Postoperative Radiotherapy for Maxillary Sinus Cancer: Long-Term Outcomes and Toxicities of Treatment

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

Bristol, Ian J.; Ahamad, Anesa; Garden, Adam S.

2007-07-01

Purpose: To determine the effects of three changes in radiotherapy technique on the outcomes for patients irradiated postoperatively for maxillary sinus cancer. Methods and Materials: The data of 146 patients treated between 1969 and 2002 were reviewed. The patients were separated into two groups according to the date of treatment. Group 1 included 90 patients treated before 1991 and Group 2 included 56 patients treated after 1991, when the three changes were implemented. The outcomes were compared between the two groups. Results: No differences were found in the 5-year overall survival, recurrence-free survival, local control, nodal control, or distant metastasismore » rates between the two groups (51% vs. 62%, 51% vs. 57%, 76% vs. 70%, 82% vs. 83%, and 28% vs. 17% for Groups 1 and 2, respectively). The three changes were to increase the portals to cover the base of the skull in patients with perineural invasion, reducing their risk of local recurrence; the addition of elective neck irradiation in patients with squamous or undifferentiated histologic features, improving the nodal control, distant metastasis, and recurrence-free survival rates (64% vs. 93%, 20% vs. 3%, and 45% vs. 67%, respectively; p < 0.05 for all comparisons); and improving the dose distributions within the target volume, reducing the late Grade 3-4 complication rates (34% in Group 1 vs. 8% in Group 2, p = 0.014). Multivariate analysis revealed advancing age, the need for enucleation, and positive margins as independent predictors of worse overall survival. The need for enucleation also predicted for worse local control. Conclusion: The three changes in radiotherapy technique improved the outcomes for select patients as predicted. Despite these changes, little demonstrable overall improvement occurred in local control or survival for these patients and additional work must be done.« less

Differential misclassification bias and dietary recall for the distant past using a food frequency questionnaire.

PubMed

Hislop, T G; Lamb, C W; Ng, V T

1990-01-01

Cases (n = 263) and controls (n = 200) returned self-administered food frequency questionnaires in 1980-1982 and again in 1986 as part of a case-control study of breast cancer. The questionnaire asked about consumption of specific food items as recalled for four different age periods. K-statistics comparing responses in the first and second questionnaires were generally similar for cases and controls and were consistent across the different age periods. The influence of recent dietary change on dietary recall diminished for the more distant past. The food frequency questionnaire was found to be more reliable for specific food items for the distant past than for the more recent past. Differential misclassification bias between cases and controls was less apparent for the more distant past. The frequency and interpretation of missing values is discussed.

Merkel Cell Carcinoma: 27-Year Experience at the Peter MacCallum Cancer Centre

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

Hui, Andrew C., E-mail: achui@bigpond.net.au; Stillie, Alison L.; Seel, Matthew

2011-08-01

Purpose: To retrospectively evaluate the treatment outcome of patients with Merkel cell carcinoma after local and/or regional treatment. Methods and Materials: Patients presenting to our center between January 1980 and July 2006 with Merkel cell carcinoma and without distant metastases were reviewed. The primary endpoint was locoregional control. Secondary endpoints were distant recurrence, survival and treatment toxicity. Results: A total of 176 patients were identified. The median age was 79 years. The median follow-up was 2.2 years for all patients and 3.9 years for those alive at the last follow-up visit. The most common primary site was the head andmore » neck (56%), and 62 patients(35%) had regional disease at presentation. The initial surgery to the primary tumor involved (wide) local excision in 140 patients and biopsy only in 28 patients (8 patients had no identifiable primary tumor); 33 patients underwent nodal surgery. Of the 176 patients, 165 (94%) underwent radiotherapy (RT) and 29 of them also underwent concurrent chemotherapy. The median radiation dose was 50 Gy (range, 18-60). Locoregional recurrence developed in 33 patients(19%), with a median interval to recurrence of 8 months. Distant metastases developed in 43 patients(24%). Age, primary tumor size, and RT (no RT vs. <45 Gy vs. {>=}45 Gy) were predictive of locoregional control on univariate analysis. However, only RT remained significant on multivariate analysis. The estimated 5-year actuarial rate for locoregional control, progression-free survival, and overall survival was 76%, 60%, and 45%, respectively. Conclusion: The locoregional control rate for Merkel cell carcinoma in our study was comparable to those from other series using combined modality treatment with RT an integral part of treatment.« less

Predictors and Patterns of Recurrence After Definitive Chemoradiation for Anal Cancer

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

Das, Prajnan; Bhatia, Sumita; Eng, Cathy

2007-07-01

Purpose: To evaluate patterns of locoregional failure, and predictors of recurrence and survival in patients treated with chemoradiation for anal cancer. Methods and Materials: Between September 1992 and August 2004, 167 patients with nonmetastatic squamous cell anal carcinoma were treated with definitive chemoradiation. The median dose of radiotherapy was 5500 cGy. Concurrent chemotherapy was given with 5-fluorouracil and cisplatin in 117 patients, 5-fluorouracil and mitomycin C in 24 patients, and other regimens in 26 patients. Results: The estimated 3-year rates of locoregional control, distant control, disease-free survival, and overall survival were 81%, 88%, 67%, and 84%, respectively. Multivariate analysis showedmore » that higher T stage and N stage independently predicted for a higher rate of locoregional failure; higher N stage and basaloid subtype independently predicted for a higher rate of distant metastasis; and higher N stage and positive human immunodeficiency virus status independently predicted for a lower rate of overall survival. Among the patients who had locoregional failure, 18 (75%) had failure involving the anus or rectum, 5 (21%) had other pelvic recurrences, and 1 (4%) had inguinal recurrence. The 5 pelvic recurrences all occurred in patients with the superior border of the radiotherapy field at the bottom of the sacroiliac joint. Conclusions: Trials of more aggressive and innovative locoregional and systemic therapies are warranted in high-risk patients, based on their T and N stages. The majority of locoregional failures involve the anus and rectum, whereas inguinal recurrences occur rarely. Placing the superior border of the radiotherapy field at L5/S1 could potentially reduce pelvic recurrences.« less

SU-F-R-46: Predicting Distant Failure in Lung SBRT Using Multi-Objective Radiomics Model

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

Zhou, Z; Folkert, M; Iyengar, P

2016-06-15

Purpose: To predict distant failure in lung stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC) by using a new multi-objective radiomics model. Methods: Currently, most available radiomics models use the overall accuracy as the objective function. However, due to data imbalance, a single object may not reflect the performance of a predictive model. Therefore, we developed a multi-objective radiomics model which considers both sensitivity and specificity as the objective functions simultaneously. The new model is used to predict distant failure in lung SBRT using 52 patients treated at our institute. Quantitative imaging features of PETmore » and CT as well as clinical parameters are utilized to build the predictive model. Image features include intensity features (9), textural features (12) and geometric features (8). Clinical parameters for each patient include demographic parameters (4), tumor characteristics (8), treatment faction schemes (4) and pretreatment medicines (6). The modelling procedure consists of two steps: extracting features from segmented tumors in PET and CT; and selecting features and training model parameters based on multi-objective. Support Vector Machine (SVM) is used as the predictive model, while a nondominated sorting-based multi-objective evolutionary computation algorithm II (NSGA-II) is used for solving the multi-objective optimization. Results: The accuracy for PET, clinical, CT, PET+clinical, PET+CT, CT+clinical, PET+CT+clinical are 71.15%, 84.62%, 84.62%, 85.54%, 82.69%, 84.62%, 86.54%, respectively. The sensitivities for the above seven combinations are 41.76%, 58.33%, 50.00%, 50.00%, 41.67%, 41.67%, 58.33%, while the specificities are 80.00%, 92.50%, 90.00%, 97.50%, 92.50%, 97.50%, 97.50%. Conclusion: A new multi-objective radiomics model for predicting distant failure in NSCLC treated with SBRT was developed. The experimental results show that the best performance can be obtained by combining all features.« less

A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

PubMed Central

Ayala-Peacock, Diandra N.; Peiffer, Ann M.; Lucas, John T.; Isom, Scott; Kuremsky, J. Griff; Urbanic, James J.; Bourland, J. Daniel; Laxton, Adrian W.; Tatter, Stephen B.; Shaw, Edward G.; Chan, Michael D.

2014-01-01

Background We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases. Materials and methods Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression. Results Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ2= 16.748, P < .001), number of metastases at SRS (χ2 = 27.216, P < .001), discovery of new metastases at time of SRS (χ2 = 9.197, P < .01), and histology (χ2 = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ2 = 11.020, P < .001) and low risk subtypes (her2 + breast, χ2 = 11.343, P < .001) were identified. Progressive systemic disease (χ2 = 9.549, P < .01), number of brain metastases (χ2 = 16.953, P < .001), minimum SRS dose (χ2 = 21.609, P < .001), and widespread metastatic disease (χ2 = 29.396, P < .001) were predictive of shorter time to WBRT. Conclusion Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases. PMID:24558022

Increased Brahma-related Gene 1 Expression Predicts Distant Metastasis and Shorter Survival in Patients with Invasive Ductal Carcinoma of the Breast.

PubMed

Do, Sung-Im; Yoon, Gun; Kim, Hyun-Soo; Kim, Kyungeun; Lee, Hyunjoo; Do, In-Gu; Kim, Dong-Hoon; Chae, Seoung Wan; Sohn, Jin Hee

2016-09-01

Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood. We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry. We also investigated whether BRG1 expression status is associated with clinicopathological characteristics and outcomes of patients with IDC. Among the 224 patients with IDC, 37.5% (84/224) exhibited high BRG1 expression. IDC exhibited significantly higher BRG1 expression compared to ductal carcinoma in situ (p=0.009) and normal breast tissue (p=0.005). High BRG1 expression in IDC significantly correlated with higher histological grade (p=0.035) and presence of distant metastasis (p=0.002). Furthermore, high BRG1 expression was an independent factor for predicting distant metastasis (relative risk=4.079; p=0.007). In addition, high BRG1 expression predicted shorter overall (p=0.011) and recurrence-free (p=0.003) survival in patients with IDC. In particular, BRG1 had a significant prognostic value in predicting recurrence-free survival of patients with IDC with lymph node metastasis or stage III disease. BRG1 is involved in the progression and metastasis of breast cancer and can serve as a novel biomarker predictive of distant metastasis and patient outcomes. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

PubMed

Lee, E S; Jung, S Y; Kim, J Y; Kim, J J; Yoo, T K; Kim, Y G; Lee, K S; Lee, E S; Kim, E K; Min, J W; Han, W; Noh, D Y; Moon, H G

2016-05-01

We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Engaging in extreme activism in support of others’ political struggles: The role of politically motivated fusion with out-groups

PubMed Central

Boos, Beverly; Kimel, Sasha Y.; Obaidi, Milan; Shani, Maor; Thomsen, Lotte

2018-01-01

Humans are a coalitional, parochial species. Yet, extreme actions of solidarity are sometimes taken for distant or unrelated groups. What motivates people to become solidary with groups to which they do not belong originally? Here, we demonstrate that such distant solidarity can occur when the perceived treatment of an out-group clashes with one’s political beliefs (e.g., for Leftists, oppressive occupation of the out-group) and that it is driven by fusion (or a feeling of oneness) with distant others with whom one does not share any common social category such as nationality, ethnicity or religion. In Study 1, being politically Leftist predicted European-Americans’ willingness to engage in extreme protest on behalf of Palestinians, which was mediated by fusion with the out-group. Next, in Study 2, we examined whether this pattern was moderated by out-group type. Here, Norwegian Leftists fused more with Palestinians (i.e., a group that, in the Norwegian context, is perceived to be occupied in an asymmetrical conflict) rather than Kurds (i.e., a group for which this perception is less salient). In Study 3, we experimentally tested the underlying mechanism by framing the Kurdish conflict in terms of an asymmetrical occupation (vs. symmetrical war or control conditions) and found that this increased Leftist European-Americans’ fusion with Kurds. Finally, in Study 4, we used a unique sample of non-Kurdish aspiring foreign fighters who were in the process of joining the Kurdish militia YPG. Here, fusion with the out-group predicted a greater likelihood to join and support the Kurdish forces in their fight against ISIS, insofar as respondents experienced that their political orientation morally compelled them to do so (Study 4). Together, our findings suggest that politically motivated fusion with out-groups underpins the extreme solidary action people may take on behalf of distant out-groups. Implications for future theory and research are discussed. PMID:29304156

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

PubMed

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

DOWNSTREAM-WATER-LEVEL CONTROL TEST RESULTS ON THE WM LATERAL CANAL

USDA-ARS?s Scientific Manuscript database

On steep canals, distant downstream water-level control can be challenging. SacMan (Software for Automated Canal Management) was developed, in part, to test various distant downstream water level controllers. It was implemented on the WM canal of the Maricopa Stanfield Irrigation and Drainage Distri...

Hedonic Benefits of Close and Distant Interaction Partners: The Mediating Roles of Social Approval and Authenticity.

PubMed

Venaglia, Rachel B; Lemay, Edward P

2017-09-01

The current research utilized ecological momentary assessment methodology to examine affective responses to interacting with close versus distant interaction partners during naturally occurring social interactions, and to test predictions regarding the mediating roles of perceived social approval and authenticity. Analysis of 4,602 social interactions reported by 176 participants suggested that, relative to interactions with distant partners, interactions with close partners were characterized by more positive affect. This effect was mediated by perceived social approval and authenticity. These findings suggest that social interactions with close others confer greater hedonic benefits relative to interactions with distant partners due to greater confidence in social approval and feelings of authenticity. Exploratory analyses suggested that interactions with close partners featured warmer and less shy behavior, and that participants who placed more importance on close relationships (as measured by high relational-interdependent self-construal) experienced more approval and authenticity in their interactions, particularly with distant partners.

The Green Chair Group. Predicting Distant Education in the Year 2001. Final Report.

ERIC Educational Resources Information Center

National Home Study Council, Washington, DC.

In a series of three workshops in 1981, a group of experienced home study educators, education technologists, and informed people from state and federal government, private industry, and trade associations tackled the questions, "What lies ahead in home study, for 'distant education,' in the next 20 years? How should educators plan for the…

Upregulation of c-mesenchymal epithelial transition expression and RAS mutations are associated with late lung metastasis and poor prognosis in colorectal carcinoma.

PubMed

Liu, Jianhua; Zeng, Weiqiang; Huang, Chengzhi; Wang, Junjiang; Xu, Lishu; Ma, Dong

2018-05-01

The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS ) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS / BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (P<0.001) were more likely to occur in patients of group 4. Furthermore, survival analyses revealed RAS/BRAF mutations may have a more powerful impact on survival than C-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.

One-step resonant controlled-phase gate on distant transmon qutrits in different 1D superconducting resonators

PubMed Central

Hua, Ming; Tao, Ming-Jie; Deng, Fu-Guo; Lu Long, Gui

2015-01-01

We propose a scheme to construct the controlled-phase (c-phase) gate on distant transmon qutrits hosted in different resonators inter-coupled by a connected transmon qutrit. Different from previous works for entanglement generation and information transfer on two distant qubits in a dispersive regime in the similar systems, our gate is constructed in the resonant regime with one step. The numerical simulation shows that the fidelity of our c-phase gate is 99.5% within 86.3 ns. As an interesting application of our c-phase gate, we propose an effective scheme to complete a conventional square lattice of two-dimensional surface code layout for fault-tolerant quantum computing on the distant transmon qutrits. The four-step coupling between the nearest distant transmon qutrits, small coupling strengths of the distant transmon qutrits, and the non-population on the connection transmon qutrit can reduce the interactions among different parts of the layout effectively, which makes the layout be integrated with a large scale in an easier way. PMID:26486426

MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer: RTOG 92-02.

PubMed

Khor, Li-Yan; Bae, Kyounghwa; Paulus, Rebecca; Al-Saleem, Tahseen; Hammond, M Elizabeth; Grignon, David J; Che, Mingxin; Venkatesan, Varagur; Byhardt, Roger W; Rotman, Marvin; Hanks, Gerald E; Sandler, Howard M; Pollack, Alan

2009-07-01

PURPOSE MDM2 regulates p53, which controls cell cycle arrest and apoptosis. Both proteins, along with Ki-67, which is an established strong determinant of metastasis, have shown promise in predicting the outcome of men treated with radiation therapy (RT) with or without short-term androgen deprivation (STAD). This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02. PATIENTS AND METHODS Adequate tissue for immunohistochemistry was available for p53, Ki-67, and MDM2 analyses in 478 patient cases. The percentage of tumor nuclei staining positive (PSP) was quantified manually or by image analysis, and the per-sample mean intensity score (MIS) was quantified by image analysis. Cox regression models were used to estimate overall mortality (OM), and Fine and Gray's regressions were applied to the end points of distant metastasis (DM) and cause-specific mortality (CSM). Results In multivariate analyses that adjusted for all markers and treatment covariates, MDM2 overexpression was significantly related to DM (P = .02) and OM (P = .003), and Ki-67 overexpression was significantly related to DM (P < .0001), CSM (P = .0007), and OM (P = .01). P53 overexpression was significantly related to OM (P = .02). When considered in combination, the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points (P < .001 for DM, CSM, and OM). CONCLUSION Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and, if validated, could be considered for risk stratification of patients with prostate cancer in clinical trials.

Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy.

PubMed

Rödel, Franz; Steinhäuser, Kerstin; Kreis, Nina-Naomi; Friemel, Alexandra; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Balermpas, Panagiotis; Fokas, Emmanouil; Louwen, Frank; Rödel, Claus; Yuan, Juping

2018-02-01

RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS). We observed significant inverse correlations between RITA expression and tumour grading, the levels of HPV-16 virus DNA load, CD8 (+) tumour infiltrating lymphocytes and programmed death protein (PD-1) immunostaining. In univariate analyses, elevated levels of RITA expression were predictive for decreased local control (p = 0.001), decreased distant control (p = 0.040), decreased disease free survival (p = 0.001) and overall survival (p < 0.0001), whereas in multivariate analyses RITA expression remained significant for decreased local control (p = 0.009), disease free survival (p = 0.032) and overall survival (p = 0.012). These data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

A Randomized Controlled Trial of Tong Len Meditation Practice in Cancer Patients: Evaluation of a Distant Psychological Healing Effect.

PubMed

Pagliaro, Gioacchino; Pandolfi, Paolo; Collina, Natalina; Frezza, Giovanni; Brandes, Alba; Galli, Margherita; Avventuroso, Federica Marzocchi; De Lisio, Sara; Musti, Muriel Assunta; Franceschi, Enrico; Esposti, Roberta Degli; Lombardo, Laura; Cavallo, Giovanna; Di Battista, Monica; Rimondini, Simonetta; Poggi, Rosalba; Susini, Cinzia; Renzi, Rina; Marconi, Linda

2016-01-01

Tong Len meditation is an important therapeutic tool in the Tibetan medicine, and it can be used for self-healing and/or to heal others. Currently, in the West, there is no scientific study concerning the efficacy of a Tong Len distant healing effect on psychological disorders in cancer patients. To evaluate a distant healing effect of Tong Len meditation on stress, anxiety, depression, fatigue, and self-perceived quality of life in cancer patients. These psychological objectives were chosen as a consequence of the limited scientific literature of present day. We performed a double-blind randomized controlled trial on 103 cancer patients with tumors. Overall, 12 meditators used Tong Len in aid of 52 patients randomly selected as experimental group, while the remaining 51 patients constituted the control group. Patients and meditators did not know each other. All patients completed profile of mood states (POMS) and European Quality of Life-5 dimensions (EQ-5D) questionnaires before treatment (T0), after two (T1) and three months of treatment (T2), and one month after treatment cessation (T3). With regard to the parameters related to depression, a statistically significant improvement (P = .003) was observed in the treatment group compared to controls. On the other hand, the vigor/activity parameter saw significant improvements in the control group (P = .009). Both groups exhibited significant improvements in the other factors assessed in the POMS and EQ-5D questionnaires. This study did not provide sufficient evidence supporting an efficacy of Tong Len meditation in distant psychological healing as compared to a control condition. The research highlighted some psychological improvements through Tong Len distant meditation in a group of patients unknown to meditators. Therefore, the enhancement detected in most parameters in both treatment and control groups raises interest on in-depth analysis and evaluation of distant meditation on cancer patients to mitigate psychological problems caused by the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Testing for the 'predictability' of dynamically triggered earthquakes in The Geysers geothermal field

NASA Astrophysics Data System (ADS)

Aiken, Chastity; Meng, Xiaofeng; Hardebeck, Jeanne

2018-03-01

The Geysers geothermal field is well known for being susceptible to dynamic triggering of earthquakes by large distant earthquakes, owing to the introduction of fluids for energy production. Yet, it is unknown if dynamic triggering of earthquakes is 'predictable' or whether dynamic triggering could lead to a potential hazard for energy production. In this paper, our goal is to investigate the characteristics of triggering and the physical conditions that promote triggering to determine whether or not triggering is in anyway foreseeable. We find that, at present, triggering in The Geysers is not easily 'predictable' in terms of when and where based on observable physical conditions. However, triggered earthquake magnitude positively correlates with peak imparted dynamic stress, and larger dynamic stresses tend to trigger sequences similar to mainshock-aftershock sequences. Thus, we may be able to 'predict' what size earthquakes to expect at The Geysers following a large distant earthquake.

Preoperative staging of rectal cancer.

PubMed

Yeung, Justin Mc; Ferris, Nicholas J; Lynch, A Craig; Heriot, Alexander G

2009-10-01

Preoperative staging is now an essential factor in the multidisciplinary management of rectal cancer because tumor stage is the strongest predictive factor for recurrence. Preoperative staging of rectal cancer can be divided into either local or distant staging. Local staging incorporates the assessment of mural wall invasion, circumferential resection margin involvement, as well as the nodal status for metastasis. Distant staging assesses for evidence of metastatic disease. The aim of this review is to consider the indications and limitations of the current preoperative imaging modalities for rectal cancer staging including clinical examination, endorectal ultrasound, magnetic resonance imaging, computed tomography and positron emission tomography-computed tomography, with respect to local and distant disease.

Planning activity for internally generated reward goals in monkey amygdala neurons

PubMed Central

Schultz, Wolfram

2015-01-01

The best rewards are often distant and can only be achieved by planning and decision-making over several steps. We designed a multi-step choice task in which monkeys followed internal plans to save rewards towards self-defined goals. During this self-controlled behavior, amygdala neurons showed future-oriented activity that reflected the animal’s plan to obtain specific rewards several trials ahead. This prospective activity encoded crucial components of the animal’s plan, including value and length of the planned choice sequence. It began on initial trials when a plan would be formed, reappeared step-by-step until reward receipt, and readily updated with a new sequence. It predicted performance, including errors, and typically disappeared during instructed behavior. Such prospective activity could underlie the formation and pursuit of internal plans characteristic for goal-directed behavior. The existence of neuronal planning activity in the amygdala suggests an important role for this structure in guiding behavior towards internally generated, distant goals. PMID:25622146

The “Minimizing Antibiotic Resistance in Colorado” Project: Impact of Patient Education in Improving Antibiotic Use in Private Office Practices

PubMed Central

Gonzales, Ralph; Corbett, Kitty K; Leeman-Castillo, Bonnie A; Glazner, Judith; Erbacher, Kathleen; Darr, Carol A; Wong, Shale; Maselli, Judith H; Sauaia, Angela; Kafadar, Karen

2005-01-01

Objective To assess the marginal impact of patient education on antibiotic prescribing to children with pharyngitis and adults with acute bronchitis in private office practices. Data Sources/Study Setting Antibiotic prescription rates based on claims data from four managed care organizations in Colorado during baseline (winter 2000) and study (winter 2001) periods. Study Design A nonrandomized controlled trial of a household and office-based patient educational intervention was performed. During both periods, Colorado physicians were mailed antibiotic prescribing profiles and practices guidelines as part of an ongoing quality improvement program. Intervention practices (n=7) were compared with local and distant control practices. Data Collection/Extraction Methods Office visits were extracted by managed care organizations using International Classification of Diseases-9-Clinical Modification codes for acute respiratory tract infections, and merged with pharmacy claims data based on visit and dispensing dates coinciding within 2 days. Principal Findings Adjusted antibiotic prescription rates during baseline and study periods increased from 38 to 39 percent for pediatric pharyngitis at the distant control practices, and decreased from 39 to 37 percent at the local control practices, and from 34 to 30 percent at the intervention practices (p=.18 compared with distant control practices). Adjusted antibiotic prescription rates decreased from 50 to 44 percent for adult bronchitis at the distant control practices, from 55 to 45 percent at the local control practices, and from 60 to 36 percent at the intervention practices (p<.002 and p=.006 compared with distant and local control practices, respectively). Conclusions In office practices, there appears to be little room for improvement in antibiotic prescription rates for children with pharyngitis. In contrast, patient education helps reduce antibiotic use for adults with acute bronchitis beyond that achieved by physician-directed efforts. PMID:15663704

Automatic Camera Control System for a Distant Lecture with Videoing a Normal Classroom.

ERIC Educational Resources Information Center

Suganuma, Akira; Nishigori, Shuichiro

The growth of a communication network technology enables students to take part in a distant lecture. Although many lectures are conducted in universities by using Web contents, normal lectures using a blackboard are still held. The latter style lecture is good for a teacher's dynamic explanation. A way to modify it for a distant lecture is to…

MUC1 Predicts Colorectal Cancer Metastasis: A Systematic Review and Meta-Analysis of Case Controlled Studies

PubMed Central

Lu, Minxun; Liu, Yang; Zheng, Tianying; Feng, Shijian; Hao, Meiqin; Shi, Huashan

2015-01-01

Objective To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC). Methods Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis. Results A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63–3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23–4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke’s stage (OR = 3.02, 95% CI = 2.11–4.33). No publication bias was found in the mate-analysis by Begg’s test or Egger’s test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg’s test p = 0.729, Egger’s test p = 0.000). Conclusions Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis. PMID:26367866

The effects of distant healing performed by a spiritual healer on chronic pain: a randomized controlled trial.

PubMed

Tsubono, Kenjiro; Thomlinson, Paul; Shealy, C Norman

2009-01-01

Many individuals suffer from various kinds of chronic pain. Some controlled studies on distant healing for chronic pain exist, but no definitive conclusion has been established. To study the effects of distant healing performed by a professional Japanese healer on chronic pain. A double-blind randomized controlled study. Holos University, Fair Grove, Missouri. People suffering from chronic pain (not caused by clear organic diseases or that persists long after a reasonable period of healing following injuries or surgery) were recruited through local radio and newspaper advertising. Subjects were randomly assigned to a treatment group or control group using a double-blind procedure. All subjects met the healer at the initial session at Holos University. At the session, a 20-minute group meditation was performed. The healer went back to Japan after the session and started distant healing only to the treatment group for a 2-month period. All participants were asked to meditate for 20 minutes every day during this 2-month period. The visual analog scale and McGill Pain Questionnaire. A total of 17 subjects were recruited, and 16 subjects completed the study. Comparison of pretreatment and posttreatment visual analog scale indicated a slightly significant effect of distant healing (P=.056). The Present Pain Intensity Scale showed significant improvement in the treatment group compared to the control group (P=.0016). The Pain Rating Index showed improvement in the treatment group, but the difference between both groups was not statistically significant (P=.12).

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

PubMed

Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

2014-12-01

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia.

PubMed

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume, and 50.4-56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. The median follow-up time was 52.2 months (range: 11-87 months). Epstein-Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16-50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein-Barr virus were independent predictors for disease-free survival. Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein-Barr virus status before IMRT were important independent prognostic factors.

DiRE: identifying distant regulatory elements of co-expressed genes

PubMed Central

Gotea, Valer; Ovcharenko, Ivan

2008-01-01

Regulation of gene expression in eukaryotic genomes is established through a complex cooperative activity of proximal promoters and distant regulatory elements (REs) such as enhancers, repressors and silencers. We have developed a web server named DiRE, based on the Enhancer Identification (EI) method, for predicting distant regulatory elements in higher eukaryotic genomes, namely for determining their chromosomal location and functional characteristics. The server uses gene co-expression data, comparative genomics and profiles of transcription factor binding sites (TFBSs) to determine TFBS-association signatures that can be used for discriminating specific regulatory functions. DiRE's unique feature is its ability to detect REs outside of proximal promoter regions, as it takes advantage of the full gene locus to conduct the search. DiRE can predict common REs for any set of input genes for which the user has prior knowledge of co-expression, co-function or other biologically meaningful grouping. The server predicts function-specific REs consisting of clusters of specifically-associated TFBSs and it also scores the association of individual transcription factors (TFs) with the biological function shared by the group of input genes. Its integration with the Array2BIO server allows users to start their analysis with raw microarray expression data. The DiRE web server is freely available at http://dire.dcode.org. PMID:18487623

Outcome of cervix uteri cancer patients: Clinical treatment results and toxicity profile in a retrospective study from Saudi Arabia.

PubMed

El Sayed, Mohamed E; Bahadur, Yasir A; Hassouna, Ashraf H; Fawzy, Ehab E; Nasr, Azza M; Sadiq, Bakr B; Dada, Reyad; Sait, Khalid H; Anfinan, Nisrin M

2017-10-01

This study evaluated the survival outcome, pattern of failure and prognostic factors in cervix uteri cancer patients. We reviewed the data of 60 patients with stages IB-IVA cancer who were treated between January 2004 and December 2010. Most patients (n = 50; 83%) had squamous cell carcinoma. Stage IIB was the most common presentation (n = 41; 68%). Forty-seven patients (78%) received Cisplatin concurrent with radiotherapy (CRT). The 2- and 4-year overall survival (OS) was 82% and 79%, respectively. Prolongation of the overall treatment time (OAT) for greater than 56 days, advanced stage and pretreatment hemoglobin (Hb) levels (<10 g/dL) negatively predicted OS (P = 0.039, P = 0.044 and P = 0.008, respectively). The 2- and 4-year disease-free survival (DFS) rates were 80% and 69%, respectively. Vaginal infiltration and brachytherapy (orthogonal versus CT-based planning) were significant factors for the prediction of relapse (P = 0.048 and P = 0.049, respectively). The 2- and 4-year loco-regional control (LRC) rates were 78% and 70%, respectively, and the distant metastasis-free survival (DMFS) rates were 82% and 79%, respectively. Vaginal infiltration was the only negative predictive factor for LRC (P = 0.045), and pathological tumor grade was the only factor indicative of distant metastases (P = 0.037). Grade 3 or 4 late rectal reactions were reported in two patients (3%), and no patients developed grade 3 or 4 urinary reactions. The treatment results in our cervix uteri cancer patients and the prognostic factors are comparable to those of previous reports. Orthogonal brachytherapy planning and vaginal infiltration negatively predicted relapse. © 2016 John Wiley & Sons Australia, Ltd.

Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.

PubMed

Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun

2018-03-01

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p<0·0001), disease-free survival (HR 3·51, 2·43-5·07; p<0·0001), and overall survival (HR 3·22, 2·18-4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status. The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis. The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genetic and phylogenetic consequences of island biogeography.

PubMed

Johnson, K P; Adler, F R; Cherry, J L

2000-04-01

Island biogeography theory predicts that the number of species on an island should increase with island size and decrease with island distance to the mainland. These predictions are generally well supported in comparative and experimental studies. These ecological, equilibrium predictions arise as a result of colonization and extinction processes. Because colonization and extinction are also important processes in evolution, we develop methods to test evolutionary predictions of island biogeography. We derive a population genetic model of island biogeography that incorporates island colonization, migration of individuals from the mainland, and extinction of island populations. The model provides a means of estimating the rates of migration and extinction from population genetic data. This model predicts that within an island population the distribution of genetic divergences with respect to the mainland source population should be bimodal, with much of the divergence dating to the colonization event. Across islands, this model predicts that populations on large islands should be on average more genetically divergent from mainland source populations than those on small islands. Likewise, populations on distant islands should be more divergent than those on close islands. Published observations of a larger proportion of endemic species on large and distant islands support these predictions.

Features and prognostic impact of distant metastases in 45 dogs with de novo stage IV cutaneous mast cell tumours: A prospective study.

PubMed

Pizzoni, S; Sabattini, S; Stefanello, D; Dentini, A; Ferrari, R; Dacasto, M; Giantin, M; Laganga, P; Amati, M; Tortorella, G; Marconato, L

2018-03-01

Distant metastases in dogs with cutaneous mast cell tumors (cMCT) are rare and incurable. The aims of this prospective study were to clarify the clinico-pathological features of stage IV cMCTs and to identify possible prognostic factors for progression-free interval (PFI) and survival time (ST). Dogs were eligible for recruitment if they had a previously untreated, histologically confirmed cMCT and if they underwent complete staging demonstrating stage IV disease. Dogs were uniformly followed-up, whereas treatment was not standardized and included no therapy, surgery, radiation therapy, chemotherapy, tyrosine-kinase inhibitors or a combination of these. 45 dogs with stage IV cMCT were enrolled. All dogs had distant metastatic disease, and 41 (91.1%) dogs had also metastasis in the regional lymph node. Histopathological grade and mutational status greatly varied among dogs. Median ST was 110 days. Notably, PFI and ST were independent of well-known prognostic factors, including anatomic site, histological grade, and mutational status. Conversely, tumor diameter >3 cm, more than 2 metastatic sites, bone marrow infiltration, and lack of tumor control at the primary site were confirmed to be negative prognostic factors by multivariate analysis. Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3 cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT. © 2017 John Wiley & Sons Ltd.

Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.

