA Astrophysics Data System (ADS)

    Tang, Qixiang; Yu, Tzuyang

    2017-04-01

    In reinforced concrete (RC) structures, corrosion of steel rebar introduces internal stress at the interface between rebar and concrete, ultimately leading to debonding and separation between rebar and concrete. Effective early-stage detection of steel rebar corrosion can significantly reduce maintenance costs and enable early-stage repair. In this paper, ultrasonic detection of early-stage steel rebar corrosion inside concrete is numerically investigated using the finite element method (FEM). Commercial FEM software (ABAQUS) was used in all simulation cases. Steel rebar was simplified and modeled by a cylindrical structure. 1MHz ultrasonic elastic waves were generated at the interface between rebar and concrete. Two-dimensional plain strain element was adopted in all FE models. Formation of surface rust in rebar was modeled by changing material properties and expanding element size in order to simulate the rust interface between rebar and concrete and the presence of interfacial stress. Two types of surface rust (corroded regions) were considered. Time domain and frequency domain responses of displacement were studied. From our simulation result, two corrosion indicators, baseline (b) and center frequency (fc) were proposed for detecting and quantifying corrosion.

  17. The use of adjuvant bisphophonates in the treatment of early-stage breast cancer.

    PubMed

    Mathew, Aju; Brufsky, Adam M

    2014-11-01

    Adjuvant treatment of breast cancer has resulted in significant improvement in breast cancer-related outcomes. In addition to chemotherapy and endocrine therapy, the bone-protective agents known as bisphosphonates have been extensively investigated for their putative antitumor effect. Backed by strong preclinical data from in vitro and in vivo models, several randomized clinical trials have evaluated the role of bisphosphonates in an adjuvant setting. The recent NSABP B-34 (National Surgical Adjuvant Breast and Bowel Project protocol B-34) and AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) studies found no disease-free survival benefit with clodronate and zoledronate, respectively, whereas the ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12) study found improvement in disease-free survival with zoledronate. Data from these trials suggested a beneficial effect of bisphosphonates in older, postmenopausal women and in premenopausal women treated with ovarian suppression. Given the acceptable toxicity profile of bisphosphonates, these agents could be a useful adjunct to adjuvant chemotherapy or endocrine treatment for early-stage breast cancer in a carefully selected subset of patients. This review aims to critically synthesize the results of clinical trials of adjuvant bisphosphonates in early-stage breast cancer, and to provide guidelines for the use of these agents in early-stage breast cancer.

  18. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    SciTech Connect

    Ward, Matthew Christopher Pham, Yvonne D.; Kotecha, Rupesh; Zakem, Sara J.; Murray, Eric; Greskovich, John F.

    2016-04-01

    Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literature are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.

  19. The Neuroprotective Effects of Carnosine in Early Stage of Focal Ischemia Rodent Model

    PubMed Central

    Park, Hui-Seung; Han, Kyung-Hoon; Shin, Jeoung-A; Park, Joo-Hyun; Song, Kwan-Young

    2014-01-01

    Objective This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke. PMID:24851146

  20. Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

    PubMed Central

    Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

    2013-01-01

    Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

  1. On the role of extracellular polymeric substances during early stages of Xylella fastidiosa biofilm formation.

    PubMed

    Lorite, Gabriela S; de Souza, Alessandra A; Neubauer, Daniel; Mizaikoff, Boris; Kranz, Christine; Cotta, Mônica A

    2013-02-01

    The structural integrity and protection of bacterial biofilms are intrinsically associated with a matrix of extracellular polymeric substances (EPS) produced by the bacteria cells. However, the role of these substances during biofilm adhesion to a surface remains largely unclear. In this study, the influence of EPS on Xylella fastidiosa biofilm formation was investigated. This bacterium is associated with economically important plant diseases; it presents a slow growth rate and thus allows us to pinpoint more precisely the early stages of cell-surface adhesion. Scanning electron microscopy and atomic force microscopy show evidence of EPS production in such early stages and around individual bacteria cells attached to the substrate surface even a few hours after inoculation. In addition, EPS formation was investigated via attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FTIR). To this end, X. fastidiosa cells were inoculated within an ATR liquid cell assembly. IR-ATR spectra clearly reveal EPS formation already during the early stages of X. fastidiosa biofilm formation, thereby providing supporting evidence for the hypothesis of the relevance of the EPS contribution to the adhesion process.

  2. Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

    PubMed

    Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

    2017-06-01

    Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R(2)  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

  3. Introduction of robot-assisted radical hysterectomy for early stage cervical cancer: impact on complications, costs and oncologic outcome.

    PubMed

    Wallin, Emelie; Flöter Rådestad, Angelique; Falconer, Henrik

    2017-05-01

    The objective was to assess the impact of robot-assisted radical hysterectomy (RRH) on surgical and oncologic outcome and costs compared with open radical hysterectomy (ORH) at a tertiary referral center in Sweden. In this retrospective analysis all patients treated with radical hysterectomy and pelvic lymphadenectomy for early stage uterine cervical cancer during 2006-2015 were included (n = 304). The patients were divided into two groups, ORH (n = 155) and RRH (n = 149). Patient characteristics, FIGO stage, histology, adjuvant therapy, operation time, length of stay (LOS), lymph node yield, recurrence rate and survival were retrieved from medical records. Complications were graded according to the Clavien-Dindo classification. In addition, costs related to the surgical treatments were calculated. Blood loss, LOS and intraoperative complications were significantly lower as well as lymph node yield after RRH. No differences in postoperative complications or costs were observed between the two groups. Recurrence of disease was detected in 13.4 and 10.3% after RRH and ORH, respectively. Regression analysis demonstrated that histology, tumor size, positive lymph nodes and type of operation (RRH) were significantly associated with recurrence. The introduction of RRH was accompanied by similar postoperative complication rates and costs but lower LOS compared with ORH. An initial learning curve may account for the higher recurrence rate observed after RRH. These data reinforce the need for structured training and monitoring of outcomes when novel treatment modalities are introduced. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  4. SBRT for early-stage glottic larynx cancer—Initial clinical outcomes from a phase I clinical trial

    PubMed Central

    Schwartz, David L.; Sosa, Alan; Chun, Stephen G.; Ding, Chiuxiong; Xie, Xian-Jin; Nedzi, Lucien A.

    2017-01-01

    Purpose To confirm safety and feasibility of hypofractionated SBRT for early-stage glottic laryngeal cancer. Methods Twenty consecutive patients with cTis-T2N0M0 carcinoma of glottic larynx were enrolled. Patients entered dose-fractionation cohorts of incrementally shorter bio-equivalent schedules starting with 50 Gy in 15 fractions (fx), followed by 45 Gy/10 fx and, finally, 42.5 Gy/5 fx. Maximum combined CTV-PTV expansion was limited to 5 mm. Patients were treated on a Model G5 Cyberknife (Accuray, Sunnyvale, CA). Results Median follow-up is 13.4 months (range: 5.6–24.6 months), with 12 patients followed for at least one year. Maximum acute toxicity consisted of grade 2 hoarseness and dysphagia. Maximum chronic toxicity was seen in one patient treated with 45 Gy/10 fx who continued to smoke >1 pack/day and ultimately required protective tracheostomy. At 1-year follow-up, estimated local disease free survival for the full cohort was 82%. Overall survival is 100% at last follow-up. Conclusions We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity. Trial registration ClinicalTrials.gov NCT01984502 PMID:28253270

  5. A qualitative analysis of interviews of men with early stage prostate cancer: the Prostate Cancer Lifestyle Trial.

    PubMed

    Kronenwetter, Carol; Weidner, Gerdi; Pettengill, Elaine; Marlin, Ruth; Crutchfield, Lila; McCormac, Patricia; Raisin, Caren J; Ornish, Dean

    2005-01-01

    We conducted interviews with a subsample of men (n = 26) participating in the Prostate Cancer Lifestyle Trial (PCLT), who had biopsy-proven prostate cancer (Gleason grade <7; prostate-specific antigen 4-10 ng/mL) and chose "watchful waiting" after diagnosis. The PCLT aimed at improving diet, exercise, stress management practices, and group support within a peer community setting. The aims of this study were to examine psychological, emotional, spiritual, and social reactions to (a) a diagnosis of early stage prostate cancer and (b) participation in the PCLT. Qualitative analyses were completed using MAXqda. Results indicated that the cancer diagnosis was met with anxiety, distress, and denial, or a "bump in the road" attitude. There was some indication that conflict with partners was exacerbated by the diagnosis. A significant component of the lifestyle intervention was involvement in the peer community. This community provided opportunities to experience connections with others facing similar health difficulties. Men generally expressed positive attitudes (emotionally, physically, and spiritually) about the lifestyle change, and felt that their participation in the program contributed to feelings of hope, optimism, and fighting spirit. Additionally, participants frequently mentioned increased comfort with emotional expression.

  6. SBRT for early-stage glottic larynx cancer-Initial clinical outcomes from a phase I clinical trial.

    PubMed

    Schwartz, David L; Sosa, Alan; Chun, Stephen G; Ding, Chiuxiong; Xie, Xian-Jin; Nedzi, Lucien A; Timmerman, Robert D; Sumer, Baran D

    2017-01-01

    To confirm safety and feasibility of hypofractionated SBRT for early-stage glottic laryngeal cancer. Twenty consecutive patients with cTis-T2N0M0 carcinoma of glottic larynx were enrolled. Patients entered dose-fractionation cohorts of incrementally shorter bio-equivalent schedules starting with 50 Gy in 15 fractions (fx), followed by 45 Gy/10 fx and, finally, 42.5 Gy/5 fx. Maximum combined CTV-PTV expansion was limited to 5 mm. Patients were treated on a Model G5 Cyberknife (Accuray, Sunnyvale, CA). Median follow-up is 13.4 months (range: 5.6-24.6 months), with 12 patients followed for at least one year. Maximum acute toxicity consisted of grade 2 hoarseness and dysphagia. Maximum chronic toxicity was seen in one patient treated with 45 Gy/10 fx who continued to smoke >1 pack/day and ultimately required protective tracheostomy. At 1-year follow-up, estimated local disease free survival for the full cohort was 82%. Overall survival is 100% at last follow-up. We were able to reduce equipotent total fractions of SBRT from 15 to 5 without exceeding protocol-defined acute/subacute toxicity limits. With limited follow-up, disease control appears comparable to standard treatment. We continue to enroll to the 42.5 Gy/5 fx cohort and follow patients for late toxicity. ClinicalTrials.gov NCT01984502.

  7. 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

  8. 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.

  9. Curative resection plus adjuvant chemotherapy for early stage primary gastric non-Hodgkin's lymphoma: a retrospective study with emphasis on prognostic factors and treatment outcome.

    PubMed

    Waisberg, Jaques; André, Eduardo Antonio; Franco, Maria Isete Fares; Abucham-Neto, Júlio Zaki; Wickbold, Daniela; Goffi, Fábio Schmidt

    2006-01-01

    There is controversy regarding the optimal therapy for primary non-Hodgkin gastric lymphoma with some authors defending surgical extirpation either alone or in association with radiotherapy and or chemotherapy, especially in relation to the earlier stages of the disease. To analyze the clinical-pathological features and the results of management approaches for patients with primary early-stage non-Hodgkin's lymphoma of the stomach operated in Surgical Gastroenterology Department, "Hospital do Servidor Público Estadual", São Paulo, SP, Brazil. The literature is reviewed to highlight the aspects of diagnosis, prognostic factors and role of the various treatment regimens. Sixteen patients with primary early-stage gastric lymphoma underwent curative surgical treatment. The variables analyzed were age, sex, location, size, type of surgery, number of lesions, depth of invasion, histological type in accordance with Kiel's classification, involvement of lymph nodes, Ann Arbor stage classification modified by Musshoff and Schmidt-Vollmer, histological grade, margins, adjuvant therapy, clinical course and survival. Ten patients (62.5%) underwent subtotal gastrectomy and six (37.5%) underwent total gastrectomy. The majority (9/56.2%) of the lesions were located in the antrum. Single lesions (10/62.5%) were more frequent than multiple lesions (6/37.5%). Thirteen patients (81.2%) were classified as stage IE and three (18.7%) as stage IIE1. Primary gastric lymphoma classified histologically as low or high grade was presented by 10 (62.5%) and 6 (37.5%) patients, respectively. The most frequent histological types were the lymphoplasmocytic cytoid (4/25.0%) and centroblastic (4/25.0%). Ten patients (62.5%) received adjuvant treatment (chemotherapy and/or radiotherapy). Nine patients (56.2%), all in stage IE, reached a survival greater than 5 years and of these eight (50.0.%) had received adjuvant therapy. Two (12.5%) patients with stage IIE1 presented peritoneal relapse and died

  10. 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

  11. Aberrant TIMELESS expression is associated with poor clinical survival and lymph node metastasis in early-stage cervical carcinoma.

    PubMed

    Zhang, Weijing; He, Weiling; Shi, Yongjie; Zhao, Jing; Liu, Sailan; Zhang, Fengxiang; Yang, Jiarui; Xie, Chuanmiao; Zhang, Yanna

    2017-01-01

    TIMELESS is a highly conserved protein required for the maintenance of normal mammalian circadian oscillations and for controlling cellular metabolism and proliferation. Recently, TIMELESS was implicated in the tumorigenesis of certain cancers. However, little is known on TIMELESS protein expression and its potential as a prognostic factor in cervical cancer. Here, we investigate TIMELESS expression pattern and its clinicopathological significance in early-stage cervical carcinoma. TIMELESS mRNA and protein expression was evaluated by real-time PCR and western blot analysis in cervical cancer cell lines, a normal cervical cell line, as well as in six pairs of surgically removed cervical cancer and adjacent normal cervical tissues. A total of 189 paraffin-embedded cervical carcinoma specimens were detected and diagnosed by immunohistochemistry (IHC), and the clinical significance of TIMELESS expression was further analyzed. Aberrant TIMELESS mRNA and protein expression were demonstrated in cervical cancer cell lines compared with the normal cervical cell line. TIMELESS mRNA and protein expression were significantly increased in cervical cancer specimens compared with adjacent non-cancerous cervical specimens. TIMELESS protein expression was significantly associated with the age (P=0.011), clinical stage (P<0.001), pelvic lymph node metastasis (P<0.001), squamous cell carcinoma antigen (P=0.003), tumor recurrence (P=0.015), vital status (P<0.001), tumor differentiation grade (P<0.001), property of the surgical margin (P=0.036) and lymphovascular space involvement (P=0.001). Patients with increased TIMELESS protein expression showed strong tendencies to receive postoperative radiotherapy (P=0.002). Upregulation of TIMELESS correlated with poorer overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox-regression analyses showed that TIMELESS can be regarded as an independent predictive biomarker for poor clinical outcome for early-stage

  12. A prospective trial of postoperative vaginal radium/cesium for grade 1-2 less than 50% myometrial invasion and pelvic radiation therapy for grade 3 or deep myometrial invasion in surgical stage I endometrial adenocarcinoma

    SciTech Connect

    Piver, M.S.; Hempling, R.E. )

    1990-09-15

    A prospective trial was performed to evaluate the recurrence rate and 5-year disease-free survival rate in patients with surgical Stage I endometrial adenocarcinoma. Patients with Stage I, Grade 1 or 2 disease, less than 50% myometrial invasion, and no evidence of disease outside the corpus of the uterus were treated by hysterectomy and bilateral salpingo-oophorectomy and postoperative vaginal radium/cesium (Group 1). Patients with surgical Stage I, Grade 3 disease or deep myometrial invasion, and histologically negative paraaortic lymph nodes were treated with postoperative pelvic radiation therapy (5000-5040 cGY) (Group 2). Patients with malignant peritoneal cytologic findings also received progesterone therapy. Of the 92 Group 1 patients, there have been no recurrences and the 5-year estimated disease-free survival rate was 99%. Of the 41 Group 2 patients, there have been four (9.7%) recurrences but only one (2.4%) within the treated field (pelvis), and the 5-year estimated disease-free survival rate was 88%. Of the 133 patients, the 5-year estimated disease-free survival rate was 96%, and only one patient (0.7%) had a local pelvic recurrence. Of the 16 patients with malignant peritoneal cytologic findings who were treated with progesterone therapy, none has had a recurrence.

  13. Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer.

    PubMed

    Vaizoglu, Ferdi; Yuce, Kunter; Salman, Mehmet Coskun; Basaran, Derman; Calis, Pinar; Ozgul, Nejat; Usubutun, Alp

    2013-12-01

    To determine clinicopathological risk factors associated with lymph node metastasis in endometrial cancer (EC). Clinicopathological data of patients who underwent comprehensive surgical staging for clinical early stage EC between 2001 and 2010 at Hacettepe University Hospital was retrospectively reviewed. Two hundred and sixty-one patients were included. There were 26 patients (10.0%) with lymph node metastasis. Of these, 14 (5.4%) had pelvic lymph node metastasis, 8 (3.1%) had both pelvic and paraaortic lymph node metastasis, and 4 (1.5%) had isolated paraaortic metastasis. Univariate analysis revealed tumor size >2 cm, type II cancer, grade III histology, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, and presence of lymphovascular space involvement (LVSI) as significant clinicopathological factors associated with retroperitoneal lymph node metastasis. For paraaortic metastasis either isolated or with pelvic lymph node metastasis, significant factors were grade III disease, cervical stromal invasion, deep myometrial invasion, positive peritoneal cytology, adnexal involvement, serosal involvement, pelvic lymph node metastasis, and presence of LVSI. The only factor associated with isolated paraaortic lymph node metastasis was LVSI. Multivariate analysis revealed LVSI as the only independent factor for both retroperitoneal and paraaortic lymph node metastasis (odds ratio 14.9; 95% confidence interval 3.8-59.0; p < 0.001, and odds ratio 20.9; 95% confidence interval 1.9-69.9; p = 0.013, respectively). Lymphovascular space involvement is the sole predictor of lymph node metastasis in EC. Therefore, LVSI status should be requested from the pathologist during frozen examination whenever possible to consider when a decision to perform or omit lymphadenectomy is made.

  14. CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer.

    PubMed Central

    Tempfer, C.; Sliutz, G.; Haeusler, G.; Speiser, P.; Reinthaller, A.; Breitenecker, G.; Vavra, N.; Kainz, C.

    1998-01-01

    Expression of alternatively spliced CD44 isoforms has been reported to correlate with poor prognosis in human squamous cell cancers, i.e. squamous cell cancer of the lung and cervix. The aim of this study was to evaluate whether CD44 isoform expression is a prognostic factor in early-stage squamous cell cancer of the vulva. Seventy cases of squamous cell carcinoma of the vulva International Federation of Gynaecology and Obstetrics (FIGO) stage I were examined immunohistochemically for expression of CD44 isoforms. We used four different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exons v3, v5, v6 and v7-8 of human variant CD44. The correlation of CD44 expression with histological grade and disease-free and overall survival was investigated. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 28% (20/70), 47% (33/70), 33% (23/70) and 17% (12/70) of the tumour samples respectively. Patients suffering from tumours expressing CD44v6 had a poorer relapse-free (log-rank test, P = 0.02) and overall survival (log-rank test, P = 0.03). Likewise, patients suffering from tumours expressing CD44v3 had a poorer relapse-free (log-rank test, P = 0.04) and overall survival (log-rank test, P = 0.01). Expression of CD44v5 and CD44v7-8 did not compromise the patients' outcome. Histological grade did not correlate with CD44 isoform expression. Immunohistochemically detected expression of CD44 isoforms containing variant exon v6 or v3 is correlated with a poor relapse-free and overall survival in FIGO stage I vulvar cancer patients. PMID:9792156

  15. 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.

  16. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: Executive Summary of an ASTRO Evidence-Based Guideline.

    PubMed

    Videtic, Gregory M M; Donington, Jessica; Giuliani, Meredith; Heinzerling, John; Karas, Tomer Z; Kelsey, Chris R; Lally, Brian E; Latzka, Karen; Lo, Simon S; Moghanaki, Drew; Movsas, Benjamin; Rimner, Andreas; Roach, Michael; Rodrigues, George; Shirvani, Shervin M; Simone, Charles B; Timmerman, Robert; Daly, Megan E

    This guideline presents evidence-based recommendations for stereotactic body radiation therapy (SBRT) in challenging clinical scenarios in early-stage non-small cell lung cancer (NSCLC). The American Society for Radiation Oncology convened a task force to perform a systematic literature review on 4 key questions addressing: (1) application of SBRT to operable patients; (2) appropriate use of SBRT in tumors that are centrally located, large, multifocal, or unbiopsied; (3) individual tailoring of SBRT in "high-risk" clinical scenarios; and (4) SBRT as salvage therapy after recurrence. Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength. Although few randomized trials have been completed for SBRT, strong consensus recommendations based on extensive, consistent publications were generated for several questions, including recommendations for fractionation for central tumors and surgery versus SBRT in standard-risk medically operable patients with early-stage NSCLC. Lower quality evidence led to conditional recommendations on use of SBRT for tumors >5 cm, patients with prior pneumonectomy, T3 tumors with chest wall invasion, synchronous multiple primary lung cancer, and as a salvage therapy after prior radiation therapy. These areas of moderate- and low-quality evidence highlight the importance of clinical trial enrollment as well as the role of prospective data registries. SBRT has an important role to play in treating early-stage NSCLC, particularly for medically inoperable patients with limited other treatment options. Shared decision-making with patients should be performed in all cases to ensure the patient understands the risks related to SBRT, the side effects, and the alternative treatments available. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights

  17. Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early-Stage Breast Cancer: The LACE and Pathways Studies.

    PubMed

    Jones, Lee W; Kwan, Marilyn L; Weltzien, Erin; Chandarlapaty, Sarat; Sternfeld, Barbara; Sweeney, Carol; Bernard, Philip S; Castillo, Adrienne; Habel, Laurel A; Kroenke, Candyce H; Langholz, Bryan M; Queensberry, Charles P; Dang, Chau; Weigelt, Britta; Kushi, Lawrence H; Caan, Bette J

    2016-09-15

    To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hours/week) and recurrence and breast cancer-related death for: (i) all patients ("unselected" cohort), and on the basis of (ii) classic clinicopathologic features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes, and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n = 6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast cancer-related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer-related death was apparent for tumors <2 cm [HR, 0.50; 95% confidence interval (CI), 0.34-0.72], well/moderately differentiated tumors (HR, 0.63; 95% CI, 0.43-0.91), and ER-positive tumors (HR, 0.72; 95% CI, 0.53-0.97). Stratification by clinical subtype indicated that the ER(+)/PR(+)/HER2(-)/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI, 0.45-0.88; breast cancer-related death: adjusted HR, 0.57; 95% CI, 0.37-0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early-stage breast cancer. Cancer Res; 76(18); 5415-22. ©2016 AACR.

  18. Prediction model of pelvic lymph node metastasis in early stage cervical cancer and its clinical value.

    PubMed

    Sun, J R; Zhang, Y N; Sun, X M; Feng, S Y; Yan, M

    2011-12-01

    This study was designed to investigate the risk factors of pelvic lymph node metastasis in early stage cervical cancer in order to establish a prediction model for this metastasis and to explore the feasibility of conservative surgery. The records of 207 stage IB-IIA cervical cancer patients were retrospectivly analyzed. The risk factors of pelvic lymph node metastasis were analyzed using univariate and multivariate methods. The prediction model for pelvic lymph node metastasis was established by logistic regression. Without preoperative adjuvant therapy, the metastatic rate of pelvic lymph node in stage IB-IIA cervical cancer was 25.1%. The serum SCCAg, the tumor diameter, the depth of cervical stroma invasion, and the cervical canal involvement were revealed as the risk factors of pelvic lymph node metastasis by univariate analysis (P<0.05). Multivariate analysis showed that the serum SCCAg and the depth of cervical stroma invasion were the independent risk factors of pelvic lymph node metastasis (P<0.05, OR = 6.917, 2.227). The patients were divided into three groups according to different independent risk factors: the low-risk group, the medium-risk group, and the high-risk group, which showed metastatic rates of pelvic lymph node of 5.7%, 16.9%, and 48.7%, respectively (P<0.001). A prediction model for pelvic lymph node metastasis was established as follows: Logti(P) = -2.534 + serum SCCAg×1.934 + depth of cervical stroma invasion×0.801. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of this prediction model were 53.8%, 83.9 %, 52.8%, 84.4%, and 76.3%, respectively. The serum SCCAg and the depth of cervical stroma invasion were the independent risk factors of pelvic lymph node metastasis in early stage cervical cancer. The proposed prediction model may help to improve the conservative surgery for early stage cervical cancer.

  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. 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.

  1. Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

    PubMed

    Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

    2017-09-01

    Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

  2. Outcomes following local therapy for early-stage breast cancer in non-trial populations.

    PubMed

    Keating, Nancy L; Landrum, Mary Beth; Brooks, John M; Chrischilles, Elizabeth A; Winer, Eric P; Wright, Kara; Volya, Rita

    2011-02-01

    Recent studies suggest trends toward more mastectomies for primary breast cancer treatment. We assessed survival after mastectomy and breast-conserving surgery (BCS) with radiation for early-stage breast cancer among non-selected populations of women and among women similar to those in clinical trials. Using population-based data from Surveillance Epidemiology, and End Results cancer registries linked with Medicare administrative data from 1992 to 2005, we conducted propensity score analysis of survival following primary therapy for early-stage breast cancer, including BCS with radiation, BCS without radiation, mastectomy with radiation, and mastectomy without radiation. Adjusted survival was greatest among women who had BCS with radiation (median survival = 10.98 years). Compared with this group, mortality was higher among women who had mastectomy without radiation (median survival 10.04 years, adjusted hazard ratio (HR) = 1.19, 95% confidence interval (CI) = 1.14-1.23), mastectomy with radiation (median survival 10.02 years, HR = 1.20, 95% CI = 1.14-1.27), and BCS without radiation (median survival 7.63 years, HR = 1.81, 95% CI = 1.70-1.92). Among women representative of those eligible for clinical trials (age ≤70 years, Charlson comorbidity score = 0/1, and stage 1 tumors), there were no differences in survival for women who underwent BCS with radiation or mastectomy. In conclusion, after careful adjustment for differences in patient, physician, and hospital characteristics, we found better survival for BCS with radiation versus mastectomy among older early-stage breast cancer patients, with no difference in survival for BCS with radiation versus mastectomy among women representative of those in clinical trials. These findings are reassuring in light of recent trends towards more aggressive primary breast cancer therapy.

  3. 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.

  4. Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis.

    PubMed

    Andrigueti, Fernando V; Arismendi, Maria I; Ebbing, Pâmela C C; Kayser, Cristiane

    2015-03-01

    Microangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc. To evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects. Thirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs. The EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1 ± 95.1 vs. 241.3 ± 184.2 EPC/10(6) lymphomononuclear cells, p=0.011; 15.4 ± 8.6 vs. 23.5 ± 10.9 CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration. The present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.

    PubMed

    Varma, Vijay R; Watts, Amber

    2017-01-01

    Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls. Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.

  6. Genome-Wide Analysis of Survival in Early-Stage Non–Small-Cell Lung Cancer

    PubMed Central

    Huang, Yen-Tsung; Heist, Rebecca S.; Chirieac, Lucian R.; Lin, Xihong; Skaug, Vidar; Zienolddiny, Shanbeh; Haugen, Aage; Wu, Michael C.; Wang, Zhaoxi; Su, Li; Asomaning, Kofi; Christiani, David C.