PubMed

Luo, Hao Lun; Kang, Chih Hsiung; Chen, Yen Ta; Chuang, Yao Chi; Lee, Wei Ching; Cheng, Yuan Tso; Chiang, Po Hui

2013-08-01

To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer. The study included 162 patients with pure ureteric cancer who were treated between January 2005 and December 2010 at a single tertiary referral centre. The association between hydronephrosis grade with pathological findings and oncological outcomes was assessed using multivariate Cox regression analysis. Hydronephrosis grade >2 was independently associated with non-organ-confined ureteric cancer (P = 0.003). Hydronephrosis grade <2 was highly prevalent in organ-confined disease. Hydronephrosis grade >2 and bladder cancer history independently predict bladder cancer recurrence (P = 0.021 and P = 0.002, respectively) Hydronephrosis of grade >2 was found to be associated with local and distant recurrence only in univariate analysis; non-organ-confined pathology independently predicted local and distant oncological failure (P ≤ 0.001 and P = 0.002, respectively). Hydronephrosis grade >2 is associated with non-organ-confined ureteric cancer and with bladder cancer recurrence. Non-organ-confined pathology is still the most important predictor for local and distant oncological failure. © 2013 BJU International.

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

PubMed

Cheng, Skye Hung-Chun; Huang, Tzu-Ting; Cheng, Yu-Hao; Tan, Tee Benita Kiat; Horng, Chen-Fang; Wang, Yong Alison; Brian, Nicholas Shannon; Shih, Li-Sun; Yu, Ben-Long

2017-01-01

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

Time perspective and attitude-behaviour consistency in future-oriented behaviours.

PubMed

Rabinovich, Anna; Morton, Thomas; Postmes, Tom

2010-03-01

The authors propose that the salience of a distant-future time perspective, compared to a near-future time perspective, should increase attitude-behaviour and attitude-intention consistency for future-oriented behaviours. To test this prediction, time perspective was experimentally manipulated in three studies. Across studies, participants in the distant-future time perspective condition demonstrated a strong positive relationship between attitudes towards future-oriented behaviours (saving and environmental protection) and corresponding intentions, as well as between attitudes and behaviour. In the near-future time perspective condition, the relationship between attitudes and intentions and attitudes and behaviour was significantly weaker than in the distant-future time perspective condition. The theoretical implications of these results and suggestions for future research are discussed.

Mucoepidermoid carcinoma of the parotid gland treated by surgery and postoperative radiation therapy: clinicopathologic correlates of outcome.

PubMed

Chen, Allen M; Lau, Valerie H; Farwell, D Gregory; Luu, Quang; Donald, Paul J

2013-12-01

To determine clinical and pathological correlates of outcome among patients treated by surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Retrospective review. The medical records of 61 patients treated by surgery and postoperative radiation therapy for localized mucoepidermoid carcinoma of the parotid gland were retrospectively reviewed in an attempt to identify clinicopathologic correlates of overall survival. Secondary endpoints included local-regional control, distant metastasis-free survival, and complications. The 3- and 5-year estimates of overall survival were 85% and 79%, respectively. Multivariate analysis identified high tumor grade (hazard ratio [HR] = 7.92) and T4 disease (HR = 3.35) as independent predictors of decreased survival, with the former also predicting for distant metastasis and the latter predicting for local-regional recurrence. The 5-year estimate of overall survival was 83% for patients with non-high-grade tumors, compared to 52% for those with high-grade histology (P = 0.001). Late complications included trismus (2 patients), osteoradionecrosis (1 patient), and hearing loss (1 patient). Patients with high-grade tumors and T4 disease are at increased risk for treatment failure after surgery and postoperative radiation therapy for mucoepidermoid carcinoma of the parotid gland. Investigative strategies to improve outcome should be considered for these particular patients in the future. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

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

Kim, Kyubo; Chie, Eui Kyu, E-mail: ekchie93@snu.ac.kr; Jang, Jin-Young

2012-09-01

Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up durationmore » was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size {>=}2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.« less

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early Breast Cancer

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

Gee, Harriet E., E-mail: harriet.gee@sydney.edu.au; The Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW; Central Clinical School, Sydney Medical School, University of Sydney, NSW

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. Methods and Materials: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series ofmore » 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers—TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1—were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. Results: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy–treated patients but not in untreated matched control individuals (n=107; P<.05). Conclusions: Biomarkers of DNA repair and cell cycle control can identify patients at high risk of treatment failure in those receiving radiation therapy for early breast cancer in independent cohorts. These should be further investigated prospectively, especially TOP2A and SKP2, for which targeted therapies are available.« less

Social distance, perceived drinking by peers, and alcohol use by college students.

PubMed

Yanovitzky, Itzhak; Stewart, Lea P; Lederman, Linda C

2006-01-01

Many colleges in the United States are employing social norms marketing campaigns with the goal of reducing college students' alcohol use by correcting misperceptions about their peers' alcohol use. Although the typical message used in these campaigns describes the quantity and frequency of alcohol use by the average student on campus, many students may find such a vague comparison to others to be socially irrelevant. This study compares the relative weight of perceptions about alcohol use by distant versus proximate peers in the prediction of college students' personal drinking behavior. The results of analyzing data collected from a sample of college students at a large public northeastern university (N=276) show that, as hypothesized, perceived alcohol use by proximate peers (best friends and friends) was a stronger predictor of students' personal alcohol use than perceived alcohol use by more distant peers (such as students in general), controlling for other strong predictors of alcohol use by college students (age, gender, race, off-campus residency, and sensation-seeking tendencies). The implications of these findings for the design of more effective social norms messages are discussed.

Predicting distant failure in early stage NSCLC treated with SBRT using clinical parameters.

PubMed

Zhou, Zhiguo; Folkert, Michael; Cannon, Nathan; Iyengar, Puneeth; Westover, Kenneth; Zhang, Yuanyuan; Choy, Hak; Timmerman, Robert; Yan, Jingsheng; Xie, Xian-J; Jiang, Steve; Wang, Jing

2016-06-01

The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

PubMed Central

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

Background We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results The median follow-up time was 52.2 months (range: 11–87 months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16–50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors. PMID:27822060

Formation Flying in Earth, Libration, and Distant Retrograde Orbits

NASA Technical Reports Server (NTRS)

Folta, David C.

2004-01-01

This slide presentation examines the current and future state of formation flying, LEO formations, control strategies for flight in the vicinity of the libration points, and distant retrograde orbit formations. This discussion of LEO formations includes background on perturbation theory/accelerations and LEO formation flying. The discussion of strategies for formation flight in the vicinity of the libration points includes libration missions and natural and controlled libration orbit formations. A reference list is included.

Branched-chain amino acids to tyrosine ratio (BTR) predicts intrahepatic distant recurrence and survival for early hepatocellular carcinoma.

PubMed

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival.

[Distant mental influence on living organisms].

PubMed

Bonilla, Ernesto

2013-12-01

This article reviews studies of distant mental influence on living organisms, including mental suggestions of sleeping and awakening, mental influence at long distances, mental interactions with remote biological systems, mental effects on physiological activity and the sense of being stared at. Significant effects of distant mental influence have been shown in several randomized controlled trials in humans, animals, plants, bacteria and cells in the laboratory. Although distant mental influence on living organisms appears to contradict our ordinary sense of reality and the laws defined by conventional science, several hypotheses have been proposed to explain the observed effects; they include skeptical, signal transfer, field, multidimensional space/time and quantum mechanics hypotheses. In conclusion, as the progress of physics continues to expand our comprehension of reality, a rational explanation for distant mind-matter interaction will emerge and, as history has shown repeatedly, the supernatural events will evolve into paranormal and then, into normal ones, as the scientific frontiers expand.

Radiotherapy on hidradenocarcinoma.

PubMed

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. POST OPERATIVE RADIOTHERAPY ALLOWS BETTER LOCAL CONTROL AND SHOULD BE MANDATORY WHEN HISTOLOGICAL FEATURES PREDICTIVE OF RECURRENCE ARE PRESENT: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread.

Protoplanetary disc response to distant tidal encounters in stellar clusters

NASA Astrophysics Data System (ADS)

Winter, A. J.; Clarke, C. J.; Rosotti, G.; Booth, R. A.

2018-04-01

The majority of stars form in a clustered environment. This has an impact on the evolution of surrounding protoplanetary discs (PPDs) due to either photoevaporation or tidal truncation. Consequently, the development of planets depends on formation environment. Here, we present the first thorough investigation of tidally induced angular momentum loss in PPDs in the distant regime, partly motivated by claims in the literature for the importance of distant encounters in disc evolution. We employ both theoretical predictions and dynamical/hydrodynamical simulations in 2D and 3D. Our theoretical analysis is based on that of Ostriker (1994) and leads us to conclude that in the limit that the closest approach distance xmin ≫ r, the radius of a particle ring, the fractional change in angular momentum scales as (xmin/r)-5. This asymptotic limit ensures that the cumulative effect of distant encounters is minor in terms of its influence on disc evolution. The angular momentum transfer is dominated by the m = 2 Lindblad resonance for closer encounters and by the m = 1, ω = 0 Lindblad resonance at large xmin/r. We contextualize these results by comparing expected angular momentum loss for the outer edge of a PPD due to distant and close encounters. Contrary to the suggestions of previous works, we do not find that distant encounters contribute significantly to angular momentum loss in PPDs. We define an upper limit for closest approach distance where interactions are significant as a function of arbitrary host to perturber mass ratio M2/M1.

Strategies for distant speech recognitionin reverberant environments

NASA Astrophysics Data System (ADS)

Delcroix, Marc; Yoshioka, Takuya; Ogawa, Atsunori; Kubo, Yotaro; Fujimoto, Masakiyo; Ito, Nobutaka; Kinoshita, Keisuke; Espi, Miquel; Araki, Shoko; Hori, Takaaki; Nakatani, Tomohiro

2015-12-01

Reverberation and noise are known to severely affect the automatic speech recognition (ASR) performance of speech recorded by distant microphones. Therefore, we must deal with reverberation if we are to realize high-performance hands-free speech recognition. In this paper, we review a recognition system that we developed at our laboratory to deal with reverberant speech. The system consists of a speech enhancement (SE) front-end that employs long-term linear prediction-based dereverberation followed by noise reduction. We combine our SE front-end with an ASR back-end that uses neural networks for acoustic and language modeling. The proposed system achieved top scores on the ASR task of the REVERB challenge. This paper describes the different technologies used in our system and presents detailed experimental results that justify our implementation choices and may provide hints for designing distant ASR systems.

Presence of non-hypervascular hypointense nodules on Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma.

PubMed

Inoue, Masanori; Ogasawara, Sadahisa; Chiba, Tetsuhiro; Ooka, Yoshihiko; Wakamatsu, Toru; Kobayashi, Kazufumi; Suzuki, Eiichiro; Tawada, Akinobu; Yokosuka, Osamu

2017-04-01

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) performed before curative therapy for hepatocellular carcinoma (HCC) can distinguish between intrahepatic distant recurrence and hypervascularization. This study aimed to retrospectively evaluate the presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI as a risk factor of the intrahepatic distant recurrence of early stage HCC following radiofrequency ablation (RFA). A total of 132 patients who underwent preprocedural Gd-EOB-DTPA-enhanced MRI followed by initial RFA were retrospectively analyzed. Post-RFA intrahepatic distant recurrence, which excluded the hypervascularization of non-hypervascular hypointense nodules detected by preprocedural Gd-EOB-DTPA-enhanced MRI, was evaluated according to the presence of non-hypervascular hypointense nodules on preprocedural Gd-EOB-DTPA-enhanced MRI. Intrahepatic distant recurrence rates following RFA were higher in patients with non-hypervascular hypointense nodules (1-year: 22.5%, 2-year: 52.1%, 5-year: 89.1%) compared with in patients without non-hypervascular hypointense nodules (1-year: 7.0%, 2-year: 28.8%, 5-year: 48.7%). The presence of non-hypervascular hypointense nodules was associated with markedly increased cumulative recurrence rates of both identical and different subsegment intrahepatic distant recurrence, being an independent risk factor for post-RFA identical and different subsegment intrahepatic distant recurrence (identical: HR = 2.365, P = 0.027; different: HR = 3.276, P < 0.001). The presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI obtained prior to RFA is an important predictive factor of intrahepatic distant recurrence following RFA of HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors.

PubMed

Filipits, Martin; Rudas, Margaretha; Jakesz, Raimund; Dubsky, Peter; Fitzal, Florian; Singer, Christian F; Dietze, Otto; Greil, Richard; Jelen, Andrea; Sevelda, Paul; Freibauer, Christa; Müller, Volkmar; Jänicke, Fritz; Schmidt, Marcus; Kölbl, Heinz; Rody, Achim; Kaufmann, Manfred; Schroth, Werner; Brauch, Hiltrud; Schwab, Matthias; Fritz, Peter; Weber, Karsten E; Feder, Inke S; Hennig, Guido; Kronenwett, Ralf; Gehrmann, Mathias; Gnant, Michael

2011-09-15

According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer treated with adjuvant endocrine therapy. RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324]. In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively. The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors. ©2011 AACR.

Action verbs are processed differently in metaphorical and literal sentences depending on the semantic match of visual primes

PubMed Central

Troyer, Melissa; Curley, Lauren B.; Miller, Luke E.; Saygin, Ayse P.; Bergen, Benjamin K.

2014-01-01

Language comprehension requires rapid and flexible access to information stored in long-term memory, likely influenced by activation of rich world knowledge and by brain systems that support the processing of sensorimotor content. We hypothesized that while literal language about biological motion might rely on neurocognitive representations of biological motion specific to the details of the actions described, metaphors rely on more generic representations of motion. In a priming and self-paced reading paradigm, participants saw video clips or images of (a) an intact point-light walker or (b) a scrambled control and read sentences containing literal or metaphoric uses of biological motion verbs either closely or distantly related to the depicted action (walking). We predicted that reading times for literal and metaphorical sentences would show differential sensitivity to the match between the verb and the visual prime. In Experiment 1, we observed interactions between the prime type (walker or scrambled video) and the verb type (close or distant match) for both literal and metaphorical sentences, but with strikingly different patterns. We found no difference in the verb region of literal sentences for Close-Match verbs after walker or scrambled motion primes, but Distant-Match verbs were read more quickly following walker primes. For metaphorical sentences, the results were roughly reversed, with Distant-Match verbs being read more slowly following a walker compared to scrambled motion. In Experiment 2, we observed a similar pattern following still image primes, though critical interactions emerged later in the sentence. We interpret these findings as evidence for shared recruitment of cognitive and neural mechanisms for processing visual and verbal biological motion information. Metaphoric language using biological motion verbs may recruit neurocognitive mechanisms similar to those used in processing literal language but be represented in a less-specific way. PMID:25538604

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

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

Devpura, S; Li, H; Liu, C

Purpose: To correlate dose distributions computed using six algorithms for recurrent early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT), with outcome (local failure). Methods: Of 270 NSCLC patients treated with 12Gyx4, 20 were found to have local recurrence prior to the 2-year time point. These patients were originally planned with 1-D pencil beam (1-D PB) algorithm. 4D imaging was performed to manage tumor motion. Regions of local failures were determined from follow-up PET-CT scans. Follow-up CT images were rigidly fused to the planning CT (pCT), and recurrent tumor volumes (Vrecur) were mapped to themore » pCT. Dose was recomputed, retrospectively, using five algorithms: 3-D PB, collapsed cone convolution (CCC), anisotropic analytical algorithm (AAA), AcurosXB, and Monte Carlo (MC). Tumor control probability (TCP) was computed using the Marsden model (1,2). Patterns of failure were classified as central, in-field, marginal, and distant for Vrecur ≥95% of prescribed dose, 95–80%, 80–20%, and ≤20%, respectively (3). Results: Average PTV D95 (dose covering 95% of the PTV) for 3-D PB, CCC, AAA, AcurosXB, and MC relative to 1-D PB were 95.3±2.1%, 84.1±7.5%, 84.9±5.7%, 86.3±6.0%, and 85.1±7.0%, respectively. TCP values for 1-D PB, 3-D PB, CCC, AAA, AcurosXB, and MC were 98.5±1.2%, 95.7±3.0, 79.6±16.1%, 79.7±16.5%, 81.1±17.5%, and 78.1±20%, respectively. Patterns of local failures were similar for 1-D and 3D PB plans, which predicted that the majority of failures occur in centraldistal regions, with only ∼15% occurring distantly. However, with convolution/superposition and MC type algorithms, the majority of failures (65%) were predicted to be distant, consistent with the literature. Conclusion: Based on MC and convolution/superposition type algorithms, average PTV D95 and TCP were ∼15% lower than the planned 1-D PB dose calculation. Patterns of failure results suggest that MC and convolution/superposition type algorithms predict different outcomes for patterns of failure relative to PB algorithms. Work supported in part by Varian Medical Systems, Palo Alto, CA.« less

Self-control and Task Timing Shift Self-efficacy and Influence Willingness to Engage in Effortful Tasks

PubMed Central

Ein-Gar, Danit; Steinhart, Yael

2017-01-01

Self-efficacy constitutes a key factor that influences people's inclination to engage in effortful tasks. In this study, we focus on an interesting interplay between two prominent factors known to influence engagement in effortful tasks: the timing of the task (i.e., whether the task is scheduled to take place in the near or distant future) and individuals' levels of self-control. Across three studies, we show that these two factors have an interacting effect on self-efficacy. Low self-control (LSC) individuals report higher self-efficacy for distant-future effortful tasks than for near-future tasks, whereas high self-control (HSC) individuals report higher self-efficacy for near-future tasks than for distant future tasks. We further demonstrate how self-efficacy then molds individuals' willingness to engage in those effortful tasks. Given that a particular task may comprise effortful aspects alongside more enjoyable aspects, we show that the effects we observe emerge with regard to a task whose effortful aspects are salient and that the effects are eliminated when the enjoyable aspects of that same task are highlighted. PMID:29075225

Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

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

Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Gomez, Daniel R.; Polkinghorn, William R.

2013-07-01

Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5more » years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.« less

Communication and Technology in Genetic Counseling for Familial Cancer

PubMed Central

Lynch, Henry T.; Snyder, Carrie; Stacey, Mark; Olson, Brooke; Peterson, Susan; Buxbaum, Sarah; Shaw, Trudy; Lynch, Patrick

2015-01-01

When a cancer predisposing germline mutation is detected in an index case, the presence of the underlying syndrome is confirmed and the potential for predictive testing of at-risk relatives is established. However, the reporting of a positive family history does not routinely lead to communication of information about risk to close, much less distant relatives. This review summarizes information technology utilized to address penetration or “reach” of knowledge of risk within extended families, including the use of telephone and video counseling to reach distant patients, and anticipate novel internet-based processes for communication between investigators and relatives. PMID:24355094

TIMING AND INTERSTELLAR SCATTERING OF 35 DISTANT PULSARS DISCOVERED IN THE PALFA SURVEY

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

Nice, D. J.; Altiere, E.; Farrington, D.

2013-07-20

We have made extensive observations of 35 distant slow (non-recycled) pulsars discovered in the ongoing Arecibo PALFA pulsar survey. Timing observations of these pulsars over several years at Arecibo Observatory and Jodrell Bank Observatory have yielded high-precision positions and measurements of rotation properties. Despite being a relatively distant population, these pulsars have properties that mirror those of the previously known pulsar population. Many of the sources exhibit timing noise, and one underwent a small glitch. We have used multifrequency data to measure the interstellar scattering properties of these pulsars. We find scattering to be higher than predicted along some linesmore » of sight, particularly in the Cygnus region. Finally, we present XMM-Newton and Chandra observations of the youngest and most energetic of the pulsars, J1856+0245, which has previously been associated with the GeV-TeV pulsar wind nebula HESS J1857+026.« less

CD44 increases the efficiency of distant metastasis of breast cancer

PubMed Central

McFarlane, Suzanne; Coulter, Jonathan A.; Tibbits, Paul; O'Grady, Anthony; McFarlane, Cheryl; Montgomery, Nicola; Hill, Ashleigh; McCarthy, Helen O.; Young, Leonie S.; Kay, Elaine W.; Isacke, Clare M.; Waugh, David J.J.

2015-01-01

Metastasis is the predominant cause of death from cancer yet we have few biomarkers to predict patients at increased risk of metastasis and are unable to effectively treat disseminated disease. Analysis of 448 primary breast tumors determined that expression of the hylauronan receptor CD44 associated with high grade (p = 0.046), ER- (p = 0.001) and PR-negative tumors (p = 0.029), and correlated with increased distant recurrence and reduced disease-free survival in patients with lymph-node positive or large tumors. To determine its functional role in distant metastasis, CD44 was knocked-down in MDA-MB-231 cells using two independent shRNA sequences. Loss of CD44 attenuated tumor cell adhesion to endothelial cells and reduced cell invasion but did not affect proliferation in vitro. To verify the importance of CD44 to post-intravasation events, tumor formation was assessed by quantitative in vivo imaging and post-mortem tissue analysis following an intra-cardiac injection of transfected cells. CD44 knock-down increased survival and decreased overall tumor burden at multiple sites, including the skeleton in vivo. We conclude that elevated CD44 expression on tumour cells within the systemic circulation increases the efficiency of post-intravasation events and distant metastasis in vivo, consistent with its association with increased distant recurrence and reduced disease-free survival in patients. PMID:25888636

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PubMed

Mannelli, Giuditta; Cecconi, Lorenzo; Fasolati, Martina; Santoro, Roberto; Franchi, Alessandro; Gallo, Oreste

Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Can Platelet and Leukocyte Indicators Give Us an Idea about Distant Metastasis in Nasopharyngeal Cancer?

PubMed

Arıcıgil, Mitat; Dündar, Mehmet Akif; Yücel, Abitter; Arbağ, Hamdi; Aziz, Suhayb Kuria

This study aimes to evaluate platelet and leucocyte indicators, such as the mean platelet volume, platelet distribution width, plateletcrit, white blood cell count, neutrophil to lymphocyte ratio in nasopharyngeal cancer patients and also to evaluate the relationship between these indicators and nasopharyngeal cancer with distant metastasis. The medical records of 118 patients diagnosed with nasopharyngeal cancer in our hospital between January 2006 and August 2015 were reviewed. The nasopharyngeal cancer group was further sub grouped according to the presence or absence of distant metastasis and TNM (tumour - T, node - N, metastasis - M) classification. A control group consisted of 120 healthy patients. The platelet and leucocyte values at the time of the initial diagnosis were recorded. Neutrophil to lymphocyte ratio and platelet distribution width values were significantly higher in the nasopharyngeal cancer group. But only platelet distribution width values were significantly higher in the nasopharyngeal cancer group with distant metastasis compared to the nasopharyngeal cancer group without distant metastasis. Neutrophil to lymphocyte ratio and platelet distribution width values may increase in nasopharyngeal cancer. But only the platelet distribution width values may give us an idea about the distant metastasis in nasopharyngeal cancer.

Radiotherapy on hidradenocarcinoma

PubMed Central

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Context: Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. Case Report: We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. Conclusion: Post operative radiotherapy allows better local control and should be mandatory when histological features predictive of recurrence are present: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread. PMID:22540063

Fermilab Muon Campus g-2 Cryogenic Distribution Remote Control System

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

Pei, L.; Theilacker, J.; Klebaner, A.

2015-11-05

The Muon Campus (MC) is able to measure Muon g-2 with high precision and comparing its value to the theoretical prediction. The MC has four 300 KW screw compressors and four liquid helium refrigerators. The centerpiece of the Muon g-2 experiment at Fermilab is a large, 50-foot-diameter superconducting muon storage ring. This one-of-a-kind ring, made of steel, aluminum and superconducting wire, was built for the previous g-2 experiment at Brookhaven. Due to each subsystem has to be far away from each other and be placed in the distant location, therefore, Siemens Process Control System PCS7-400, Automation Direct DL205 & DL05more » PLC, Synoptic and Fermilab ACNET HMI are the ideal choices as the MC g-2 cryogenic distribution real-time and on-Line remote control system. This paper presents a method which has been successfully used by many Fermilab distribution cryogenic real-time and On-Line remote control systems.« less

Two Anatomically and Computationally Distinct Learning Signals Predict Changes to Stimulus-Outcome Associations in Hippocampus.

PubMed

Boorman, Erie D; Rajendran, Vani G; O'Reilly, Jill X; Behrens, Tim E

2016-03-16

Complex cognitive processes require sophisticated local processing but also interactions between distant brain regions. It is therefore critical to be able to study distant interactions between local computations and the neural representations they act on. Here we report two anatomically and computationally distinct learning signals in lateral orbitofrontal cortex (lOFC) and the dopaminergic ventral midbrain (VM) that predict trial-by-trial changes to a basic internal model in hippocampus. To measure local computations during learning and their interaction with neural representations, we coupled computational fMRI with trial-by-trial fMRI suppression. We find that suppression in a medial temporal lobe network changes trial-by-trial in proportion to stimulus-outcome associations. During interleaved choice trials, we identify learning signals that relate to outcome type in lOFC and to reward value in VM. These intervening choice feedback signals predicted the subsequent change to hippocampal suppression, suggesting a convergence of signals that update the flexible representation of stimulus-outcome associations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Location of subventricular zone recurrence and its radiation dose predicts survival in patients with glioblastoma.

PubMed

Weinberg, Brent D; Boreta, Lauren; Braunstein, Steve; Cha, Soonmee

2018-07-01

Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement. Survival was compared based on recurrence type, distance from the initial enhancing tumor (local ≤ 2 cm, distant > 2 cm), and the radiation dose at the recurrence site. Progression of enhancing subventricular tumor was common at both local (58%) and distant (42%) sites. Median survival was better after local SVZ recurrence than distant SVZ recurrence (8.7 vs. 4.3 months, p = 0.04). Radiation doses at local SVZ recurrence sites recurrence averaged 57.0 ± 4.0 Gy compared to 44.7 ± 6.7 Gy at distant SVZ recurrence sites (p = 0.008). Distant subventricular progression at a site receiving ≤ 45 Gy predicted worse subsequent survival (p = 0.05). Glioblastomas frequently recurred in the subventricular zone, and patient survival was worse when enhancing tumor occurred at sites that received lower radiation doses. This recurrent disease may represent disease undertreated at the time of diagnosis, and further study is needed to determine if improved treatment strategies, such as including the subventricular zone in radiation fields, could improve clinical outcomes.

Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma.

PubMed

Rasmussen, Gregers Brünnich; Håkansson, Katrin E; Vogelius, Ivan R; Rasmussen, Jacob H; Friborg, Jeppe T; Fischer, Barbara M; Schumaker, Lisa; Cullen, Kevin; Therkildsen, Marianne H; Bentzen, Søren M; Specht, Lena

2017-11-01

To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis. Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ 2 for difference p = .003. The final model for locoregional failure included p53 (HR: 1.9; p: .055), concomitant cisplatin (HR: 0.41; p: .008), β-tubulin-1 (HR: 1.8; p: .08), β-tubulin-2 (HR: 0.49; p: .057) and SUVmax (HR: 2.1; p: .046). The final model for distant metastasis included p53 (HR: 0.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed.

Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.

PubMed

Sgroi, Dennis C; Sestak, Ivana; Cuzick, Jack; Zhang, Yi; Schnabel, Catherine A; Schroeder, Brock; Erlander, Mark G; Dunbier, Anita; Sidhu, Kally; Lopez-Knowles, Elena; Goss, Paul E; Dowsett, Mitch

2013-10-01

Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial. In this prospective comparison study, we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived. We did BCI analysis in matched samples with sufficient residual RNA using two BCI models-cubic (BCI-C) and linear (BCI-L)-using previously validated cutoffs. We assessed prognostic ability of BCI for distant recurrence over 10 years (the primary endpoint) and compared it with that of the 21-gene recurrence score and IHC4. We also tested the ability of the assays to predict early (0-5 years) and late (5-10 years) distant recurrence. To assess the ability of the biomarkers to predict recurrence beyond standard clinicopathological variables, we calculated the change in the likelihood-ratio χ(2) (LR-Δχ(2)) from Cox proportional hazards models. Suitable tissue was available from 665 patients with oestrogen-receptor-positive, N0 breast cancer for BCI analysis. The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups (p<0·0001) with 6·8% (95% CI 4·4-10·0) of patients in the low-risk group, 17·3% (12·0-24·7) in the intermediate group, and 22·2% (15·3-31·5) in the high-risk group having distant recurrence. The secondary analysis showed that BCI-L was a much stronger predictor for overall (0-10 year) distant recurrence compared with BCI-C (interquartile HR 2·30 [95% CI 1·62-3·27]; LR-Δχ(2)=22·69; p<0·0001). When compared with BCI-L, the 21-gene recurrence score was less predictive (HR 1·48 [95% CI 1·22-1·78]; LR-Δχ(2)=13·68; p=0·0002) and IHC4 was similar (HR 1·69 [95% CI 1·51-2·56]; LR-Δχ(2)=22·83; p<0·0001). All further analyses were done with the BCI-L model. In a multivariable analysis, all assays had significant prognostic ability for early distant recurrence (BCI-L HR 2·77 [95% CI 1·63-4·70], LR-Δχ(2)=15·42, p<0·0001; 21-gene recurrence score HR 1·80 [1·42-2·29], LR-Δχ(2)=18·48, p<0·0001; IHC4 HR 2·90 [2·01-4·18], LR-Δχ(2)=29·14, p<0·0001); however, only BCI-L was significant for late distant recurrence (BCI-L HR 1·95 [95% CI 1·22-3·14], LR-Δχ(2)=7·97, p=0·0048; 21-gene recurrence score HR 1·13 [0·82-1·56], LR-Δχ(2)=0·48, p=0·47; IHC4 HR 1·30 [0·88-1·94], LR-Δχ(2)=1·59, p=0·20). BCI-L was the only significant prognostic test for risk of both early and late distant recurrence and identified two risk populations for each timeframe. It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy. Avon Foundation, National Institutes of Health, Breast Cancer Foundation, US Department of Defense Breast Cancer Research Program, Susan G Komen for the Cure, Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation, AstraZeneca, Cancer Research UK, and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden (London, UK). Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of distant drug off-targets by direct superposition of binding pocket surfaces.

PubMed

Schumann, Marcel; Armen, Roger S

2013-01-01

Correctly predicting off-targets for a given molecular structure, which would have the ability to bind a large range of ligands, is both particularly difficult and important if they share no significant sequence or fold similarity with the respective molecular target ("distant off-targets"). A novel approach for identification of off-targets by direct superposition of protein binding pocket surfaces is presented and applied to a set of well-studied and highly relevant drug targets, including representative kinases and nuclear hormone receptors. The entire Protein Data Bank is searched for similar binding pockets and convincing distant off-target candidates were identified that share no significant sequence or fold similarity with the respective target structure. These putative target off-target pairs are further supported by the existence of compounds that bind strongly to both with high topological similarity, and in some cases, literature examples of individual compounds that bind to both. Also, our results clearly show that it is possible for binding pockets to exhibit a striking surface similarity, while the respective off-target shares neither significant sequence nor significant fold similarity with the respective molecular target ("distant off-target").

Identification of Distant Drug Off-Targets by Direct Superposition of Binding Pocket Surfaces

PubMed Central

Schumann, Marcel; Armen, Roger S.

2013-01-01

Correctly predicting off-targets for a given molecular structure, which would have the ability to bind a large range of ligands, is both particularly difficult and important if they share no significant sequence or fold similarity with the respective molecular target (“distant off-targets”). A novel approach for identification of off-targets by direct superposition of protein binding pocket surfaces is presented and applied to a set of well-studied and highly relevant drug targets, including representative kinases and nuclear hormone receptors. The entire Protein Data Bank is searched for similar binding pockets and convincing distant off-target candidates were identified that share no significant sequence or fold similarity with the respective target structure. These putative target off-target pairs are further supported by the existence of compounds that bind strongly to both with high topological similarity, and in some cases, literature examples of individual compounds that bind to both. Also, our results clearly show that it is possible for binding pockets to exhibit a striking surface similarity, while the respective off-target shares neither significant sequence nor significant fold similarity with the respective molecular target (“distant off-target”). PMID:24391782

Cavity Mediated Manipulation of Distant Spin Currents Using a Cavity-Magnon-Polariton.

PubMed

Bai, Lihui; Harder, Michael; Hyde, Paul; Zhang, Zhaohui; Hu, Can-Ming; Chen, Y P; Xiao, John Q

2017-05-26

Using electrical detection of a strongly coupled spin-photon system comprised of a microwave cavity mode and two magnetic samples, we demonstrate the long distance manipulation of spin currents. This distant control is not limited by the spin diffusion length, instead depending on the interplay between the local and global properties of the coupled system, enabling systematic spin current control over large distance scales (several centimeters in this work). This flexibility opens the door to improved spin current generation and manipulation for cavity spintronic devices.

Probabilistic Risk Analysis of Run-up and Inundation in Hawaii due to Distant Tsunamis

NASA Astrophysics Data System (ADS)

Gica, E.; Teng, M. H.; Liu, P. L.

2004-12-01

Risk assessment of natural hazards usually includes two aspects, namely, the probability of the natural hazard occurrence and the degree of damage caused by the natural hazard. Our current study is focused on the first aspect, i.e., the development and evaluation of a methodology that can predict the probability of coastal inundation due to distant tsunamis in the Pacific Basin. The calculation of the probability of tsunami inundation could be a simple statistical problem if a sufficiently long record of field data on inundation was available. Unfortunately, such field data are very limited in the Pacific Basin due to the reason that field measurement of inundation requires the physical presence of surveyors on site. In some areas, no field measurements were ever conducted in the past. Fortunately, there are more complete and reliable historical data on earthquakes in the Pacific Basin partly because earthquakes can be measured remotely. There are also numerical simulation models such as the Cornell COMCOT model that can predict tsunami generation by an earthquake, propagation in the open ocean, and inundation onto a coastal land. Our objective is to develop a methodology that can link the probability of earthquakes in the Pacific Basin with the inundation probability in a coastal area. The probabilistic methodology applied here involves the following steps: first, the Pacific Rim is divided into blocks of potential earthquake sources based on the past earthquake record and fault information. Then the COMCOT model is used to predict the inundation at a distant coastal area due to a tsunami generated by an earthquake of a particular magnitude in each source block. This simulation generates a response relationship between the coastal inundation and an earthquake of a particular magnitude and location. Since the earthquake statistics is known for each block, by summing the probability of all earthquakes in the Pacific Rim, the probability of the inundation in a coastal area can be determined through the response relationship. Although the idea of the statistical methodology applied here is not new, this study is the first to apply it to study the probability of inundation caused by earthquake-generated distant tsunamis in the Pacific Basin. As a case study, the methodology is applied to predict the tsunami inundation risk in Hilo Bay in Hawaii. Since relatively more field data on tsunami inundation are available for Hilo Bay, this case study can help to evaluate the applicability of the methodology for predicting tsunami inundation risk in the Pacific Basin. Detailed results will be presented at the AGU meeting.