    2009-01-01

    Purpose Lung cancer, of which 85% is non–small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. Patients and Methods One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. Results Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P ≤ 2.5 × 10−4) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (Ptrend = 3.80 × 10−12 and 2.48 × 10−7 for MGH and Norwegian cohorts, respectively). Conclusion Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC. PMID:19414679

  7. Low-dose consolidation radiation therapy for early stage unfavorable Hodgkin lymphoma.

    PubMed

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

    2015-05-01

    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. 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Frequency of Early-Stage Lymphedema and Risk Factors in Postoperative Patients with Breast Cancer

    PubMed Central

    Soyder, Aykut; Taştaban, Engin; Özbaş, Serdar; Boylu, Şükrü; Özgün, Hedef

    2014-01-01

    Objective Lymphedema is a chronic major complication that is seen frequently post-operatively and has negative effects on quality of life. In our study, determining the early-stage postoperative lymphedema frequency and specifying the risk factors in its development has been aimed. Materials and Methods One hundred one cases that were operated on for breast cancer were evaluated regarding the 12-month control of their clinical specifications, histopathological specifications, and specifications related with the surgical intervention retrospectively. The data related to the parameters envisioned as risk factors were evaluated. Results Lymphedema development was found in 7 (6.9%) out of 101 cases constituting the study group. No significant difference (p>0.05) in terms of lymphedema development was determined among age, body mass index (BMI), chemotherapy (CT), postoperative seroma or infection, mastectomy with the dominant arm, and breast-conserving surgery (BCS), which were evaluated as risk factors. There was a significance (p<0.05) between the other risk factors, which were axillary dissection (AD), number of positive lymph nodes (LN), radiotherapy (RT), the tumor size (T), and lymphedema existence. In every case in which lymphedema was determined, it was seen that there was axillary LN involvement and 15≤LN were ablated in the dissection (p<0.05). Conclusion It is seen that AD, RT applied to the breast cancer patients, and T are important risk factors in early-stage lymphedema development. No early-stage lymphedema development was determined in any of the patients to whom sentinel lymph node dissection (SLND) was applied.

  9. Patient-specific core decompression surgery for early-stage ischemic necrosis of the femoral head

    PubMed Central

    Wang, Wei; Hu, Wei; Yang, Pei; Dang, Xiao Qian; Li, Xiao Hui; Wang, Kun Zheng

    2017-01-01

    Introduction Core decompression is an efficient treatment for early stage ischemic necrosis of the femoral head. In conventional procedures, the pre-operative X-ray only shows one plane of the ischemic area, which often results in inaccurate drilling. This paper introduces a new method that uses computer-assisted technology and rapid prototyping to enhance drilling accuracy during core decompression surgeries and presents a validation study of cadaveric tests. Methods Twelve cadaveric human femurs were used to simulate early-stage ischemic necrosis. The core decompression target at the anterolateral femoral head was simulated using an embedded glass ball (target). Three positioning Kirschner wires were drilled into the top and bottom of the large rotor. The specimen was then subjected to computed tomography (CT). A CT image of the specimen was imported into the Mimics software to construct a three-dimensional model including the target. The best core decompression channel was then designed using the 3D model. A navigational template for the specimen was designed using the Pro/E software and manufactured by rapid prototyping technology to guide the drilling channel. The specimen-specific navigation template was installed on the specimen using positioning Kirschner wires. Drilling was performed using a guide needle through the guiding hole on the templates. The distance between the end point of the guide needle and the target was measured to validate the patient-specific surgical accuracy. Results The average distance between the tip of the guide needle drilled through the guiding template and the target was 1.92±0.071 mm. Conclusions Core decompression using a computer-rapid prototyping template is a reliable and accurate technique that could provide a new method of precision decompression for early-stage ischemic necrosis. PMID:28464029

  10. VEGF polymorphisms and survival in early-stage non-small-cell lung cancer.

    PubMed

    Heist, Rebecca Suk; Zhai, Rihong; Liu, Geoffrey; Zhou, Wei; Lin, Xihong; Su, Li; Asomaning, Kofi; Lynch, Thomas J; Wain, John C; Christiani, David C

    2008-02-20

    Polymorphisms in the VEGF gene have been identified that are believed to have functional activity. We hypothesized that such polymorphisms may affect survival outcomes among early-stage non-small-cell lung cancer (NSCLC) patients. We evaluated the relationship between VEGF polymorphisms and overall survival (OS) among patients with early-stage NSCLC treated with surgical resection at Massachusetts General Hospital from 1992 to 2001. We specifically investigated the VEGF polymorphisms +936C>T (rs3025039), -460T>C (rs833061), and +405G>C (rs2010963). Analyses of genotype associations with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test. There were 462 patients and 237 deaths. Patients carrying the variant C allele of the VEGF +405G>C polymorphism had significantly improved survival (crude hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.90; P = .006; adjusted HR = 0.70; 95% CI, 0.54 to 0.91; P = .008). Five-year OS for patients carrying the variant C allele of the VEGF +405G>C polymorphism was 61% (95% CI, 54% to 67%) versus 51% (95% CI, 43% to 59%) for those who had the wild-type variant. There was a trend toward improved survival among patients carrying the variant T allele of the VEGF +936C>T polymorphism (crude HR = 0.74; 95% CI, 0.53 to 1.03; P = .07; adjusted HR = 0.73; 95% CI, 0.52 to 1.03; P = .07). Moreover, patients with higher number of variant alleles of the +405G>C and +936C>T polymorphisms had better survival. There was no association found with the -460T>C polymorphism. Polymorphisms in VEGF may affect survival in early-stage lung cancer.

  11. Genome-wide analysis of survival in early-stage non-small-cell lung cancer.

    PubMed

    Huang, Yen-Tsung; Heist, Rebecca S; Chirieac, Lucian R; Lin, Xihong; Skaug, Vidar; Zienolddiny, Shanbeh; Haugen, Aage; Wu, Michael C; Wang, Zhaoxi; Su, Li; Asomaning, Kofi; Christiani, David C

    2009-06-01

    Lung cancer, of which 85% is non-small-cell (NSCLC), is the leading cause of cancer-related death in the United States. We used genome-wide analysis of tumor tissue to investigate whether single nucleotide polymorphisms (SNPs) in tumors are prognostic factors in early-stage NSCLC. One hundred early-stage NSCLC patients from Massachusetts General Hospital (MGH) were used as a discovery set and 89 NSCLC patients collected by the National Institute of Occupational Health, Norway, were used as a validation set. DNA was extracted from flash-frozen lung tissue with at least 70% tumor cellularity. Genome-wide genotyping was done using the high-density SNP chip. Copy numbers were inferred using median smoothing after intensity normalization. Cox models were used to screen and validate significant SNPs associated with the overall survival. Copy number gains in chromosomes 3q, 5p, and 8q were observed in both MGH and Norwegian cohorts. The top 50 SNPs associated with overall survival in the MGH cohort (P < or = 2.5 x 10(-4)) were selected and examined using the Norwegian cohort. Five of the top 50 SNPs were validated in the Norwegian cohort with false discovery rate lower than 0.05 (P < .016) and all five were located in known genes: STK39, PCDH7, A2BP1, and EYA2. The numbers of risk alleles of the five SNPs showed a cumulative effect on overall survival (P(trend) = 3.80 x 10(-12) and 2.48 x 10(-7) for MGH and Norwegian cohorts, respectively). Five SNPs were identified that may be prognostic of overall survival in early-stage NSCLC.

  12. Evaluating the performance of the Montreal Cognitive Assessment in early stage Parkinson's disease.

    PubMed

    Kletzel, Sandra L; Hernandez, Juan Manuel; Miskiel, Elizabeth F; Mallinson, Trudy; Pape, Theresa Louise-Bender

    2017-04-01

    Mild cognitive impairment is common in Parkinson's disease, even in the early stages, and can be a risk for developing dementia. To properly track development and progression of cognitive impairment, reliable measurement tools are necessary. The Montreal Cognitive Assessment is currently used as a global cognitive screening tool and has been recommended as an abbreviated diagnostic tool to measure mild cognitive impairment in the context of global cognitive function. However psychometric properties of the Montreal Cognitive Assessment in PD have not been assessed in this context. Data were obtained from the Parkinson's Progression Markers Initiative (n = 395). We examine psychometric properties of the Montreal Cognitive Assessment among newly diagnosed Parkinson's disease patients using Rasch analysis. Only one item misfit the measurement model and principle component analysis indicated the Montreal Cognitive Assessment was unidimensional. Distribution of items calibrations formed a logical hierarchy from least to most challenging. Test items were markedly off-target (i.e., too easy) for this sample; this was also reflected in low person separation reliability. While 37% of participants performed all items correctly indicating a large ceiling effect, 22% of participants obtained a raw score in the range of 21-25 indicating mild cognitive impairment. No meaningful differential item functioning was detected. Results suggest that in the context of early stage Parkinson's disease, the Montreal Cognitive Assessment is a unidimensional measure of global cognitive function. Implications for the use of the Montreal Cognitive Assessment in early stage Parkinson's disease and potential improvements to the assessment are discussed. Published by Elsevier Ltd.

  13. 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

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

    PubMed

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

    2016-08-01

    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.

  15. The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease.

    PubMed

    Sung, Victor W; Watts, Ray L; Schrandt, Christian J; Guthrie, Stephanie; Wang, Deli; Amara, Amy W; Guthrie, Barton L; Walker, Harrison C

    2013-12-01

    While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (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 STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients 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 analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

  16. Evaluation of the enhanced permeability and retention effect in the early stages of lymph node metastasis.

    PubMed

    Mikada, Mamoru; Sukhbaatar, Ariunbuyan; Miura, Yoshinobu; Horie, Sachiko; Sakamoto, Maya; Mori, Shiro; Kodama, Tetsuya

    2017-02-17

    Most solid cancers spread to new sites via the lymphatics before hematogenous dissemination. However, only a small fraction of an intravenously administered anti-cancer drug enters the lymphatic system to reach metastatic lymph nodes (LNs). Here, we show that the enhanced permeability and retention (EPR) effect is not induced during the early stages of LN metastasis. Luciferase-expressing tumor cells were injected into the subiliac LN of the MXH10/Mo-lpr/lpr mouse to induce metastasis to the proper axillary LN (PALN). In vivo biofluorescence imaging was used to confirm metastasis induction and to quantify the EPR effect, measured as PALN accumulation of intravenously injected indocyanine green (ICG) liposomes. PALN blood vessel volume changes were measured by contrast-enhanced high-frequency ultrasound imaging. The volume and density of blood vessels in the PALN increased until day 29 after inoculation whereas the LN volume remained constant. ICG retention was first detected on day 29 post-inoculation. While CD31-positive cells increased up to day 29 post-inoculation, α-smooth muscle actin-positive cells were detected on day 29 post-inoculation for the first time. These results suggest that the EPR effect was not induced in the early stages of LN metastasis; therefore, systemic chemotherapy would likely not be beneficial during the early stages of LN metastasis. The development of an alternative drug delivery system, independent of the EPR effect, is required for the treatment of LN metastasis. This article is protected by copyright. All rights reserved.

  17. Open lung biopsy in early-stage acute respiratory distress syndrome

    PubMed Central

    Kao, Kuo-Chin; Tsai, Ying-Huang; Wu, Yao-Kuang; Chen, Ning-Hung; Hsieh, Meng-Jer; Huang, Shiu-Feng; Huang, Chung-Chi

    2006-01-01

    Introduction Acute respiratory distress syndrome (ARDS) has heterogeneous etiologies, rapid progressive change and a high mortality rate. To improve the outcome of ARDS, accurate diagnosis is essential to the application of effective early treatment. The present study investigated the clinical effects and safety of open lung biopsy (OLB) in patients with early-stage ARDS of suspected non-infectious origin. Methods We undertook a retrospective study of 41 patients with early-stage ARDS (defined as one week or less after intubation) who underwent OLB in two medical intensive care units of a tertiary care hospital from 1999 to 2005. Data analyzed included baseline characteristics, complication rate, pathological diagnoses, treatment alterations, and hospital survival. Results The age of patients was 55 ± 17 years (mean ± SD). The average ratio of arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) was 116 ± 43 mmHg (mean ± SD) at biopsy. Seventeen patients (41%) were immunocompromised. Postoperative complications occurred in 20% of patients (8/41). All biopsies provided a pathological diagnosis with a diagnostic yield of 100%. Specific pathological diagnoses were made for 44% of patients (18/41). Biopsy findings led to an alteration of treatment modality in 73% of patients (30/41). The treatment alteration rate was higher in patients with nonspecific diagnoses than in patients with specific diagnoses (p = 0.0024). Overall mortality was 50% (21/41) and was not influenced by age, gender, pre-OLB oxygenation, complication rate, pathological results, and alteration of treatment. There was no surgery-related mortality. The survival rate for immunocompromised patients was better than that for immunocompetent patients (71% versus 33%; p = 0.0187) in this study. Conclusion Our retrospective study suggests that OLB was a useful and acceptably safe diagnostic procedure in some selected patients with early-stage ARDS. PMID:16859510

  18. Mapping Thalamocortical Functional Connectivity in Chronic and Early Stages of Psychotic Disorders.

    PubMed

    Woodward, Neil D; Heckers, Stephan

    2016-06-15

    There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state functional magnetic resonance imaging has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Resting-state functional magnetic resonance imaging was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early-stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions of interest (ROIs) on the basis of connectivity with six a priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxelwise seed-based analyses to further localize thalamic dysconnectivity. ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early-stage psychosis patients. PFC hypoconnectivity and motor cortex hyperconnectivity correlated in patients, suggesting that they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypoconnectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described executive control network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. Copyright

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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 stages of Parkinson's disease.

  20. [Comparative proteome analysis of blood plasma of patients with early-stage chronic cerebral ischemia].

    PubMed

    Kisrieva, Y S; Petushkova, N A; Samenkova, N F; Kuznetsova, G P; Larina, O V; Zavialova, M G; Teryaeva, N B; Belyaev, A Y; Karuzina, I I

    2016-07-01

    In the present study, we explored the technology of liquid chromatography-mass spectrometry (HPLC-MS/MS) for the proteome analysis of blood plasma of patients with early chronic cerebral ischemia. Analysis of mass-spectrometer data carried out in automatic mode using the software Progenesis LS-MS. As a result of this study identified 43 proteins. The differences identified in the study group compared with the control in 7 proteins. It was found that in the early stages of chronic cerebral ischemia proteome changes in blood plasma affect proteins related to the immune system, the system for the maintenance of hemostasis and lipid metabolism.

  1. '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.

  2. A case of painless thyroiditis in a very early stage of pregnancy.

    PubMed

    Sato, Shiori; Endo, Kei; Iizaka, Toru; Saiki, Ryo; Iwaku, Kenji; Sato, Shotaro; Takahashi, Yasuyoshi; Otsuka, Fumiko; Taniyama, Matsuo

    2012-01-01

    We report a case of painless thyroiditis detected during the first trimester of pregnancy. A 29-year-old Japanese woman was hospitalized because of thyrotoxicosis and she was confirmed to be pregnant. The gestational age was 4 weeks. Blood examinations revealed negative TSH receptor antibodies, however, we started potassium iodide because we were unable to rule out Graves' disease. Thyroid hormone levels were normalized in 3 weeks and remained low even after discontinuation of medication. She received replacement therapy with levothyroxine sodium hydrate till 3 months after delivery. Painless thyroiditis can be one of the differential diagnoses of thyrotoxicosis in a very early stage of pregnancy.

  3. The effects of bromazepam on the early stage of visual information processing (P100).

    PubMed

    Puga, Fernanda; Sampaio, Isabel; Veiga, Heloisa; Ferreira, Camila; Cagy, Maurício; Piedade, Roberto; Ribeiro, Pedro

    2007-12-01

    The early stages of visual information processing, involving the detection and perception of simple visual stimuli, have been demonstrated to be sensitive to psychotropic agents. The present study investigated the effects of an acute dose of bromazepam (3 mg), compared with placebo, on the P100 component of the visual evoked potential and reaction time. The sample, consisting of 14 healthy subjects (6 male and 8 female), was submitted to a visual discrimination task, which employed the "oddball" paradigm. Results suggest that bromazepam (3 mg) impairs the initial stage of visual information processing, as observed by an increase in P100 latency.

  4. Hydrodynamic instability of elastic-plastic solid plates at the early stage of acceleration

    NASA Astrophysics Data System (ADS)

    Piriz, A. R.; Sun, Y. B.; Tahir, N. A.

    2015-03-01

    A model is presented for the linear Rayleigh-Taylor instability taking place at the early stage of acceleration of an elastic-plastic solid, when the shock wave is still running into the solid and is driven by a time varying pressure on the interface. When the the shock is formed sufficiently close to the interface, this stage is considered to follow a previous initial phase controlled by the Ritchmyer-Meshkov instability that settles new initial conditions. The model reproduces the behavior of the instability observed in former numerical simulation results and provides a relatively simpler physical picture than the currently existing one for this stage of the instability evolution.

  5. Photoluminescence due to early stage of oxygen precipitation in multicrystalline Si for solar cells

    NASA Astrophysics Data System (ADS)

    Higuchi, Fumito; Tajima, Michio; Ogura, Atsushi

    2017-07-01

    To analyze the early stage of oxygen precipitation in n-type multicrytalline Si, the spectral change of photoluminescence (PL) induced by thermal treatment at 450-650 °C was investigated in relation to the changes in excess donor and interstitial oxygen concentrations. We observed the characteristic PL bands in the near-band-edge region and sharp lines in the deep-level region in correspondence with the generation of thermal donors and new donors. The observed PL spectral variation is essentially the same as that in Czochralski-grown Si annealed at 450-650 °C.

  6. Early-Stage Folding in Proteins (In Silico) Sequence-to-Structure Relation

    PubMed Central

    2005-01-01

    A sequence-to-structure library has been created based on the complete PDB database. The tetrapeptide was selected as a unit representing a well-defined structural motif. Seven structural forms were introduced for structure classification. The early-stage folding conformations were used as the objects for structure analysis and classification. The degree of determinability was estimated for the sequence-to-structure and structure-to-sequence relations. Probability calculus and informational entropy were applied for quantitative estimation of the mutual relation between them. The structural motifs representing different forms of loops and bends were found to favor particular sequences in structure-to-sequence analysis. PMID:16046811

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

    PubMed

    Meyerson, Nicholas R; Sharma, Amit; Wilkerson, Gregory K; Overbaugh, Julie; Sawyer, Sara L

    2015-08-01

    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. 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 from captive owl

  8. 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

  9. Free energy and structure of calcium carbonate nanoparticles during early stages of crystallization

    NASA Astrophysics Data System (ADS)

    Quigley, D.; Rodger, P. M.

    2008-06-01

    We introduce a metadynamics based scheme for computing the free energy of nanoparticles as a function of their crystalline order. The method is applied to small nanoparticles of the biomineral calcium carbonate to determine the preferred structure during early stages of crystal growth. For particles 2 nm in diameter, we establish a large energetic preference for amorphous particle morphologies. Particles with partial crystalline order consistent with vaterite are also observed with substantially lower probability. The absence of the stable calcite phase and stability of the amorphous state support recent conjectures that calcite formation starts via the deposition of amorphous calcium carbonate.

  10. [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.

  11. Histopathologic findings of spontaneous osteonecrosis of the knee at an early stage: a case report.

    PubMed

    Hatanaka, Hiroyuki; Yamamoto, Takuaki; Motomura, Goro; Sonoda, Kazuhiko; Iwamoto, Yukihide

    2016-05-01

    We histopathologically examined a surgically resected full specimen obtained from an early-stage spontaneous osteonecrosis of the knee (SPONK). On a mid-coronal cut section of the resected medial femoral condyle, a linear fracture line paralleling the subchondral bone endplate was found. Histopathologically, prominent callus formation was seen comprising of reactive woven bone and granulation tissue on both sides of the fracture. Fracture-related bone debris was focally observed at the osteochondral side of the fracture. Definitive features of antecedent bone infarction such as creeping substitution and bone marrow necrosis were not detected. These findings suggested that SPONK was the result of a subchondral fracture rather than primary osteonecrosis.

  12. 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.

  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. Modeling of thin films growth processes in the early stage for atoms with covalent bonds

    NASA Astrophysics Data System (ADS)

    Tupik, V. A.; Margolin, V. I.; Trong Su, Chu

    2017-07-01

    Computer simulation for obtaining thin film’s growth process at an early stage with the proposed model of atoms with isotropic and anisotropic interactions been considered. Carrying out the procedure for analyzing the problem on the basis of the program being implemented, computer simulation of thin film growth processes has been carried out on several examples. The results of computer simulation of the growth process of thin film on a given substrate and an aggregate in a vacuum condition are shown. Some characteristic distributions of the obtained structure have been carried out to evaluate the proposed adequate model and to reflect the high complexity of thin films growth process.

  15. Nonlinear Langevin model for the early-stage dynamics of electrospinning jets

    NASA Astrophysics Data System (ADS)

    Lauricella, Marco; Pontrelli, Giuseppe; Pisignano, Dario; Succi, Sauro

    2015-09-01

    We present a nonlinear Langevin model to investigate the early-stage dynamics of electrified polymer jets in electrospinning experiments. In particular, we study the effects of air drag force on the uniaxial elongation of the charged jet, right after ejection from the nozzle. Numerical simulations show that the elongation of the jet filament close to the injection point is significantly affected by the nonlinear drag exerted by the surrounding air. These results provide useful insights for the optimal design of current and future electrospinning experiments.

  16. The Utility of Stroop Task Switching as a Marker for Early Stage Alzheimer’s Disease

    PubMed Central

    Hutchison, Keith A.; Balota, David A.; Duchek, Janet M.

    2009-01-01

    Past studies have suggested attentional control tasks such as the Stroop task and the task switching paradigm may be sensitive to the early detection of Dementia of the Alzheimer type (DAT). The current study combined these tasks to create a Stroop switching task. Performance was compared across young adults, older adults, and individuals diagnosed with “Very Mild” dementia. Results indicated that this task strongly discriminated healthy aging from early stage DAT. In a logistic regression analysis, incongruent error rates from the Stroop Switch discriminated healthy aging from DAT better than any of the other 18 cognitive tasks given in a psychometric battery. PMID:20853964

  17. A functional account of verb use in the early stages of English multiword development.

    PubMed

    Cameron-Faulkner, Thea

    2012-09-01

    The present study investigates flexibility of verb use in the early stages of English multiword development, and its relationship with patterns attested in the input. The data is taken from a case study of a monolingual English-speaking boy aged 2 ; 5-2 ; 9 and his mother while engaged in daily activities in the home. Data were coded according to Halliday's (1975) functional system. The findings suggest that early multiword verb use is functionally restricted and closely tied to verb use in the input.

  18. 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.

  19. Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

    PubMed

    Heusinkveld, Lauren; Hacker, Mallory; Turchan, Maxim; Bollig, Madelyn; Tamargo, Christina; Fisher, William; McLaughlin, Lauren; Martig, Adria; Charles, David

    2017-01-01

    The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

  20. A model of knowledge acquisition in early stage breast cancer patients.

    PubMed

    Warren, Laura E; Mendlinger, Sheryl E; Corso, Katherine A; Greenberg, Caprice C

    2012-01-01

    To meaningfully participate in the decision-making regarding a newly diagnosed breast cancer, a patient must acquire new knowledge. We describe a model of knowledge acquisition that can provide a framework for exploring the process and types of knowledge that breast cancer patients gain following their diagnosis. The four types of knowledge presented in this model-authoritative, technical, embodied, and traditional-are described and potential sources discussed. An understanding of knowledge acquisition in early stage breast cancer patients can provide healthcare practitioners with an important framework for optimizing decision-making in this population. © 2012 Wiley Periodicals, Inc.

  1. [Dynamic changes of blister fluid amikacin concentration after its early-stage administration in severely burned patients].

    PubMed

    Hua, Rong; Rong, Xin-Zhou; Zhang, Tao; Yang, Rong-Hua

    2007-10-01

    To determine the adequate timing of antibiotics application in severely burned patients by observing the dynamic changes of amikacin in blister fluid during early postburn stage. Twenty patients in early stage of sever burns were divided into 4 groups (n=5) according to the timing of amikacin administration, namely at 3-4 h (group A), 10 h (group B, 20 h (group C), and 30 h (group D) postburn. Amikacin was administered intravenously via a single dose of 400 mg within 30 min, and at the time points of 0.25 to 7 h after completion of the infusion, the blister fluid was collected from each patient for determination of amikacin concentration with fluorescence polarization immunoassay. Fifteen minutes after intravenous administration, amikacin could be detected in the blister fluid, reaching the highest level at 1-2 h after administration followed by gradual declination. In group B, blister fluid amikacin concentration reached 4.96+1.60 microg/ml 15 min after administration, and at the subsequent time points until 4 h, amikacin concentration was significantly higher in groups A and B than in groups C and D (P<0.05). Amikacin concentration in the blister fluid in group D was not sufficient for effective antibacterial therapy. Amikacin administration in the early postburn stage may ensure higher amikacin concentration in the blister fluid and wound exudate. Better antibacterial effect can be expected when amikacin is applied within the initial 10 h postburn.

  2. Computed tomography-guided percutaneous microwave ablation of patients 75 years of age and older with early-stage nonsmall cell lung cancer.

    PubMed

    Han, X; Yang, X; Ye, X; Liu, Q; Huang, G; Wang, J; Li, W; Zheng, A; Ni, Y; Men, M

    2015-12-01

    We aimed to assess the clinical outcome of computed tomography (CT)-guided percutaneous microwave ablation (MWA) in patients 75 years of age and older with early stage peripheral nonsmall cell lung cancer (NSCLC). Twenty-eight patients, aged ≥ 75 years, with Stage I and lymph node-negative IIa peripheral NSCLC underwent CT-guided percutaneous MWA in our hospital between July 2007 and March 2015. The overall 1-, 2-, 3-, and 4-year survival rates were estimated using Kaplan-Meier analysis. Adverse events were recorded. The median follow-up time was 22.5 months. The overall median survival time (MST) was 35 months (95% confidence interval [CI] 22.3-47.7 months), and the cancer-specific MST was 41.9 months (95% CI 38.8-49.9 months). The 1-, 2-, 3-, and 4-year overall survival rates were 91.7%, 76.5%, 47.9%, and 47.9%, while the cancer-specific survival rates were 94.7%, 73.9%, 64.7%, and 64.7%, respectively. Median time to local progression was 28.0 months (95% CI 17.7-38.3 months). Major complications were included pneumothorax (21.4%, requiring drainage), pleural effusions (3.6%, requiring drainage), and pulmonary infection (3.6%). CT-guided percutaneous MWA is safe and effective for the treatment of patients 75 years of age and older with medically inoperable early stage peripheral NSCLC.

  3. 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.

  4. Detection of Recurrence Patterns After Wedge Resection for Early Stage Lung Cancer: Rationale for Radiologic Follow-Up.

    PubMed

    Billè, Andrea; Ahmad, Usman; Woo, Kaitlin M; Suzuki, Kei; Adusumilli, Prasad; Huang, James; Jones, David R; Rizk, Nabil Pierre

    2016-10-01

    Wedge resection for selected patients with early stage non-small cell lung cancer is considered to be a valid treatment option. The aim of this study was to evaluate the recurrence patterns after wedge resection, to analyze the survival of patients under routine follow-up, and to recommend a follow-up regimen. A retrospective analysis was done of 446 consecutive patients between May 2000 and December 2012 who underwent a wedge resection for clinical stage I non-small cell lung cancer. All patients were followed up with a computed tomography scan with or without contrast. The recurrence was recorded as local (involving the same lobe of wedge resection), regional (involving mediastinal or hilar lymph nodes or a different lobe), or distant (including distant metastasis and pleural disease). Median follow-up for survivors (n = 283) was 44.6 months. In all, 163 patients died; median overall survival was 82.6 months. Thirty-six patients were diagnosed with new primary non-small cell lung cancer, and 152 with recurrence (79 local, 45 regional, and 28 distant). There was no difference in the incidence of recurrence detection detected by computed tomography scans with versus without contrast (p = 0.18). The cumulative incidence of local recurrences at 1, 2, and 3 years was higher than the cumulative incidence for local, regional, and distant recurrences: 5.2%, 11.1%, and 14.9% versus 3.7%, 6.6%, and 9.5% versus 2.3%, 4.7%, and 6.4%, respectively. Primary tumor diameter was associated with local recurrence in univariate analysis. Wedge resection for early stage non-small cell lung cancer is associated with a significant risk for local and regional recurrence. Long-term follow-up using noncontrast computed tomography scans at consistent intervals is appropriate to monitor for these recurrences. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. 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.