Quantum state transfer and controlled-phase gate on one-dimensional superconducting resonators assisted by a quantum bus.

PubMed

Hua, Ming; Tao, Ming-Jie; Deng, Fu-Guo

2016-02-24

We propose a quantum processor for the scalable quantum computation on microwave photons in distant one-dimensional superconducting resonators. It is composed of a common resonator R acting as a quantum bus and some distant resonators rj coupled to the bus in different positions assisted by superconducting quantum interferometer devices (SQUID), different from previous processors. R is coupled to one transmon qutrit, and the coupling strengths between rj and R can be fully tuned by the external flux through the SQUID. To show the processor can be used to achieve universal quantum computation effectively, we present a scheme to complete the high-fidelity quantum state transfer between two distant microwave-photon resonators and another one for the high-fidelity controlled-phase gate on them. By using the technique for catching and releasing the microwave photons from resonators, our processor may play an important role in quantum communication as well.

Proposed Lymph Node Staging System Using the International Consensus Guidelines for Lymph Node Levels Is Predictive for Nasopharyngeal Carcinoma Patients From Endemic Areas Treated With Intensity Modulated Radiation Therapy

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

Li, Wen-Fei; Sun, Ying; Mao, Yan-Ping

2013-06-01

Purpose: To propose a lymph node (N) staging system for nasopharyngeal carcinoma (NPC) based on the International Consensus Guidelines for lymph node (LN) levels and MRI-determined nodal variables. Methods and Materials: The MRI scans and medical records of 749 NPC patients receiving intensity modulated radiation therapy with or without chemotherapy were retrospectively reviewed. The prognostic significance of nodal level, laterality, maximal axial diameter, extracapsular spread, necrosis, and Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) size criteria were analyzed. Results: Nodal level and laterality were the only independent prognostic factors for distant failure and disease failure in multivariatemore » analysis. Compared with unilateral levels Ib, II, III, and/or Va involvement (hazard ratio [HR] 1), retropharyngeal lymph node involvement alone had a similar prognostic value (HR 0.71; 95% confidence interval [CI] 0.43-1.17; P=.17), whereas bilateral levels Ib, II, III, and/or Va involvement (HR 1.65; 95% CI 1.06-2.58; P=.03) and levels IV, Vb, and/or supraclavicular fossa involvement (HR 3.47; 95% CI 1.92-6.29; P<.01) both significantly increased the HR for distant failure. Thus we propose that the N category criteria could be revised as follows: N0, no regional LN metastasis; N1, retropharyngeal lymph node involvement, and/or unilateral levels Ib, II, III, and/or Va involvement; N2, bilateral levels Ib, II, III, and/or Va involvement; N3, levels IV, Vb, and/or supraclavicular fossa involvement. Compared with the 7th edition of the UICC/AJCC criteria, the proposed N staging system provides a more satisfactory distinction between the HRs for regional failure, distant failure, and disease failure in each N category. Conclusions: The proposed N staging system defined by the International Consensus Guidelines and laterality is predictive and practical. However, because of no measurements of the maximal nodal diameter on MRI slices, the prognostic significance of LN size needs further evaluation.« less

Incidence and sites of distant metastases from head and neck cancer.

PubMed

Ferlito, A; Shaha, A R; Silver, C E; Rinaldo, A; Mondin, V

2001-01-01

The incidence of distant metastases in head and neck squamous cell carcinoma (SCC) is relatively small in comparison to other malignancies. Distant metastases adversely impact survival and may significantly affect treatment planning. The incidence of distant metastases is influenced by location of the primary tumor, initial T and N stage of the neoplasm, and the presence or absence of regional control above the clavicle. Patients with advanced nodal disease have a high incidence of distant metastases, particularly in the presence of jugular vein invasion or extensive soft tissue disease in the neck. Primary tumors of advanced T stages in the hypopharynx, oropharynx and oral cavity are associated with the highest incidence of distant metastases. Pulmonary metastases are the most frequent in SCC, accounting for 66% of distant metastases. It may be difficult to distinguish pulmonary metastasis from a new primary tumor, particularly if solitary. Other metastatic sites include bone (22%), liver (10%), skin, mediastinum and bone marrow. An important question remains as to how intensely pre- and postoperative screening for distant metastases should be performed. Preoperative chest X-ray is warranted in all cases. If the primary tumor and nodal status place the patient at high risk for pulmonary metastasis, then preoperative computed tomography scan of the chest should be done. Screening for distant metastases at other sites is usually not indicated in SCC of the upper aerodigestive tract. Postoperatively, annual X-rays of the chest are usually sufficient, but in high-risk situations a chest X-ray performed every 3-6 months may be beneficial. Certain histologic types of primary tumor have greater or lesser propensity to metastasize distantly, and have a different natural history. Adenoid cystic carcinoma metastasizes frequently, even in the absence of extensive local or regional disease. Basaloid squamous cell carcinoma and neuroendocrine carcinomas also metastasize widely. Extensive evaluation for distant metastases is justified for these tumors. Knowledge of the natural history of various neoplasms and the factors that contribute to distant metastases as well as good judgement are essential for cost-effective treatment planning and decision-making with regard to pre- and postoperative evaluation for distant metastases in cancer of the head and neck. Copyright 2001 S. Karger AG, Basel

Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

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

Perez, Bradford A.; Mettu, Pradeep; Vajzovic, Lejla

2014-05-01

Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex. Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with {sup 125}I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpointmore » variables. Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001). Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis–free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.« less

T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

PubMed

Mackenzie, P; Pryor, D; Burmeister, E; Foote, M; Panizza, B; Burmeister, B; Porceddu, S

2014-10-01

To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Relationship between Functional Visual Acuity and Useful Field of View in Elderly Drivers

PubMed Central

Negishi, Kazuno; Masui, Sachiko; Mimura, Masaru; Fujita, Yoshio; Tsubota, Kazuo

2016-01-01

Purpose To investigate the relationship between the functional visual acuity (FVA) and useful field of view (UFOV) in elderly drivers and assess the usefulness of the FVA test to screen driving aptitude in elderly drivers. Methods This study included 45 elderly drivers (31 men, 14 women; mean age, 68.1 years) and 30 younger drivers (26 men, 4 women; mean age, 34.2 years) who drive regularly. All participants underwent measurement of the binocular corrected distant visual acuity (CDVA), binocular corrected distant FVA (CDFVA), and Visual Field with Inhibitory Tasks Elderly Version (VFIT-EV) to measure UFOV. The tear function and cognitive status also were evaluated. Results The CDVA, the CDFVA, cognitive status, and the correct response rate (CAR) of the VFIT-EV were significantly worse in the elderly group than in the control group (P = 0.000 for all parameters). The cognitive status was correlated significantly with the CDVA (r = -0.301, P = 0.009), CDFVA (r = -0.402, P = 0.000), and the CAR of the VFIT-EV (r = 0.348, P = 0.002) in all subjects. The results of the tear function tests were not correlated with the CDVA, CDFVA, or VFIT-EV in any subjects. Stepwise regression analysis for all subjects in the elderly and control groups showed that the CDFVA predicted the CAR most significantly among the clinical factors evaluated. Conclusion The FVA test is a promising method to screen the driving aptitude, including both visual and cognitive functions, in a short time. PMID:26808364

A clinical study of 407 cases of nasopharyngeal carcinoma in Hong Kong

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

Teo, P.; Tsao, S.Y.; Shiu, W.

Four hundred and seven cases of nasopharyngeal carcinoma were analyzed retrospectively; 403/407 were evaluable for recurrence and survival. Parapharyngeal boost significantly decreased local recurrences in parapharyngeal diseases without base of skull involvement (T2p), but not with base of skull involvement (T3p). Enhanced local control of T2p with boost was significant without neoadjuvant chemotherapy. Tumors localized within the nasopharynx (T1) and tumors with nasal involvement (T2n) suffering from local persistences after external radiation therapy were treated with an intracavitary afterloading method. They had survival and recurrence rates comparable to complete responders to external radiation therapy. Patients with bulky cervical nodes (maximalmore » diameter greater than or equal to 4 cm, N1-N3), treated with neoadjuvant chemotherapy with cis-diamminedichloroplatinum II and 5-fluorouracil, had a regional failure rate, distant metastasis rate, actuarial survival rate, and disease-free survival rate comparable to those with smaller nodes treated with external radiation therapy alone. A simple modification of the Ho's classification by regrouping the T-stages into 'early T-stages' and 'advanced T-stages' and by combining the N1 and the N2 has greatly increased the power of the system in predicting local recurrence and distant metastasis, respectively. There was an overall improvement of the actuarial survival rate and disease-free survival rate over the historical control, and its significance is discussed.« less

Adaptation measures to drought in Mongolian rangeland: The long-distant movement of people and livestock

NASA Astrophysics Data System (ADS)

Kakinuma, K.; Kanae, S.

2015-12-01

Coping with droughts are one of the most important issues in arid and semi-arid regions. Mongolia, where are located in central Asia, are concerned the increase of droughts in the future (IPCC 2014). Mongolia has long history of livestock grazing. Herders have developed the mobile grazing systems to use spatiotemporal variable vegetation. Especially, they often take a rapid and long-distant movement to avoid drought condition ("otor" in Mongolia). The movement is a main adaptation measure to droughts for herders, and it would be applicable to other regions where will be increase the frequency of droughts in the future. However there are few knowledge about processes and actual conditions of the long-distant movement of herders and livestock across Mongolia. Therefore our objective is to discuss the long-distance movement as adaptation measures to droughts. Mongolia has a climatic gradient along the latitude; rainfall variability in southern regions are higher than that in northern regions. Previous theoretical studies predicted that rainfall variability affect the grazing strategies. Based on them, we established two hypotheses about the relationship between climatic variability and the form of long distant movement. (1) The long-distance movement likely occur in southern regions because the frequency of drought are higher in southern regions than in northern regions (2) Cooperation among herders, such as acceptance of livestock that from other prefectures, are likely occur in southern regions while exclusive management are likely occur in northern regions. We interviewed to local herders, decision makers about the long-distant movement, and investigated the number of livestock that across the border of prefectures in recent year across Mongolia. We will discuss long-distant movements as an adaptation measure to drought thorough these results.

Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study

PubMed Central

Dickmann, Boris; Ahlbrecht, Jonas; Ay, Cihan; Dunkler, Daniela; Thaler, Johannes; Scheithauer, Werner; Quehenberger, Peter; Zielinski, Christoph; Pabinger, Ingrid

2013-01-01

Advanced cancer is a risk factor for venous thromboembolism. However, lymph node metastases are usually not considered an established risk factor. In the framework of the prospective, observational Vienna Cancer and Thrombosis Study we investigated the association between local (N0), regional (N1–3), and distant (M1) cancer stages and the occurrence of venous thromboembolism. Furthermore, we were specifically interested in the relationship between stage and biomarkers that have been reported to be associated with venous thromboembolism. We followed 832 patients with solid tumors for a median of 527 days. The study end-point was symptomatic venous thromboembolism. At study inclusion, 241 patients had local, 138 regional, and 453 distant stage cancer. The cumulative probability of venous thromboembolism after 6 months in patients with local, regional and distant stage cancer was 2.1%, 6.5% and 6.0%, respectively (P=0.002). Compared to patients with local stage disease, patients with regional and distant stage disease had a significantly higher risk of venous thromboembolism in multivariable Cox-regression analysis including age, newly diagnosed cancer (versus progression of disease), surgery, radiotherapy, and chemotherapy (regional: HR=3.7, 95% CI: 1.5–9.6; distant: HR=5.4, 95% CI: 2.3–12.9). Furthermore, patients with regional or distant stage disease had significantly higher levels of D-dimer, factor VIII, and platelets, and lower hemoglobin levels than those with local stage disease. These results demonstrate an increased risk of venous thromboembolism in patients with regional disease. Elevated levels of predictive biomarkers in patients with regional disease underpin the results and are in line with the activation of the hemostatic system in the early phase of metastatic dissemination. PMID:23585523

The prediction, observation and study of long-distant undamped thermal waves generated in pulse radiative processes

NASA Astrophysics Data System (ADS)

Vysotskii, V. I.; Kornilova, A. A.; Vasilenko, A. O.; Krit, T. B.; Vysotskyy, M. V.

2017-07-01

The problems of the existence, generation, propagation and registration of long-distant undamped thermal waves formed in pulse radiative processes have been theoretically analyzed and confirmed experimentally. These waves may be used for the analysis of short-time processes of interaction of particles or electromagnetic fields with different targets. Such undamped waves can only exist in environments with a finite (nonzero) time of local thermal relaxation and their frequencies are determined by this time. The results of successful experiments on the generation and registration of undamped thermal waves at a large distance (up to 2 m) are also presented.

Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

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

Hodges, Joseph C.; Das, Prajnan, E-mail: PrajDas@mdanderson.or; Eng, Cathy

2009-11-01

Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions weremore » treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.« less

Twenty-Five-Year Experience With Radical Chemoradiation for Anal Cancer

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

Tomaszewski, Jonathan M., E-mail: jonathan.tomaszewski@petermac.org; Link, Emma; Leong, Trevor

2012-06-01

Purpose: To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials: Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results: Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dosemore » to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions: CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.« less

Twenty-five-year experience with radical chemoradiation for anal cancer.

PubMed

Tomaszewski, Jonathan M; Link, Emma; Leong, Trevor; Heriot, Alexander; Vazquez, Melisa; Chander, Sarat; Chu, Julie; Foo, Marcus; Lee, Mark T; Lynch, Craig A; Mackay, John; Michael, Michael; Tran, Phillip; Ngan, Samuel Y

2012-06-01

To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Identification of Distant Metastatic Disease in Uterine Cervical and Endometrial Cancers with FDG PET/CT: Analysis from the ACRIN 6671/GOG 0233 Multicenter Trial.

PubMed

Gee, Michael S; Atri, Mostafa; Bandos, Andriy I; Mannel, Robert S; Gold, Michael A; Lee, Susanna I

2018-04-01

Purpose To assess the accuracy of staging positron emission tomography (PET)/computed tomography (CT) in detecting distant metastasis in patients with local-regionally advanced cervical and high-risk endometrial cancer in the clinical trial by the American College of Radiology Imaging Network (ACRIN) and the Gynecology Oncology Group (GOG) (ACRIN 6671/GOG 0233) and to compare central and institutional reader performance. Materials and Methods In this prospective multicenter trial, PET/CT and clinical data were reviewed for patients enrolled in ACRIN 6671/GOG 0233. Two central readers, blinded to site read and reference standard, reviewed PET/CT images for distant metastasis. Central review was then compared with institutional point-of-care interpretation. Reference standard was pathologic and imaging follow-up. Test performance for central and site reviews of PET/CT images was calculated and receiver operating characteristic analysis was performed. Generalized estimating equations and nonparametric bootstrap procedure for clustered data were used to assess statistical significance. Results There were 153 patients with cervical cancer and 203 patients with endometrial cancer enrolled at 28 sites. Overall prevalence of distant metastasis was 13.7% (21 of 153) for cervical cancer and 11.8% (24 of 203) for endometrial cancer. Central reader PET/CT interpretation demonstrated sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 54.8%, 97.7%, 79.3%, and 93.1% for cervical cancer metastasis versus 64.6%, 98.6%, 86.1%, and 95.4% for endometrial cancer, respectively. By comparison, local institutional review demonstrated sensitivity, specificity, PPV, and negative predictive value of 47.6%, 93.9%, 55.6%, and 91.9% for cervical cancer metastasis and 66.7%, 93.9%, 59.3%, and 95.5% for endometrial cancer, respectively. For central readers, the specificity and PPV of PET/CT detection of cervical and endometrial cancer metastases were all significantly higher compared with that of local institutional review (P < .05). Central reader area under the receiver operating characteristic curve (AUC) values were 0.78 and 0.89 for cervical and endometrial cancer, respectively; these were not significantly different from local institutional AUC values (0.75 and 0.84, respectively; P > .05 for both). Conclusion FDG PET/CT demonstrates high specificity and PPV for detecting distant metastasis in cervical and endometrial cancer and should be included in the staging evaluation. Blinded central review of imaging provides improved specificity and PPV for the detection of metastases and should be considered for future oncologic imaging clinical trials. © RSNA, 2017.

Frequency and Correlates of Distant Visual Impairment in Patients with Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.

PubMed

Zheng, W; Tang, L R; Correll, C U; Ungvari, G S; Chiu, H F K; Xiang, Y Q; Xiang, Y T

2015-09-01

Distant visual impairment in the severely mentally ill is under-researched. This study aimed to assess the frequency and correlates of distant visual impairment in a cohort of Chinese psychiatric patients, including its effect on their quality of life. Adult psychiatric inpatients with schizophrenia, bipolar disorder, and major depressive disorder consecutively admitted to a psychiatric hospital in Beijing, China underwent assessments of psychopathology (Brief Psychiatric Rating Scale, 16-item Quick Inventory of Depressive Symptomatology [Self-Report]), quality of life (12-item Short-Form Medical Outcomes Study [SF-12], 25-item National Eye Institute Visual Function Questionnaire [NEI-VFQ25]), adverse effects (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale), and presenting (as opposed to uncorrected) distant visual acuity (Logarithm of the Minimum Angle of Resolution [LogMAR] chart with patients wearing spectacles, if they owned them). Distant visual impairment was defined as binocular distant visual acuity of a LogMAR score of ≥ 0.5 (< 6/18 Snellen acuity). Among 356 patients who met the study criteria, the frequency of distant visual impairment was 12.6% (15.2% with schizophrenia, 11.9% with bipolar disorder, 8.8% with major depressive disorder). In multiple logistic regression analysis, distant visual impairment was significantly associated with ocular disease only (p = 0.002, odds ratio = 3.2, 95% confidence interval = 1.5-6.7). Controlling for the confounding effect of ocular disease, patients with distant visual impairment had a lower quality of life in the general vision domain of the NEI-VFQ25 (F[2, 353] = 9.5, p = 0.002) compared with those without. No differences in the physical and mental domains of the SF-12 and in other domains of the NEI-VFQ25 were noted in these 2 groups. One-eighth of middle-aged severely mentally ill patients had distant visual impairment. Considering the impact of distant visual impairment on daily functioning, severely mentally ill patients need to be screened for impaired eyesight as part of their comprehensive health assessment.

ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

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

Visel, Axel; Blow, Matthew J.; Li, Zirong

2009-02-01

A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover since they are scattered amongst the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here, we performed chromatin immunoprecipitation with the enhancer-associated protein p300, followed by massively-parallel sequencing, to map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain, and limb tissue. Wemore » tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases revealed reproducible enhancer activity in those tissues predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities and suggest that such datasets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.« less

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

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

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

The effect of distant reiki on pain in women after elective Caesarean section: a double-blinded randomised controlled trial

PubMed Central

vanderVaart, Sondra; Berger, Howard; Tam, Carolyn; Goh, Y Ingrid; Gijsen, Violette M G J; de Wildt, Saskia N; Taddio, Anna

2011-01-01

Introduction Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. Methods In this randomised, double-blinded study, women who underwent an elective C-section were allocated to either usual care (control, n=40) or three distant reiki sessions in addition to usual care (n=40). Pain was assessed using a visual analogue scale (VAS). The primary endpoint was the Area Under the VAS-Time Curve (AUC) for days 1–3. Secondary measures included: the proportion of women who required opioid medications and dose consumed, rate of healing and vital signs. Results AUC for pain was not significantly different in the distant reiki and control groups (mean±SD; 212.1±104.7 vs 223.1±117.8; p=0.96). There were no significant differences in opioid consumption or rate of healing; however, the distant reiki group had a significantly lower heart rate (74.3±8.1 bpm vs 79.8±7.9 bpm, p=0.003) and blood pressure (106.4±9.7 mm Hg vs 111.9±11.0 mm Hg, p=0.02) post surgery. Conclusion Distant reiki had no significant effect on pain following an elective C-section. Clinical Trial Registration Number ISRCTN79265996. PMID:22021729

The antecedents and consequences of a beyond-choice view of decision situations: A construal level theory perspective.

PubMed

Halamish, Vered; Borovoi, Leah; Liberman, Nira

2017-02-01

Evaluating alternatives and comparing them to each other are integral to decision-making. In addition, however, decision makers may adopt a view that goes beyond choice and make inferences about the entire set of alternatives, about the dimensions that are relevant in similar decisions, and about the range of values on a specific dimension. We examined some antecedents and consequences of adopting a beyond-choice view of decision situations. Based on Construal Level Theory we suggest that a beyond-choice view entails high (vs. low) level of construal of the decision situation and hence is more likely to occur for decisions that are more psychologically distant. We further suggest that a consequence of a beyond-choice view might be a later difficulty to remember which attribute belongs to which alternative. To examine these predictions we conducted an experiment in which participants evaluated decision scenarios that were described as being relevant for the distant (vs. the near) future. One day later they answered a decision-related source recognition test in which they were asked to remember which attribute belongs to which alternative. As predicted, people had more source-memory errors in the distant than in the near future condition. These results suggest that a beyond-choice view of decision situations is an important consequence of psychological distance (vs. proximity). Copyright © 2016 Elsevier B.V. All rights reserved.

Driving many distant atoms into high-fidelity steady state entanglement via Lyapunov control.

PubMed

Li, Chuang; Song, Jie; Xia, Yan; Ding, Weiqiang

2018-01-22

Based on Lyapunov control theory in closed and open systems, we propose a scheme to generate W state of many distant atoms in the cavity-fiber-cavity system. In the closed system, the W state is generated successfully even when the coupling strength between the cavity and fiber is extremely weak. In the presence of atomic spontaneous emission or cavity and fiber decay, the photon-measurement and quantum feedback approaches are proposed to improve the fidelity, which enable efficient generation of high-fidelity W state in the case of large dissipation. Furthermore, the time-optimal Lyapunov control is investigated to shorten the evolution time and improve the fidelity in open systems.

Three or More Courses of Stereotactic Radiosurgery for Patients with Multiply Recurrent Brain Metastases.

PubMed

Kotecha, Rupesh; Damico, Nicholas; Miller, Jacob A; Suh, John H; Murphy, Erin S; Reddy, Chandana A; Barnett, Gene H; Vogelbaum, Michael A; Angelov, Lilyana; Mohammadi, Alireza M; Chao, Samuel T

2017-06-01

Although patients with brain metastasis are treated with primary stereotactic radiosurgery (SRS), the use of salvage therapies and their consequence remains understudied. To study the intracranial recurrence patterns and salvage therapies for patients who underwent multiple SRS courses. A retrospective review was performed of 59 patients with brain metastases who underwent ≥3 SRS courses for new lesions. Cox regression analyzed factors predictive for overall survival. The median age at diagnosis was 52 years. Over time, patients underwent a median of 3 courses of SRS (range: 3-8) to a total of 765 different brain metastases. The 6-month risk of distant intracranial recurrence after the first SRS treatment was 64% (95% confidence interval: 52%-77%). Overall survival was 40% (95% confidence interval: 28%-53%) at 24 months. Only 24 patients (41%) had a decline in their Karnofsky Performance Status ≤70 at last office visit. Quality of life was preserved among 77% of patients at 12 months, with 45% experiencing clinically significant improvement during clinical follow-up. Radiation necrosis developed in 10 patients (17%). On multivariate analysis, gender (males, Hazard Ratio [HR]: 2.0, P < .05), Karnofsky Performance Status ≤80 (HR 3.2, P < .001), extracranial metastases (HR: 3.6, P < .001), and a distant intracranial recurrence ≤3 months from initial to repeat SRS (HR: 3.8, P < .001) were associated with a poorer survival. In selected patients, performing ≥3 SRS courses controls intracranial disease. Patients may need salvage SRS for distant intracranial relapse, but focal retreatments are associated with modest toxicity, do not appear to negatively affect a patient's performance status, and help preserve quality of life. Copyright © 2017 by the Congress of Neurological Surgeons

Psychological distance reduces literal imitation: Evidence from an imitation-learning paradigm.

PubMed

Hansen, Jochim; Alves, Hans; Trope, Yaacov

2016-03-01

The present experiments tested the hypothesis that observers engage in more literal imitation of a model when the model is psychologically near to (vs. distant from) the observer. Participants learned to fold a dog out of towels by watching a model performing this task. Temporal (Experiment 1) and spatial (Experiment 2) distance from the model were manipulated. As predicted, participants copied more of the model's specific movements when the model was near (vs. distant). Experiment 3 replicated this finding with a paper-folding task, suggesting that distance from a model also affects imitation of less complex tasks. Perceived task difficulty, motivation, and the quality of the end product were not affected by distance. We interpret the findings as reflecting different levels of construal of the model's performance: When the model is psychologically distant, social learners focus more on the model's goal and devise their own means for achieving the goal, and as a result show less literal imitation of the model. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase III trial.

PubMed

Fei, F; Messina, C; Slaets, L; Chakiba, C; Cameron, D; Bogaerts, J; Bonnefoi, H

2015-02-01

Although achieving a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer predicts a better outcome, some patients still relapse. The objectives of this study were to describe the types of events in this group of patients and to identify predictive factors for relapse. Patients with large operable or locally advanced breast cancers (T4d tumours were excluded) were randomised to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel followed by three cycles of eprirubicin/docetaxel. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in the primary tumour and axillary lymph nodes at surgery. Two Cox regression analyses were performed to identify predictive factors of relapse: one for recurrence-free interval (RFI) and one for distant recurrence-free interval (DRFI). Out of 283 eligible patients who achieved a pCR, 40 (14.1%) and 28 (9.9%) presented an event of interest for the RFI and DRFI analyses, respectively. Five-year RFI, DRFI and overall survival (OS) were 85.3% (95% confidence interval (CI), 80.1-89.3), 89.6% (95% CI, 85.0-92.9) and 91.9% (95% CI, 87.2-94.9), respectively. No predictors for RFI after pCR were identified. For DRFI, tumour size was the only predictor: Hazard ratio (HR) T3 versus T1-2=3.62 (95% CI, 1.66-7.89); HR T4 versus T1-2: HR, 2.80 (95% CI, 0.62-12.64) p=0.0048. In this study, clinical tumour size emerged as the only predictor for DRFI after pCR, with T3 and T4 tumours having an increased risk for distant recurrence compared to T1-2 tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

SU-D-207B-03: A PET-CT Radiomics Comparison to Predict Distant Metastasis in Lung Adenocarcinoma

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

Coroller, T; Yip, S; Lee, S

2016-06-15

Purpose: Early prediction of distant metastasis may provide crucial information for adaptive therapy, subsequently improving patient survival. Radiomic features that extracted from PET and CT images have been used for assessing tumor phenotype and predicting clinical outcomes. This study investigates the values of radiomic features in predicting distant metastasis (DM) in non-small cell lung cancer (NSCLC). Methods: A total of 108 patients with stage II–III lung adenocarcinoma were included in this retrospective study. Twenty radiomic features were selected (10 from CT and 10 from PET). Conventional features (metabolic tumor volume, SUV, volume and diameter) were included for comparison. Concordance indexmore » (CI) was used to evaluate features prognostic value. Noether test was used to compute p-value to consider CI significance from random (CI = 0.5) and were adjusted for multiple testing using false rate discovery (FDR). Results: A total of 70 patients had DM (64.8%) with a median time to event of 8.8 months. The median delivered dose was 60 Gy (range 33–68 Gy). None of the conventional features from PET (CI ranged from 0.51 to 0.56) or CT (CI ranged from 0.57 to 0.58) were significant from random. Five radiomics features were significantly prognostic from random for DM (p-values < 0.05). Four were extracted from CT (CI = 0.61 to 0.63, p-value <0.01) and one from PET which was also the most prognostic (CI = 0.64, p-value <0.001). Conclusion: This study demonstrated significant association between radiomic features and DM for patients with locally advanced lung adenocarcinoma. Moreover, conventional (clinically utilized) metrics were not significantly associated with DM. Radiomics can potentially help classify patients at higher risk of DM, allowing clinicians to individualize treatment, such as intensification of chemotherapy) to reduce the risk of DM and improve survival. R.M. has consulting interests with Amgen.« less

Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors.

PubMed

Tang, Gong; Cuzick, Jack; Costantino, Joseph P; Dowsett, Mitch; Forbes, John F; Crager, Michael; Mamounas, Eleftherios P; Shak, Steven; Wolmark, Norman

2011-11-20

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors

PubMed Central

Tang, Gong; Cuzick, Jack; Costantino, Joseph P.; Dowsett, Mitch; Forbes, John F.; Crager, Michael; Mamounas, Eleftherios P.; Shak, Steven; Wolmark, Norman

2011-01-01

Purpose The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. Results RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). Conclusion RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit. PMID:22010013

Unravelling site-specific breast cancer metastasis: a microRNA expression profiling study

PubMed Central

Schrijver, Willemijne A.M.E.; van Diest, Paul J.; Moelans, Cathy B

2017-01-01

Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling. To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays. For validation, we performed quantitative real-time (qRT) PCR on the discovery cohort and on an independent validation cohort of 29 primary breast cancer specimens and their matched metastases. miR expression was highly patient specific and miR signatures in the primary tumor were largely retained in the metastases, with the exception of several differentially expressed, location specific miRs. Validation with qPCR demonstrated that hsa-miR-106b-5p was predictive for the development of lung metastases. In time, the second metastasis often showed a miR upregulation compared to the first metastasis. This study discovered a metastatic site-specific miR and found miR expression to be highly patient specific. This may lead to novel biomarkers predicting site of distant metastases, and to adjuvant, personalized targeted therapy strategies that could prevent such metastases from becoming clinically manifest. PMID:27902972

Unravelling site-specific breast cancer metastasis: a microRNA expression profiling study.

PubMed

Schrijver, Willemijne A M E; van Diest, Paul J; Moelans, Cathy B

2017-01-10

Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling.To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays. For validation, we performed quantitative real-time (qRT) PCR on the discovery cohort and on an independent validation cohort of 29 primary breast cancer specimens and their matched metastases.miR expression was highly patient specific and miR signatures in the primary tumor were largely retained in the metastases, with the exception of several differentially expressed, location specific miRs. Validation with qPCR demonstrated that hsa-miR-106b-5p was predictive for the development of lung metastases. In time, the second metastasis often showed a miR upregulation compared to the first metastasis.This study discovered a metastatic site-specific miR and found miR expression to be highly patient specific. This may lead to novel biomarkers predicting site of distant metastases, and to adjuvant, personalized targeted therapy strategies that could prevent such metastases from becoming clinically manifest.

Peripheral doses from pediatric IMRT

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

Klein, Eric E.; Maserang, Beth; Wood, Roy

Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 tomore » 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged from 0.47-0.94) doses {approx}[0.4-1.8 cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields 10 cm or greater, while pediatric central nervous system fields range from 4 to 7 cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close proximity (<10 cm from the field edge) is dominated by internal scatter; therefore, field-size differences overwhelm phantom size affects and increased MU. Distant peripheral dose, dominated by head leakage, was higher than predicted, even when accounting for MUs ({approx}factor of 3) likely due to the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large-field full phantom studies. For regional OAR, doses are likely lower than predicted by existing ''large field'' data, while the distant PD is higher.« less

Plant performance was greater in the soils of more distantly related plants for an herbaceous understory species.

PubMed

Sweet, Drake D; Burns, Jean H

2017-01-01

Growing evidence suggests that plant-soil interactions have important implications for plant community composition. However, the role of phylogenetic relatedness in governing interactions between plants and soil biota is unclear, and more case studies are needed to help build a general picture of whether and how phylogeny might influence plant-soil interactions. We performed a glasshouse experiment to test whether degree of phylogenetic relatedness between Aquilegia canadensis and six co-occurring heterospecifics affects A. canadensis biomass through soil legacy effects. We also compared performance of A. canadensis in soils conditioned by invasive Alliaria petiolata versus native heterospecifics, hypothesizing that conditioning by A. petiolata would suppress the performance of the focal native plant. A. canadensis performed significantly better in distant relatives' soils than in close relatives' soils, and this effect disappeared with soil sterilization, consistent with close relatives sharing similar pathogens. Contrary to our expectations, soils conditioned by the invasive species A. petiolata versus by native species had similar effects on A. canadensis . The greater performance of A. canadensis in soils of more versus less distant relatives is consistent with a hypothesis of phylogenetically constrained pathogen escape, a phenomenon expected to promote coexistence of phylogenetically distant species. However, pairwise plant-soil feedback experiments are needed to create a stronger coexistence prediction.

Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

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

Bergom, Carmen; Kelly, Tracy; Bedi, Meena

Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with themore » BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m{sup 2}; 91% of the patients were overweight (BMI ≥25 kg/m{sup 2}) and 69% of the patients were clinically obese (BMI ≥30 kg/m{sup 2}). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m{sup 2} (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation therapy.« less

Prediction of high-frequency vibration transmission across coupled, periodic ribbed plates by incorporating tunneling mechanisms.