  6. The impact of lymph node dissection and adjuvant chemotherapy on survival: A nationwide cohort study of patients with clinical early-stage ovarian cancer.

    PubMed

    Kleppe, Marjolein; van der Aa, Maaike A; Van Gorp, Toon; Slangen, Brigitte F M; Kruitwagen, Roy F P M

    2016-10-01

    To establish the impact of lymph node dissection and chemotherapy on survival in patients with early-stage epithelial ovarian cancer (EOC). All Dutch patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-IIA and IIIA1 EOC between 2000 and 2012 were included. Data concerning age, stage, tumour grade, histological subtype, hospital type, lymph node dissection, adjuvant chemotherapy and survival were extracted from the Netherlands Cancer Registry. Of 3658 patients included, 1813 (49.6%) had lymph nodes removed. Relative survival of patients with lymph node dissection (including those with lymph node metastases) was significantly better than that of patients without, also after correcting for stage, tumour grade, histology and age (89% and 82%, respectively; relative excess risk [RER], 0.64; 95% confidence interval [CI]: 0.52-0.78). There was a positive correlation between the number of removed lymph nodes and overall survival (after excluding patients with lymph node metastases). Of patients with stage I-IIA EOC who had ≥10 lymph nodes removed, there was no difference in relative survival between those who received chemotherapy and those who did not (RER, 0.51; 95% CI: 0.15-1.64). This was also true for a subgroup of patients with high-risk features (stage IC and IIA and/or tumour grade 3 and/or clear cell histology [RER, 0.90; 95% CI: 0.46-1.99]). Adequate dissection of at least 10 but preferably ≥20 lymph nodes should be standard procedure for the staging of early-stage EOC. Adjuvant chemotherapy after an adequate lymph node dissection does not seem to contribute to a better relative survival. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients - An analysis of NRG Oncology/Gynecologic Oncology Group trials.

    PubMed

    Chan, John K; Java, James J; Fuh, Katherine; Monk, Bradley J; Kapp, Daniel S; Herzog, Thomas; Bell, Jeffrey; Young, Robert

    2016-12-01

    To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients. Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses. Of 497 stage I-II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23days (25th-75th%: 12-33days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: <2weeks, 2-4weeks, and >4weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p=0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p=0.51; p=0.33 - global test). As compared to <2weeks, the hazard ratio for recurrence-free survival was 0.90 (95%CI=0.59-1.37) for 2-4weeks and 0.72 (95%CI=0.46-1.13) for >4weeks. Age, stage, grade, and cytology were important prognostic factors. Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

    Cancer.gov

    Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

  9. 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

  10. Effect of light Sphagnum peat on odour formation in the early stages of biowaste composting.

    PubMed

    Kurola, Jukka M; Arnold, Mona; Kontro, Merja H; Talves, Matti; Romantschuk, Martin

    2010-05-01

    In the present study, we investigated the effects of two bulking materials, Sphagnum peat and pine wood chips, on the early stages of biowaste composting in two pilot-scale processes. Emphasis was placed on studying the formation conditions of malodorous compost gases in the initial phases of the processes. The results showed that gas emission leaving an open windrow and a closed drum composting system contained elevated concentrations of fermentative microbial metabolites when acid Sphagnum peat (pH 3.2) was used as a bulking material. Moreover, the gas emission of the peat amended drum composter contained a high concentration of odour (up to 450,000oum(-3) of air). The highest odour values in the outlet gas of peat amended composts coincided with the elevated concentrations of volatile organic compounds such as acetoin and buthanedion. We conclude that the acidifying qualities of composting substrates or bulking material may intensify odour emission from biowaste composts and prolong the early stages of the composting process.

  11. Apply radiomics approach for early stage prognostic evaluation of ovarian cancer patients: a preliminary study

    NASA Astrophysics Data System (ADS)

    Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille; Moxley, Katherine; Moore, Kathleen; Mannel, Robert; Liu, Hong; Zheng, Bin; Qiu, Yuchen

    2017-03-01

    Predicting metastatic tumor response to chemotherapy at early stage is critically important for improving efficacy of clinical trials of testing new chemotherapy drugs. However, using current response evaluation criteria in solid tumors (RECIST) guidelines only yields a limited accuracy to predict tumor response. In order to address this clinical challenge, we applied Radiomics approach to develop a new quantitative image analysis scheme, aiming to accurately assess the tumor response to new chemotherapy treatment, for the advanced ovarian cancer patients. During the experiment, a retrospective dataset containing 57 patients was assembled, each of which has two sets of CT images: pre-therapy and 4-6 week follow up CT images. A Radiomics based image analysis scheme was then applied on these images, which is composed of three steps. First, the tumors depicted on the CT images were segmented by a hybrid tumor segmentation scheme. Then, a total of 115 features were computed from the segmented tumors, which can be grouped as 1) volume based features; 2) density based features; and 3) wavelet features. Finally, an optimal feature cluster was selected based on the single feature performance and an equal-weighed fusion rule was applied to generate the final predicting score. The results demonstrated that the single feature achieved an area under the receiver operating characteristic curve (AUC) of 0.838+/-0.053. This investigation demonstrates that the Radiomic approach may have the potential in the development of high accuracy predicting model for early stage prognostic assessment of ovarian cancer patients.

  12. Carbon Ion Therapy for Early-Stage Non-Small-Cell Lung Cancer

    PubMed Central

    Demizu, Yusuke; Fujii, Osamu; Iwata, Hiromitsu; Fuwa, Nobukazu

    2014-01-01

    Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT), proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80–90% and 40–50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation. PMID:25295269

  13. 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.

  14. Brain Event-Related Potentials: Diagnosing Early-Stage Alzheimer’s Disease

    PubMed Central

    Chapman, Robert M.; Nowlis, Geoffrey H.; McCrary, John W.; Chapman, John A.; Sandoval, Tiffany C.; Guillily, Maria D.; Gardner, Margaret N.; Reilly, Lindsey A.

    2009-01-01

    A pattern of components from brain Event-Related Potentials (ERP) (cognitive non-invasive electrical brain measures) performed well in separating early-stage Alzheimer’s disease (AD) subjects from normal-aging control subjects and shows promise for developing a clinical diagnostic for Probable AD. A Number-Letter task elicited brain activity related to cognitive processes. In response to the task stimuli, brain activity was recorded as ERPs, whose components were measured by Principal Components Analysis (PCA). The ERP component scores to relevant and irrelevant stimuli were used in Discriminant Analyses to develop functions that successfully classified individuals as belonging to an early-stage Alzheimer’s disease group or a like-aged Control group, with probabilities of an individual belonging to each group. Applying the discriminant function to the developmental half of the data showed 92% of the subjects were correctly classified into either the AD group or the Control group with a sensitivity of 1.00. The two crossvalidation results were good with sensitivities of 0.83 and classification accuracies of 0.75–0.79. P3 and CNV components, as well as other, earlier ERP components, e.g. C145 and the memory “Storage” component, were useful in the discriminant functions. PMID:16430992

  15. Marital relationship quality in early-stage dementia: perspectives from people with dementia and their spouses.

    PubMed

    Clare, Linda; Nelis, Sharon M; Whitaker, Christopher J; Martyr, Anthony; Markova, Ivana S; Roth, Ilona; Woods, Robert T; Morris, Robin G

    2012-01-01

    Spouse caregivers of people with dementia (PwD) report relatively poor marital relationship quality (RQ), but few studies have obtained the perspective of the PwD, examined discrepancies between spouses, or considered changes in RQ over time. This study explored caregiver and PwD perceptions of RQ, identified associated factors, and examined changes over an 18-month period. Participants were 54 couples where one spouse had early-stage dementia and 54 were control couples. RQ was assessed with the Positive Affect Index. Measures of mood, stress, and quality of life (QoL) were also administered. The clinical couples were followed up after 9 and 18 months. Caregivers gave significantly lower RQ ratings than controls. PwD ratings did not differ significantly from those of caregivers or controls. Dyadic discrepancies were significantly greater in the clinical than in the control group. Caregiver ratings were associated with stress, whereas PwD ratings were associated with depression and QoL. Discrepancies were associated with caregiver stress and with PwD mood, QoL, and age. Caregiver ratings declined significantly over time; PwD ratings did not decline significantly, but showed different trends for men and women. It is important to consider RQ when considering how to support couples where one partner has early-stage dementia.

  16. Meaningful end points and outcomes in men on active surveillance for early-stage prostate cancer.

    PubMed

    Welty, Christopher J; Cooperberg, Matthew R; Carroll, Peter R

    2014-05-01

    Active surveillance is a management strategy for early-stage prostate cancer designed to balance early detection of aggressive disease and overtreatment of indolent disease. We evaluate recently reported outcomes and discuss the potentially most important endpoints for such an approach. The past 2 years have seen the publication of two trials of watchful waiting versus immediate treatment and updates of multiple active surveillance cohorts for men with early-stage prostate cancer. The watchful waiting trials demonstrated a small potential mortality benefit to immediate treatment when applied to all risk levels (6% absolute difference at 15 years), emphasizing the importance of a risk-adapted strategy. In reported active surveillance cohorts, prostate cancer death and metastasis remain rare events. Intermediate outcomes such as progression to treatment and upgrading/upstaging on final disease appear consistent among cohorts, but must be interpreted with caution when compared with historical controls of immediate treatment because of potential selection bias. The safety of active surveillance has been reinforced by recent reports. Accumulation of additional data on men with intermediate risk cancer and development and validation of new biomarkers of risk will allow refined and, likely, expanded use of this approach.

  17. 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.

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

    PubMed

    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

    2016-03-29

    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.

  19. 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.

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

    PubMed

    Xu, Lu; Qiu, Lingling; 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.

  1. 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

  2. Development sites, feeding modes and early stages of seven European Palloptera species (Diptera, Pallopteridae).

    PubMed

    Rotheray, Graham E

    2014-12-19

    Two hundred and ninety-eight rearing records and 87 larvae and puparia were obtained of seven species of Palloptera Fallén (Diptera, Pallopteridae), mainly in Scotland during 2012-2013. The third stage larva and puparium of each species were assessed morphologically and development sites and feeding modes investigated by rearing, observation and feeding tests. Early stages appear to be distinguished by the swollen, apico-lateral margins of the prothorax which are coated in vestiture and a poorly developed anal lobe with few spicules. Individual pallopteran species are separated by features of the head skeleton, locomotory spicules and the posterior respiratory organs. Five species can be distinguished by unique character states. Observations and feeding tests suggest that the frequently cited attribute of zoophagy is accidental and that saprophagy is the primary larval feeding mode with autumn/winter as the main period of development. Food plants were confirmed for flowerhead and stem developing species and rain is important for maintaining biofilms on which larvae feed. Due to difficulties in capturing adults, especially males, the distribution and abundance of many pallopteran species is probably underestimated. Better informed estimates are possible if early stages are included in biodiversity assessments. To facilitate this for the species investigated, a key to the third stage larva and puparium along with details on finding them, is provided. 

  3. 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.

  4. An informational diversity framework, illustrated with sexually deceptive orchids in early stages of speciation.

    PubMed

    Smouse, Peter E; Whitehead, Michael R; Peakall, Rod

    2015-11-01

    Reconstructing evolutionary history for emerging species complexes is notoriously difficult, with newly isolated taxa often morphologically cryptic and the signature of reproductive isolation often restricted to a few genes. Evidence from multiple loci and genomes is highly desirable, but multiple inputs require 'common currency' translation. Here we deploy a Shannon information framework, converting into diversity analogue, which provides a common currency analysis for maternally inherited haploid and bi-parentally inherited diploid nuclear markers, and then extend that analysis to construction of minimum-spanning networks for both genomes. The new approach is illustrated with a quartet of cryptic congeners from the sexually deceptive Australian orchid genus Chiloglottis, still in the early stages of speciation. Divergence is more rapid for haploid plastids than for nuclear markers, consistent with the effective population size differential (N(ep) < (N(en)), but divergence patterns are broadly correlated for the two genomes. There are nevertheless intriguing discrepancies between the emerging plastid and nuclear signals of early phylogenetic radiation of these taxa, and neither pattern is entirely consistent with the available information on the sexual cues used by the orchids to lure the pollinators enforcing reproductive isolation. We describe possible extensions of this methodology to multiple ploidy levels and other types of markers, which should increase the range of application to any taxonomic assemblage in the very early stages of reproductive isolation and speciation.

  5. 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.