PubMed

Yin, Jianfei; Hopkins, Carl

2013-04-01

Prediction of structure-borne sound transmission on built-up structures at audio frequencies is well-suited to Statistical Energy Analysis (SEA) although the inclusion of periodic ribbed plates presents challenges. This paper considers an approach using Advanced SEA (ASEA) that can incorporate tunneling mechanisms within a statistical approach. The coupled plates used for the investigation form an L-junction comprising a periodic ribbed plate with symmetric ribs and an isotropic homogeneous plate. Experimental SEA (ESEA) is carried out with input data from Finite Element Methods (FEM). This indicates that indirect coupling is significant at high frequencies where bays on the periodic ribbed plate can be treated as individual subsystems. SEA using coupling loss factors from wave theory leads to significant underestimates in the energy of the bays when the isotropic homogeneous plate is excited. This is due to the absence of tunneling mechanisms in the SEA model. In contrast, ASEA shows close agreement with FEM and laboratory measurements. The errors incurred with SEA rapidly increase as the bays become more distant from the source subsystem. ASEA provides significantly more accurate predictions by accounting for the spatial filtering that leads to non-diffuse vibration fields on these more distant bays.

Management of Mediastinal Relapse after Treatment with Stereotactic Body Radiotherapy or Accelerated Hypofractionated Radiotherapy for Stage I/II Non–Small-Cell Lung Cancer

PubMed Central

Kilburn, Jeremy M.; Lester, Scott C.; Lucas, John T.; Soike, Michael H.; Blackstock, A. William; Kearns, William T.; Hinson, William H.; Miller, Antonius A.; Petty, William J.; Munley, Michael T.; Urbanic, James J.

2014-01-01

Purpose/Objective(s) Regional failures occur in up to 15% of patients treated with stereotactic body radiotherapy (SBRT) for stage I/II lung cancer. This report focuses on the management of the unique scenario of isolated regional failures. Methods Patients treated initially with SBRT or accelerated hypo-fractionated radiotherapy were screened for curative intent treatment of isolated mediastinal failures (IMFs). Local control, regional control, progression-free survival, and distant control were estimated from the date of salvage treatment using the Kaplan–Meier method. Results Among 160 patients treated from 2002 to 2012, 12 suffered IMF and were amenable to salvage treatment. The median interval between treatments was 16 months (2–57 mo). Median salvage dose was 66 Gy (60–70 Gy). With a median follow-up of 10 months, the median overall survival was 15 months (95% confidence interval, 5.8–37 mo). When estimated from original treatment, the median overall survival was 38 months (95% confidence interval, 17–71 mo). No subsequent regional failures occurred. Distant failure was the predominant mode of relapse following salvage for IMF with a 2-year distant control rate of 38%. At the time of this analysis, three patients have died without recurrence while four are alive and no evidence of disease. High-grade toxicity was uncommon. Conclusions To our knowledge, this is first analysis of salvage mediastinal radiation after SBRT or accelerated hypofractionated radiotherapy in lung cancer. Outcomes appear similar to stage III disease at presentation. Distant failures were common, suggesting a role for concurrent or sequential chemotherapy. A standard full course of external beam radiotherapy is advisable in this unique clinical scenario. PMID:24736084

Going that extra mile: individuals travel further to maintain face-to-face contact with highly related kin than with less related kin.

PubMed

Pollet, Thomas V; Roberts, Sam G B; Dunbar, Robin I M

2013-01-01

The theory of inclusive fitness has transformed our understanding of cooperation and altruism. However, the proximate psychological underpinnings of altruism are less well understood, and it has been argued that emotional closeness mediates the relationship between genetic relatedness and altruism. In this study, we use a real-life costly behaviour (travel time) to dissociate the effects of genetic relatedness from emotional closeness. Participants travelled further to see more closely related kin, as compared to more distantly related kin. For distantly related kin, the level of emotional closeness mediated this relationship--when emotional closeness was controlled for, there was no effect of genetic relatedness on travel time. However, participants were willing to travel further to visit parents, children and siblings as compared to more distantly related kin, even when emotional closeness was controlled for. This suggests that the mediating effect of emotional closeness on altruism varies with levels of genetic relatedness.

Communication and technology in genetic counseling for familial cancer.

PubMed

Lynch, H T; Snyder, C; Stacey, M; Olson, B; Peterson, S K; Buxbaum, S; Shaw, T; Lynch, P M

2014-03-01

When a cancer predisposing germline mutation is detected in an index case, the presence of the underlying syndrome is confirmed and the potential for predictive testing of at-risk relatives is established. However, the reporting of a positive family history does not routinely lead to communication of information about risk to close, much less distant relatives. This review summarizes information technology utilized to address penetration or 'reach' of knowledge of risk within extended families, including the use of telephone and video counseling to reach distant patients, and anticipate novel internet-based processes for communication between investigators and relatives. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Gravity Probe B Experiment

NASA Technical Reports Server (NTRS)

Kolodziejczak, Jeffrey

2008-01-01

This presentation briefly describes the Gravity Probe B (GP-B) Experiment which is designed to measure parts of Einstein's general theory of relativity by monitoring gyroscope orientation relative to a distant guide star. To measure the miniscule angles predicted by Einstein's theory, it was necessary to build near-perfect gyroscopes that were approximately 50 million times more precise than the best navigational gyroscopes. A telescope mounted along the central axis of the dewar and spacecraft provided the experiment's pointing reference to a guide star. The telescope's image divide precisely split the star's beam into x-axis and y-axis components whose brightness could be compared. GP-B's 650-gallon dewar, kept the science instrument inside the probe at a cryogenic temperature for 17.3 months and also provided the thruster propellant for precision attitude and translation control. Built around the dewar, the GP-B spacecraft was a total-integrated system, comprising both the space vehicle and payload, dedicated as a single entity to experimentally testing predictions of Einstein's theory.

Construal level as a moderator of the role of affective and cognitive attitudes in the prediction of health-risk behavioural intentions.

PubMed

Carrera, Pilar; Caballero, Amparo; Muñoz, Dolores; González-Iraizoz, Marta; Fernández, Itziar

2014-12-01

In two preliminary control checks it was shown that affective attitudes presented greater abstraction than cognitive attitudes. Three further studies explored how construal level moderated the role of affective and cognitive attitudes in predicting one health-promoting behaviour (exercising) and two risk behaviours (sleep debt and binge drinking). There was a stronger influence of affective attitudes both when participants were in abstract (vs. concrete) mindsets induced by a priming task in Studies 1a and 1b, and when behavioural intentions were formed for the distant (vs. near) future in Study 2. In the case of concrete mindsets, the results were inconclusive; the interaction between construal level and cognitive attitudes was only marginally significant in Study 1b. The present research supports the assertion that in abstract mindsets (vs. concrete mindsets) people use more affective attitudes to construe their behavioural intentions. Practical implications for health promotion are discussed in the framework of construal-level theory. © 2014 The British Psychological Society.

Assessment of the Role of Different Imaging Modalities with Emphasis on Fdg Pet/Ct in the Management of Well Differentiated Thyroid Cancer (WDTC).

PubMed

Kendi A, Tuba Karagulle; Mudalegundi, Shwetha; Switchenko, Jeffrey; Lee, Daniel; Halkar, Raghuveer; Chen, Amy Y

2016-01-01

Positron emission tomography/computed tomography is suggested to have a role in detection of iodine negative recurrence in well differentiated thyroid cancer. The aim of this study is to identify role of different imaging modalities in the management of well differentiated thyroid cancer. We reviewed 900 well differentiated thyroid cancer patients after post-thyroidectomy who underwent recombinant human thyroid stimulating hormone stimulated Sodium Iodide I 131 imaging. Out of 900 patients, 74 had positron emission tomography/computed tomography. Multivariate analysis was performed by controlling positron emission tomography/computed tomography, Sodium Iodide I 131 scan, neck ultrasonography, age, sex, primary tumor size, stage, histology, thyroglobulin. Patients were grouped according to results of Sodium Iodide I 131 scan and positron emission tomography/computed tomography. Positron emission tomography/computed tomography was positive in 23 of 74 patients. The sensitivity for positron emission tomography was 11/11(100%), the specificity was 51/63 (81.0%), the positive predictive value was 11/23 (47.8%), and the negative predictive value was 51/51 (100%). The sensitivity for the neck ultrasonography was 4/8 (50%), the specificity was 53/60 (88.3%), positive predictive value was 4/11 (36.4%), and negative predictive value was 53/57 (93.0%). 50% of patients who had Sodium Iodide I 131 negative scan and positive positron emission tomography/computed tomography had a change in management. Thirty-six percent with positive neck ultrasonography had a change in management. Out of 11 recurrences, 6 had distant metastatic disease, and 5/11 had regional nodal disease. Neck ultrasonography showed nodal metastasis in 4/5 (80%). Positron emission tomography/computed tomography altered management in the presence of a high thyroglobulin level and a negative Sodium Iodide I 131 scan. Neck ultrasonography should be the first line of imaging with rising thyroglobulin levels. Positron emission tomography/computed tomography should be considered for cases with high thyroglobulin levels and normal neck ultrasonography to look for distant metastatic disease.

Comparative analyses of quaternary arrangements in homo-oligomeric proteins in superfamilies: Functional implications.

PubMed

Sudha, Govindarajan; Srinivasan, Narayanaswamy

2016-09-01

A comprehensive analysis of the quaternary features of distantly related homo-oligomeric proteins is the focus of the current study. This study has been performed at the levels of quaternary state, symmetry, and quaternary structure. Quaternary state and quaternary structure refers to the number of subunits and spatial arrangements of subunits, respectively. Using a large dataset of available 3D structures of biologically relevant assemblies, we show that only 53% of the distantly related homo-oligomeric proteins have the same quaternary state. Considering these homologous homo-oligomers with the same quaternary state, conservation of quaternary structures is observed only in 38% of the pairs. In 36% of the pairs of distantly related homo-oligomers with different quaternary states the larger assembly in a pair shows high structural similarity with the entire quaternary structure of the related protein with lower quaternary state and it is referred as "Russian doll effect." The differences in quaternary state and structure have been suggested to contribute to the functional diversity. Detailed investigations show that even though the gross functions of many distantly related homo-oligomers are the same, finer level differences in molecular functions are manifested by differences in quaternary states and structures. Comparison of structures of biological assemblies in distantly and closely related homo-oligomeric proteins throughout the study differentiates the effects of sequence divergence on the quaternary structures and function. Knowledge inferred from this study can provide insights for improved protein structure classification and function prediction of homo-oligomers. Proteins 2016; 84:1190-1202. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of Distant Reiki On Pain, Anxiety and Fatigue in Oncology Patients in Turkey: A Pilot Study.

PubMed

Demir, Melike; Can, Gulbeyaz; Kelam, Ayhan; Aydıner, Aydın

2015-01-01

Fatigue, stress and pain are common symptoms among cancer patients, affecting the quality of life. The purpose of the present study was to determine the effect of distant Reiki on pain, anxiety and fatigue in oncology patients. Participants in the control group received usual medical and nursing care during their stay. The intervention group received usual care plus five distant Reiki sessions, one each night for 30 min. A face to face interview was performed and patient personal and illness related characteristics were evaluated using the Patient Characteristics form. Pain, stress and fatigue were evaluated according to a numeric rating scale. The experimental group was predominantly composed of women (71.4%), married individuals (40%), and primary school graduates (40%). The control group was predominantly male (72.7%), married (60%), and primary school graduates (60%). The control group demonstrated greater levels of pain (p=0.002), stress (p=0.001) and fatigue (p=0.001). The Reiki group pain score (p<0.0001), stress score (p<0.001) and fatigue score were also significantly lower. The results of this study indicate that Reiki may decreasepain, anxiety and fatigue in oncology patients.

[The Role of Supraclavicular lymph node dissection in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis].

PubMed

Zhang, W; Qi, X M; Chen, A X; Zhang, P; Cao, X C; Xiao, C H

2017-05-23

Objective: In this study, we evaluated the effect of supraclavicular lymph node dissection in breast cancer patients who presented with ipsilateral supraclavicular lymph node metastasis (ISLM) without distant metastasis. Methods: A total of 90 patients with synchronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Patients were retrospectively divided into two groups, namely supraclavicular lymph node dissection group(34 patients) and non-dissection group(56 patients), according to whether they underwentsupraclavicular lymph node dissection or not.The Kaplan-Meier method was applied to analyze the locoregional relapse free survival (LRFS) and overall survival(OS). Results: Median follow-upwas 85 months(range, 6 to 11 months). Local recurrence in 32 cases, 47 cases of distant metastasis, of which 25 patients were accompanied by both locoregional relapse and distant metastasis. Of the 32 patients with locoregional relapse, 11 patients were in the lymph node dissection group and 21 patients in the control group. Of the 47 patients with distant metastases, 17 were treated with lymph node dissection, 30 in the control group. Thirty-two patients died in the whole group and 16 patients underwentlymph node dissection and 16 patients didn't. There was no significant difference between the rate of 5-year LRFS and 5-year OS ( P =0.359, P =0.246). For patients of ER negative, the 5-year loco-regional relapse free survival rates were 63.7% and 43.3% in supraclavicular lymph node dissection group and control group, respectively. The 5-year overall survival rates were 52.1% and 52.3%, respectively, and there were no statistically significant differences ( P =0.118, P =0.951). For patients of PR negative, the 5-yearloco-regional relapse free rates were 59.8% and 46.2%, respectively, and the 5-year overall survival rates were 50.6% and 43.2%, respectively, and there was no significant difference between the two groups ( P =0.317, P =0.973). The 5-year recurrence-free survival rates of human epidermal growth factor receptor 2 (HER2)-positive patients were 61.2% and 48.0%( P =0.634), respectively, and the 5-year overall survival rates were 37.2% and 65.4%( P =0.032). Forty-seven patients suffered distant metastases and the 5-year metastases free survival rates were 37.3% and 38.5% in supraclavicular lymph node dissection group and control group, respectively. Conclusion: Supraclavicular lymph node dissection maybe an effective approach to improve the loco-regional control for the patients with ISLM, especially for ER negative and PR negative subtypes, but it might has adverseeffects for the patients with negative HER2 status.

The two sides of adversity: the effect of distant versus recent adversity on updating emotional content in working memory.

PubMed

Levens, Sara M; Armstrong, Laura Marie; Orejuela-Dávila, Ana I; Alverio, Tabitha

2017-09-01

Previous research suggests that adversity can have both adaptive and maladaptive effects, yet the emotional and working memory processes that contribute to more or less adaptive outcomes are unclear. The present study sought to investigate how updating emotional content differs in adolescents who have experienced past, recent, or no adversity. Participants who had experienced distant adversity (N = 53), no adversity (N = 58), or recent adversity only (N = 20) performed an emotion n-back task with emotional facial expressions. Results revealed that the distant adversity group exhibited significantly faster reaction times (RTs) than the no adversity and recent adversity only groups. In contrast, the recent adversity only group exhibited significantly slower RTs and more errors than the distant adversity and no adversity groups. These results suggest an emotion and executive control pathway by which both the benefits and negative effects of adversity may be conferred. Results also highlight the importance of time in assessing the impact of adversity.

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case-control study.

PubMed

Song, Sung Eun; Shin, Sung Ui; Moon, Hyeong-Gon; Ryu, Han Suk; Kim, Kwangsoo; Moon, Woo Kyung

2017-04-01

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer. Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical-pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical-pathologic features was assessed using Cox proportional hazard models. Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages. Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

You'll change more than I will: Adults' predictions about their own and others' future preferences.

PubMed

Renoult, Louis; Kopp, Leia; Davidson, Patrick S R; Taler, Vanessa; Atance, Cristina M

2016-01-01

It has been argued that adults underestimate the extent to which their preferences will change over time. We sought to determine whether such mispredictions are the result of a difficulty imagining that one's own current and future preferences may differ or whether it also characterizes our predictions about the future preferences of others. We used a perspective-taking task in which we asked young people how much they liked stereotypically young-person items (e.g., Top 40 music, adventure vacations) and stereotypically old-person items (e.g., jazz, playing bridge) now, and how much they would like them in the distant future (i.e., when they are 70 years old). Participants also made these same predictions for a generic same-age, same-sex peer. In a third condition, participants predicted how much a generic older (i.e., age 70) same-sex adult would like items from both categories today. Participants predicted less change between their own current and future preferences than between the current and future preferences of a peer. However, participants estimated that, compared to a current older adult today, their peer would like stereotypically young items more in the future and stereotypically old items less. The fact that peers' distant-future estimated preferences were different from the ones they made for "current" older adults suggests that even though underestimation of change of preferences over time is attenuated when thinking about others, a bias still exists.

Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

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

Breeuwsma, Anthonius J., E-mail: a.j.breeuwsma@uro.umcg.n; Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen; Pruim, Jan

2010-05-01

Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society formore » Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.« less

18F-FDG PET/CT as a staging procedure in primary stage II and III breast cancer: comparison with conventional imaging techniques.

PubMed

Koolen, Bas B; Vrancken Peeters, Marie-Jeanne T F D; Aukema, Tjeerd S; Vogel, Wouter V; Oldenburg, Hester S A; van der Hage, Jos A; Hoefnagel, Cornelis A; Stokkel, Marcel P M; Loo, Claudette E; Rodenhuis, Sjoerd; Rutgers, Emiel J Th; Valdés Olmos, Renato A

2012-01-01

The aim of the present study was to investigate if 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) outperforms conventional imaging techniques for excluding distant metastases prior to neoadjuvant chemotherapy (NAC) treatment in patients with stage II and III breast cancer. Second, we assessed the clinical importance of false positive findings. One hundred and fifty four patients with stage II or III breast cancer, scheduled to receive NAC, underwent an 18F-FDG PET/CT scan and conventional imaging, consisting of bone scintigraphy, ultrasound of the liver, and chest radiography. Suspect additional lesions at staging examination were confirmed by biopsy and histopathology and/or additional imaging. Metastases that were detected within 6 months after the PET/CT scan were considered evidence of occult metastasis, missed by staging examination. Forty-two additional distant lesions were seen in 25 patients with PET/CT and could be confirmed in 20 (13%) of 154 patients. PET/CT was false positive for 8 additional lesions (19%) and misclassified the presence of metastatic disease in 5 (3%) of 154 patients. In 16 (80%) of 20 patients, additional lesions were exclusively seen with PET/CT, leading to a change in treatment in 13 (8%) of 154 patients. In 129 patients with a negative staging PET/CT, no metastases developed during the follow-up of 9.0 months. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in the detection of additional distant lesions in patients with stage II or III breast cancer are 100, 96, 80, 100, and 97%, respectively. FDG PET/CT is superior to conventional imaging techniques in the detection of distant metastases in patients with untreated stage II or III breast cancer and is associated with a low false positive rate. PET/CT may be of additional value in the staging of breast cancer prior to NAC.

A HEL Testbed for High Accuracy Beam Pointing and Control

DTIC Science & Technology

2009-07-01

Control by Dojong Kim, Duane Frist, Jae Jun Kim, Brij Agrawal 01 July 2009 Approved for......distant targets immediately. The issues of the technology on the HEL system include various types of high energy laser devices, beam control systems

Diameter Growth Models for Inventory Applications

Treesearch

Ronald E. McRoberts; Christopher W. Woodall; Veronica C. Lessard; Margaret R. Holdaway

2002-01-01

Distant-independent, individual-tree, diametar growth models were constructed to update information for forest inventory plots measured in previous years. The models are nonlinear in the parameters and were calibrated weighted nonlinear least squares techniques and forest inventory plot data. Analyses of residuals indicated that model predictions compare favorably to...

Spatial Vertical Directionality and Correlation of Low-Frequency Ambient Noise in Deep Ocean Direct-Arrival Zones.

PubMed

Yang, Qiulong; Yang, Kunde; Cao, Ran; Duan, Shunli

2018-01-23

Wind-driven and distant shipping noise sources contribute to the total noise field in the deep ocean direct-arrival zones. Wind-driven and distant shipping noise sources may significantly and simultaneously affect the spatial characteristics of the total noise field to some extent. In this work, a ray approach and parabolic equation solution method were jointly utilized to model the low-frequency ambient noise field in a range-dependent deep ocean environment by considering their calculation accuracy and efficiency in near-field wind-driven and far-field distant shipping noise fields. The reanalysis databases of National Center of Environment Prediction (NCEP) and Volunteer Observation System (VOS) were used to model the ambient noise source intensity and distribution. Spatial vertical directionality and correlation were analyzed in three scenarios that correspond to three wind speed conditions. The noise field was dominated by distant shipping noise sources when the wind speed was less than 3 m/s, and then the spatial vertical directionality and vertical correlation of the total noise field were nearly consistent with those of distant shipping noise field. The total noise field was completely dominated by near field wind generated noise sources when the wind speed was greater than 12 m/s at 150 Hz, and then the spatial vertical correlation coefficient and directionality pattern of the total noise field was approximately consistent with that of the wind-driven noise field. The spatial characteristics of the total noise field for wind speeds between 3 m/s and 12 m/s were the weighted results of wind-driven and distant shipping noise fields. Furthermore, the spatial characteristics of low-frequency ambient noise field were compared with the classical Cron/Sherman deep water noise field coherence function. Simulation results with the described modeling method showed good agreement with the experimental measurement results based on the vertical line array deployed near the bottom in deep ocean direct-arrival zones.

Spatial Vertical Directionality and Correlation of Low-Frequency Ambient Noise in Deep Ocean Direct-Arrival Zones

PubMed Central

Yang, Qiulong; Yang, Kunde; Cao, Ran; Duan, Shunli

2018-01-01

Wind-driven and distant shipping noise sources contribute to the total noise field in the deep ocean direct-arrival zones. Wind-driven and distant shipping noise sources may significantly and simultaneously affect the spatial characteristics of the total noise field to some extent. In this work, a ray approach and parabolic equation solution method were jointly utilized to model the low-frequency ambient noise field in a range-dependent deep ocean environment by considering their calculation accuracy and efficiency in near-field wind-driven and far-field distant shipping noise fields. The reanalysis databases of National Center of Environment Prediction (NCEP) and Volunteer Observation System (VOS) were used to model the ambient noise source intensity and distribution. Spatial vertical directionality and correlation were analyzed in three scenarios that correspond to three wind speed conditions. The noise field was dominated by distant shipping noise sources when the wind speed was less than 3 m/s, and then the spatial vertical directionality and vertical correlation of the total noise field were nearly consistent with those of distant shipping noise field. The total noise field was completely dominated by near field wind generated noise sources when the wind speed was greater than 12 m/s at 150 Hz, and then the spatial vertical correlation coefficient and directionality pattern of the total noise field was approximately consistent with that of the wind-driven noise field. The spatial characteristics of the total noise field for wind speeds between 3 m/s and 12 m/s were the weighted results of wind-driven and distant shipping noise fields. Furthermore, the spatial characteristics of low-frequency ambient noise field were compared with the classical Cron/Sherman deep water noise field coherence function. Simulation results with the described modeling method showed good agreement with the experimental measurement results based on the vertical line array deployed near the bottom in deep ocean direct-arrival zones. PMID:29360793

Muscle Dysmorphia and the Perception of Men's Peer Muscularity Preferences.

PubMed

Lin, Linda; DeCusati, Frank

2016-11-01

Research suggests that peer muscularity norms preferences are related to men's body image, but little information is known about how perceptions of specific peer group norms preferences are related to men's body image disturbances and specific health behaviors. This study investigated how men perceived the muscularity preferences of male, female, close, and distant peers and whether the perceptions of specific peer preferences were related to muscle dysmorphia and steroid use. Data on muscle dysmorphia and the perceptions of peer muscularity norms were collected from 117 male college students. Results indicated that men perceived distant and male peers as having the most exaggerated preferences for muscularity and that those perceptions were not an accurate reflection of their distant male peers' reported preferences. Results also indicated that perceptions of close female peer muscularity preferences were predictive of symptoms of muscle dysmorphia, but this relationship did not exist for other peer groups, suggesting that the perceptions of close female peer preferences may play a role in the development of muscle dysmorphia. No relationship was found between perceptions of peer muscularity preferences and steroid use. © The Author(s) 2015.

Nuclear magnetic resonance signal dynamics of liquids in the presence of distant dipolar fields, revisited

PubMed Central

Barros, Wilson; Gochberg, Daniel F.; Gore, John C.

2009-01-01

The description of the nuclear magnetic resonance magnetization dynamics in the presence of long-range dipolar interactions, which is based upon approximate solutions of Bloch–Torrey equations including the effect of a distant dipolar field, has been revisited. New experiments show that approximate analytic solutions have a broader regime of validity as well as dependencies on pulse-sequence parameters that seem to have been overlooked. In order to explain these experimental results, we developed a new method consisting of calculating the magnetization via an iterative formalism where both diffusion and distant dipolar field contributions are treated as integral operators incorporated into the Bloch–Torrey equations. The solution can be organized as a perturbative series, whereby access to higher order terms allows one to set better boundaries on validity regimes for analytic first-order approximations. Finally, the method legitimizes the use of simple analytic first-order approximations under less demanding experimental conditions, it predicts new pulse-sequence parameter dependencies for the range of validity, and clarifies weak points in previous calculations. PMID:19425789

Solar wind-magnetosphere coupling and the distant magnetotail: ISEE-3 observations

NASA Technical Reports Server (NTRS)

Slavin, J. A.; Smith, E. J.; Sibeck, D. G.; Baker, D. N.; Zwickl, R. D.; Akasofu, S. I.; Lepping, R. P.

1985-01-01

ISEE-3 Geotail observations are used to investigate the relationship between the interplanetary magnetic field, substorm activity, and the distant magnetotail. Magnetic field and plasma observations are used to present evidence for the existence of a quasi-permanent, curved reconnection neutral line in the distant tail. The distance to the neutral line varies from absolute value of X = 120 to 140 R/sub e near the center of the tail to beyond absolute value of X = 200 R/sub e at the flanks. Downstream of the neutral line the plasma sheet magnetic field is shown to be negative and directly proportional to negative B/sub z in the solar wind as observed by IMP-8. V/sub x in the distant plasma sheet is also found to be proportional to IMF B/sub z with southward IMF producing the highest anti-solar flow velocities. A global dayside reconnection efficiency of 20 +- 5% is derived from the ISEE-3/IMP-8 magnetic field comparisons. Substorm activity, as measured by the AL index, produces enhanced negative B/sub z and tailward V/sub x in the distant plasma sheet in agreement with the basic predictions of the reconnection-based models of substorms. The rate of magnetic flux transfer out of the tail as a function of AL is found to be consistent with previous near-Earth studies. Similarly, the mass and energy fluxes carried by plasma sheet flow down the tail are consistent with theoretical mass and energy budgets for an open magnetosphere. In summary, the ISEE-3 Geotail observations appear to provide good support for reconnection models of solar wind-magnetosphere coupling and substorm energy rates.

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.

PubMed

Pan, Hongchao; Gray, Richard; Braybrooke, Jeremy; Davies, Christina; Taylor, Carolyn; McGale, Paul; Peto, Richard; Pritchard, Kathleen I; Bergh, Jonas; Dowsett, Mitch; Hayes, Daniel F

2017-11-09

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan-Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients' outcomes during the period from 5 to 20 years. Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1-3), and 34% with four to nine nodes involved (T1N4-9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1-3, and 41% with T2N4-9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.).

Review of the leafhopper genus Penthimia Germar (Hemiptera: Cicadellidae: Deltocephalinae) from the Indian subcontinent with description of seven new species.

PubMed

Shobharani, M; Viraktamath, C A; Webb, M D

2018-01-02

Species of the leafhopper genus Penthimia Germar known from the Indian subcontinent are reviewed based on the examination of type specimens. Seven new species of the genus, Penthimia curvata sp. nov. (Karnataka: Bandipur), P. meghalayensis sp. nov. (Meghalaya: Nangpoh), P. neoattenuata sp. nov. (India: Tamil Nadu), P. ribhoi sp. nov. (India: Meghalaya), P. sahyadrica sp. nov. (Karnataka: Dharmasthala, Agumbe; Kerala: Thekkady), P. spiculata sp. nov. (Karnataka: Nagarahole) and P. tumida sp. nov. (Tamil Nadu: Ootacamund; Kerala: Munnar) are described. The following nomenclatorial changes are proposed: Penthimia alba Zahniser, McKamey Dmitriev, 2012 (replacement name for P. thoracica Distant, 1918, nec Panzer, 1799), syn. nov. of P. quadrinotata Distant, 1918; Neodartus scutellatus Distant, 1908 syn. nov. of Penthimia ereba Distant 1908; P. nilgiriensis Distant, 1918 syn. nov. of P. montana Distant, 1918; P. scutellata (Distant) comb. nov. (from genus Neodartus); a lectotype is designated for P. maculosa Distant, stat. revived, thereby removing its synonymy with P. scapularis Distant. The following other lectotypes are designated: P. attenuata Distant, P. subniger Distant, P. scapularis Distant, P. distanti Baker, P. ereba Distant, N. scutellatus Distant, P. fraterna Distant, P. funebris Distant, P. juno Distant, P. maculosa Distant, P. montana Distant, P. noctua Distant, P. quadrinotata Distant, P. alba Zahniser, McKamey Dmitriev. Examination of types of Penthimia rufopunctata Motschulsky revealed that it belongs to Penthimia and hence it is transferred back to that genus from Neodartus, revised placement. The following species previously included in the genus Penthimia are transferred to the genera Tambila Distant and Vulturnus Kirkaldy: Tambila badia (Distant) comb. nov., T. majuscula (Distant) comb. nov., T. vittatifrons (Distant) comb. nov., T. variabilis (Distant) comb. nov. and Vulturnus flavocapitata (Distant) comb. nov. Three species are treated in a new Penthimia compacta Walker complex, i.e., Penthimia compacta Walker 1851, Penthimia subniger Distant 1908 and Penthimia scapularis Distant 1908. All taxa are described and a key to Penthimiini genera found in the subcontinent and also a key to species of Penthimia are included.

Radiofrequency ablation of liver tumors in combination with local OK-432 injection prolongs survival and suppresses distant tumor growth in the rabbit model with intra- and extrahepatic VX2 tumors.

PubMed

Kageyama, Ken; Yamamoto, Akira; Okuma, Tomohisa; Hamamoto, Shinichi; Takeshita, Toru; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio

2013-10-01

To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

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

Kageyama, Ken, E-mail: kageyamaken0112@gmail.com; Yamamoto, Akira, E-mail: loveakirayamamoto@gmail.com; Okuma, Tomohisa, E-mail: o-kuma@msic.med.osaka-cu.ac.jp

Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at amore » single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.« less

Event construal and temporal distance in natural language.

PubMed

Bhatia, Sudeep; Walasek, Lukasz

2016-07-01

Construal level theory proposes that events that are temporally proximate are represented more concretely than events that are temporally distant. We tested this prediction using two large natural language text corpora. In study 1 we examined posts on Twitter that referenced the future, and found that tweets mentioning temporally proximate dates used more concrete words than those mentioning distant dates. In study 2 we obtained all New York Times articles that referenced U.S. presidential elections between 1987 and 2007. We found that the concreteness of the words in these articles increased with the temporal proximity to their corresponding election. Additionally the reduction in concreteness after the election was much greater than the increase in concreteness leading up to the election, though both changes in concreteness were well described by an exponential function. We replicated this finding with New York Times articles referencing US public holidays. Overall, our results provide strong support for the predictions of construal level theory, and additionally illustrate how large natural language datasets can be used to inform psychological theory. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Predictors and Patterns of Local, Regional, and Distant Failure in Squamous Cell Carcinoma of the Vulva.

PubMed

Bogani, Giorgio; Cromi, Antonella; Serati, Maurizio; Uccella, Stefano; Donato, Violante Di; Casarin, Jvan; Naro, Edoardo Di; Ghezzi, Fabio

2017-06-01

To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

Controlled comparison of species- and community-level models across novel climates and communities

PubMed Central

Maguire, Kaitlin C.; Blois, Jessica L.; Fitzpatrick, Matthew C.; Williams, John W.; Ferrier, Simon; Lorenz, David J.

2016-01-01

Species distribution models (SDMs) assume species exist in isolation and do not influence one another's distributions, thus potentially limiting their ability to predict biodiversity patterns. Community-level models (CLMs) capitalize on species co-occurrences to fit shared environmental responses of species and communities, and therefore may result in more robust and transferable models. Here, we conduct a controlled comparison of five paired SDMs and CLMs across changing climates, using palaeoclimatic simulations and fossil-pollen records of eastern North America for the past 21 000 years. Both SDMs and CLMs performed poorly when projected to time periods that are temporally distant and climatically dissimilar from those in which they were fit; however, CLMs generally outperformed SDMs in these instances, especially when models were fit with sparse calibration datasets. Additionally, CLMs did not over-fit training data, unlike SDMs. The expected emergence of novel climates presents a major forecasting challenge for all models, but CLMs may better rise to this challenge by borrowing information from co-occurring taxa. PMID:26962143

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

PubMed Central

Fan, Huijie; Yuan, Yuan; Wang, Junsheng; Zhou, Fuyou; Zhang, Mingzhi; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

2013-01-01

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. PMID:23570416

From early family systems to internalizing symptoms: The role of emotion regulation and peer relations.

PubMed

Lindblom, Jallu; Vänskä, Mervi; Flykt, Marjo; Tolvanen, Asko; Tiitinen, Aila; Tulppala, Maija; Punamäki, Raija-Leena

2017-04-01

Research has demonstrated the importance of early family characteristics, such as the quality of caregiving, on children's later mental health. Information is, however, needed about the role of more holistic family systems and specific child-related socioemotional mechanisms. In this study, we conceptualize families as dynamic family system types, consisting of both marital and parenting trajectories over the transition to parenthood. First, we examine how early family system types predict children's anxiety, depression, peer exclusion, and emotion regulation. Second, we test whether couples' infertility history and other family related contextual factors moderate the effects of family system types on child outcomes. Third, we test whether children's emotion regulation and peer exclusion mediate the effects of family system types on anxiety and depression. The participants were 452 families representing cohesive, distant, authoritative, enmeshed, and discrepant family types, identified on the basis of relationship autonomy and intimacy from pregnancy to the child's age of 2 and 12 months. Children's anxiety, depression, emotion regulation, and peer exclusion were assessed at the age of 7-8 years. Structural equation modeling showed that distant, enmeshed, and discrepant families similarly predicted children's heightened anxiety and depression. Infertility history, parental education, and parity moderated the associations between certain family system types and child outcomes. Finally, emotion regulation, but not peer exclusion, was a common mediating mechanism between distant and enmeshed families and children's depression. The results emphasize the importance of early family environments on children's emotion regulation development and internalizing psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

How adolescents construct their future: the effect of loneliness on future orientation.