  6. Effects of Marine Toxins on the Reproduction and Early Stages Development of Aquatic Organisms

    PubMed Central

    Vasconcelos, Vítor; Azevedo, Joana; Silva, Marisa; Ramos, Vítor

    2010-01-01

    Marine organisms, and specially phytoplankton species, are able to produce a diverse array of toxic compounds that are not yet fully understood in terms of their main targets and biological function. Toxins such as saxitoxins, tetrodotoxin, palytoxin, nodularin, okadaic acid, domoic acid, may be produced in large amounts by dinoflagellates, cyanobacteria, bacteria and diatoms and accumulate in vectors that transfer the toxin along food chains. These may affect top predator organisms, including human populations, leading in some cases to death. Nevertheless, these toxins may also affect the reproduction of aquatic organisms that may be in contact with the toxins, either by decreasing the amount or quality of gametes or by affecting embryonic development. Adults of some species may be insensitive to toxins but early stages are more prone to intoxication because they lack effective enzymatic systems to detoxify the toxins and are more exposed to the toxins due to a higher metabolic growth rate. In this paper we review the current knowledge on the effects of some of the most common marine toxins on the reproduction and development of early stages of some organisms. PMID:20161971

  7. Problem-solving therapy for psychological distress in Japanese early-stage breast cancer patients.

    PubMed

    Hirai, Kei; Motooka, Hiroko; Ito, Naoshi; Wada, Naoko; Yoshizaki, Arika; Shiozaki, Mariko; Momino, Kanae; Okuyama, Toru; Akechi, Tatsuo

    2012-12-01

    The current report provides the result of a Phase II clinical trial regarding the effectiveness and feasibility of problem-solving therapy for psychological distress experienced by Japanese early-stage breast cancer patients. Participants were 36 post-surgery Japanese breast cancer patients in a university hospital located in Osaka Prefecture, Japan. After screening for psychological distress using the Distress and Impact Thermometer and the Hospital Anxiety and Depression Scale, highly distressed patients were exposed to 5 weekly sessions of the problem-solving therapy program. Nineteen patients completed the intervention and follow-up. There was a significant difference between the pre-intervention and the 3-month follow-up in the total Hospital Anxiety and Depression Scale score (P = 0.02), and the mean change score from the pre-intervention to the follow-up was 6.05 (SD = 1.94). The intervention had a large effect size (d = 0.82). There were also significant changes in worry, self-efficacy and quality of life measures. The findings of our study suggest that the problem-solving therapy program has potential to be effective for alleviating psychological distress experienced by Japanese early-stage breast cancer patients. The true effectiveness of the program should be confirmed by a future randomized control trial.

  8. The pitfalls of bedside regional cerebral oxygen saturation in the early stage of post cardiac arrest.

    PubMed

    Kinoshita, Kosaku; Sakurai, Atsushi; Ihara, Shingo

    2015-11-11

    It remains uncertain whether neuromonitoring reliably predicts outcome in adult post-cardiac arrest patients in the early stage treated with therapeutic hypothermia. Recent reports demonstrated a regional cerebral oxygen saturation of cardiac arrest patients on hospital arrival could predict their neurological outcome. There has been little discussion about the significance of regional cerebral oxygen saturation in patients with post-cardiac arrest syndrome. Amplitude-integrated electroencephalography monitoring may also provide early prognostic information for post-cardiac arrest syndrome. However, even when the initial electroencephalography is flat after the return of spontaneous circulation, good neurological outcome may still be obtainable if the electroencephalography shifts to a continuous pattern. The electroencephalography varied from flat to various patterns, such as flat, epileptic, or continuous during the first 24 h, while regional cerebral oxygen saturation levels varied even when the electroencephalography was flat. It is therefore difficult to estimate whether regional cerebral oxygen saturation accurately indicates the coupling of cerebral blood flow and metabolism in the early stage after cardiac arrest. Careful assessment of prognosis is necessary when relying solely on regional cerebral oxygen saturation as a single monitoring modality.

  9. Prenatal sonography in hydranencephaly: findings during the early stages of disease.

    PubMed

    Sepulveda, Waldo; Cortes-Yepes, Hernan; Wong, Amy E; Dezerega, Victor; Corral, Edgardo; Malinger, Gustavo

    2012-05-01

    The purpose of this report is to describe the prenatal sonographic findings in fetuses with hydranencephaly diagnosed during the early stages of disease. Four cases with characteristics of hydranencephaly were retrospectively identified from 2 Latin American fetal medicine referral centers. Information on maternal demographics, sonographic findings, antenatal courses, and pregnancy outcomes was retrieved from the ultrasound reports and medical records. Cases were diagnosed between 21 and 23 weeks' gestation. The sonographic findings were similar in all cases and included absent cerebral hemispheres, which were replaced by homogeneous echogenic material filling the supratentorial space, and preservation of the thalami, brain stem, and cerebellum. The head circumference measurement was within the normal range, but the transverse cerebellar diameter was below the fifth percentile in 3 of the 4 cases. A follow-up scan in 1 of these cases demonstrated the classic anechoic fluid-filled appearance of hydranencephaly 2 weeks after diagnosis. Confirmation of the diagnosis was available in 2 cases, by postmortem examination in 1 and by fetal magnetic resonance imaging in the other. No further investigations were performed in the 2 women who opted for termination of pregnancy. In conclusion, during the early stages of disease, hydranencephaly is characterized by the presence of a large intracranial saclike structure containing homogeneous echogenic material, representing blood and necrotic debris secondary to massive liquefaction of the developing cerebral hemispheres.

  10. 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

  11. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775-875 cm-1, lectins at 1003, 1238, 1340, 1449 and 1672 cm-1, DNA in the region 1040-1140 cm-1 and alpha and beta structures of proteins in the region 933-967 cm-1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  12. Genome-scale transcriptomic insights into early-stage fruit development in woodland strawberry Fragaria vesca.

    PubMed

    Kang, Chunying; Darwish, Omar; Geretz, Aviva; Shahan, Rachel; Alkharouf, Nadim; Liu, Zhongchi

    2013-06-01

    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.

  13. ICD Therapy In RVOT-VT And Early Stage ARVD/C Patients.

    PubMed

    Aizawa Md, Yoshiyasu; Takatsuki Md, Seiji; Fukuda Md, Keiichi

    2014-01-01

    Implantable cardioverter-defibrillators (ICDs) improve the survival of patients with ischemic or non-ischemic cardiomyopathy and a reduced ejection fraction. However, the efficacy of ICD therapy in patients with right ventricular outflow tract ventricular tachycardia (RVOT-VT) and early stage arrhythmogenic right ventricular dysplasia / cardiomyopathy (ARVD/C) has not been well clarified. Although the prognosis of RVOT-VT is generally good, malignant forms of RVOT-VT resulting in polymorphic VT have been reported by several investigators. Radiofrequency catheter ablation is still effective in such patients, and thus an ICD implantation is usually not required. On the other hand, according to the current guidelines in patients with ARVD/C, an ICD implantation is recommended for secondary prevention when the patients develop sustained VT or VF. An ICD implantation may also be considered for primary prevention in high-risk patients: extensive disease, family history of sudden cardiac death, or undiagnosed syncope. Since an ICD implantation in the early stage of ARVD/C is controversial, physicians should well consider its risks and benefits. Early intervention with ICD therapy in ARVD/C patients may reduce the arrhythmic death rate but increases the device related complications especially in younger patients.

  14. Evaluation of the use of freehand SPECT for sentinel node biopsy in early stage oral carcinoma.

    PubMed

    Heuveling, Derrek A; van Weert, Stijn; Karagozoglu, K Hakki; de Bree, Remco

    2015-03-01

    Inadequate intraoperative visualization of the sentinel node can hamper its harvest. Freehand SPECT is a 3D tomographic imaging modality based on the concepts of SPECT, which can be used for intraoperative visualization and navigation towards the sentinel node in order to improve its localization and removal during surgery. The use of freehand SPECT was evaluated during 66 sentinel node biopsy procedures in early stage oral cancer patients. Intraoperative detection of sentinel nodes was compared with preoperative identified sentinel nodes on lymphoscinitigraphic examination. Additional value of freehand SPECT was subjectively scored by the surgeon directly following the biopsy procedure. Freehand SPECT was able to detect 94% of sentinel nodes intraoperatively. Most sentinel nodes not detected (7 out of 9) were located in level I of the neck. Freehand SPECT appeared to be of additional value for facilitating the intraoperative detection of the sentinel node in 24% of procedures. The use of the freehand SPECT system is feasible in the intraoperative detection of sentinel nodes in early stage oral cancer. Freehand SPECT provides helpful information facilitating the SN biopsy procedure in a quarter of cases. However, freehand SPECT cannot detect all SNs which are located in the vicinity of the injection site. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. [GABA--the basic mediator of excitation in the early stages of hippocampal development].

    PubMed

    Khazipov, R N; Zefirov, A L; Ben-Ari, E

    1998-01-01

    GABA is the principal neurotransmitter of inhibition in the adult mammalian brain. However, at early stages of development, including embryonic period and first week of postnatal life, GABA plays the role of main neurotransmitter of excitation. The paradoxical excitatory effect of GABA is due to an inversed chloride gradient and therefore a depolarizing direction of GABA-A receptor mediated responses. In addition, another type of GABAergic inhibition mediated by postsynaptic GABA-B receptors is not functional at early stage of life. In the neonatal rat hippocampus, GABA, acting via GABA-A receptors, activates voltage gated sodium and calcium channels and potentiates the activity of NMDA receptors by reducing their voltage dependent Mg2+ block. The temporal window when GABA exerts excitatory actions coincides with a particular pattern of activity of hippocampal neuronal network that is characterized by periodical giant depolarizing potentials (GDPs) reminiscent of interictal-like epileptiform discharges. Recent studies have shown that GDPs result from the synchronous discharge of GABAergic interneurons and principal glutamatergic pyramidal cells and are mediated by the synergistic excitatory actions of GABA-A and glutamate receptors. GDPs provide synchronous intracellular Ca2+ oscillations and may therefore be implicated in hebbian modulation of developing synapses and activity-dependent formation of the hippocampal network.

  16. Early-stage primary signet ring cell carcinoma of the colon

    PubMed Central

    Kim, Jae Hyun; Park, Seun Ja; Park, Moo In; Moon, Won; Kim, Sung Eun

    2013-01-01

    Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature. PMID:23840131

  17. Adenosine stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease at an early stage.

    PubMed

    Chen, Gui-Bing; Wu, Hua; He, Xiao-Jiang; Huang, Jin-Xiong; Yu, Dan; Xu, Wei-Yi; Yu, Hao

    2013-01-01

    The aims of this study were to evaluate the diagnostic value of adenosine thallium-201 myocardial perfusion imaging and to compare it with exercise stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease (CAD) at an early stage. Forty-one patients suspected with CAD were randomly divided into two groups. In Group 1 (n=21) adenosine stress was undertaken; the exercise stress myocardial perfusion imaging was performed in Group 2 (n=20). Coronary angiography (CAG) was performed in each patient within 2 weeks before or after single photon emission computed tomography (SPECT). Adenosine stress group vs. exercise stress group, the sensitivity was 92.86% vs. 100.0%, specificity 57.14% vs. 60.0%, positive predictive value 81.25% vs. 71.43%, negative predictive value 80.0% vs. 100.0%, accuracy 80.95% vs. 80.0% respectively. Detection rates of vessels of coronary artery lesions were 66.67% in Group 1 and 72.22% in Group 2 (P> 0.05). The side effects were mild and transient. Our results demonstrated that adenosine stress myocardial perfusion imaging is a safe and reliable diagnostic method for an early stage of CAD. As a comparative sensitivity and accuracy with exercise stress thallium-201 myocardial perfusion imaging, adenosine stress testing may provide a feasible alternative pharmacological stress method in myocardial SPECT for detection of CAD.

  18. Neuroprotection of Granulocyte Colony-Stimulating Factor for Early Stage Parkinson's Disease.

    PubMed

    Tsai, Sheng-Tzung; Chu, Sung-Chao; Liu, Shu-Hsin; Pang, Cheng-Yoong; Hou, Ting-Wen; Lin, Shinn-Zong; Chen, Shin-Yuan

    2017-03-13

    Parkinson's disease (PD) is a slowly progressive neurodegenerative disease. Both medical and surgical choices provide symptomatic treatment. Granulocyte colony-stimulating factor (G-CSF), a conventional treatment for hematological diseases, has demonstrated its effectiveness in acute and chronic neurological diseases through its anti-inflammatory and antiapoptosis mechanisms. Based on previous in vitro and in vivo studies, we administered a lower dose (3.3 μg/kg) G-CSF injection for 5 days and six courses for 1 year in early-stage PD patients as a phase I trial. The four PD patient's mean unified PD rating scale motor scores in medication off status remained stable from 23 before the first G-CSF injection to 22 during the 2-year follow-up. 3,4-Dihydroxy-6-18F-fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) studies also revealed an annual 3.5% decrease in radiotracer uptake over the caudate nucleus and 7% in the putamen, both slower than those of previous reports of PD. Adverse effects included transient muscular-skeletal pain, nausea, vomiting, and elevated liver enzymes. Based on this preliminary report, G-CSF seems to alleviate disease deterioration for early stage PD patients. The effectiveness of G-CSF was possibly due to its amelioration of progressive dopaminergic neuron degeneration.

  19. Insular cognitive impairment at the early stage of dementia with Lewy bodies: a preliminary study.

    PubMed

    Philippi, Nathalie; Kemp, Jennifer; Constans-Erbs, Morgane; Hamdaoui, Malik; Monjoin, Laetitia; Ehrhard, Emmanuelle; Albasser, Timothée; Botzung, Anne; Demuynck, Catherine; Heim, Géraldine; Martin-Hunyadi, Catherine; Bilger, Mathias; Berly, Laetitia; Soulier, David; Cretin, Benjamin; Després, Olivier; Blanc, Frédéric

    2017-09-01

    The anterior part of the insula appears atrophied in the early stage of dementia with Lewy bodies (DLB) whereas it is not the case in early Alzheimer's disease (AD). The objective of this study was to develop neuropsychological markers supposed to reflect insular dysfunction, which would facilitate early diagnosis of DLB, namely in comparison to AD. Twelve patients with DLB, 12 patients with AD, all at the stage of Mild cognitive impairment (MCI) or mild dementia, as well as 10 Controls subjects (CS) participated in the study. Cognitive functions supposedly related to the insula were evaluated with a battery of tests: a facial expression recognition test, a test assessing the feeling of disgust with images, a test evaluating idioms' comprehension, an empathy questionnaire and a questionnaire screening for disgusting behaviors. Compared to AD patients and CS, DLB patients experienced less disgust when they were shown disgusting images, whereas their ability to recognize emotional expression of disgust appeared to be preserved. Furthermore, DLB patients seemed less empathetic than AD patients. Finally, compared to CS, DLB patients were less effective to provide an intuitive decision about idioms' signification since they needed significantly more time to answer. This preliminary study suggests the existence of a potential « insular cognitive impairment » profile in DLB at the early stage. These results provide interesting leads to develop tools facilitating the differential diagnosis of DLB and AD.

  20. Deficits in early-stage face perception in excessive internet users.

    PubMed

    He, Jin-bo; Liu, Chia-ju; Guo, Yong-yu; Zhao, Lun

    2011-05-01

    Excessive Internet use is associated with a limited ability to communicate effectively socially, which depends largely on the capacity for perception of the human face. We used a passive visual detection paradigm to compare the early stages of the processing of face-related information in young excessive Internet users (EIUs) and healthy normal subjects by analyzing event-related potentials (ERPs) elicited by faces and by nonface stimuli (tables), each presented in the upright and inverted position. The P1 and N170 components of the spectrum of ERPs elicited at occipital-temporal sites by the viewing of faces were larger and peaked sooner than the same ERP components elicited by tables, and inverted faces significantly enhanced and delayed the N170 component. EIUs had a generally smaller P1 component than did normal subjects, whether elicited by faces or by tables, and the N170 effect, or difference in amplitude of the N170 component for faces versus tables, was significantly smaller in the EIUs than in normal subjects. However, the N170 inversion effect, or difference in amplitude of the N170 component elicited by upright versus inverted faces, was similar in the EIUs and normal subjects. These data indicate that EIUs have deficits in the early stage of face-perception processing but may have intact holistic/configural processing of faces. Whether some deeper processes of face perception, such as face memory and face identification, are affected in EIUs needs to be investigated further with more specific procedures.

  1. 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.

  2. Sham Feeding with Chewing Gum in Early Stage of Acute Pancreatitis: A Randomized Clinical Trial

    PubMed Central

    Jiang, Zongxing; Liang, Hongyin; Huang, Zhu; Tang, Jiajia; Tang, Lijun

    2017-01-01

    Background The correlation between sham feeding and acute pancreatitis (AP) has only been examined in limited studies. We aimed to investigate the efficacy and safety of sham feeding in the early stage of AP. Material/Methods A randomized controlled clinical trial was performed. Equal groups of AP patients were recruited. Patients in the sham feeding group received chewing gum 4 times a day after admission. All patients in the trial received standard treatment consistent with the guidelines for AP. The primary outcomes were mortality, length of stay (LOS), and medical expenses. Secondary outcomes were the incidence of complications and other adverse events, return of gastrointestinal function, the details of enteral nutrition and intra-abdominal pressure. Results From May 2014 to December 2015, a total of 204 patients were recruited. The LOS and hospital costs in the sham feeding group were reduced, although mortality was equivalent between groups. The return of gastrointestinal function occurred earlier in the sham feeding group, with no complications related to gum chewing. Conclusions Sham feeding with chewing gum is safe and efficacious in the early stage of AP. PMID:28154369

  3. 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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 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

  5. Neck circumference and early stage atherosclerosis: the cardiometabolic risk in Chinese (CRC) study

    PubMed Central

    2014-01-01

    Background Neck circumference (NC) has been previously related to cardiometabolic risk factors. In this study we examined the association between NC and early stage atherosclerosis in Chinese adults. Methods The study samples were from a community-based health examination survey in central China. In total 2,318 men and women (18-64 y) were included in the final analyses. Carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and NC were measured. Results After adjustment for age, sex, lipids, glucose, blood pressure, heart rate, body mass index (BMI), high NC was significantly associated with an increasing trend of cfPWV, cdPWV and crPWV (P = 0.001, 0.049, and 0.038; respectively). In addition, we found significant interaction between hypertension status and NC level in relation to cfPWV, adjusted for age, sex, BMI, fasting glucose, lipids and heart rate(P for interaction = 0.034). The associations between NC and cfPWV were significant (P = 0.02) among those with hypertension, but not significant among those without hypertension. Conclusions Our data showed that high NC was associated with an increased risk of early stage atherosclerosis in Chinese adults, independent of other metabolic risk factors. Hypertension might modify the association between NC and cfPWV. PMID:25001365

  6. 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.

  7. Unusual Presentation of Recurrent Early Stage Endometrial Carcinoma 28 Years after Primary Surgery

    PubMed Central

    Franchello, Alessandro; Fronda, Gianruggero; Deiro, Giacomo; Fiore, Alessia; Cassine, Davide; Molinaro, Luca; Chiusa, Luigi; Galati, Sara; Resegotti, Andrea; Silvestri, Stefano

    2015-01-01

    Endometrial carcinoma is the most common neoplasia of female genital tract. The prognosis of early stage disease (FIGO I and FIGO II) is excellent: recurrence after surgery is less than 15%, most of which are reported within 3 years after primary treatment. Herein we report a case of late rectal recurrence from FIGO Ib endometrial adenocarcinoma. Patient had also familiar and personal history of colonic adenocarcinoma and previous findings of microsatellite instability (MSI); molecular analysis evidenced heterozygotic somatic mutation in MLH1 gene. Twenty-eight years after hysterectomy and bilateral salpingoovariectomy, a rectal wall mass was detected during routine colonoscopy. Patients underwent CT scan, pelvic MRI, and rectal EUS with FNA: histopathological and immunohistochemical analysis revealed differentiated carcinoma cells of endometrial origin. No neoadjuvant treatment was planned and low rectal anterior resection with protective colostomy was performed; histology confirmed rectal lesion as metastasis from endometrial carcinoma. Recurrence of early stage endometrial carcinoma after a long period from primary surgery is possible. It is important to keep in mind this possibility in order to set a correct diagnostic and therapeutic algorithm, including preoperative immunohistochemical staining, and to plan a prolonged follow-up program. PMID:26783488

  8. An approach to quantitative sustainability assessment in the early stages of process design.

    PubMed

    Tugnoli, Alessandro; Santarelli, Francesco; Cozzani, Valerio

    2008-06-15

    A procedure was developed for the quantitative assessment of key performance indicators suitable for the sustainability analysis of alternative processes, mainly addressing the early stages of process design. The methodology was based on the calculation of a set of normalized impact indices allowing a direct comparison of the additional burden of each process alternative on a selected reference area. Innovative reference criteria were developed to compare and aggregate the impact indicators on the basis of the site-specific impact burden and sustainability policy. An aggregation procedure also allows the calculation of overall sustainability performance indicators and of an "impact fingerprint" of each process alternative. The final aim of the method is to support the decision making process during process development, providing a straightforward assessment of the expected sustainability performances. The application of the methodology to case studies concerning alternative waste disposal processes allowed a preliminary screening of the expected critical sustainability impacts of each process. The methodology was shown to provide useful results to address sustainability issues in the early stages of process design.

  9. 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.

  10. 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.

  11. Functional magnetic resonance imaging and cognition at the very early stage of MS.

    PubMed

    Audoin, Bertrand; Au Duong, My Van; Malikova, Irina; Confort-Gouny, Sylviane; Ibarrola, Danielle; Cozzone, Patrick J; Pelletier, Jean; Ranjeva, Jean-Philippe

    2006-06-15

    Dysfunction of high controlled information processing is present in patients with multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is that disruption of communication inside large-scale cortical networks, occurring as a consequence of white matter damage, may constitute the anatomical substrate of cognitive impairment at the very early stage of MS. Disturbance of interregional synchronization might be the main pathogenic factor in controlled information processing deficiency in early MS. Preliminary functional MRI studies (fMRI) have provided important clues to corroborate the connectivity hypotheses. First, brain connectivity assessed by fMRI has brought new data about the influence of diffuse white matter damage on connectivity efficiency inside large-scale networks. These studies have suggested that connectivity disturbances occur inside the working memory network in patients at the very early stage of MS and appear related to the extent of structural white matter damage. Also, fMRI studies have suggested that patients may partially compensate for connectivity impairment by a greater cognitive control. Such a compensatory mechanism could limit the determinant functional impact of diffuse white matter damage on high controlled information processing.

  12. Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease

    PubMed Central

    Turk, James R; Henderson, Kyle K; Vanvickle, Gregory D; Watkins, Justin; Laughlin, M Harold

    2005-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20–24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I–III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I–III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function. PMID:16191105

  13. Laminin and beta1 integrin distribution in the early stages of human kidney development.

    PubMed

    Bernardini, N; Bianchi, F; Dolfi, A

    1999-01-01

    Laminin, an extracellular matrix molecule (EMM) widely expressed in the basal laminae, interacts with specific membrane receptors among which the integrin molecules are the best known. During embryo development laminin is the first synthesized EMM and plays a significant role in the morphogenesis of organs in which epithelial-mesenchymal interactions and branching take place. The present study describes the distribution of laminin and of beta1 integrin receptors during the very early stages of human kidney development. The observations were carried out on paraffin sections of human embryos ranging between the 4th and the 7th gestational week. Laminin was detected within the basement membranes of mesonephric duct, vesicles, glomerular vessels and celomic epithelium. The metanephric anlage reacted with anti-laminin immunoglobulins in the basement membrane underlying the ampullae and in few blastemic cap cells. Low levels of beta1 integrin reactivity were found in both the mesonephric and metanephric structures. This study provides for the first time data about the distribution of laminin and beta1 integrin in the early stages of human renal organogenesis suggesting a key role for these molecules in the epithelial-mesenchymal interactions necessary for kidney development.

  14. 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.

  15. Efficient and Rapid Isolation of Early-stage Embryos from Arabidopsis thaliana Seeds

    PubMed Central

    Raissig, Michael T.; Gagliardini, Valeria; Jaenisch, Johan; Grossniklaus, Ueli; Baroux, Célia

    2013-01-01

    In flowering plants, the embryo develops within a nourishing tissue - the endosperm - surrounded by the maternal seed integuments (or seed coat). As a consequence, the isolation of plant embryos at early stages (1 cell to globular stage) is technically challenging due to their relative inaccessibility. Efficient manual dissection at early stages is strongly impaired by the small size of young Arabidopsis seeds and the adhesiveness of the embryo to the surrounding tissues. Here, we describe a method that allows the efficient isolation of young Arabidopsis embryos, yielding up to 40 embryos in 1 hr to 4 hr, depending on the downstream application. Embryos are released into isolation buffer by slightly crushing 250-750 seeds with a plastic pestle in an Eppendorf tube. A glass microcapillary attached to either a standard laboratory pipette (via a rubber tube) or a hydraulically controlled microinjector is used to collect embryos from droplets placed on a multi-well slide on an inverted light microscope. The technical skills required are simple and easily transferable, and the basic setup does not require costly equipment. Collected embryos are suitable for a variety of downstream applications such as RT-PCR, RNA sequencing, DNA methylation analyses, fluorescence in situ hybridization (FISH), immunostaining, and reporter gene assays. PMID:23770918

  16. Efficient and rapid isolation of early-stage embryos from Arabidopsis thaliana seeds.

    PubMed

    Raissig, Michael T; Gagliardini, Valeria; Jaenisch, Johan; Grossniklaus, Ueli; Baroux, Célia

    2013-06-07

    In flowering plants, the embryo develops within a nourishing tissue - the endosperm - surrounded by the maternal seed integuments (or seed coat). As a consequence, the isolation of plant embryos at early stages (1 cell to globular stage) is technically challenging due to their relative inaccessibility. Efficient manual dissection at early stages is strongly impaired by the small size of young Arabidopsis seeds and the adhesiveness of the embryo to the surrounding tissues. Here, we describe a method that allows the efficient isolation of young Arabidopsis embryos, yielding up to 40 embryos in 1 hr to 4 hr, depending on the downstream application. Embryos are released into isolation buffer by slightly crushing 250-750 seeds with a plastic pestle in an Eppendorf tube. A glass microcapillary attached to either a standard laboratory pipette (via a rubber tube) or a hydraulically controlled microinjector is used to collect embryos from droplets placed on a multi-well slide on an inverted light microscope. The technical skills required are simple and easily transferable, and the basic setup does not require costly equipment. Collected embryos are suitable for a variety of downstream applications such as RT-PCR, RNA sequencing, DNA methylation analyses, fluorescence in situ hybridization (FISH), immunostaining, and reporter gene assays.

  17. A decision-analytic model for early stage breast cancer: lumpectomy vs mastectomy.

    PubMed

    Büyükdamgaci-Alogan, G; Elele, T; Hayran, M; Erman, M; Kiliçkap, S

    2008-01-01

    The purpose was to construct a decision model that incorporated patient preferences over differing health state prospects and to analyze the decision context of early stage breast cancer patients in relation to two main surgical treatment options. A Markov chain was constructed to project the clinical history of breast carcinoma following surgery. A Multi Attribute Utility Model was developed for outcome evaluation. Transition probabilities were obtained by using subjective probability assessment. This study was performed on the sample population of female university students and utilities were elicited from these healthy volunteers. The results were validated by using Standard Gamble technique. Finally, Monte Carlo Simulation was utilized in Treeage-Pro 2006-Suit software program in order to calculate expected utility generated by each treatment option. The results showed that, if the subject had mastectomy, mean value for the quality adjusted life years gained was 6.42; on the other hand, if the preference was lumpectomy, it was 7.00 out of a possible 10 years. Sensitivity analysis on transition probabilities to local recurrence and salvaged states was performed and two threshold values were observed. Additionally, sensitivity analysis on utilities showed that the model was more sensitive to no evidence of disease state; however, was not sensitive to utilities of local recurrence and salvaged states. The decision model was developed with reasonable success for early stage breast cancer patients, and tested by using general public data. The results obtained from these data showed that lumpectomy was more favourable for these participants.

  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

    2016-09-08

    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. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  19. Circulating microRNAs, possible indicators of progress of rat hepatocarcinogenesis from early stages.