PubMed

Seginer, Rachel; Lilach, Efrat

2004-12-01

This study examined the effect of loneliness, gender, and two dimensions of prospective life domains on adolescent future orientation. Future orientation was studied in four prospective domains: social relations, marriage and family, higher education and work and career. These domains are described in terms of two dimensions: theme (relational vs. instrumental) and distance (near vs. distant future). Data collected from Israeli Jewish adolescents (11th graders) were analysed by repeated measures ANOVAs and ANCOVAs (covariate: depressive experiences) for seven future orientation variables: value, expectance, control (motivational variables), hopes, fears (cognitive representation variables), exploration, commitment (behavioural variables). As predicted, lonely adolescents scored lower than socially embedded adolescents on future orientation variables applied to the relational and near future domains and lonely boys scored lower than lonely girls. However, effects were found only on the three future orientation motivational variables and not on the cognitive representation and behavioural variables. Contrary to prediction controlling for the effect of depressive experiences did not reduce the effect of loneliness on the future orientation variables, but reduced the tendency of adolescents to score higher on all future orientation variables in the instrumental than in the relational prospective domains. The contribution of these findings to the understanding of adolescent loneliness and future orientation was discussed and directions for future research were suggested.

Multiple distant origins for green sea turtles aggregating off Gorgona Island in the Colombian eastern Pacific.

PubMed

Amorocho, Diego F; Abreu-Grobois, F Alberto; Dutton, Peter H; Reina, Richard D

2012-01-01

Mitochondrial DNA analyses have been useful for resolving maternal lineages and migratory behavior to foraging grounds (FG) in sea turtles. However, little is known about source rookeries and haplotype composition of foraging green turtle aggregations in the southeastern Pacific. We used mitochondrial DNA control region sequences to identify the haplotype composition of 55 green turtles, Chelonia mydas, captured in foraging grounds of Gorgona National Park in the Colombian Pacific. Amplified fragments of the control region (457 bp) revealed the presence of seven haplotypes, with haplotype (h) and nucleotide (π) diversities of h = 0.300±0.080 and π = 0.009±0.005 respectively. The most common haplotype was CMP4 observed in 83% of individuals, followed by CMP22 (5%). The genetic composition of the Gorgona foraging population primarily comprised haplotypes that have been found at eastern Pacific rookeries including Mexico and the Galapagos, as well as haplotypes of unknown stock origin that likely originated from more distant western Pacific rookeries. Mixed stock analysis suggests that the Gorgona FG population is comprised mostly of animals from the Galapagos rookery (80%). Lagrangian drifter data showed that movement of turtles along the eastern Pacific coast and eastward from distant western and central Pacific sites was possible through passive drift. Our results highlight the importance of this protected area for conservation management of green turtles recruited from distant sites along the eastern Pacific Ocean.

Multiple Distant Origins for Green Sea Turtles Aggregating off Gorgona Island in the Colombian Eastern Pacific

PubMed Central

Amorocho, Diego F.; Abreu-Grobois, F. Alberto; Dutton, Peter H.; Reina, Richard D.

2012-01-01

Mitochondrial DNA analyses have been useful for resolving maternal lineages and migratory behavior to foraging grounds (FG) in sea turtles. However, little is known about source rookeries and haplotype composition of foraging green turtle aggregations in the southeastern Pacific. We used mitochondrial DNA control region sequences to identify the haplotype composition of 55 green turtles, Chelonia mydas, captured in foraging grounds of Gorgona National Park in the Colombian Pacific. Amplified fragments of the control region (457 bp) revealed the presence of seven haplotypes, with haplotype (h) and nucleotide (π) diversities of h = 0.300±0.080 and π = 0.009±0.005 respectively. The most common haplotype was CMP4 observed in 83% of individuals, followed by CMP22 (5%). The genetic composition of the Gorgona foraging population primarily comprised haplotypes that have been found at eastern Pacific rookeries including Mexico and the Galapagos, as well as haplotypes of unknown stock origin that likely originated from more distant western Pacific rookeries. Mixed stock analysis suggests that the Gorgona FG population is comprised mostly of animals from the Galapagos rookery (80%). Lagrangian drifter data showed that movement of turtles along the eastern Pacific coast and eastward from distant western and central Pacific sites was possible through passive drift. Our results highlight the importance of this protected area for conservation management of green turtles recruited from distant sites along the eastern Pacific Ocean. PMID:22319635

Efficient multi-scenario Model Predictive Control for water resources management with ensemble streamflow forecasts

NASA Astrophysics Data System (ADS)

Tian, Xin; Negenborn, Rudy R.; van Overloop, Peter-Jules; María Maestre, José; Sadowska, Anna; van de Giesen, Nick

2017-11-01

Model Predictive Control (MPC) is one of the most advanced real-time control techniques that has been widely applied to Water Resources Management (WRM). MPC can manage the water system in a holistic manner and has a flexible structure to incorporate specific elements, such as setpoints and constraints. Therefore, MPC has shown its versatile performance in many branches of WRM. Nonetheless, with the in-depth understanding of stochastic hydrology in recent studies, MPC also faces the challenge of how to cope with hydrological uncertainty in its decision-making process. A possible way to embed the uncertainty is to generate an Ensemble Forecast (EF) of hydrological variables, rather than a deterministic one. The combination of MPC and EF results in a more comprehensive approach: Multi-scenario MPC (MS-MPC). In this study, we will first assess the model performance of MS-MPC, considering an ensemble streamflow forecast. Noticeably, the computational inefficiency may be a critical obstacle that hinders applicability of MS-MPC. In fact, with more scenarios taken into account, the computational burden of solving an optimization problem in MS-MPC accordingly increases. To deal with this challenge, we propose the Adaptive Control Resolution (ACR) approach as a computationally efficient scheme to practically reduce the number of control variables in MS-MPC. In brief, the ACR approach uses a mixed-resolution control time step from the near future to the distant future. The ACR-MPC approach is tested on a real-world case study: an integrated flood control and navigation problem in the North Sea Canal of the Netherlands. Such an approach reduces the computation time by 18% and up in our case study. At the same time, the model performance of ACR-MPC remains close to that of conventional MPC.

Modeling Brain Dynamics in Brain Tumor Patients Using the Virtual Brain.

PubMed

Aerts, Hannelore; Schirner, Michael; Jeurissen, Ben; Van Roost, Dirk; Achten, Eric; Ritter, Petra; Marinazzo, Daniele

2018-01-01

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

Depression, anxiety and quality of life in suicide survivors: a comparison of close and distant relationships.

PubMed

Mitchell, Ann M; Sakraida, Teresa J; Kim, Yookyung; Bullian, Leann; Chiappetta, Laurel

2009-02-01

The study's purpose was to describe and compare depression, anxiety, and quality of life, by degree of relationship, between closely related and distantly related survivors (persons close to the suicide victim, or "suicide survivors"; N = 60) during the acute phase of bereavement (within 1 month of the death). The close relationship category included spouses, parents, children, and siblings, whereas the distant relationship category included in-laws, aunts/uncles, and nieces/nephews. Analysis of covariance examined differences between the two groups on the symptom measures. Results indicate that, after controlling for age and gender effects, closely related survivors had significantly higher mean levels of depression and anxiety and had lower levels of mental health quality of life. There were no statistically significant differences on the physical health quality of life subscale.

Mitochondrial markers predict recurrence, metastasis and tamoxifen-resistance in breast cancer patients: Early detection of treatment failure with companion diagnostics.

PubMed

Sotgia, Federica; Fiorillo, Marco; Lisanti, Michael P

2017-09-15

Here, we used a data-mining and informatics approach to discover new biomarkers of resistance to hormonal therapy in breast cancer. More specifically, we investigated whether nuclear-encoded genes associated with mitochondrial biogenesis can be used to predict tumor recurrence, distant metastasis and treatment failure in high-risk breast cancer patients. Overall, this strategy allowed us to directly provide in silico validation of the prognostic value of these mitochondrial components in large and clinically relevant patient populations, with >15 years of follow-up data. For this purpose, we employed a group of 145 ER(+) luminal A breast cancer patients, with lymph-node (LN) metastasis at diagnosis, that were treated with tamoxifen, but not any chemotherapy agents. Using this approach, we identified >60 new individual mitochondrial biomarkers that predicted treatment failure and tumor recurrence, with hazard-ratios (HR) of up to 4.17 ( p =2.2e-07). These include mitochondrial chaperones (HSPD1, HSPA9), membrane proteins (VDAC2, TOMM70A) and anti-oxidants (SOD2), as well as 18 different mitochondrial ribosomal proteins (MRPs) and >20 distinct components of the OXPHOS complexes. In addition, we combined 4 mitochondrial proteins (HSPD1, UQCRB, MRPL15, COX17), to generate a compact mitochondrial gene signature, associated with a HR of 5.34 ( p =1e-09). This signature also successfully predicted distant metastasis and was effective in larger groups of ER(+) ( N =2,447), basal ( N =540) and HER2(+) ( N =193) breast cancers. It was also effective in all breast cancers ( N =3,180), if considered together as a single group. Based on this analysis, we conclude that mitochondrial biogenesis should be considered as a new therapeutic target for overcoming tumor recurrence, distant metastasis and treatment failure in patients with breast cancer. In summary, we identified individual mitochondrial biomarkers and 2 compact mitochondrial gene signatures that can be used to predict tamoxifen-resistance and tumor recurrence, at their initial diagnosis, in patients with advanced breast cancer. In the long-term, these mitochondrial biomarkers could provide a new companion diagnostics platform to help clinicians to accurately predict the response to hormonal therapy in ER(+) breast cancer patients, facilitating more personalized and effective treatment. Similarly, these mitochondrial markers could be used as companion diagnostics, to determine which breast cancer patients would benefit most from clinical treatments with mitochondrially-targeted anti-cancer therapeutics. Finally, we also showed that these mitochondrial markers are superior when directly compared with conventional biomarkers, such as Ki67 and PCNA.

Extended (5-year) Outcomes of Accelerated Partial Breast Irradiation Using MammoSite Balloon Brachytherapy: Patterns of Failure, Patient Selection, and Dosimetric Correlates for Late Toxicity

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

Vargo, John A.; Verma, Vivek; Kim, Hayeon

2014-02-01

Purpose: Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial. Methods and Materials: A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate {sup 192}Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicatormore » to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry. Results: At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer–specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001). Conclusions: Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy applicators and a more rigorous skin dose constraint of ≤100%.« less

The Electronic Library: The Student/Scholar Workstation, CD-ROM and Hypertext.

ERIC Educational Resources Information Center

Triebwasser, Marc A.

Predicting that a large component of the library of the not so distant future will be an electronic network of file servers where information is stored for access by personal computer workstations in remote locations as well as the library, this paper discusses innovative computer technologies--particularly CD-ROM (Compact Disk-Read Only Memory)…

US Geological Survey begins seismic ground response experiments in Washington State

USGS Publications Warehouse

Tarr, A.C.; King, K.W.

1988-01-01

This article briefly describes the experimental monitoring of minor seismic features caused by distant nuclear explosions, mining blasts and rhythmic human pushing against wooden homes. Some means of response prediction are outlined in Washington State and some effects of seismic amplification by weak clayey sediments are described. The results of several experiments are described. -A.Scarth

Excellent Local Control Rates and Distinctive Patterns of Failure in Myxoid Liposarcoma Treated With Conservation Surgery and Radiotherapy

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

Guadagnolo, B. Ashleigh; Zagars, Gunar K.; Ballo, Matthew T.

2008-03-01

Purpose: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). Patients and Methods: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. Results: The median follow-up was 9.1 years. The overall survivalmore » rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at {>=}5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. Conclusion: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.« less

A Novel Expression Cassette of Lyssavirus Shows that the Distantly Related Mokola Virus Can Rescue a Defective Rabies Virus Genome

PubMed Central

Le Mercier, Philippe; Jacob, Yves; Tanner, Kyle; Tordo, Noël

2002-01-01

By comparing three expression vectors for the rabies virus (Rv) minigenome, we show that the characteristic of the Rv RNA is important for efficient rescue despite its not being crucial for replication. Moreover, we show that the coexpression of the viral proteins from helper Rv and Mokola virus could rescue the Rv minigenome while Rv-related European bat lyssavirus 1 could not, suggesting that the signals controlling transcription and replication are conserved in the distantly related Rv and Mokola virus. PMID:11799201

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

NASA Technical Reports Server (NTRS)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% Cl =-0.2 to 1.9). Conclusions: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, %Kith reasonable accuracy, risks for radiationinduced leukemia associated with exposure to therapeutic doses of radiation.

Is Einsteinian no-signalling violated in Bell tests?

NASA Astrophysics Data System (ADS)

Kupczynski, Marian

2017-11-01

Relativistic invariance is a physical law verified in several domains of physics. The impossibility of faster than light influences is not questioned by quantum theory. In quantum electrodynamics, in quantum field theory and in the standard model relativistic invariance is incorporated by construction. Quantum mechanics predicts strong long range correlations between outcomes of spin projection measurements performed in distant laboratories. In spite of these strong correlations marginal probability distributions should not depend on what was measured in the other laboratory what is called shortly: non-signalling. In several experiments, performed to test various Bell-type inequalities, some unexplained dependence of empirical marginal probability distributions on distant settings was observed. In this paper we demonstrate how a particular identification and selection procedure of paired distant outcomes is the most probable cause for this apparent violation of no-signalling principle. Thus this unexpected setting dependence does not prove the existence of superluminal influences and Einsteinian no-signalling principle has to be tested differently in dedicated experiments. We propose a detailed protocol telling how such experiments should be designed in order to be conclusive. We also explain how magical quantum correlations may be explained in a locally causal way.

Auditory and behavioral responses of bottlenose dolphins (Tursiops truncatus) and a beluga whale (Delphinapterus leucas) to impulsive sounds resembling distant signatures of underwater explosions.

PubMed

Finneran, J J; Schlundt, C E; Carder, D A; Clark, J A; Young, J A; Gaspin, J B; Ridgway, S H

2000-07-01

A behavioral response paradigm was used to measure masked underwater hearing thresholds in two bottlenose dolphins and one beluga whale before and after exposure to impulsive underwater sounds with waveforms resembling distant signatures of underwater explosions. An array of piezoelectric transducers was used to generate impulsive sounds with waveforms approximating those predicted from 5 or 500 kg HBX-1 charges at ranges from 1.5 to 55.6 km. At the conclusion of the study, no temporary shifts in masked-hearing thresholds (MTTSs), defined as a 6-dB or larger increase in threshold over pre-exposure levels, had been observed at the highest impulse level generated (500 kg at 1.7 km, peak pressure 70 kPa); however, disruptions of the animals' trained behaviors began to occur at exposures corresponding to 5 kg at 9.3 km and 5 kg at 1.5 km for the dolphins and 500 kg at 1.9 km for the beluga whale. These data are the first direct information regarding the effects of distant underwater explosion signatures on the hearing abilities of odontocetes.

Intratumoral Heterogeneity of SMAD4 Immunohistochemical Expression and Its Role in Prediction of Recurrence Pattern in Patients with Resectable Pancreatic Cancer.

PubMed

Pokataev, Ilya; Kudaibergenova, Asel; Artemyeva, Anna; Popova, Anna; Rumyantsev, Alexey; Podluzhny, Danil; Kudashkin, Nikolay; Fedyanin, Mikhail; Tryakin, Alexey; Tjulandin, Sergey

2018-04-20

The aim of our study was to evaluate consistency of SMAD4 expression in different tumor areas and its correlation with recurrence pattern in patients after resection for pancreatic cancer (PC). Records of patients who underwent resection for nonmetastatic PC between 2001 and 2015 were analyzed. Formalin-fixed, paraffin-embedded tissue sections from different areas of primary tumor and lymph node metastases were analyzed immunohistochemically (IHC) for SMAD4 expression using TMA technology. SMAD4 expression was assessed in 356 tissue sections obtained from 91 patients. SMAD4 expression was positive in all assessed tumor slides only in 7 of 26 patients (26.9%). There were 54 recurrences (9 locoregional, 41 distant, and 4 both local and distant) with median follow-up of 21.7 months. There was no correlation between SMAD4 expression and locoregional recurrence pattern (p = 0.30). SMAD4 status influenced neither distant recurrence-free survival (p = 0.99) nor overall survival (p = 0.13). Different areas inside primary tumor and lymph node metastases express SMAD4 heterogeneously. SMAD4 IHC expression is not a biomarker of the recurrence pattern after surgical resection for PC.

Counterfactual distributed controlled-phase gate for quantum-dot spin qubits in double-sided optical microcavities

NASA Astrophysics Data System (ADS)

Guo, Qi; Cheng, Liu-Yong; Chen, Li; Wang, Hong-Fu; Zhang, Shou

2014-10-01

The existing distributed quantum gates required physical particles to be transmitted between two distant nodes in the quantum network. We here demonstrate the possibility to implement distributed quantum computation without transmitting any particles. We propose a scheme for a distributed controlled-phase gate between two distant quantum-dot electron-spin qubits in optical microcavities. The two quantum-dot-microcavity systems are linked by a nested Michelson-type interferometer. A single photon acting as ancillary resource is sent in the interferometer to complete the distributed controlled-phase gate, but it never enters the transmission channel between the two nodes. Moreover, we numerically analyze the effect of experimental imperfections and show that the present scheme can be implemented with high fidelity in the ideal asymptotic limit. The scheme provides further evidence of quantum counterfactuality and opens promising possibilities for distributed quantum computation.

When do I wear me out? Mental simulation and the diminution of self-control.

PubMed

Macrae, C Neil; Christian, Brittany M; Golubickis, Marius; Karanasiou, Magdalene; Troksiarova, Lenka; McNamara, Diana L; Miles, Lynden K

2014-08-01

Exerting self-control can diminish people's capacity to engage in subsequent acts of behavioral regulation, a phenomenon termed ego depletion. But what of imaginary regulatory experiences-does simulated restraint elicit comparable lapses in self-control? Here we demonstrate such effects under theoretically tractable imagery conditions. Across 3 experiments, temporal, structural, and spatial components of mental simulation were observed to drive the efficacy of imaginary self-control. In Experiment 1, lapses in restraint (i.e., financial impulsivity) were more pronounced when imaginary regulation (i.e., dietary restraint) focused on an event in the near versus distant future. In Experiment 2, comparable effects (i.e., increased stereotyping) emerged when simulated self-control (i.e., emotional suppression) was imagined from a first-person (cf. third-person) visual perspective. In Experiment 3, restraint was diminished (i.e., increased risk taking) when self-regulation (i.e., action control) centered on an event at a near versus distant location. These findings further delineate the conditions under which mental simulation impacts core aspects of social-cognitive functioning. PsycINFO Database Record (c) 2014 APA, all rights reserved.

US surveillance of regional lymph node recurrence after breast cancer surgery.

PubMed

Moon, Hee Jung; Kim, Min Jung; Kim, Eun-Kyung; Park, Byeong-Woo; Youk, Ji Hyun; Kwak, Jin Young; Sohn, Joohyuk; Kim, Seung-Il

2009-09-01

To determine the diagnostic indexes of lymph node ultrasonography (US) of the axillary and supraclavicular regions for detecting lymph node recurrence (LNR) after breast cancer surgery and assess the effect of lymph node evaluation on prognosis during bilateral breast US. Institutional review board approved this retrospective study and waived informed consent. Between January 2003 and December 2004, 3982 lymph node US examinations, including bilateral axillary and supraclavicular areas, were performed in 1817 women (mean age, 49.9 years; range, 22-86 years) after breast cancer surgery, nine of whom had palpable lesions. Final diagnosis was based on cytopathologic results, clinical follow-up, and imaging studies for at least 12 months after breast US. Diagnostic indexes of US for detecting LNR were assessed. The frequency of distant metastases between patients with ipsilateral LNR and those without was compared. Three-year mortality rates of patients with ipsilateral LNR only and those with distant metastases were evaluated. Of 1817 patients, 54 had suspicious LNR at US (28 at first, 20 at second, five at third, and one at fourth US examination). Thirty-nine of 1817 patients (2.1%), including nine with palpable lesions, had LNR, 11 of whom had ipsilateral LNR only. At first lymph node US, LNR was detected in 17 patients; at second, in 10; at third, in two; and at fourth, in one. Nine had false-negative results. The respective sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of lymph node US for detecting LNR per woman was 76.9% (30 of 39), 98.7% (1754 of 1778), 98.2% (1784 of 1817), 55.6% (30 of 54), and 99.5% (1754 of 1763); those of first lymph node US were 85.0% (17 of 20), 99.4% (1786 of 1797), 99.2% (1803 of 1817), 60.7% (17 of 28), and 99.8% (1786 of 1789); and those of total US examinations were 78.0% (32 of 41), 99.4% (3917 of 3941), 99.2% (3949 of 3982), 57.1% (32 of 56), and 99.8% (3917 of 3926). Distant metastases were found more frequently in patients with ipsilateral LNR (62%) than in those without (2.3%) (P < .0001). The 3-year mortality rate of patients with ipsilateral LNR only was significantly lower than that in patients with distant metastases (P = .03). Ipsilateral LNR is a predictor of distant metastasis, and lymph node evaluation during breast US is useful for early detection of LNR in asymptomatic patients.

Prediction of stellar occultations by distant solar system bodies in the Gaia era

NASA Astrophysics Data System (ADS)

Desmars, Josselin; Camargo, Julio; Sicardy, Bruno; Braga-Ribas, Felipe; Vieira-Martins, Roberto; Assafin, Marcelo; Bérard, Diane; Benedetti-Rossi, Gustavo

2018-04-01

Stellar occultations are a unique technique to access physical characteristics of distant solar system objects from the ground. They allow the measure of the size and the shape at kilometric level, the detection of tenuous atmospheres (few nanobars), and the investigation of close vicinity (satellites, rings) of Transneptunian objects and Centaurs. This technique is made successful thanks to accurate predictions of occultations. Accuracy of the predictions depends on the uncertainty in the position of the occulted star and the object's orbit. The Gaia stellar catalogue (Gaia Collaboration (2017)) now allows to get accurate astrometric stellar positions (to the mas level). The main uncertainty remains on the orbit. In this context, we now take advantage of the NIMA method (Desmars et al.(2015)) for the orbit determination and of the Gaia DR1 catalogue for the astrometry. In this document, we show how the orbit determination is improved by reducing current and some past observations with Gaia DR1. Moreover, we also use more than 45 past positive occultations observed in the 2009-2017 period to derive very accurate astrometric positions only depending on the position of the occulted stars (about few mas with Gaia DR1). We use the case of (10199) Chariklo as an illustration. The main limitation lies in the imprecision of the proper motions which is going to be solved by the Gaia DR2 release.

49 CFR 218.93 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... button or radio control when such switch is protected by distant switch indicators, switch point... units are connected so that they may be operated from a single control stand. Locomotive means, for... one or more propelling motors designed for moving other equipment; (2) With one or more propelling...

Heralded quantum controlled-phase gates with dissipative dynamics in macroscopically distant resonators

NASA Astrophysics Data System (ADS)

Qin, Wei; Wang, Xin; Miranowicz, Adam; Zhong, Zhirong; Nori, Franco

2017-07-01

Heralded near-deterministic multiqubit controlled-phase gates with integrated error detection have recently been proposed by Borregaard et al. [Phys. Rev. Lett. 114, 110502 (2015), 10.1103/PhysRevLett.114.110502]. This protocol is based on a single four-level atom (a heralding quartit) and N three-level atoms (operational qutrits) coupled to a single-resonator mode acting as a cavity bus. Here we generalize this method for two distant resonators without the cavity bus between the heralding and operational atoms. Specifically, we analyze the two-qubit controlled-Z gate and its multiqubit-controlled generalization (i.e., a Toffoli-like gate) acting on the two-lowest levels of N qutrits inside one resonator, with their successful actions being heralded by an auxiliary microwave-driven quartit inside the other resonator. Moreover, we propose a circuit-quantum-electrodynamics realization of the protocol with flux and phase qudits in linearly coupled transmission-line resonators with dissipation. These methods offer a quadratic fidelity improvement compared to cavity-assisted deterministic gates.

Pain thresholds and tenderness in neck and head following acute whiplash injury: a prospective study.

PubMed

Kasch, H; Stengaard-Pedersen, K; Arendt-Nielsen, L; Staehelin Jensen, T

2001-04-01

OBJECTIVE OF THE INVESTIGATION: In a 6-month prospective study of 141 consecutive acute whiplash-injured participants, and 40 acute, ankle-injured controls, pain and tenderness in the neck/head, and at a distant control site, were measured. Muscle palpation and pressure algometry in five head/neck muscle-pairs were performed after 1 week and 1, 3 and 6 months after injury. Algometry was performed at a distant control site. Whiplash-injured patients had lowered pressure-pain-detection thresholds and higher palpation-score initially in the neck/head, but the groups were similar after 6 months, and the control site was not sensitized. Focal, but not generalized, sensitization to musculoskeletal structure is present until 3 months, but not 6 months, after whiplash injury, and probably does not play a major role in the development of late whiplash syndrome. Pressure algometry and palpation are useful clinical tools in the evaluation of neck and jaw pain in acute whiplash injury.

Robust distant-entanglement generation using coherent multiphoton scattering

NASA Astrophysics Data System (ADS)

Chan, Ching-Kit; Sham, L. J.

2013-03-01

The generation and controllability of entanglement between distant quantum states have been the heart of quantum computation and quantum information processing. Existing schemes for solid state qubit entanglement are based on the single-photon spectroscopy that has the merit of a high fidelity entanglement creation, but with a very limited efficiency. This severely restricts the scalability for a qubit network system. Here, we describe a new distant entanglement protocol using coherent multiphoton scattering. The scheme makes use of the postselection of large and distinguishable photon signals, and has both a high success probability and a high entanglement fidelity. Our result shows that the entanglement generation is robust against photon fluctuations, and has an average entanglement duration within the decoherence time in various qubit systems, based on existing experimental parameters. This research was supported by the U.S. Army Research Office MURI award W911NF0910406 and by NSF grant PHY-1104446.

External validity of two nomograms for predicting distant brain failure after radiosurgery for brain metastases in a bi-institutional independent patient cohort.

PubMed

Prabhu, Roshan S; Press, Robert H; Boselli, Danielle M; Miller, Katherine R; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Burri, Stuart H

2018-03-01

Patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) are at increased risk of distant brain failure (DBF). Two nomograms have been recently published to predict individualized risk of DBF after SRS. The goal of this study was to assess the external validity of these nomograms in an independent patient cohort. The records of consecutive patients with BM treated with SRS at Levine Cancer Institute and Emory University between 2005 and 2013 were reviewed. Three validation cohorts were generated based on the specific nomogram or recursive partitioning analysis (RPA) entry criteria: Wake Forest nomogram (n = 281), Canadian nomogram (n = 282), and Canadian RPA (n = 303) validation cohorts. Freedom from DBF at 1-year in the Wake Forest study was 30% compared with 50% in the validation cohort. The validation c-index for both the 6-month and 9-month freedom from DBF Wake Forest nomograms was 0.55, indicating poor discrimination ability, and the goodness-of-fit test for both nomograms was highly significant (p < 0.001), indicating poor calibration. The 1-year actuarial DBF in the Canadian nomogram study was 43.9% compared with 50.9% in the validation cohort. The validation c-index for the Canadian 1-year DBF nomogram was 0.56, and the goodness-of-fit test was also highly significant (p < 0.001). The validation accuracy and c-index of the Canadian RPA classification was 53% and 0.61, respectively. The Wake Forest and Canadian nomograms for predicting risk of DBF after SRS were found to have limited predictive ability in an independent bi-institutional validation cohort. These results reinforce the importance of validating predictive models in independent patient cohorts.

Nonlinear times series analysis of epileptic human electroencephalogram (EEG)

NASA Astrophysics Data System (ADS)

Li, Dingzhou

The problem of seizure anticipation in patients with epilepsy has attracted significant attention in the past few years. In this paper we discuss two approaches, using methods of nonlinear time series analysis applied to scalp electrode recordings, which is able to distinguish between epochs temporally distant from and just prior to, the onset of a seizure in patients with temporal lobe epilepsy. First we describe a method involving a comparison of recordings taken from electrodes adjacent to and remote from the site of the seizure focus. In particular, we define a nonlinear quantity which we call marginal predictability. This quantity is computed using data from remote and from adjacent electrodes. We find that the difference between the marginal predictabilities computed for the remote and adjacent electrodes decreases several tens of minutes prior to seizure onset, compared to its value interictally. We also show that these difl'crcnc es of marginal predictability intervals are independent of the behavior state of the patient. Next we examine the please coherence between different electrodes both in the long-range and the short-range. When time is distant from seizure onsets ("interictally"), epileptic patients have lower long-range phase coherence in the delta (1-4Hz) and beta (18-30Hz) frequency band compared to nonepileptic subjects. When seizures approach (''preictally"), we observe an increase in phase coherence in the beta band. However, interictally there is no difference in short-range phase coherence between this cohort of patients and non-epileptic subjects. Preictally short-range phase coherence also increases in the alpha (10-13Hz) and the beta band. Next we apply the quantity marginal predictability on the phase difference time series. Such marginal predictabilities are lower in the patients than in the non-epileptic subjects. However, when seizure approaches, the former moves asymptotically towards the latter.

Audiovisual Delay as a Novel Cue to Visual Distance.

PubMed

Jaekl, Philip; Seidlitz, Jakob; Harris, Laurence R; Tadin, Duje

2015-01-01

For audiovisual sensory events, sound arrives with a delay relative to light that increases with event distance. It is unknown, however, whether humans can use these ubiquitous sound delays as an information source for distance computation. Here, we tested the hypothesis that audiovisual delays can both bias and improve human perceptual distance discrimination, such that visual stimuli paired with auditory delays are perceived as more distant and are thereby an ordinal distance cue. In two experiments, participants judged the relative distance of two repetitively displayed three-dimensional dot clusters, both presented with sounds of varying delays. In the first experiment, dot clusters presented with a sound delay were judged to be more distant than dot clusters paired with equivalent sound leads. In the second experiment, we confirmed that the presence of a sound delay was sufficient to cause stimuli to appear as more distant. Additionally, we found that ecologically congruent pairing of more distant events with a sound delay resulted in an increase in the precision of distance judgments. A control experiment determined that the sound delay duration influencing these distance judgments was not detectable, thereby eliminating decision-level influence. In sum, we present evidence that audiovisual delays can be an ordinal cue to visual distance.

Physical and social activities mediate the associations between social network types and ventilatory function in Chinese older adults.

PubMed

Cheng, Sheung-Tak; Leung, Edward M F; Chan, Trista Wai Sze

2014-06-01

This study examined the associations between social network types and peak expiratory flow (PEF), and whether these associations were mediated by social and physical activities and mood. Nine hundred twenty-four community-dwelling Chinese older adults, who were classified into five network types (diverse, friend-focused, family-focused, distant family, and restricted), provided data on demographics, social and physical activities, mood, smoking, chronic diseases, and instrumental activities of daily living. PEF and biological covariates, including blood lipids and glucose, blood pressure, and height and weight, were assessed. Two measures of PEF were analyzed: the raw reading in L/min and the reading expressed as percentage of predicted normal value on the basis of age, sex, and height. Diverse, friend-focused, and distant family networks were hypothesized to have better PEF values compared with restricted networks, through higher physical and/or social activities. No relative advantage was predicted for family-focused networks because such networks tend to be associated with lower physical activity. Older adults with diverse, friend-focused, and distant family networks had significantly better PEF measures than those with restricted networks. The associations between diverse network and PEF measures were partially mediated by physical exercise and socializing activity. The associations between friend-focused network and PEF measures were partially mediated by socializing activity. No significant PEF differences between family-focused and restricted networks were found. Findings suggest that social network types are associated with PEF in older adults, and that network-type differences in physical and socializing activity is partly responsible for this relationship. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Preoperative [18F]fluorodeoxyglucose positron emission tomography standardized uptake value of neck lymph nodes predicts neck cancer control and survival rates in patients with oral cavity squamous cell carcinoma and pathologically positive lymph nodes.

PubMed

Liao, Chun-Ta; Chang, Joseph Tung-Chieh; Wang, Hung-Ming; Ng, Shu-Hang; Hsueh, Chuen; Lee, Li-Yu; Lin, Chih-Hung; Chen, I-How; Huang, Shiang-Fu; Cheng, Ann-Joy; Yen, Tzu-Chen

2009-07-15

Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this prospective study, we sought to investigate whether preoperative maximum standardized uptake value of the neck lymph nodes (SUVnodal-max) may predict prognosis in OSCC patients. A total of 120 OSCC patients with pathologically positive lymph nodes were investigated. All subjects underwent a [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan within 2 weeks before radical surgery and neck dissection. All patients were followed up for at least 24 months after surgery or until death. Postoperative adjuvant therapy was performed in the presence of pathologic risk factors. Optimal cutoff values of SUVnodal-max were chosen based on 5-year disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Independent prognosticators were identified by Cox regression analysis. The median follow-up for surviving patients was 41 months. The optimal cutoff value for SUVnodal-max was 5.7. Multivariate analyses identified the following independent predictors of poor outcome: SUVnodal-max >or=5.7 for the 5-year neck cancer control rate, distant metastatic rate, DFS, DSS, and extracapsular spread (ECS) for the 5-year DSS and OS. Among ECS patients, the presence of a SUVnodal-max >or=5.7 identified patients with the worst prognosis. A SUVnodal-max of 5.7, either alone or in combination with ECS, is an independent prognosticator for 5-year neck cancer control and survival rates in OSCC patients with pathologically positive lymph nodes.

Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

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

Patel, Samir; Portelance, Lorraine; Gilbert, Lucy

2007-08-01

Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less

Effects of number of training generations on genomic prediction for various traits in a layer chicken population.

PubMed

Weng, Ziqing; Wolc, Anna; Shen, Xia; Fernando, Rohan L; Dekkers, Jack C M; Arango, Jesus; Settar, Petek; Fulton, Janet E; O'Sullivan, Neil P; Garrick, Dorian J

2016-03-19

Genomic estimated breeding values (GEBV) based on single nucleotide polymorphism (SNP) genotypes are widely used in animal improvement programs. It is typically assumed that the larger the number of animals is in the training set, the higher is the prediction accuracy of GEBV. The aim of this study was to quantify genomic prediction accuracy depending on the number of ancestral generations included in the training set, and to determine the optimal number of training generations for different traits in an elite layer breeding line. Phenotypic records for 16 traits on 17,793 birds were used. All parents and some selection candidates from nine non-overlapping generations were genotyped for 23,098 segregating SNPs. An animal model with pedigree relationships (PBLUP) and the BayesB genomic prediction model were applied to predict EBV or GEBV at each validation generation (progeny of the most recent training generation) based on varying numbers of immediately preceding ancestral generations. Prediction accuracy of EBV or GEBV was assessed as the correlation between EBV and phenotypes adjusted for fixed effects, divided by the square root of trait heritability. The optimal number of training generations that resulted in the greatest prediction accuracy of GEBV was determined for each trait. The relationship between optimal number of training generations and heritability was investigated. On average, accuracies were higher with the BayesB model than with PBLUP. Prediction accuracies of GEBV increased as the number of closely-related ancestral generations included in the training set increased, but reached an asymptote or slightly decreased when distant ancestral generations were used in the training set. The optimal number of training generations was 4 or more for high heritability traits but less than that for low heritability traits. For less heritable traits, limiting the training datasets to individuals closely related to the validation population resulted in the best predictions. The effect of adding distant ancestral generations in the training set on prediction accuracy differed between traits and the optimal number of necessary training generations is associated with the heritability of traits.

[Impacts of rotating or lifting-thrusting manipulation on distant vision of naked eye in patients of juvenile myopia: a randomized controlled trial].

PubMed

Tao, Xiao-Yan; Zhao, Bai-Yiao; Han, Xiao; Dong, Xiao-Yu; Yan, An; Ren, Xu-Ru; Liu, Yan-Wen; Qu, Chang; Xia, Shu-Fen; Yang, Jia-Le

2014-05-01

To compare the differences in the efficacy on distant version of naked eye in the patients of juvenile myopia between rotating manipulation and lifting-thrusting manipulation of acupuncture. One hundred and twenty cases (240 eyes) were randomized into a rotating manipulation group and a lifting-thrusting manipulation group, 60 cases (120 eyes) in each group. Additionally, a corrective lenses group, 60 cases (120 eyes), was set up as the control. In both manipulation groups, Cuanzhu (BL 2),Yuyao (EX-HN 4), Sizhukong (TE 23), Taiyang (EX-HN 5), Fengchi (GB 20), Zusanli (ST 36), Guangming (GB 37) and Sanyinjiao (SP 6) were punctured, but stimulated with rotating manipulation and lifting-thrusting manipulation respectively three times per week, 10 times as a treatment session and totally one session was required. In the corrective lenses group, the glasses were applied at daytime. The clinical efficacy and the changes in distant vision of naked eye before and after treatment were compared among the three groups. The total effective rate was 87.5% (105/120) in the rotating manipulation group, which was better than 69.2% (83/120) in the lifting-thrusting manipulation group (P < 0.05). The distant vision of naked eye was improved apparently in the rotating manipulation group and the lifting-thrusting manipulation group after treatment (both P < 0.05). But it was not improved in the corrective lenses group (P > 0.05). The distant vision of naked eye was improved more apparently after treatment in the rotating manipulation group as compared with that in the lifting-thrusting manipulation group (0.75 +/- 0.23 vs 0.68 +/- 0.24, P < 0.05). For 96 cases (192 eyes) with acupuncture treatment, in 3-month follow-up, 87.0% (167/192) of the cases maintained the stable vision as the original level and 13.0% (25/192) of them were reduced in the vision In the acupuncture groups, it was found that the improvement of distant vision of naked eye was more obvious after treatment with younger age, better basic vision and shorter duration of sickness (all P < 0.05). Acupuncture achieves the positive and sustainable clinical effect on juvenile myopia, and the results of rotating manipulation are superior to that of lifting-thrusting manipulation. Age, basic vision and duration of sickness impact the clinical efficacy.

Identification of Histone Deacetylase (HDAC) as a drug target against MRSA via interolog method of protein-protein interaction prediction.

PubMed

Uddin, Reaz; Tariq, Syeda Sumayya; Azam, Syed Sikander; Wadood, Abdul; Moin, Syed Tarique

2017-08-30

Patently, Protein-Protein Interactions (PPIs) lie at the core of significant biological functions and make the foundation of host-pathogen relationships. Hence, the current study is aimed to use computational biology techniques to predict host-pathogen Protein-Protein Interactions (HP-PPIs) between MRSA and Humans as potential drug targets ultimately proposing new possible inhibitors against them. As a matter of fact this study is based on the Interolog method which implies that homologous proteins retain their ability to interact. A distant homolog approach based on Interolog method was employed to speculate MRSA protein homologs in Humans using PSI-BLAST. In addition the protein interaction partners of these homologs as listed in Database of Interacting Proteins (DIP) were predicted to interact with MRSA as well. Moreover, a direct approach using BLAST was also applied so as to attain further confidence in the strategy. Consequently, the common HP-PPIs predicted by both approaches are suggested as potential drug targets (22%) whereas, the unique HP-PPIs estimated only through distant homolog approach are presented as novel drug targets (12%). Furthermore, the most repeated entry in our results was found to be MRSA Histone Deacetylase (HDAC) which was then modeled using SWISS-MODEL. Eventually, small molecules from ZINC, selected randomly, were docked against HDAC using Auto Dock and are suggested as potential binders (inhibitors) based on their energetic profiles. Thus the current study provides basis for further in-depth analysis of such data which not only include MRSA but other deadly pathogens as well. Copyright © 2017 Elsevier B.V. All rights reserved.

A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

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

Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org; Rotondo, Ronny L.; Begosh-Mayne, Dustin

Purpose: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Methods and Materials: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Results: The mean follow-up time was 3.7 yearsmore » (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). Conclusion: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by treating patients at the time of initial diagnosis. The impact of age is a novel finding of this study.« less

Literature mining of protein-residue associations with graph rules learned through distant supervision.

PubMed

Ravikumar, Ke; Liu, Haibin; Cohn, Judith D; Wall, Michael E; Verspoor, Karin

2012-10-05

We propose a method for automatic extraction of protein-specific residue mentions from the biomedical literature. The method searches text for mentions of amino acids at specific sequence positions and attempts to correctly associate each mention with a protein also named in the text. The methods presented in this work will enable improved protein functional site extraction from articles, ultimately supporting protein function prediction. Our method made use of linguistic patterns for identifying the amino acid residue mentions in text. Further, we applied an automated graph-based method to learn syntactic patterns corresponding to protein-residue pairs mentioned in the text. We finally present an approach to automated construction of relevant training and test data using the distant supervision model. The performance of the method was assessed by extracting protein-residue relations from a new automatically generated test set of sentences containing high confidence examples found using distant supervision. It achieved a F-measure of 0.84 on automatically created silver corpus and 0.79 on a manually annotated gold data set for this task, outperforming previous methods. The primary contributions of this work are to (1) demonstrate the effectiveness of distant supervision for automatic creation of training data for protein-residue relation extraction, substantially reducing the effort and time involved in manual annotation of a data set and (2) show that the graph-based relation extraction approach we used generalizes well to the problem of protein-residue association extraction. This work paves the way towards effective extraction of protein functional residues from the literature.

Impacts of Non-Divergence-Free Flows on the Coalescence of Initially Distant Buoyant Scalars on a Turbulent Free Surface

NASA Astrophysics Data System (ADS)

Pratt, K.; Crimaldi, J. P.

2016-02-01

Lagrangian Coherent Structures (LCS) have been shown to play a predictive role in the coalescence of initially distant scalars in incompressible flows. Buoyant scalars on the free surface of a 3D incompressible turbulent fluid, however, are advected by a 2D compressible velocity field, resulting in scalar distributions that differ from those seen in a 2D incompressible flow. Our research uses both numerical and experimental approaches to investigate the coalescence of two initially distant reactive scalars to infer the impact of non-divergence-free behavior on buoyant scalar coalescence. Preliminary numerical results, utilizing incompressible and compressible chaotic 2D models, indicate that non-divergence-free behavior increases the likelihood of scalar coalescence and therefore enhances any interactions or reactions between the scalars. In addition, the shape and distribution of LCS is altered in compressible flows, which may explain the increased likelihood of scalar coalescence. Experimentally, we have constructed a 60 X 60 X 60 cm tank that generates three-dimensional turbulence via random pulsing of 36 jets on the tank bottom. Buoyant fluorescent red and green particles are used to quantify coalescence. Through the addition of a thin surfactant film on the free surface, results for incompressible flow cases are also obtained and directly compared to the compressible results. From these results, we hope to elucidate the role of free-surface flow on the coalescence of initially distant buoyant scalars, and extend these results to oceanic mixing problems, such as the transport of phytoplankton blooms and oil spills.

Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

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

Ferris, Matthew J., E-mail: mjferri@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; Danish, Hasan

Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gymore » with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.« less

Environmental durability diagnostic for printed identification codes of polymer insulation for distribution pipelines

NASA Astrophysics Data System (ADS)

Zhuravleva, G. N.; Nagornova, I. V.; Kondratov, A. P.; Bablyuk, E. B.; Varepo, L. G.

2017-08-01

A research and modelling of weatherability and environmental durability of multilayer polymer insulation of both cable and pipelines with printed barcodes or color identification information were performed. It was proved that interlayer printing of identification codes in distribution pipelines insulation coatings provides high marking stability to light and atmospheric condensation. This allows to carry out their distant damage control. However, microbiological fouling of upper polymer layer hampers the distant damage pipelines identification. The color difference values and density changes of PE and PVC printed insolation due to weather and biological factors were defined.

Atom-atom entanglement by single-photon detection.

PubMed

Slodička, L; Hétet, G; Röck, N; Schindler, P; Hennrich, M; Blatt, R

2013-02-22

A scheme for entangling distant atoms is realized, as proposed in the seminal paper by [C. Cabrillo et al., Phys. Rev. A 59, 1025 (1999)]. The protocol is based on quantum interference and detection of a single photon scattered from two effectively one meter distant laser cooled and trapped atomic ions. The detection of a single photon heralds entanglement of two internal states of the trapped ions with high rate and with a fidelity limited mostly by atomic motion. Control of the entangled state phase is demonstrated by changing the path length of the single-photon interferometer.

Application of software for automated canal management (SacMan) to the WM lateral canal

USDA-ARS?s Scientific Manuscript database

Simulation studies have demonstrated that automatic control of canals is more effective when feedforward scheduling, or routing of know demand changes, is combined with centralized, automatic, distant, downstream-water-level control. In practice, few canals use this approach. To help further develop...

Precision Attitude Determination for an Infrared Space Telescope

NASA Technical Reports Server (NTRS)

Benford, Dominic J.

2008-01-01

We have developed performance simulations for a precision attitude determination system using a focal plane star tracker on an infrared space telescope. The telescope is being designed for the Destiny mission to measure cosmologically distant supernovae as one of the candidate implementations for the Joint Dark Energy Mission. Repeat observations of the supernovae require attitude control at the level of 0.010 arcseconds (0.05 microradians) during integrations and at repeat intervals up to and over a year. While absolute accuracy is not required, the repoint precision is challenging. We have simulated the performance of a focal plane star tracker in a multidimensional parameter space, including pixel size, read noise, and readout rate. Systematic errors such as proper motion, velocity aberration, and parallax can be measured and compensated out. Our prediction is that a relative attitude determination accuracy of 0.001 to 0.002 arcseconds (0.005 to 0.010 microradians) will be achievable.

Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior

PubMed Central

Grosenick, Logan; Warden, Melissa R.; Amatya, Debha; Katovich, Kiefer; Mehta, Hershel; Patenaude, Brian; Ramakrishnan, Charu; Kalanithi, Paul; Etkin, Amit; Knutson, Brian; Glover, Gary H.; Deisseroth, Karl

2016-01-01

Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions. PMID:26722001

Testing the Glucose Hypothesis among Capuchin Monkeys: Does Glucose Boost Self-Control?

PubMed

Parrish, Audrey E; Emerson, Ishara D; Rossettie, Mattea S; Beran, Michael J

2016-08-03

The ego-depletion hypothesis states that self-control diminishes over time and with exertion. Accordingly, the glucose hypothesis attributes this depletion of self-control resources to decreases in blood glucose levels. Research has led to mixed findings among humans and nonhuman animals, with limited evidence for such a link between glucose and self-control among closely-related nonhuman primate species, but some evidence from more distantly related species (e.g., honeybees and dogs). We tested this hypothesis in capuchin monkeys by manipulating the sugar content of a calorie-matched breakfast meal following a nocturnal fast, and then presenting each monkey with the accumulation self-control task. Monkeys were presented with food items one-by-one until the subject retrieved and ate the accumulating items, which required continual inhibition of food retrieval in the face of an increasingly desirable reward. Results indicated no relationship between self-control performance on the accumulation task and glucose ingestion levels following a fast. These results do not provide support for the glucose hypothesis of self-control among capuchin monkeys within the presented paradigm. Further research assessing self-control and its physiological correlates among closely- and distantly-related species is warranted to shed light on the mechanisms underlying self-control behavior.

Going Home: The Influence of Workforce Performance Management Systems on the Decision to Engage in Remote Work Environments

ERIC Educational Resources Information Center

Jones, Kenneth E., Jr.

2011-01-01

Since 1975, the advance of home-based or remote work has been predicted and encouraged (Nilles). Remote work entails the ability of workers to function as productively from distant locations as those workers in face-to-face office environments: e.g. secondary offices, co-workplace offices, mobile workstations, and home. This study will look at the…

Percentage of Positive Biopsy Cores: A Better Risk Stratification Model for Prostate Cancer?

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

Huang Jiayi; Vicini, Frank A.; Williams, Scott G.

2012-07-15

Purpose: To assess the prognostic value of the percentage of positive biopsy cores (PPC) and perineural invasion in predicting the clinical outcomes after radiotherapy (RT) for prostate cancer and to explore the possibilities to improve on existing risk-stratification models. Methods and Materials: Between 1993 and 2004, 1,056 patients with clinical Stage T1c-T3N0M0 prostate cancer, who had four or more biopsy cores sampled and complete biopsy core data available, were treated with external beam RT, with or without a high-dose-rate brachytherapy boost at William Beaumont Hospital. The median follow-up was 7.6 years. Multivariate Cox regression analysis was performed with PPC, Gleasonmore » score, pretreatment prostate-specific antigen, T stage, PNI, radiation dose, androgen deprivation, age, prostate-specific antigen frequency, and follow-up duration. A new risk stratification (PPC classification) was empirically devised to incorporate PPC and replace the T stage. Results: On multivariate Cox regression analysis, the PPC was an independent predictor of distant metastasis, cause-specific survival, and overall survival (all p < .05). A PPC >50% was associated with significantly greater distant metastasis (hazard ratio, 4.01; 95% confidence interval, 1.86-8.61), and its independent predictive value remained significant with or without androgen deprivation therapy (all p < .05). In contrast, PNI and T stage were only predictive for locoregional recurrence. Combining the PPC ({<=}50% vs. >50%) with National Comprehensive Cancer Network risk stratification demonstrated added prognostic value of distant metastasis for the intermediate-risk (hazard ratio, 5.44; 95% confidence interval, 1.78-16.6) and high-risk (hazard ratio, 4.39; 95% confidence interval, 1.70-11.3) groups, regardless of the use of androgen deprivation and high-dose RT (all p < .05). The proposed PPC classification appears to provide improved stratification of the clinical outcomes relative to the National Comprehensive Cancer Network classification. Conclusions: The PPC is an independent and powerful predictor of clinical outcomes of prostate cancer after RT. A risk model replacing T stage with the PPC to reduce subjectivity demonstrated potentially improved stratification.« less

A Multifactorial Analysis of Melanoma: Prognostic Histopathological Features Comparing Clark's and Breslow's Staging Methods

PubMed Central

Balch, Charles M.; Murad, Tariq M.; Soong, Seng-Jaw; Ingalls, Anna Lee; Halpern, Norman B.; Maddox, William A.

1978-01-01

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (≥4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors. PMID:736651

A decision aid for intensity-modulated radiation-therapy plan selection in prostate cancer based on a prognostic Bayesian network and a Markov model.

PubMed

Smith, Wade P; Doctor, Jason; Meyer, Jürgen; Kalet, Ira J; Phillips, Mark H

2009-06-01

The prognosis of cancer patients treated with intensity-modulated radiation-therapy (IMRT) is inherently uncertain, depends on many decision variables, and requires that a physician balance competing objectives: maximum tumor control with minimal treatment complications. In order to better deal with the complex and multiple objective nature of the problem we have combined a prognostic probabilistic model with multi-attribute decision theory which incorporates patient preferences for outcomes. The response to IMRT for prostate cancer was modeled. A Bayesian network was used for prognosis for each treatment plan. Prognoses included predicting local tumor control, regional spread, distant metastases, and normal tissue complications resulting from treatment. A Markov model was constructed and used to calculate a quality-adjusted life-expectancy which aids in the multi-attribute decision process. Our method makes explicit the tradeoffs patients face between quality and quantity of life. This approach has advantages over current approaches because with our approach risks of health outcomes and patient preferences determine treatment decisions.

Defining the consequences of genetic variation on a proteome–wide scale

PubMed Central

Chick, Joel M.; Munger, Steven C.; Simecek, Petr; Huttlin, Edward L.; Choi, Kwangbom; Gatti, Daniel M.; Raghupathy, Narayanan; Svenson, Karen L.; Churchill, Gary A.; Gygi, Steven P.

2016-01-01

Genetic variation modulates protein expression through both transcriptional and post-transcriptional mechanisms. To characterize the consequences of natural genetic diversity on the proteome, here we combine a multiplexed, mass spectrometry-based method for protein quantification with an emerging outbred mouse model containing extensive genetic variation from eight inbred founder strains. By measuring genome-wide transcript and protein expression in livers from 192 Diversity outbred mice, we identify 2,866 protein quantitative trait loci (pQTL) with twice as many local as distant genetic variants. These data support distinct transcriptional and post-transcriptional models underlying the observed pQTL effects. Using a sensitive approach to mediation analysis, we often identified a second protein or transcript as the causal mediator of distant pQTL. Our analysis reveals an extensive network of direct protein–protein interactions. Finally, we show that local genotype can provide accurate predictions of protein abundance in an independent cohort of collaborative cross mice. PMID:27309819

Cortical Oscillatory Mechanisms Supporting the Control of Human Social-Emotional Actions.

PubMed

Bramson, Bob; Jensen, Ole; Toni, Ivan; Roelofs, Karin

2018-06-20

The human anterior prefrontal cortex (aPFC) is involved in regulating social-emotional behavior, presumably by modulating effective connectivity with downstream parietal, limbic, and motor cortices. Regulating that connectivity might rely on theta-band oscillations (4-8 Hz), a brain rhythm known to create overlapping periods of excitability between distant regions by temporally releasing neurons from inhibition. Here, we used MEG to understand how aPFC theta-band oscillations implement control over prepotent social-emotional behaviors; that is, the control over automatically elicited approach and avoidance actions. Forty human male participants performed a social approach-avoidance task in which they approached or avoided visually displayed emotional faces (happy or angry) by pulling or pushing a joystick. Approaching angry and avoiding happy faces (incongruent condition) requires rapid application of cognitive control to override prepotent habitual action tendencies to approach appetitive and to avoid aversive situations. In the time window before response delivery, trial-by-trial variations in aPFC theta-band power (6 Hz) predicted reaction time increases during emotional control and were inversely related to beta-band power (14-22 Hz) over parietofrontal cortex. In sensorimotor areas contralateral to the moving hand, premovement gamma-band rhythms (60-90 Hz) were stronger during incongruent than congruent trials, with power increases phase locked to peaks of the aPFC theta-band oscillations. These findings define a mechanistic relation between cortical areas involved in implementing rapid control over human social-emotional behavior. The aPFC may bias neural processing toward rule-driven actions and away from automatic emotional tendencies by coordinating tonic disinhibition and phasic enhancement of parietofrontal circuits involved in action selection. SIGNIFICANCE STATEMENT Being able to control social-emotional behavior is crucial for successful participation in society, as is illustrated by the severe social and occupational difficulties experienced by people suffering from social motivational disorders such as social anxiety. In this study, we show that theta-band oscillations in the anterior prefrontal cortex (aPFC), which are thought to provide temporal organization for neural firing during communication between distant brain areas, facilitate this control by linking aPFC to parietofrontal beta-band and sensorimotor gamma-band oscillations involved in action selection. These results contribute to a mechanistic understanding of cognitive control over automatic social-emotional action and point to frontal theta-band oscillations as a possible target of rhythmic neurostimulation techniques during treatment for social anxiety. Copyright © 2018 the authors 0270-6474/18/385739-11$15.00/0.

[The development of a distribution system for medical lasers and its clinical application].

PubMed

Okae, S; Ishiguchi, T; Ishigaki, T; Sakuma, S

1991-02-25

We developed a new laser beam generator system which can deliver laser beam to multiple terminals in distant clinical therapy rooms. The system possesses the distribution equipment by which Nd-YAG laser power is distributed to 8 output terminals under the computer control. Distributed laser beam is delivered to each distant terminal with clinical informations through the optical fiber. In the fundamental studies, possibility of distant transportation of laser beam (30 m) only with 10% loss of energy and without dangerous heating at the connection parts was shown. There seems to be no disadvantage associated with distribution laser beam. In the clinical study, the system was applied to five patients with the symptoms including hemosputum, esophageal stenosis, hemorrhage, lip ulcer and pain. Clinical usefulness of the system was proved. The advantages of the system are as follows: 1. Benefit of cost reduction due to multiple use of single laser source. 2. No necessity of transport of the equipment. 3. No requirement of a wide space to install the equipment in the distant room. 4. Efficient management and maintenance of the system by centralization. Further improvements, e.g., simultaneous use at multiple terminals and elongation of transportation up to 340 m, make the system more useful for clinical application.

Role of pelvic radiotherapy for locally advanced rectal cancer and synchronous unresectable distant metastases.

PubMed

Liu, K T; Wan, J F; Zhu, J; Li, G C; Sun, W J; Shen, L J; Cai, S J; Gu, W L; Lian, P; Zhang, Z

2016-12-01

To evaluate the efficacy and safety of pelvic irradiation combined systematic chemotherapy in patients with locally advanced (cT3-T4 and/or cN+) rectal cancer and synchronous unresectable distant metastases. A total of 76 eligible patients who received pelvic radiotherapy and concurrent capecitabine-based chemotherapy were retrospectively reviewed. Patients survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. Most of the adverse events were mild during the period of combined chemoradiotherapy. Twenty-two patients experienced resection of primary tumour and 16 patients underwent radical surgery of all lesions. Only five patients had pelvic progression during the follow-up period. The median progression-free survival and median overall survival were 13 and 30 months, respectively. Radical surgery of all lesions following chemoradiotherapy was found to be an independent prognostic factor according to multivariate analysis. Pelvic irradiation combined with systematic chemotherapy in patients with locally advanced rectal cancer and synchronous unresectable distant metastases is effective and tolerable, both for pelvic and distant control. A curative resection following chemoradiotherapy was associated with prolonged survival. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

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

Dierickx, Marion I. P.; Loeb, Abraham, E-mail: mdierickx@cfa.harvard.edu, E-mail: aloeb@cfa.harvard.edu

The extensive span of the Sagittarius (Sgr) stream makes it a promising tool for studying the gravitational potential of the Milky Way (MW). Characterizing its stellar kinematics can constrain halo properties and provide a benchmark for the paradigm of galaxy formation from cold dark matter. Accurate models of the disruption dynamics of the Sgr progenitor are necessary to employ this tool. Using a combination of analytic modeling and N -body simulations, we build a new model of the Sgr orbit and resulting stellar stream. In contrast to previous models, we simulate the full infall trajectory of the Sgr progenitor frommore » the time it first crossed the MW virial radius 8 Gyr ago. An exploration of the parameter space of initial phase-space conditions yields tight constraints on the angular momentum of the Sgr progenitor. Our best-fit model is the first to accurately reproduce existing data on the 3D positions and radial velocities of the debris detected 100 kpc away in the MW halo. In addition to replicating the mapped stream, the simulation also predicts the existence of several arms of the Sgr stream extending to hundreds of kiloparsecs. The two most distant stars known in the MW halo coincide with the predicted structure. Additional stars in the newly predicted arms can be found with future data from the Large Synoptic Survey Telescope. Detecting a statistical sample of stars in the most distant Sgr arms would provide an opportunity to constrain the MW potential out to unprecedented Galactocentric radii.« less

Using temporal distancing to regulate emotion in adolescence: modulation by reactive aggression.

PubMed

Ahmed, S P; Somerville, L H; Sebastian, C L

2018-06-01

Adopting a temporally distant perspective on stressors reduces distress in adults. Here we investigate whether the extent to which individuals project themselves into the future influences distancing efficacy. We also examined modulating effects of age across adolescence and reactive aggression: factors associated with reduced future-thinking and poor emotion regulation. Participants (N = 83, aged 12-22) read scenarios and rated negative affect when adopting a distant-future perspective, near-future perspective, or when reacting naturally. Self-report data revealed significant downregulation of negative affect during the distant-future condition, with a similar though non-significant skin conductance pattern. Importantly, participants who projected further ahead showed the greatest distress reductions. While temporal distancing efficacy did not vary with age, participants reporting greater reactive aggression showed reduced distancing efficacy, and projected themselves less far into the future. Findings demonstrate the importance of temporal extent in effective temporal distancing; shedding light on a potential mechanism for poor emotional control associated with reactive aggression.

Most Distant X-Ray Jet Yet Discovered Provides Clues To Big Bang

NASA Astrophysics Data System (ADS)

2003-11-01

The most distant jet ever observed was discovered in an image of a quasar made by NASA's Chandra X-ray Observatory. Extending more than 100,000 light years from the supermassive black hole powering the quasar, the jet of high-energy particles provides astronomers with information about the intensity of the cosmic microwave background radiation 12 billion years ago. The discovery of this jet was a surprise to the astronomers, according to team members. Astronomers had previously known the distant quasar GB1508+5714 to be a powerful X-ray source, but there had been no indication of any complex structure or a jet. "This jet is especially significant because it allows us to probe the cosmic background radiation 1.4 billion years after the Big Bang," said Aneta Siemiginowska of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass., lead author of a report on this research in the November 20th Astrophysical Journal Letters. Prior to this discovery, the most distant confirmed X-ray jet corresponded to a time about 3 billion years after the Big Bang. Quasars are thought to be galaxies that harbor an active central supermassive black hole fueled by infalling gas and stars. This accretion process is often observed to be accompanied by the generation of powerful high-energy jets. Radio image of GB1508 Radio Image of GB1508 As the electrons in the jet fly away from the quasar at near the speed of light, they move through the sea of cosmic background radiation left over from the hot early phase of the universe. When a fast-moving electron collides with one of these background photons, it can boost the photon's energy up into the X-ray band. The X-ray brightness of the jet depends on the power in the electron beam and the intensity of the background radiation. "Everyone assumes that the background radiation will change in a predictable way with time, but it is important to have this check on the predictions," said Siemiginowska. "This jet is hopefully just the first in a large sample of these distant objects that can be used to tell us how the intensity of the cosmic microwave background changed over time." "In fact, if this interpretation is correct, then discovery of this jet is consistent with our previous prediction that X-ray jets can be detected at arbitrarily large distances!" said team member Dan Schwartz, also of the Harvard-Smithsonian Center for Astrophysics. Chandra originally observed GB1508+5714 with the purpose of studying the X-ray emission from the dust located between the Earth and the far-flung quasar. The jet was found by Siemiginowska and her colleagues when they examined the data once it became available publicly in the Chandra archive. This led another astronomer to then carefully look at radio observations of the object. Indeed, archived Very Large Array data confirmed the existence of the jet associated with the quasar GB1508+5714. A paper on the radio observations of GB1508+5714 has been accepted by Astrophysical Journal Letters from Teddy Cheung of Brandeis University in Waltham, Mass. Another group of astronomers led by Weimin Yuan of the University of Cambridge, UK independently reported the discovery of the extended emission in GB1508+5714 in X-rays. In a paper to be published in an upcoming issue of the Monthly Notices of the Royal Astronomical Society, the authors note that significant energy is being deposited in the outer regions of the host galaxy at a very early stage. This energy input could have a profound effect on the evolution of the galaxy by triggering the formation of stars, or inhibiting the growth of the galaxy through accretion of matter from intergalactic space. NASA's Marshall Space Flight Center, Huntsville, Ala., manages the Chandra program for the Office of Space Science, NASA Headquarters, Washington. Northrop Grumman of Redondo Beach, Calif., formerly TRW, Inc., was the prime development contractor for the observatory. The Smithsonian Astrophysical Observatory controls science and flight operations from the Chandra X-ray Center in Cambridge, Mass.

Mapping all the mass in the universe (with weak gravitational lensing) - Oral Presentation

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

Everett, Spencer

Recent discoveries have shown that most of the universe is made of an exotic dark matter that behaves much differently than the normal matter that we experience in everyday life. As we cannot detect dark matter directly, we must infer its location in the universe by indirect effects, such as the distortion of light from distant galaxies as it travels through large clouds of dark matter. While the degree of distortion should be proportional to the amount of dark matter present, we don't know the original shape of the galaxy so the distortion is difficult to quantify. If we hadmore » a model of how dark matter is linked to galaxies, and thus be able predict the amount of distortion that should occur, we could apply the model to galaxy surveys to map out the dark matter in our universe. In this research, I attach a spherical 'halo' of dark matter to each galaxy in a simulated universe to approximate its known complex dark matter structure. I then predict how the halos distort the light from distant galaxies generated behind the halos. As the data is simulated, the true distortion of the light is known which is compared to the halo-predicted distortion. I find that, on average, the model under-predicts the degree of distortion on all scales and fails to capture distortions from large-scale dark matter structure. These issues are likely due to missing features in the model, as the halo model is a greatly simplified version of the actual distribution of dark matter. Potential improvements to the model for future work are discussed.« less

Method and System for Gamma-Ray Localization Induced Spacecraft Navigation Using Celestial Gamma-Ray Sources

NASA Technical Reports Server (NTRS)

Hisamoto, Chuck (Inventor); Arzoumanian, Zaven (Inventor); Sheikh, Suneel I. (Inventor)

2015-01-01

A method and system for spacecraft navigation using distant celestial gamma-ray bursts which offer detectable, bright, high-energy events that provide well-defined characteristics conducive to accurate time-alignment among spatially separated spacecraft. Utilizing assemblages of photons from distant gamma-ray bursts, relative range between two spacecraft can be accurately computed along the direction to each burst's source based upon the difference in arrival time of the burst emission at each spacecraft's location. Correlation methods used to time-align the high-energy burst profiles are provided. The spacecraft navigation may be carried out autonomously or in a central control mode of operation.

Of Fighting Flies, Mice, and Men: Are Some of the Molecular and Neuronal Mechanisms of Aggression Universal in the Animal Kingdom?

PubMed

Thomas, Amanda L; Davis, Shaun M; Dierick, Herman A

2015-08-01

Aggressive behavior is widespread in the animal kingdom, but the degree of molecular conservation between distantly related species is still unclear. Recent reports suggest that at least some of the molecular mechanisms underlying this complex behavior in flies show remarkable similarities with such mechanisms in mice and even humans. Surprisingly, some aspects of neuronal control of aggression also show remarkable similarity between these distantly related species. We will review these recent findings, address the evolutionary implications, and discuss the potential impact for our understanding of human diseases characterized by excessive aggression.

Of Fighting Flies, Mice, and Men: Are Some of the Molecular and Neuronal Mechanisms of Aggression Universal in the Animal Kingdom?

PubMed Central

Dierick, Herman A.

2015-01-01

Aggressive behavior is widespread in the animal kingdom, but the degree of molecular conservation between distantly related species is still unclear. Recent reports suggest that at least some of the molecular mechanisms underlying this complex behavior in flies show remarkable similarities with such mechanisms in mice and even humans. Surprisingly, some aspects of neuronal control of aggression also show remarkable similarity between these distantly related species. We will review these recent findings, address the evolutionary implications, and discuss the potential impact for our understanding of human diseases characterized by excessive aggression. PMID:26312756

Conventional Risk Stratification Fails to Predict Progression of Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors: A Clinicopathologic Study of 76 Cases.