    PubMed

    Sukata, Tokuo; Sumida, Kayo; Kushida, Masahiko; Ogata, Keiko; Miyata, Kaori; Yabushita, Setsuko; Uwagawa, Satoshi

    2011-01-15

    MicroRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level, are believed promising biomarkers for several diseases as well as a novel target of drugs, including cancer. In particular, miRNAs might allow detection of early stages of carcinogenesis. The present study was conducted to provide concrete evidence using chemical-induced hepatocarcinogenesis in rat as a model. We thereby observed aberrant fluctuation of circulating miRNAs in the serum of rats not only with neoplastic lesions such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), but also with preneoplastic lesions, such as foci of hepatocellular alteration (FHA). Additional qRT-PCR analysis revealed gradual elevation of some circulating miRNAs (i.e., let-7a, let-7f, miR-34a, miR-98, miR-331, miR-338 and miR-652) with progress of hepatocarcinogenesis. Interestingly, increased levels of let-7a, let-7f and miR-98 were statistically significant even in the serum of rats at very early stages. These findings provide the first evidences that circulating miRNAs have the potential to predict carcinogenesis at earlier stages, preneoplastic lesions than with previous biomarkers and that they might be utilized to monitor the progress of tumor development.

  20. Ovarian preservation improves overall survival in young patients with early-stage endometrial cancer.

    PubMed

    Jia, Peng; Zhang, Yan

    2017-08-29

    We searched Medline, Embase, Cochrane library, the Chinese Biomedicine Literature Database, the Chinese Scientific Journal Full-text Database, the Chinese Journal Full-text Database, and the Wanfang Database to collect observational studies on the effects of ovary-saving surgery in comparison to bilateral salpingo-oophorectomy (BSO) in young patients with early-stage endometrial cancer (EC). The literature search included studies up to March 2017, and 10 retrospective cohort studies met our selection criteria. Random and fixed effect models revealed that ovarian preservation (OP) was associated with better overall survival (OS) (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.57-0.99, P = 0.044), and was not associated with reduced recurrence-free survival (RFS) in pre-menopausal patients with early-stage endometrial cancer (HR 1.22, 95% CI 0.32-4.72, P = 0.648; risk ratio [RR] 1.11, 95% CI 0.59-2.10, P = 0.745). Preservation of the ovaries appears to be a safe option with significant benefit for this low risk population after a thorough preoperative evaluation and extensive intraoperative exploration.

  1. 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).

  2. Inflammation-nutrition scope predicts prognosis of early-stage hepatocellular carcinoma after curative resection.

    PubMed

    Zhu, Ying; Li, Jian-Hua; Yang, Jing; Gao, Xiao-Mei; Jia, Hu-Liang; Yang, Xin

    2017-09-01

    We developed a novel inflammation-nutrition scope (INS) based on systemic inflammatory response and nutritional status, and explored its prognostic value in hepatocellular carcinoma (HCC), especially for those with early-stage disease.The INS was developed based on a retrospective study of 185 patients with HCC undergoing hepatectomy between 2006 and 2007, and validated in a prospective study of 131 patients enrolled from 2009 to 2010. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUCs).The INS was constructed as follows: patients with both an elevated red blood cell distribution width (RDW, ≥13.25%) and platelet-lymphocyte ratio (PLR, ≥1.1) were allocated a score of 2. Patients in whom only 1 or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. An elevated INS was associated with larger tumor size, tumor thrombus, and high tumor lymph nodes metastasis (TNM) stage. Univariate and multivariate analyses revealed the INS was an independent predictor for overall survival, and a prognostic factor for patients with TNM I stage. The AUCs of the INS for survival were higher than other conventional clinical indices.The INS is a promising predictor of poor outcome in patients with HCC, especially for those with early-stage disease, and is a promising tool for HCC treatment strategy decisions for future clinical trials targeting nutritional decline.

  3. 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. (c) Georg Thieme Verlag KG Stuttgart . New York.

  4. Dynamics of laser ablation at the early stage during and after ultrashort pulse

    NASA Astrophysics Data System (ADS)

    Ilnitsky, D. K.; Khokhlov, V. A.; Zhakhovsky, V. V.; Petrov, Yu V.; Migdal, K. P.; Inogamov, N. A.

    2016-11-01

    Study of material flow in two-temperature states is needed for a fundamental understanding the physics of femtosecond laser ablation. To explore phenomena at a very early stage of laser action on a metallic target our in-house two-temperature hydrodynamics code is used here. The early stage covers duration of laser pulse with next first few picoseconds. We draw attention to the difference in behavior at this stage between the cases: (i) of an ultrathin film (thickness of order of skin depth d skin or less), (ii) thin films (thickness of a film is 4-7 of d skin for gold), and (iii) bulk targets (more than 10d skin for gold). We demonstrate that these differences follow from a competition among conductive cooling of laser excited electrons in a skin layer, electron-ion coupling, and hydrodynamics of unloading caused by excess of pressure of excited free electrons. Conductive cooling of the skin needs a heat sink, which is performed by the cold material outside the skin. Such sink is unavailable in the ultrathin films.

  5. Effects of marine toxins on the reproduction and early stages development of aquatic organisms.

    PubMed

    Vasconcelos, Vítor; Azevedo, Joana; Silva, Marisa; Ramos, Vítor

    2010-01-19

    Marine organisms, and specially phytoplankton species, are able to produce a diverse array of toxic compounds that are not yet fully understood in terms of their main targets and biological function. Toxins such as saxitoxins, tetrodotoxin, palytoxin, nodularin, okadaic acid, domoic acid, may be produced in large amounts by dinoflagellates, cyanobacteria, bacteria and diatoms and accumulate in vectors that transfer the toxin along food chains. These may affect top predator organisms, including human populations, leading in some cases to death. Nevertheless, these toxins may also affect the reproduction of aquatic organisms that may be in contact with the toxins, either by decreasing the amount or quality of gametes or by affecting embryonic development. Adults of some species may be insensitive to toxins but early stages are more prone to intoxication because they lack effective enzymatic systems to detoxify the toxins and are more exposed to the toxins due to a higher metabolic growth rate. In this paper we review the current knowledge on the effects of some of the most common marine toxins on the reproduction and development of early stages of some organisms.

  6. Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays

    PubMed Central

    Schuur, Eric; Angel Aristizabal, Javier; Bargallo Rocha, Juan Enrique; Cabello, Cesar; Elizalde, Roberto; García‐Estévez, Laura; Gomez, Henry L.; Katz, Artur; Nuñez De Pierro, Aníbal

    2017-01-01

    Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision‐making. This review details the development and validation of six multi‐gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use. PMID:28211064

  7. Early Stages of Microstructure and Texture Evolution during Beta Annealing of Ti 6Al 4V (Preprint)

    DTIC Science & Technology

    2016-09-27

    AFRL-RX-WP-JA-2017-0243 EARLY STAGES OF MICROSTRUCTURE AND TEXTURE EVOLUTION DURING BETA ANNEALING OF TI-6AL-4V (PREPRINT) A.L...August 2016 4. TITLE AND SUBTITLE EARLY STAGES OF MICROSTRUCTURE AND TEXTURE EVOLUTION DURING BETA ANNEALING OF TI-6AL-4V (PREPRINT) 5a. CONTRACT...microstructure evolution during annealing of Ti-6Al-4V in the beta phase field were established. For this purpose, a series of short-time heat

  8. 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.

  9. Early Stage Hepatocellular Carcinomas Not Feasible for Ultrasound-Guided Radiofrequency Ablation: Comparison of Transarterial Chemoembolization Alone and Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation

    SciTech Connect

    Hyun, Dongho; Cho, Sung Ki Shin, Sung Wook; Park, Kwang Bo; Park, Hong Suk; Choo, Sung Wook; Do, Young Soo; Choo, In-wook; Lee, Min Woo; Rhim, Hyunchul; Lim, Hyo Keun

    2016-03-15

    PurposeTo report the results of combined therapy with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early stage hepatocellular carcinoma (HCC) considered infeasible for ultrasound (US)-guided RFA in comparison with those of TACE monotherapy.MethodsFrom January 2007 through December 2010, 91 patients with early or very early stage HCC infeasible for US-guided RFA received either TACE alone (TACE group; n = 54) or TACE immediately followed by RFA (TACE–RFA group; n = 37) as a first-line treatment. 1-month tumor response, time to progression (TTP), and overall survival (OS) rates were calculated. Univariate and multivariate analyses were performed to identify prognostic factors.ResultsTACE–RFA group showed a better 1-month tumor response than TACE group (P < .001). The mean TTP was 29.7 ± 3.4 months (95 % confidence intervals [CIs] 23.0–36.5) in TACE group and 34.9 ± 2.8 months (95 % CIs 29.4–40.4) in TACE–RFA group. TACE–RFA group had a significantly longer TTP (P = .014). Cumulative 1-, 2-, and 3-year OS rates in the TACE and TACE–RFA groups were 91, 79, and 71 % and 100, 97, and 93 %, respectively (P = .008). Initial treatment of TACE was found to be the only significant risk factor for tumor progression and OS in multivariate analysis.ConclusionTACE–RFA combination therapy appears superior to TACE monotherapy in terms of 1-month tumor response, TTP, and OS when performed for early stage HCC infeasible for US-guided RFA.

  10. Tumor-targeted SN38 inhibits growth of early stage non-small cell lung cancer (NSCLC) in a KRas/p53 transgenic mouse model.

    PubMed

    Deneka, Alexander Y; Haber, Leora; Kopp, Meghan C; Gaponova, Anna V; Nikonova, Anna S; Golemis, Erica A

    2017-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities. In this study, we explored the use of a recently described small molecule agent, STA-8666, as a potential agent for controlling early stage tumor growth. STA-8666 uses a cleavable linker to merge a tumor-targeting moiety that binds heat shock protein 90 (HSP90) with the cytotoxic chemical SN38, and has been shown to have high efficacy and low toxicity, associated with efficient tumor targeting, in preclinical studies using patient-derived and other xenograft models for pancreatic, bladder, and small cell lung cancer. Using a genetically engineered model of NSCLC arising from induced mutation of KRas and knockout of Trp53, we continuously dosed mice with STA-8666 from immediately after tumor induction for 15 weeks. STA-8666 significantly slowed the rate of tumor growth, and was well tolerated over this extended dosing period. STA-8666 induced DNA damage and apoptosis, and reduced proliferation and phosphorylation of the proliferation-associated protein ERK1/2, selectively in tumor tissue. In contrast, STA-8666 did not affect tumor features, such as degree of vimentin staining, associated with epithelial-mesenchymal transition (EMT), or downregulate tumor expression of HSP90. These data suggest STA-8666 and other similar targeted compounds may be useful additions to control the growth of early stage NSCLC in patient populations.

  11. Robotic stereotactic body radiation therapy for elderly medically inoperable early-stage non-small cell lung cancer

    PubMed Central

    Karam, Sana D; Horne, Zachary D; Hong, Robert L; Baig, Nimrah; Gagnon, Gregory J; McRae, Don; Duhamel, David; Nasr, Nadim M

    2013-01-01

    Introduction Stereotactic body radiation therapy (SBRT) is being increasingly applied in the treatment of non-small cell lung cancer (NSCLC) because of its high local efficacy. This study aims to examine survival outcomes in elderly patients with inoperable stage I NSCLC treated with SBRT. Methods A total of 31 patients with single lesions treated with fractionated SBRT from 2008 to 2011 were retrospectively analyzed. A median prescribed dose of 48 Gy was delivered to the prescription isodose line, over a median of four treatments. The median biologically effective dose (BED) was 105.6 (range 37.50–180), and the median age was 73 (65–90 years). No patient received concurrent chemotherapy. Results With a median follow up of 13 months (range, 4–40 months), the actuarial median overall survival (OS) and progression-free survival (PFS) were 32 months, and 19 months, respectively. The actuarial median local control (LC) time was not reached. The survival outcomes at median follow up of 13 months were 80%, 68%, and 70% for LC, PFS, and OS, respectively. Univariate analysis revealed a BED of >100 Gy was associated with improved LC rates (P = 0.02), while squamous cell histology predicted for worse LC outcome at median follow up time of 13 months (P = 0.04). Increased tumor volume was a worse prognostic indicator of both LC and OS outcomes (P < 0.05). Finally, female gender was a better prognostic factor for OS than male gender (P = 0.006). There were no prognostic indicators of PFS that reached statistical significance. No acute or subacute high-grade toxicities were documented. Conclusion SBRT is a safe, feasible, and effective treatment option for elderly patients with inoperable early stage NSCLC. BED, histology, and tumor size are predictors of local control, while tumor size and gender predict OS. PMID:28210133

  12. Outcome of allo simple limbal epithelial transplantation (alloSLET) in the early stage of ocular chemical injury.

    PubMed

    Iyer, Geetha; Srinivasan, Bhaskar; Agarwal, Shweta; Tarigopula, Anil

    2017-06-01

    To analyse the outcome of allo simple limbal epithelial transplantation (alloSLET) in eyes in the early stage following ocular chemical injury to achieve rapid epithelialisation. Records of 18 eyes of 17 patients who underwent alloSLET between April 2013 and Jan 2016 were analysed retrospectively. Patients with grade 4 or worse Dua's classification for chemical injury, who presented within a month of the injury or with a non-healing epithelial defect since the injury despite earlier medical or surgical interventions, were included in the study. The time to epithelialisation was the primary outcome measure and the best corrected visual acuity, the clinically assessed epithelial phenotype and symblepharon formation were the secondary outcome measures. The mean time to epithelialisation was noted to be 22.5±9.14 days. A best corrected visual acuity of better than 20/120 was achieved in 13 eyes in a mean duration of 33.06+10.73 days following alloSLET. Corneal phenotype with complete epithelialisation was achieved in the immediate postoperative period in 17 of the 18 eyes (94.11%). Seven eyes had a gradual failure of the allograft and 5 eyes underwent subsequent limbal autograft. Symblepharon formation involving one to two quadrants was noted in 3 eyes (16.7%). AlloSLET seems to be a useful technique to achieve rapid epithelialisation in severe chemical injuries thereby preventing the adverse effects of delayed epithelial healing. Visual rehabilitative procedures in the chronic phase of chemical injury, in most instances following an alloSLET in the acute stage, did not require keratoplasty, either lamellar or penetrating. Published