PubMed

Mason, Emily F; Hornick, Jason L

2016-12-01

Gastrointestinal stromal tumors (GISTs) that lack kinase mutations often show loss of function of the succinate dehydrogenase (SDH) complex, due to germline mutation or promoter hypermethylation. SDH-deficient GISTs are exclusive to the stomach and have a multinodular architecture. It has been suggested that conventional risk stratification criteria may not predict outcome for this group of tumors, although data are limited. Here, we report the clinical, histologic, and genetic findings from a large cohort of 76 SDH-deficient GISTs diagnosed from 2005 to 2015, identified on the basis of histologic features or family history (45 female/31 male; mean age at diagnosis 32 y; range 11 to 71 y; 10 patients 50 y of age or above). Immunohistochemistry for SDHB and SDHA showed loss of SDHB in all cases and loss of SDHA in 28 (37%) tumors. Tumor size ranged from 1.9 to 22.5 cm; the primary tumor was multifocal in 29%. Mitotic rate ranged from 1 to 80 per 5 mm (median 5.5). Lymph node metastases were found at primary resection in 14 (18%) patients. Twenty-four patients (32%) had distant metastases at presentation, and 52 of 70 patients (74%) with follow-up developed distant metastases, most often to the liver, but also bone, lungs, breast, and brain. Applying conventional criteria (size and mitotic rate), 60% to 82% of patients with tumors ranging from very low risk to high risk for progressive disease developed distant metastases, regardless of the category. Carney-Stratakis syndrome and Carney triad were diagnosed in 6 and 8 patients, respectively. Of 35 patients tested, 26 harbored SDH mutations (11 SDHA, 8 SDHB, 6 SDHC, 1 SDHD). Follow-up data available for 70 patients ranged from 1 month to 39.3 years: 20 patients had no evidence of disease (mean 6.1 y), 32 were alive with metastases (mean 10.9 y), and 18 died of disease (mean 7.0 y after diagnosis). In summary, SDH-deficient GISTs account for approximately 8% of gastric GISTs and are associated with a high rate of distant metastasis, regardless of conventional risk category. Many affected patients have germline SDH mutations (most often SDHA). Identification of SDH-deficient GISTs is critical for prognostication and genetic counseling.

Preoperative [18F]Fluorodeoxyglucose Positron Emission Tomography Standardized Uptake Value of Neck Lymph Nodes Predicts Neck Cancer Control and Survival Rates in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

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

Liao, C.-T.; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Chang, J.T.-C.

Purpose: Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this prospective study, we sought to investigate whether preoperative maximum standardized uptake value of the neck lymph nodes (SUVnodal-max) may predict prognosis in OSCC patients. Methods and Materials: A total of 120 OSCC patients with pathologically positive lymph nodes were investigated. All subjects underwent a [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan within 2 weeks before radical surgery and neck dissection. All patients were followed up for at least 24 months after surgery or until death. Postoperative adjuvant therapy was performed in the presence ofmore » pathologic risk factors. Optimal cutoff values of SUVnodal-max were chosen based on 5-year disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for surviving patients was 41 months. The optimal cutoff value for SUVnodal-max was 5.7. Multivariate analyses identified the following independent predictors of poor outcome: SUVnodal-max {>=}5.7 for the 5-year neck cancer control rate, distant metastatic rate, DFS, DSS, and extracapsular spread (ECS) for the 5-year DSS and OS. Among ECS patients, the presence of a SUVnodal-max {>=}5.7 identified patients with the worst prognosis. Conclusion: A SUVnodal-max of 5.7, either alone or in combination with ECS, is an independent prognosticator for 5-year neck cancer control and survival rates in OSCC patients with pathologically positive lymph nodes.« less

Integrated Attitude Control Strategy for the Asteroid Redirect Mission

NASA Technical Reports Server (NTRS)

Lopez, Pedro, Jr.; Price, Hoppy; San Martin, Miguel

2014-01-01

A deep-space mission has been proposed to redirect an asteroid to a distant retrograde orbit around the moon using a robotic vehicle, the Asteroid Redirect Vehicle (ARV). In this orbit, astronauts will rendezvous with the ARV using the Orion spacecraft. The integrated attitude control concept that Orion will use for approach and docking and for mated operations will be described. Details of the ARV's attitude control system and its associated constraints for redirecting the asteroid to the distant retrograde orbit around the moon will be provided. Once Orion is docked to the ARV, an overall description of the mated stack attitude during all phases of the mission will be presented using a coordinate system that was developed for this mission. Next, the thermal and power constraints of both the ARV and Orion will be discussed as well as how they are used to define the optimal integrated stack attitude. Lastly, the lighting and communications constraints necessary for the crew's extravehicular activity planned to retrieve samples from the asteroid will be examined. Similarly, the joint attitude control strategy that employs both the Orion and the ARV attitude control assets prior, during, and after each extravehicular activity will also be thoroughly discussed.

Optometric measurements predict performance but not comfort on a virtual object placement task with a stereoscopic three-dimensional display

NASA Astrophysics Data System (ADS)

McIntire, John P.; Wright, Steve T.; Harrington, Lawrence K.; Havig, Paul R.; Watamaniuk, Scott N. J.; Heft, Eric L.

2014-06-01

Twelve participants were tested on a simple virtual object precision placement task while viewing a stereoscopic three-dimensional (S3-D) display. Inclusion criteria included uncorrected or best corrected vision of 20/20 or better in each eye and stereopsis of at least 40 arc sec using the Titmus stereotest. Additionally, binocular function was assessed, including measurements of distant and near phoria (horizontal and vertical) and distant and near horizontal fusion ranges using standard optometric clinical techniques. Before each of six 30 min experimental sessions, measurements of phoria and fusion ranges were repeated using a Keystone View Telebinocular and an S3-D display, respectively. All participants completed experimental sessions in which the task required the precision placement of a virtual object in depth at the same location as a target object. Subjective discomfort was assessed using the simulator sickness questionnaire. Individual placement accuracy in S3-D trials was significantly correlated with several of the binocular screening outcomes: viewers with larger convergent fusion ranges (measured at near distance), larger total fusion ranges (convergent plus divergent ranges, measured at near distance), and/or lower (better) stereoscopic acuity thresholds were more accurate on the placement task. No screening measures were predictive of subjective discomfort, perhaps due to the low levels of discomfort induced.

SU-F-R-53: CT-Based Radiomics Analysis of Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

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

Huynh, E; Coroller, T; Narayan, V

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable non-small cell lung cancer (NSCLC) patients and has demonstrated excellent local control and survival. However, some patients still develop distant metastases and local recurrence, and therefore, there is a clinical need to identify patients at high-risk of disease recurrence. The aim of the current study is to use a radiomics approach to identify imaging biomarkers, based on tumor phenotype, for clinical outcomes in SBRT patients. Methods: Radiomic features were extracted from free breathing computed tomography (CT) images of 113 Stage I-II NSCLC patients treated with SBRT.more » Their association to and prognostic performance for distant metastasis (DM), locoregional recurrence (LRR) and survival was assessed and compared with conventional features (tumor volume and diameter) and clinical parameters (e.g. performance status, overall stage). The prognostic performance was evaluated using the concordance index (CI). Multivariate model performance was evaluated using cross validation. All p-values were corrected for multiple testing using the false discovery rate. Results: Radiomic features were associated with DM (one feature), LRR (one feature) and survival (four features). Conventional features were only associated with survival and one clinical parameter was associated with LRR and survival. One radiomic feature was significantly prognostic for DM (CI=0.670, p<0.1 from random), while none of the conventional and clinical parameters were significant for DM. The multivariate radiomic model had a higher median CI (0.671) for DM than the conventional (0.618) and clinical models (0.617). Conclusion: Radiomic features have potential to be imaging biomarkers for clinical outcomes that conventional imaging metrics and clinical parameters cannot predict in SBRT patients, such as distant metastasis. Development of a radiomics biomarker that can identify patients at high-risk of recurrence could facilitate personalization of their treatment regimen for an optimized clinical outcome. R.M. had consulting interest with Amgen (ended in 2015).« less

Protein Structure and Function Prediction Using I-TASSER

PubMed Central

Yang, Jianyi; Zhang, Yang

2016-01-01

I-TASSER is a hierarchical protocol for automated protein structure prediction and structure-based function annotation. Starting from the amino acid sequence of target proteins, I-TASSER first generates full-length atomic structural models from multiple threading alignments and iterative structural assembly simulations followed by atomic-level structure refinement. The biological functions of the protein, including ligand-binding sites, enzyme commission number, and gene ontology terms, are then inferred from known protein function databases based on sequence and structure profile comparisons. I-TASSER is freely available as both an on-line server and a stand-alone package. This unit describes how to use the I-TASSER protocol to generate structure and function prediction and how to interpret the prediction results, as well as alternative approaches for further improving the I-TASSER modeling quality for distant-homologous and multi-domain protein targets. PMID:26678386

Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.

PubMed

Wlodarski, Tomasz; Kutner, Jan; Towpik, Joanna; Knizewski, Lukasz; Rychlewski, Leszek; Kudlicki, Andrzej; Rowicka, Maga; Dziembowski, Andrzej; Ginalski, Krzysztof

2011-01-01

Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.

Distant stereoacuity in children with anisometropic amblyopia.

PubMed

Chung, Yeon Woong; Park, Shin Hae; Shin, Sun Young

2017-09-01

To characterize changes in distant stereoacuity using Frisby-Davis Distance test (FD2) and Distant Randot test (DR) during treatment for anisometropic amblyopia, to determine factors that influence posttreatment stereoacuity and to compare the two distant stereotests. Fifty-eight anisometropic amblyopic patients with an interocular difference of ≥1.00 diopter who achieved the visual acuity 20/20 following amblyopia treatment were retrospectively included. Stereoacuity using FD2 and DR for distant and Titmus test for near measurement were assessed and compared at the initial, intermediate, and final visit. Multivariate regression models were used to identify factors associated with initial and final stereoacuity. The two distant stereotests revealed a significant improvement in distant stereoacuity after successful amblyopia treatment. Distant stereoacuity using FD2 showed the greatest improvement during the follow up period. The number of nil scores was higher in DR than FD2 at each period. In multivariate analysis, better final stereoacuity was associated with better initial amblyopic eye acuity in both distant stereotests, but not in the Titmus test. Comparing the two distant stereotests, final stereoacuity using FD2 was associated with initial stereoacuity and was moderately related with the Titmus test at each period, but final stereoacuity using DR was not. Distant stereoacuity measured with both FD2 and DR showed significant improvement when the visual acuity of the amblyopic eye achieved 20/20. Changes in distant stereoacuity by FD2 and DR during the amblyopia treatment were somewhat different.

Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.

PubMed

Ray, Michael E; Bae, Kyounghwa; Hussain, Maha H A; Hanks, Gerald E; Shipley, William U; Sandler, Howard M

2009-02-18

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

Model and Scenario Variations in Predicted Number of Generations of Spodoptera litura Fab. on Peanut during Future Climate Change Scenario

PubMed Central

Srinivasa Rao, Mathukumalli; Swathi, Pettem; Rama Rao, Chitiprolu Anantha; Rao, K. V.; Raju, B. M. K.; Srinivas, Karlapudi; Manimanjari, Dammu; Maheswari, Mandapaka

2015-01-01

The present study features the estimation of number of generations of tobacco caterpillar, Spodoptera litura. Fab. on peanut crop at six locations in India using MarkSim, which provides General Circulation Model (GCM) of future data on daily maximum (T.max), minimum (T.min) air temperatures from six models viz., BCCR-BCM2.0, CNRM-CM3, CSIRO-Mk3.5, ECHams5, INCM-CM3.0 and MIROC3.2 along with an ensemble of the six from three emission scenarios (A2, A1B and B1). This data was used to predict the future pest scenarios following the growing degree days approach in four different climate periods viz., Baseline-1975, Near future (NF) -2020, Distant future (DF)-2050 and Very Distant future (VDF)—2080. It is predicted that more generations would occur during the three future climate periods with significant variation among scenarios and models. Among the seven models, 1–2 additional generations were predicted during DF and VDF due to higher future temperatures in CNRM-CM3, ECHams5 & CSIRO-Mk3.5 models. The temperature projections of these models indicated that the generation time would decrease by 18–22% over baseline. Analysis of variance (ANOVA) was used to partition the variation in the predicted number of generations and generation time of S. litura on peanut during crop season. Geographical location explained 34% of the total variation in number of generations, followed by time period (26%), model (1.74%) and scenario (0.74%). The remaining 14% of the variation was explained by interactions. Increased number of generations and reduction of generation time across the six peanut growing locations of India suggest that the incidence of S. litura may increase due to projected increase in temperatures in future climate change periods. PMID:25671564

Leadership Theory Taught in Air Force Distant Learning Programs

DTIC Science & Technology

2013-03-01

information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM...be considered critical components. Reward power comes from compliance based on the control of a precious commodity such as pay, promotion, and...managers monitor and staff its progress. Lastly, management controls and leadership motivates.22 Managers are there to ensure the goals are

Age-differences in the temporal properties of proactive interference in working memory.

PubMed

Samrani, George; Bäckman, Lars; Persson, Jonas

2017-12-01

The inability to suppress irrelevant information has been suggested as a primary cause of proactive interference (PI), and this deficit may be enhanced in aging. The current study examines age differences and temporal boundaries of PI, by manipulating lure distances in a verbal 2-back working memory task. Both younger and older adults showed effects of interference for proximal 3- and 4-back lures, and this effect was greater for older adults. Whereas younger adults showed less interference during 4-back compared to 3-back lures, in both reaction times and accuracy, older adults improved only in accuracy. For distant lures, when the time between the 1st presentation of an item to its reappearance as a lure item was longer (e.g., 5- to 10-back lures), younger adults were no longer affected by PI. However, older adults were affected by PI throughout all distant lures, up to the most distant lure (9-/10-back). The results suggest that older adults were less successful in resolving interference from both proximal and distant familiar lures. Further, younger adults were able to overcome the effects of PI completely after a specific lure distance. The age differences in temporal properties of PI may therefore highlight a unique component linked to impaired interference control and aging. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Radical redo surgery for local rectal cancer recurrence improves overall survival: a single center experience.

PubMed

Schurr, Paulus; Lentz, Edda; Block, Suzette; Kaifi, Jussuf; Kleinhans, Helge; Cataldegirmen, Guellue; Kutup, Asad; Schneider, Claus; Strate, Tim; Yekebas, Emre; Izbicki, Jakob

2008-07-01

To date, the survival benefit of redo surgery in locally recurrent rectal adenocarcinoma remains unclear. In an institutional study, operations for recurrence were retrospectively analyzed. Survival was calculated using the Kaplan-Meier plot and Cox regression analysis. A total of 72 patients with local recurrence were explored or resected. In 38 patients, there was synchronous distant organ recurrence. Forty-five of 72 were re-resected and in 37 of 45 cases, R0 situations were achieved. In 11 of 38 metastasized patients, both local and distant organ recurrence were successfully removed. For obtaining tumor control, resections of inner genitals, bladder, and sacral bone were necessary in 10, 4, and 11 patients, respectively. Survival was better for patients re-resected with a median overall survival of 54.9 months, as compared with 31.1 months among non-resected patients (p = 0.0047, log-rank test). Subgroup analysis revealed that a benefit of re-resection was observed to a lesser extent in synchronous local and in distant disease. Cox analysis showed that initial Dukes stage and complete resections of local recurrences were independently determining prognosis (relative risk 1.762 and 0.689, p = 0.008 and p = 0.002, respectively). Radical surgery for local recurrence can improve survival if complete tumor clearance is achieved, and concomitant distant tumor load should not principally preclude re-resection.

Cryptic Distant Relatives Are Common in Both Isolated and Cosmopolitan Genetic Samples

PubMed Central

Macpherson, J. Michael; Eriksson, Nick; Saxonov, Serge; Pe'er, Itsik; Mountain, Joanna L.

2012-01-01

Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2nd to 9th cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100–300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD) in a subset of individuals from the 23andMe customer database (n = 22,757) and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952). With data from 121 populations, we show that the average amount of DNA shared IBD in most ethnolinguistically-defined populations, for example Native American groups, Finns and Ashkenazi Jews, differs from continentally-defined populations by several orders of magnitude. Via extensive pedigree-based simulations, we determined bounds for predicted degrees of relationship given the amount of genomic IBD sharing in both endogamous and ‘unrelated’ population samples. Using these bounds as a guide, we detected tens of thousands of 2nd to 9th degree cousin pairs within a heterogenous set of 5,000 Europeans. The ubiquity of distant relatives, detected via IBD segments, in both ethnolinguistic populations and in large ‘unrelated’ populations samples has important implications for genetic genealogy, forensics and genotype/phenotype mapping studies. PMID:22509285

TIME STRUCTURE OF GAMMA-RAY SIGNALS GENERATED IN LINE-OF-SIGHT INTERACTIONS OF COSMIC RAYS FROM DISTANT BLAZARS

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

Prosekin, Anton; Aharonian, Felix; Essey, Warren

2012-10-01

Blazars are expected to produce both gamma rays and cosmic rays. Therefore, observed high-energy gamma rays from distant blazars may contain a significant contribution from secondary gamma rays produced along the line of sight by the interactions of cosmic-ray protons with background photons. Unlike the standard models of blazars that consider only the primary photons emitted at the source, models that include the cosmic-ray contribution predict that even {approx}10 TeV photons should be detectable from distant objects with redshifts as high as z {>=} 0.1. Secondary photons contribute to signals of point sources only if the intergalactic magnetic fields aremore » very small, B {approx}< 10{sup -14} G, and their detection can be used to set upper bounds on magnetic fields along the line of sight. Secondary gamma rays have distinct spectral and temporal features. We explore the temporal properties of such signals using a semi-analytical formalism and detailed numerical simulations, which account for all the relevant processes, including magnetic deflections. In particular, we elucidate the interplay of time delays coming from the proton deflections and from the electromagnetic cascade, and we find that, at multi-TeV energies, secondary gamma rays can show variability on timescales of years for B {approx} 10{sup -15} G.« less

An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

PubMed Central

2010-01-01

Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID:20584321

Abstract Mindsets Increase Believability of Spatially Distant Online Messages

PubMed Central

Sungur, Hande; Hartmann, Tilo; van Koningsbruggen, Guido M.

2016-01-01

Growing evidence from online credibility research reveals that online users rely on heuristic processes to evaluate the credibility of online information. The current paper, which is based on the construal level theory (CLT), proposes that congruency between the psychological distance of a stimulus and the way it is mentally construed can act as a heuristic for believability. According to CLT, psychologically close (e.g., spatially, temporally, socially) stimuli are represented concretely whereas psychologically distant stimuli are represented abstractly. The level of mental construals and the psychological distance of information have been shown to influence people’s truth judgments in offline contexts. This study tests whether congruency between the construal level of people’s mindsets (abstract vs. concrete) and the psychological distance implied in an online message (far vs. close) enhances message believability. By partially confirming CLT predictions, we found that believability of an online news item about a distant location increased when people maintained an abstract mindset rather than a concrete one. The effect of a concrete mindset on believability was not significant for the close psychological distance condition. Our findings provide initial evidence that congruency between the construal level of people’s mindsets and psychological distance cues in online messages can act as a heuristic for believability. We discuss the potential of applying the CLT framework to the growing literature on online cognitive heuristics in the area of online information credibility. PMID:27468272

A detailed examination of a X-line region in the distant tail: ISEE-3 observations of jet flow and B(sub z) reversals and a pair of slow shocks

NASA Technical Reports Server (NTRS)

Ho, C. M.; Tsurutani, B. T.; Smith, E. J.; Feldman, W. C.

1994-01-01

We report an observation of Petschek-type magnetic reconnection at a distant neutral line (X = -230 R(sub e)) with a full set of signatures of the magnetic merging process. These features include a reversal of plasma flows from earthward to tailward, a pair of slow shocks and the magnetic field X-type line. These two slow shocks are shown to satisfy the shock criteria used by Feldman et al. (1987). The spacecraft first crosses a slow shock to enter the earthward flowing plasmasheet with velocity of about 440 km/s. The embedded magnetic field has a positive B(sub z) component. The spacecraft next enters a region of tailward plasma flow with speed approximately 670 km/s and an embedded negative B(sub z), indicating entry into the plasmasheet tailward of the X-line. These observed velocities are comparable to calculated velocities based on Rankine-Hugoniot conservation relationships. The spacecraft subsequently returns into the south tail lobe by crossing another slow shock. Coplanarity analyses shows that the two slow shocks have orientations consistent with that predicted by the Petschek reconnection model. We note that this event occurs during northward interplanetary magnetic fields. Thus, a magnetic stress built-up in the distant tail may be responsible for this reconnection process.

Promoting interdomain analogical transfer: When creating a problem helps to solve a problem.

PubMed

Minervino, Ricardo A; Olguín, Valeria; Trench, Máximo

2017-02-01

Research on analogical thinking has devised several ways of promoting an abstract encoding of base analogs, thus rendering them more retrievable during later encounters with similar situations lacking surface similarities. Recent studies have begun to explore ways of facilitating transfer at retrieval time, which could facilitate the retrieval of distant analogs learned within contexts that were not specially directed to emphasize their abstract structure. Such studies demonstrate that comparing a target problem to an analogous problem helps students retrieve base analogs that lack surface similarities. To devise more portable ways of enhancing analogical transfer, Experiment 1 replicated Kurtz and Loewenstein's (Memory & Cognition, 35, 334-341, 2007) target-comparison procedure with an additional condition in which participants compared the target to a nonanalogous problem before attempting to reach its solution. Although comparing two analogous targets outperformed the standard transfer condition in promoting analogical transfer, comparing nonanalogous problems did not yield a transfer advantage. Based on prior studies that showed that the activity of creating analogous problems during their initial encoding elicits a more abstract representation of base analogs, in Experiment 2 we assessed whether constructing a second analogous target problem at retrieval time helps participants retrieve superficially dissimilar base analogs. As predicted, target invention increased the retrieval of distant sources. In both experiments we found an association between the quality of the generated schemas and the probability of retrieving a distant base analog from memory.

One shot, one kill: the forces delivered by archer fish shots to distant targets.

PubMed

Burnette, Morgan F; Ashley-Ross, Miriam A

2015-10-01

Archer fishes are skillful hunters of terrestrial prey, firing jets of water that dislodge insects perched on overhead vegetation. In the current investigation, we sought an answer to the question: are distant targets impractical foraging choices? Targets far from the shooter might not be hit with sufficient force to cause them to fall. However, observations from other investigators show that archer fish fire streams of water that travel in a non-ballistic fashion, which is thought to keep on-target forces high, even to targets that are several body lengths distant from the fish. We presented targets at different distances and investigated three aspects of foraging behavior: (i) on-target forces, (ii) shot velocity, (iii) a two-target choice assay to determine if fish would show any preference for downing closer targets or more distant targets. In general, shots from our fish (Toxotes chatareus) showed a mild decrease (less than 15% on average) in on-target forces at our most distant target offered (5.8 body lengths) with respect to the closest target offered (2.3 body lengths). One individual in our investigation showed slightly, but significantly, greater on-target forces as target distance increased. Forces on the furthest targets offered were found to double that of attachment forces for 200mg insects, even for individuals whose on-target forces showed mild decreases with increases in target distance. High-speed video analysis of jet impact with the target revealed that the shot was traveling in a non-ballistic manner, even to our most distant target offered, corroborating previous suppositions that on-target forces should remain high. Fish were able to accomplish this without large changes to shot velocity, but we did find evidence that the water jets appeared to differ in the timing of their acceleration as target distance increased. Our two-target choice experiment revealed that fish show preference for downing the closer target first, even though impact forces on distant targets only showed mild decreases. Our overall findings (and the findings of others) suggest that archer fish modulate many aspects of their shooting behavior: from target selection to active control over the water jet that allows the fish to deliver reliably forceful impacts to prey over a wide range of distances. Copyright © 2015 Elsevier GmbH. All rights reserved.

Scalable Engineering of Quantum Optical Information Processing Architectures (SEQUOIA)

DTIC Science & Technology

2016-12-13

arrays. Figure 4: An 8-channel fiber-coupled SNSPD array. 1.4 Post -fabrication-tunable linear optic fabrication We have analyzed the...performance of the programmable nanophotonic processor (PNP) that is dynamically tunable via post -fabrication active phase tuning to predict the scaling of...various device losses. PACS numbers: 42.50. Ex , 03.67.Dd, 03.67.Lx, 42.50.Dv I. INTRODUCTION Quantum key distribution (QKD) enables two distant authenticated

The Soldier-Cyborg Transformation: A Framework for Analysis of Social and Ethical Issues of Future Warfare

DTIC Science & Technology

1998-05-26

attitude about the use of chemical and biologic weapons , one must question the deterrent value of WMD. With perhaps the 19 exception of nuclear...ENHANCING, TRANSFORMING AND TRANSCENDING 1 TRENDS AND PREDICTIONS ABOUT FUTURE WARFARE 3 CHANGING DEMOGRAPHICS 8 THE BIOLOGIC SHIFT 10 STRATEGIC...without widespread loss of life. Thus, low lethality weapons and distant applications of precisely- applied force are mandatory to make future

Solar eclipses as a vehicle for international astronomy education.

NASA Astrophysics Data System (ADS)

Pasachoff, J. M.

The public's attention is drawn to astronomy whenever solar eclipse - partial, annular, or total - is visible, and we must take advantage of the opportunity to teach about the nature of science, the ability of astronomers to predict and analyze distant bodies and events, and the value of scientific research. We must also instruct people how to watch the partial and annular phases safely and that the total phase is not harmful.

Estimation of changes in alveolar-arterial oxygen gradient induced by hypoxia.

PubMed

Hoffstein, V; Duguid, N; Zamel, N; Rebuck, A S

1984-11-01

The alveolar-arterial oxygen tension difference provides a useful clinical indication of ventilation-blood flow mismatching in the lungs. In some clinical situations involving alveolar hypoxia (e.g., patients with chronic obstructive lung disease flying in commercial aircraft or normal humans at high altitudes) it would be useful to know this tension difference to predict the likely arterial PO2 under such potentially stressful conditions. Such estimates would require multiple arterial punctures performed under a variety of trying circumstances, conditions usually far distant from a suitable analytic facility. Consequently, we induced controlled hypoxia in 23 healthy humans and calculated changes in the alveolar-arterial oxygen tension difference during the hypoxic challenge test. We plotted this difference as a function of the alveolar oxygen tension over a range from 35 to 110 mm Hg. In addition to a series of control studies in which multiple arterial blood samples were obtained, we calculated arterial PO2 by converting the arterial oxyhemoglobin saturation (measured with an ear oximeter) into partial pressure of oxygen. During hypoxic procedures in which levels of oxygenation fell on the steep section of the oxyhemoglobin dissociation curve, fixing PCO2 at constant predetermined levels allowed accurate predictions of arterial PO2. We were able to demonstrate that the alveolar-arterial oxygen tension difference narrowed with decreasing alveolar oxygen tension, and that measurement with an ear oximeter provided data that allowed a reasonable estimate of the tension difference during hypoxic conditions.

Scheme for generating the singlet state of three atoms trapped in distant cavities coupled by optical fibers

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

Wang, Dong-Yang; Wen, Jing-Ji; Bai, Cheng-Hua

2015-09-15

An effective scheme is proposed to generate the singlet state with three four-level atoms trapped in three distant cavities connected with each other by three optical fibers, respectively. After a series of appropriate atom–cavity interactions, which can be arbitrarily controlled via the selective pairing of Raman transitions and corresponding optical switches, a three-atom singlet state can be successfully generated. The influence of atomic spontaneous decay, photon leakage of cavities and optical fibers on the fidelity of the state is numerically simulated showing that the three-atom singlet state can be generated with high fidelity by choosing the experimental parameters appropriately.

Detection and genetic characterization of a novel parvovirus distantly related to human bufavirus in domestic pigs.

PubMed

Hargitai, Renáta; Pankovics, Péter; Kertész, Attila Mihály; Bíró, Hunor; Boros, Ákos; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

2016-04-01

In this study, a novel parvovirus (strain swine/Zsana3/2013/HUN, KT965075) was detected in domestic pigs and genetically characterized by viral metagenomics and PCR methods. The novel parvovirus was distantly related to the human bufaviruses and was detected in 19 (90.5 %) of the 21 and five (33.3 %) of the 15 faecal samples collected from animals with and without cases of posterior paraplegia of unknown etiology from five affected farms and one control farm in Hungary, respectively. Swine/Zsana3/2013/HUN is highly prevalent in domestic pigs and potentially represents a novel parvovirus species in the subfamily Parvovirinae.

A pilot study of sphincter-sparing management of adenocarcinoma of the rectum.

PubMed

Steele, G; Busse, P; Huberman, M S; LeClair, J M; Falchuk, Z M; Mayer, R J; Bothe, A; Ravikumar, T S; Stone, M; Jessup, J M

1991-06-01

After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy.

[Usefulness of ¹⁸F-fluoro-2-deoxyglucose positron emission tomography in evaluation of gastric cancer stage].

PubMed

Yoon, Na Ri; Park, Jae Myung; Jung, Hee Sun; Cho, Yu Kyung; Lee, In Seok; Choi, Myung Gyu; Chung, In Sik; Song, Kyo Young; Park, Cho Hyun

2012-05-01

The usefulness of ¹⁸F-fluoro-2-deoxyglucose (FDG)-PET in detecting primary cancer, lymph node metastasis, and distant metastasis were studied in the gastric cancer patients. The subjects were 392 gastric cancer patients who received FDG-PET and an abdominal CT test prior to surgery. The results of FDG-PET and CT were compared with the surgical and pathologic results. The primary site detection rate of FDG-PET was 74.4%, 50.3% in early gastric cancer and 92.0% in advanced gastric cancer. Detection rate was higher when tumors were larger than 3.5 cm, had deeper depth of invasion, and at a later stage (p<0.05, respectively). In multivariate analysis, tumor size, spread of tumor cells beyond the muscle layer (≥T2), and lymph node metastasis were statistically significant factors in primary site detection rate. The sensitivity, specificity, and positive predictive value of FDG-PET to lymph node metastasis were 59.6%, 88.8%, and 81.1% respectively, sensitivity being lower compared to CT while specificity and positive predictive value were higher. Sensitivity, specificity, and positive predictive value to distant metastasis were, respectively, 66.7%, 99.2%, and 88.0%, similar to CT. In 21 of the 392 patients (5.4%), synchronous double primary cancers were detected. In gastric cancer, usefullness of FDG-PET is limited to the advanced stage. Diagnostic value of this test was not superior to CT. However, FDG-PET may be useful in detecting synchronous double primary cancers.

Predicting Protein-Protein Interactions by Combing Various Sequence-Derived.

PubMed

Zhao, Xiao-Wei; Ma, Zhi-Qiang; Yin, Ming-Hao

2011-09-20

Knowledge of protein-protein interactions (PPIs) plays an important role in constructing protein interaction networks and understanding the general machineries of biological systems. In this study, a new method is proposed to predict PPIs using a comprehensive set of 930 features based only on sequence information, these features measure the interactions between residues a certain distant apart in the protein sequences from different aspects. To achieve better performance, the principal component analysis (PCA) is first employed to obtain an optimized feature subset. Then, the resulting 67-dimensional feature vectors are fed to Support Vector Machine (SVM). Experimental results on Drosophila melanogaster and Helicobater pylori datasets show that our method is very promising to predict PPIs and may at least be a useful supplement tool to existing methods.

78. GENERAL VIEW OF SLC3W FUEL APRON FROM NORTH. HELIUM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

78. GENERAL VIEW OF SLC-3W FUEL APRON FROM NORTH. HELIUM AND NITROGEN STORAGE TANKS AND CONTROL SKIDS IN LEFT CENTER. FUEL STORAGE TANK AND CONTROL SKID IN RIGHT BACKGROUND. SLC-3E MST IN DISTANT RIGHT BACKGROUND. - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

Predictable transcriptome evolution in the convergent and complex bioluminescent organs of squid

PubMed Central

Pankey, M. Sabrina; Minin, Vladimir N.; Imholte, Greg C.; Suchard, Marc A.; Oakley, Todd H.

2014-01-01

Despite contingency in life’s history, the similarity of evolutionarily convergent traits may represent predictable solutions to common conditions. However, the extent to which overall gene expression levels (transcriptomes) underlying convergent traits are themselves convergent remains largely unexplored. Here, we show strong statistical support for convergent evolutionary origins and massively parallel evolution of the entire transcriptomes in symbiotic bioluminescent organs (bacterial photophores) from two divergent squid species. The gene expression similarities are so strong that regression models of one species’ photophore can predict organ identity of a distantly related photophore from gene expression levels alone. Our results point to widespread parallel changes in gene expression evolution associated with convergent origins of complex organs. Therefore, predictable solutions may drive not only the evolution of novel, complex organs but also the evolution of overall gene expression levels that underlie them. PMID:25336755

Identification of a distant cis-regulatory element controlling pharyngeal arch-specific expression of zebrafish gdf6a/radar

PubMed Central

Reed, Nykolaus P.; Mortlock, Douglas P.

2011-01-01

Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous skeletal abnormalities including joint fusions and cartilage reductions. The expression of Gdf6 is dynamic and in part regulated by distant evolutionarily conserved cis-regulatory elements. radar/gdf6a is a zebrafish ortholog of Gdf6 and has an essential role in embryonic patterning. Here we show that radar is transcribed in the cells surrounding and between the developing cartilages of the ventral pharyngeal arches, similar to mouse Gdf6. A 312 bp evolutionarily conserved region (ECR5), 122 kilobases downstream, drives expression in a pharyngeal arch-specific manner similar to endogenous radar/gdf6a. Deletion analysis identified a 78 bp region within ECR5 that is essential for transgene activity. This work illustrates that radar is regulated in the pharyngeal arches by a distant conserved element and suggests radar has similar functions in skeletal development in fish and mammals. PMID:20201106

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

PubMed

Vuilleumier, Patrik; Richardson, Mark P; Armony, Jorge L; Driver, Jon; Dolan, Raymond J

2004-11-01

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Quantum tagging for tags containing secret classical data

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

Kent, Adrian

Various authors have considered schemes for quantum tagging, that is, authenticating the classical location of a classical tagging device by sending and receiving quantum signals from suitably located distant sites, in an environment controlled by an adversary whose quantum information processing and transmitting power is potentially unbounded. All of the schemes proposed elsewhere in the literature assume that the adversary is able to inspect the interior of the tagging device. All of these schemes have been shown to be breakable if the adversary has unbounded predistributed entanglement. We consider here the case in which the tagging device contains a finitemore » key string shared with distant sites but kept secret from the adversary, and show this allows the location of the tagging device to be authenticated securely and indefinitely. Our protocol relies on quantum key distribution between the tagging device and at least one distant site, and demonstrates a new practical application of quantum key distribution. It also illustrates that the attainable security in position-based cryptography can depend crucially on apparently subtle details in the security scenario considered.« less

Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery.

PubMed

Keung, Emily Z; Hornick, Jason L; Bertagnolli, Monica M; Baldini, Elizabeth H; Raut, Chandrajit P

2014-02-01

Although sarcoma histology is recognized as a prognostic factor, most studies of retroperitoneal sarcomas report results combining multiple histologies and are inadequately powered to identify prognostic factors specific to a particular histology. We reviewed our experience with retroperitoneal dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of outcomes. All patients with RP DDLPS treated at our institution between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were performed to identify factors predictive of progression-free survival (PFS), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). We identified 119 patients with primary DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in 72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1 months. One hundred patients (84%) experienced recurrence or progression, with 92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1, 21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2 resection. On multivariate analysis, tumor integrity (intact vs fragmented) was predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1 vs R2), grade, and tumor integrity predicted OS. In this cohort of primary RP DDLPS, factors under surgeon control (tumor integrity, extent of resection) and reflective of tumor biology (grade, multifocality) impact patient outcomes. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Predicting Pharmacodynamic Drug-Drug Interactions through Signaling Propagation Interference on Protein-Protein Interaction Networks.

PubMed

Park, Kyunghyun; Kim, Docyong; Ha, Suhyun; Lee, Doheon

2015-01-01

As pharmacodynamic drug-drug interactions (PD DDIs) could lead to severe adverse effects in patients, it is important to identify potential PD DDIs in drug development. The signaling starting from drug targets is propagated through protein-protein interaction (PPI) networks. PD DDIs could occur by close interference on the same targets or within the same pathways as well as distant interference through cross-talking pathways. However, most of the previous approaches have considered only close interference by measuring distances between drug targets or comparing target neighbors. We have applied a random walk with restart algorithm to simulate signaling propagation from drug targets in order to capture the possibility of their distant interference. Cross validation with DrugBank and Kyoto Encyclopedia of Genes and Genomes DRUG shows that the proposed method outperforms the previous methods significantly. We also provide a web service with which PD DDIs for drug pairs can be analyzed at http://biosoft.kaist.ac.kr/targetrw.

Nasopharyngeal cancer: a review of 1605 patients treated radically with cobalt 60. [5- and 10-year survival rates and complications of radiotherapy

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

Huang, S.C.

A retrospective study was performed on 1605 patients with histologically proven and radically treated nasopharyngeal carcinoma. All were followed for a minimum of five years; 833 patients had a minimum follow-up period of ten years. Treatment results were reviewed according to: (1) size of primary tumor; (2) base of skull invasion; (3) cranial nerve involvement; (4) cervical node metastases; and (5) distant spread. An appropriate staging system was developed that reflected these prognostic factors. The evidence presented indicates that in this series of patients, base of skull involvement was less ominous than cranial nerve involvement. Unilteral lymph node involvement carriedmore » a better prognosis than bilateral neck nodes, this was the poorest sign of all since it predicted distant metastases. The average 5-year survival rate for 1605 patients in all stages, was 529/1605(32.1%); the 10-year survival rate for 833 patients in all stages was 20.2%.« less

Magnetospheric access of solar particles and the configuration of the distant geomagnetic field, volume 1. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Evans, L. C.

1972-01-01

The access of 1.2 to 40 MeV protons and 0.4 to 1.0 MeV electrons from interplanetary space to the polar cap regions was investigated with an experiment on board a low altitude, polar-orbiting satellite (0G0 4). A total of 333 quiet time observations of the electron polar cap boundary give a mapping of the boundary between open and closed geomagnetic field lines. Observations of events associated with co-rotating regions of enhanced proton flux in interplanetary space were used to establish the characteristics of the 1.2 to 40 MeV proton access windows. The results were compared to particle access predictions of the distant geomagnetic tail configurations. The role played by interplanetary anisotropies in the observation of persistent polar cap features is discussed. Special emphasis is given to the problem of nonadiabatic particle entry through regions where the magnetic field is changing direction.

Predicted contextual modulation varies with distance from pinwheel centers in the orientation preference map

PubMed Central

Okamoto, Tsuyoshi; Ikezoe, Koji; Tamura, Hiroshi; Watanabe, Masataka; Aihara, Kazuyuki; Fujita, Ichiro

2011-01-01

In the primary visual cortex (V1) of some mammals, columns of neurons with the full range of orientation preferences converge at the center of a pinwheel-like arrangement, the ‘pinwheel center' (PWC). Because a neuron receives abundant inputs from nearby neurons, the neuron's position on the cortical map likely has a significant impact on its responses to the layout of orientations inside and outside its classical receptive field (CRF). To understand the positional specificity of responses, we constructed a computational model based on orientation preference maps in monkey V1 and hypothetical neuronal connections. The model simulations showed that neurons near PWCs displayed weaker but detectable orientation selectivity within their CRFs, and strongly reduced contextual modulation from extra-CRF stimuli, than neurons distant from PWCs. We suggest that neurons near PWCs robustly extract local orientation within their CRF embedded in visual scenes, and that contextual information is processed in regions distant from PWCs. PMID:22355631

Prognostic significance of combined pretreatment lymphocyte counts and body mass index in patients with head and neck cancer treated with radiation therapy.

PubMed

Wu, Yao-Yu; Chang, Kai-Ping; Lin, Chien-Yu; Pai, Ping-Ching; Wang, Hung-Ming; Hsu, Cheng-Lung; Liao, Chun-Ta; Yen, Tzu-Chen; Fang, Tuan-Jen; Huang, Shiang-Fu; Kang, Chung-Jan; Fang, Ku-Hao; Lin, Wan-Ni; Wang, Yu-Chien; Hsin, Li-Jen; Tsang, Ngan-Ming

2018-05-23

We aimed to investigate the prognostic significance of combined pretreatment lymphocyte counts (LCs) and body mass index (BMI) in patients with head and neck cancer (HNC) treated with radiation therapy (RT). Nine hundred and twelve patients with HNC who were treated with RT were retrospectively reviewed. Survival was analyzed by stratifying the patients according to pretreatment LCs and BMI. Patients with low pretreatment LCs and BMI were characterized by a more advanced T stage, fewer nasopharyngeal subsites, less smoking and drinking, and fewer comorbidities. Patients with low pretreatment LCs and BMI had a significantly poorer overall and distant metastasis-free survival than those with high pretreatment LCs and BMI. No significant differences were observed in terms of local or regional recurrence-free survival. Combined pretreatment LCs and BMI may be more effective at predicting overall and distant metastasis-free survival in patients with HNC treated with RT. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis.

PubMed

Thavaneswaran, Subotheni; Kok, Peey Sei; Price, Timothy

2017-10-01

Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC. We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included. Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation. There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed.

Metastatic patterns and metastatic sites in mucosal melanoma: a retrospective study.

PubMed

Grözinger, Gerd; Mann, Steven; Mehra, Tarun; Klumpp, Bernhard; Grosse, Ulrich; Nikolaou, Konstantin; Garbe, Claus; Clasen, Stephan

2016-06-01

Melanomas arising from mucosa are rare and associated with a poor prognosis. This study aims to provide an analysis of metastatic pathways, time intervals, factors influencing metastatic spread and organs for distant metastases. A total of 116 patients with mucosal melanomas of different sites were included. The mean follow-up interval was 47 ± 52 months. Patients were assigned to two different metastatic pathways, either presenting loco-regional lymph node metastases as first spread or direct distant metastases. The distribution of distant metastases was assessed. Twenty-six patients presented with a pre-existing metastatic spread and were not assigned to pathways. Of the included patients, 44 developed metastases after treatment of the primary tumour; 25 patients directly developed distant metastases; 16 patients developed regional lymph node metastases prior to distant metastases. Location of the primary tumour in the upper airway or GI tract and advanced T stage were significant risk factors of direct distant metastases. Distant metastases are mainly located in the lung, the liver and non-regional lymph nodes. Mucosal melanomas show a high rate of direct distant metastases rather than regional lymph node metastases. Thus the follow-up should always include a whole-body cross-sectional imaging in high-risk tumours. • Mucosal melanomas show a high rate of direct distant metastases. • T stage and primary location are predictors for direct distant metastases. • Distant metastases were mainly found in lung, liver and lymph nodes. • Follow-up of a high-risk mucosal melanoma should include whole-body imaging.

Too young for rainforests? The impact of a rainforest curriculum on elementary students' affective responses to nature

NASA Astrophysics Data System (ADS)

Matteson, Kathryn Alice

A theory relating to children's affective responses to education about large-scale, distant environmental issues has become fairly widely accepted among environmental educators. The theory is encapsulated in the term "ecophobia," coined by David Sobel in Beyond Ecophobia (1996). According to this notion, elementary school children may become fearful of, or dissociated from, nature as they receive little direct exposure to nature and as they learn about distant environmental issues such as rainforest depletion. However, this seems a conflation of two discrete factors (lack of exposure to nature and education about distant environmental issues) that should be examined separately. Although children's exposure to nature has been studied, there appears to be no scientific research that examines elementary school students' affective responses to nature following education about distant environmental issues. This study endeavors to fill the apparent gap by measuring 4th graders' affective responses to nature following a unit on tropical rainforests. Deforestation represents a "distant" environmental issue that is thought to cause fear of, or dissociation from, nature among elementary school students. This quasi-experimental study involved a pretest, a posttest, and 150 4th grade participants in 8 classes. Students in all eight classes were administered a pretest questionnaire, inquiring about their affective responses to nature. Four classes then underwent a week-long unit on rainforests while four control group classes did not. All eight classes were then administered a posttest questionnaire. The data did not support the hypotheses that participants would feel more appreciative of nature and more empowered to protect nature following the rainforest unit. However, the data do support the hypotheses that the unit would not cause participants to feel increased fear of or dissociation from, nature. The data also suggest that greater amounts of time spent in nature were associated with greater appreciation of nature and less fear of nature. This research represents an initial effort to understand the developmental appropriateness of educating elementary school students about distant environmental issues. Further research on this topic is needed.

From Breast to Bone: Tracking Gene Expression Changes Responsible for Breast Cancer Metastasis in a Humanized Mouse Model with Molecular Imaging

DTIC Science & Technology

2015-11-01

strategies to predict and prevent metastasis. 15. SUBJECT TERMS triple-negative breast cancer, metastasis, p53, BTG2, PDX Models 16. SECURITY CLASSIFICATION...membrane and into the circulation, survival in the circulation, extravasation into distant organs, tumor dormancy, and finally tumor growth in the...sequencing analysis are novel targets for metastasis prevention or are more effective at destroying metastatic cells while minimizing the risk of

Lower-Hybrid-Drift Wave Turbulence in the Distant Magnetotail

DTIC Science & Technology

1978-05-01

kV ɘ with =• Y ~~ <» (Krall and Liewer, 1971). In this situation a Doppler shifted ,1; lower hybrid wave (u), - kV, . = ± u...satellite includes the relevant Doppler shifts since, in general, proton bulk flows are not directed parallel to the local magnetic field vector...theory of Section II predicts a relatively narrow frequency spectrum, the dominance of the Doppler shifting term k • Vp in Eq.(23)acts to

Local and long-range endogenous resting potential gradients antagonistically regulate apoptosis and proliferation in the embryonic CNS.

PubMed

Pai, Vaibhav P; Lemire, Joan M; Chen, Ying; Lin, Gufa; Levin, Michael

2015-01-01

Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play an important role in large-scale patterning during embryonic development. Endogenous bioelectric gradients across tissues function as instructive factors during eye, brain, and other morphogenetic processes. An important and still poorly-understood aspect is the control of cell behaviors by the voltage states of distant cell groups. Here, experimental alteration of endogenous Vmem was induced in Xenopus laevis embryos by misexpression of well-characterized ion channel mRNAs, a strategy often used to identify functional roles of Vmem gradients during embryonic development and regeneration. Immunofluorescence analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections was used to characterize apoptosis and proliferation. Disrupting local bioelectric signals (within the developing neural tube region) increased caspase 3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and highly increased H3P within the brain, with normal brain patterning. Disrupting both the local and distant bioelectric signals produced antagonistic effects on caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis-proliferation balance within the developing brain and spinal cord: local (developing neural tube region) and distant (ventral non-neural region). Together, the local and long-range bioelectric signals create a binary control system capable of fine-tuning apoptosis and proliferation with the brain and spinal cord to achieve correct pattern and size control. Our data suggest a roadmap for utilizing bioelectric state as a diagnostic modality and convenient intervention parameter for birth defects and degenerative disease states of the CNS.

Radiomic machine-learning classifiers for prognostic biomarkers of advanced nasopharyngeal carcinoma.

PubMed

Zhang, Bin; He, Xin; Ouyang, Fusheng; Gu, Dongsheng; Dong, Yuhao; Zhang, Lu; Mo, Xiaokai; Huang, Wenhui; Tian, Jie; Zhang, Shuixing

2017-09-10

We aimed to identify optimal machine-learning methods for radiomics-based prediction of local failure and distant failure in advanced nasopharyngeal carcinoma (NPC). We enrolled 110 patients with advanced NPC. A total of 970 radiomic features were extracted from MRI images for each patient. Six feature selection methods and nine classification methods were evaluated in terms of their performance. We applied the 10-fold cross-validation as the criterion for feature selection and classification. We repeated each combination for 50 times to obtain the mean area under the curve (AUC) and test error. We observed that the combination methods Random Forest (RF) + RF (AUC, 0.8464 ± 0.0069; test error, 0.3135 ± 0.0088) had the highest prognostic performance, followed by RF + Adaptive Boosting (AdaBoost) (AUC, 0.8204 ± 0.0095; test error, 0.3384 ± 0.0097), and Sure Independence Screening (SIS) + Linear Support Vector Machines (LSVM) (AUC, 0.7883 ± 0.0096; test error, 0.3985 ± 0.0100). Our radiomics study identified optimal machine-learning methods for the radiomics-based prediction of local failure and distant failure in advanced NPC, which could enhance the applications of radiomics in precision oncology and clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

June 2017 Ancho Canyon RF Collects: Final Report

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

Junor, William; Layne, John Preston; Goglio, Joshua Henry

2017-09-21

We report the results from the June 8, 2017, Ancho Canyon RF collection. While bright, electromagnetic signals were seen close to the firing point, there were no detections of signals from the explosively-fired fuse (EFF) at a collection point about 600m distant on the East Mesa. The East Mesa site was unable to collect data because the uninterruptible power supply (UPS) was exhausted by the time of the shot. We did see signals from the EFF at the Bunker 57 antennas, about 123m distant from the Point 88 firing point. The strength of these signals is consistent with our limitedmore » knowledge of the collection antenna performance and the use of the standard model to predict the electric field strength. From our knowledge of the geometry of the EFF loop and the current in the loop in this test, and from measurements at the Bunker 57 site, we predict that we would have seen signals of about 50mV at 3.67MHz in a 100 kHz channel on the Rohde & Schwarz HE010 antennas at the East Mesa location. The noise oor there is about 0.113mV (based on the March 2017 collects). Thus we would have had an SNR of 53 dB from the collect, had the data collection system been running.« less

The Fit between School Board Control and Behaviour of Middle Managers, Team Leaders and Teachers in Dutch Colleges for Vocational Education and Training

ERIC Educational Resources Information Center

Honingh, Marlies; van Genugten, Marieke

2017-01-01

The inspectorate's judgements about a school's educational quality in the Netherlands are to a large extent based on sophisticated desk research, risk analyses and analyses of the school's self-evaluation reports. This relatively distant mode of inspecting schools relies on rational ideas about organizational management and control while aspects…

Evaluation of Distant Education Programs with Regards to Various Shareholder Opinions

ERIC Educational Resources Information Center

Tonbuloglu, Betül; Gürol, Aysun

2016-01-01

The strong demand and rapid increase in the number of programs concerning distant education programs has put the quality problem of distant education services into the agenda. It is crucial to determine the strengths and weaknesses of distant education programs, the problems encountered by these programs and making the required improvements. The…

Distant, delayed and ancient earthquake-induced landslides

NASA Astrophysics Data System (ADS)

Havenith, Hans-Balder; Torgoev, Almaz; Braun, Anika; Schlögel, Romy; Micu, Mihai

2016-04-01

On the basis of a new classification of seismically induced landslides we outline particular effects related to the delayed and distant triggering of landslides. Those cannot be predicted by state-of-the-art methods. First, for about a dozen events the 'predicted' extension of the affected area is clearly underestimated. The most problematic cases are those for which far-distant triggering of landslides had been reported, such as for the 1988 Saguenay earthquake. In Central Asia reports for such cases are known for areas marked by a thick cover of loess. One possible contributing effect could be a low-frequency resonance of the thick soils induced by distant earthquakes, especially those in the Pamir - Hindu Kush seismic region. Such deep focal and high magnitude (>>7) earthquakes are also found in Europe, first of all in the Vrancea region (Romania). For this area and others in Central Asia we computed landslide event sizes related to scenario earthquakes with M>7.5. The second particular and challenging type of triggering is the one delayed with respect to the main earthquake event: case histories have been reported for the Racha earthquake in 1991 when several larger landslides only started moving 2 or 3 days after the main shock. Similar observations were also made after other earthquake events in the U.S., such as after the 1906 San Francisco, the 1949 Tacoma, the 1959 Hebgen Lake and the 1983 Bora Peak earthquakes. Here, we will present a series of detailed examples of (partly monitored) mass movements in Central Asia that mainly developed after earthquakes, some even several weeks after the main shock: e.g. the Tektonik and Kainama landslides triggered in 1992 and 2004, respectively. We believe that the development of the massive failures is a consequence of the opening of tension cracks during the seismic shaking and their filling up with water during precipitations that followed the earthquakes. The third particular aspect analysed here is the use of large ancient landslides for paleoseismic studies. As Central Asian mountain regions are marked by a relatively high ratio of seismically versus climatically triggered landslides, they represent a prime test area for such studies. This observation is contrasting with known landslide activity in Europe where by far most landslides are triggered by climatic factors, besides for some seismically active regions in the Eastern Alps, around the Mediterranean Sea and in the Carpathians (Vrancea, Romania). We will discuss how we may identify such earthquake-triggered landslides and how we may distinguish them from rainfall-induced slope failures.

Uncovering the spatially distant feedback loops of global trade: A network and input-output approach.

PubMed

Prell, Christina; Sun, Laixiang; Feng, Kuishuang; He, Jiaying; Hubacek, Klaus

2017-05-15

Land-use change is increasingly driven by global trade. The term "telecoupling" has been gaining ground as a means to describe how human actions in one part of the world can have spatially distant impacts on land and land-use in another. These interactions can, over time, create both direct and spatially distant feedback loops, in which human activity and land use mutually impact one another over great expanses. In this paper, we develop an analytical framework to clarify spatially distant feedbacks in the case of land use and global trade. We use an innovative mix of multi-regional input-output (MRIO) analysis and stochastic actor-oriented models (SAOMs) for analyzing the co-evolution of changes in trade network patterns with those of land use, as embodied in trade. Our results indicate that the formation of trade ties and changes in embodied land use mutually impact one another, and further, that these changes are linked to disparities in countries' wealth. Through identifying this feedback loop, our results support ongoing discussions about the unequal trade patterns between rich and poor countries that result in uneven distributions of negative environmental impacts. Finally, evidence for this feedback loop is present even when controlling for a number of underlying mechanisms, such as countries' land endowments, their geographical distance from one another, and a number of endogenous network tendencies. Copyright © 2017 Elsevier B.V. All rights reserved.

Negative and positive life events are associated with small but lasting change in neuroticism.

PubMed

Jeronimus, B F; Ormel, J; Aleman, A; Penninx, B W J H; Riese, H

2013-11-01

High neuroticism is prospectively associated with psychopathology and physical health. However, within-subject changes in neuroticism due to life experiences (LEs) or state effects of current psychopathology are largely unexplored. In this 2-year follow-up study, four hypotheses were tested: (1) positive LEs (PLEs) decrease and negative LEs (NLEs) increase neuroticism; (2) LE-driven change in neuroticism is partly long-lasting; and (3) partly independent of LE-driven changes in anxiety/depression; and (4) childhood adversity (before age 16 years) moderates the influence of NLEs/PLEs on neuroticism scores in adult life. Data came from the Netherlands Study of Depression and Anxiety [NESDA, n = 2981, mean age 41.99 years (s.d. = 13.08), 66.6% women]. At follow-up (T₂) we assessed PLEs/NLEs with the List of Threatening Experiences (LTE) over the prior 24 months and categorized them over recent and distant PLE/NLE measures (1-3 and 4-24 months prior to T₂ respectively) to distinguish distant NLE/PLE-driven change in trait neuroticism (using the Dutch version of the Neuroticism-Extroversion-Openness Five Factor Inventory, NEO-FFI) from state deviations due to changes in symptoms of depression (self-rated version of the 30-item Inventory of Depressive Symptomatology, IDS-SR30) and anxiety (Beck Anxiety Inventory, BAI). Distant NLEs were associated with higher and distant PLEs with lower neuroticism scores. The effects of distant LEs were weak but long-lasting, especially for distant PLEs. Distant NLE-driven change in neuroticism was associated with change in symptoms of anxiety/depression whereas the effect of distant PLEs on neuroticism was independent of any such changes. Childhood adversity weakened the impact of distant NLEs but enhanced the impact of distant PLEs on neuroticism. Distant PLEs are associated with small but long-lasting decreases in neuroticism regardless of changes in symptom levels of anxiety/depression. Long-lasting increases in neuroticism associated with distant NLEs are mediated by anxiety/depression.

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

PubMed Central

2010-01-01

Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial. PMID:21047402

Predicting protein-protein interactions by combing various sequence- derived features into the general form of Chou's Pseudo amino acid composition.

PubMed

Zhao, Xiao-Wei; Ma, Zhi-Qiang; Yin, Ming-Hao

2012-05-01

Knowledge of protein-protein interactions (PPIs) plays an important role in constructing protein interaction networks and understanding the general machineries of biological systems. In this study, a new method is proposed to predict PPIs using a comprehensive set of 930 features based only on sequence information, these features measure the interactions between residues a certain distant apart in the protein sequences from different aspects. To achieve better performance, the principal component analysis (PCA) is first employed to obtain an optimized feature subset. Then, the resulting 67-dimensional feature vectors are fed to Support Vector Machine (SVM). Experimental results on Drosophila melanogaster and Helicobater pylori datasets show that our method is very promising to predict PPIs and may at least be a useful supplement tool to existing methods.

Heat and hydration status: Predictors of repeated measures of urine specific gravity among Tsimane' adults in the Bolivian Amazon.

PubMed

Rosinger, Asher

2015-12-01

Hydration status is critical to physiological and cognitive health, yet it is unclear how populations living in hot-humid environments experiencing lifestyle transitions manage this underexplored facet of heat adaptation. This study assesses the predictors of repeated measures of hydration status for adults from two villages (close and distant from a market town) in the Bolivian Amazon. Interviews and focal follows were conducted with 36 Tsimane' (50% male). Urine samples, temperature, activity levels, and anthropometrics were measured pre-interview and post-follow and yielded a small panel (72 observations). Urine samples were analyzed for urine specific gravity (USG), a biomarker of hydration, with a refractometer. The mean USG was 1.020 g/ml (SD ± 0.008) with men (1.022 ± 0.008) slightly more dehydrated than women (1.018 ± 0.007). Using 1.020 as the criteria for clinical dehydration, 42% of the participants were dehydrated at both intervals and 21% were extremely dehydrated. Controlling for activity level, village membership, and covariates in random-effects linear regression models, each degree centigrade increase was associated with a USG increase of 0.0008 g/ml (P = 0.000). Adults from the village closer to the market town had significantly higher USG (B = 0.0041; P = 0.04) than those in the distant village. Dehydration was predicted to occur at 29°C, just above the thermoneutral range, and extreme dehydration at 37°C. These findings suggest that hotter temperatures coupled with lifestyle transitions may create conditions that increase vulnerability to dehydration among rural populations through landscape modifications and diet changes. © 2015 Wiley Periodicals, Inc.

37 CFR 256.2 - Royalty fee for compulsory license for secondary transmission by cable systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... receipts for the first distant signal equivalent; (3) .668 of 1 per centum of such gross receipts for each of the second, third and fourth distant signal equivalents; and (4) .314 of 1 per centum of such gross receipts for the fifth distant signal equivalent and each additional distant signal equivalent...

37 CFR 256.2 - Royalty fee for compulsory license for secondary transmission by cable systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... receipts for the first distant signal equivalent; (3) .668 of 1 per centum of such gross receipts for each of the second, third and fourth distant signal equivalents; and (4) .314 of 1 per centum of such gross receipts for the fifth distant signal equivalent and each additional distant signal equivalent...

37 CFR 256.2 - Royalty fee for compulsory license for secondary transmission by cable systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... receipts for the first distant signal equivalent; (3) .668 of 1 per centum of such gross receipts for each of the second, third and fourth distant signal equivalents; and (4) .314 of 1 per centum of such gross receipts for the fifth distant signal equivalent and each additional distant signal equivalent...

37 CFR 256.2 - Royalty fee for compulsory license for secondary transmission by cable systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... gross receipts for the first distant signal equivalent; (3) .668 of 1 per centum of such gross receipts for each of the second, third and fourth distant signal equivalents; and (4) .314 of 1 per centum of such gross receipts for the fifth distant signal equivalent and each additional distant signal...

37 CFR 256.2 - Royalty fee for compulsory license for secondary transmission by cable systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... receipts for the first distant signal equivalent; (3) .668 of 1 per centum of such gross receipts for each of the second, third and fourth distant signal equivalents; and (4) .314 of 1 per centum of such gross receipts for the fifth distant signal equivalent and each additional distant signal equivalent...

Experimental evidence for route integration and strategic planning in wild capuchin monkeys.

PubMed

Janson, Charles H

2007-07-01

Both in captivity and the wild, primates are found to travel mostly to the nearest available resource, but they may skip over the closest resource and travel to more distant resources, which are often found to be more productive. This study examines the tradeoff between distance and reward in the foraging choices of one group of wild capuchin monkeys (Cebus apella nigritus) using feeding platforms in large-scale foraging experiments conducted over four years. Three feeding sites were arrayed in an oblique triangle, such that once the monkey group had chosen one site to feed, they had a choice between two remaining sites, a close one with less food and the other up to 2.3 times as far away but with more food. Sites were provisioned once per day. The capuchins generally chose the closer feeding site, even when the more distant site offered up to 12 times as much food. The distances to, rewards of, or various profitability measures applied to each alternative site individually did not explain the group's choices in ways consistent with foraging theory or principles of operant psychology. The group's site choices were predicted only by comparing efficiency measures of entire foraging pathways: (1) direct travel to the more rewarding distant site, versus (2) the longer 'detour' through the closer site on the way to the more distant one. The group chose the detour more often when the reward was larger and the added detour distance shorter. They appeared to be more sensitive to the absolute increase in detour distance than to the relative increase compared to the straight route. The qualitative and quantitative results agree with a simple rule: do not use the detour unless the energy gain from extra food outweighs the energy cost of extra travel. These results suggest that members of this group integrate information on spatial location, reward, and perhaps potential food competition in their choice of multi-site foraging routes, with important implications for social foraging.

The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

PubMed

Pierie, J P; Choudry, U; Muzikansky, A; Yeap, B Y; Souba, W W; Ott, M J

2001-04-01

Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence.

Origins of coevolution between residues distant in protein 3D structures

PubMed Central

Ovchinnikov, Sergey; Kamisetty, Hetunandan; Baker, David

2017-01-01

Residue pairs that directly coevolve in protein families are generally close in protein 3D structures. Here we study the exceptions to this general trend—directly coevolving residue pairs that are distant in protein structures—to determine the origins of evolutionary pressure on spatially distant residues and to understand the sources of error in contact-based structure prediction. Over a set of 4,000 protein families, we find that 25% of directly coevolving residue pairs are separated by more than 5 Å in protein structures and 3% by more than 15 Å. The majority (91%) of directly coevolving residue pairs in the 5–15 Å range are found to be in contact in at least one homologous structure—these exceptions arise from structural variation in the family in the region containing the residues. Thirty-five percent of the exceptions greater than 15 Å are at homo-oligomeric interfaces, 19% arise from family structural variation, and 27% are in repeat proteins likely reflecting alignment errors. Of the remaining long-range exceptions (<1% of the total number of coupled pairs), many can be attributed to close interactions in an oligomeric state. Overall, the results suggest that directly coevolving residue pairs not in repeat proteins are spatially proximal in at least one biologically relevant protein conformation within the family; we find little evidence for direct coupling between residues at spatially separated allosteric and functional sites or for increased direct coupling between residue pairs on putative allosteric pathways connecting them. PMID:28784799

Plant-soil feedbacks from 30-year family-specific soil cultures: phylogeny, soil chemistry and plant life stage.

PubMed

Mehrabi, Zia; Bell, Thomas; Lewis, Owen T

2015-06-01

Intraspecific negative feedback effects, where performance is reduced on soils conditioned by conspecifics, are widely documented in plant communities. However, interspecific feedbacks are less well studied, and their direction, strength, causes, and consequences are poorly understood. If more closely related species share pathogens, or have similar soil resource requirements, plants may perform better on soils conditioned by more distant phylogenetic relatives. There have been few empirical tests of this prediction across plant life stages, and none of which attempt to account for soil chemistry. Here, we test the utility of phylogeny for predicting soil feedback effects on plant survival and performance (germination, seedling survival, growth rate, biomass). We implement a full factorial experiment growing species representing five families on five plant family-specific soil sources. Our experiments exploit soils that have been cultured for over 30 years in plant family-specific beds at Oxford University Botanic Gardens. Plant responses to soil source were idiosyncratic, and species did not perform better on soils cultured by phylogenetically more distant relatives. The magnitude and sign of feedback effects could, however, be explained by differences in the chemical properties of "home" and "away" soils. Furthermore, the direction of soil chemistry-related plant-soil feedbacks was dependent on plant life stage, with the effects of soil chemistry on germination success and accumulation of biomass inversely related. Our results (1) suggest that the phylogenetic distance between plant families cannot predict plant-soil feedbacks across multiple life stages, and (2) highlight the need to consider changes in soil chemistry as an important driver of population responses. The contrasting responses at plant life stages suggest that studies focusing on brief phases in plant demography (e.g., germination success) may not give a full picture of plant-soil feedback effects.

SU-F-R-10: Selecting the Optimal Solution for Multi-Objective Radiomics Model

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

Zhou, Z; Folkert, M; Wang, J

2016-06-15

Purpose: To develop an evidential reasoning approach for selecting the optimal solution from a Pareto solution set obtained by a multi-objective radiomics model for predicting distant failure in lung SBRT. Methods: In the multi-objective radiomics model, both sensitivity and specificity are considered as the objective functions simultaneously. A Pareto solution set with many feasible solutions will be resulted from the multi-objective optimization. In this work, an optimal solution Selection methodology for Multi-Objective radiomics Learning model using the Evidential Reasoning approach (SMOLER) was proposed to select the optimal solution from the Pareto solution set. The proposed SMOLER method used the evidentialmore » reasoning approach to calculate the utility of each solution based on pre-set optimal solution selection rules. The solution with the highest utility was chosen as the optimal solution. In SMOLER, an optimal learning model coupled with clonal selection algorithm was used to optimize model parameters. In this study, PET, CT image features and clinical parameters were utilized for predicting distant failure in lung SBRT. Results: Total 126 solution sets were generated by adjusting predictive model parameters. Each Pareto set contains 100 feasible solutions. The solution selected by SMOLER within each Pareto set was compared to the manually selected optimal solution. Five-cross-validation was used to evaluate the optimal solution selection accuracy of SMOLER. The selection accuracies for five folds were 80.00%, 69.23%, 84.00%, 84.00%, 80.00%, respectively. Conclusion: An optimal solution selection methodology for multi-objective radiomics learning model using the evidential reasoning approach (SMOLER) was proposed. Experimental results show that the optimal solution can be found in approximately 80% cases.« less

The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

PubMed

Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

2018-05-04

The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

Discovery, Orbit and Orbital Evolution of the Distant Object (463368) 2012 VU85

NASA Astrophysics Data System (ADS)

Wlodarczyk, I.; Černis, K.; Boyle, R. P.

2017-03-01

We present the discovery and time evolution of orbital elements of the distant Centaur-type object (463368) 2012 VU85. From all 2135 distant objects listed in the Minor Planet Center we select all 347 numbered distant object and integrate their equations of motion in the 1 Gyr forward and backward integration. The asteroid (463368) 2012 VU85 lies on the border of the group of 347 distant objects, which have a semimajor axis about 44 a.u., eccentricity 0.1 and inclination between 0° and 30°. We show that after 1 Gyr of forward integration, about half of the objects are expelled from the Solar System, \\ie their median lifetime is about 1 Gyr. We note that the long-lived distant objects are mainly located between the regions where Neptune controls aphelia of asteroids and the asteroids are in the mean motion resonance 2/3 with Neptune. We find eight almost regular approaches of clones of the asteroid (463368) 2012 VU85 to Neptune and several generally shorter in time regular approaches to Uranus. For other outer planets we did not detect any approaches below 5 a.u. for a period of 15 000 yr in forward and backward integrations. In our calculations we find eight episodes, each lasting about 3000 yr when the value of inclination oscillates around its average. These changes look similar to the changes of semimajor axis during the occurrence of orbital mean motion resonance with a planet. We find that half of the clones of the asteroid (463368) 2012 VU85 remain in the Solar System for a forward integration of 44 Myr, and for a backward integration of 34 Myr. This is a significantly shorter escape time as compared to the group of distant objects. Almost all long-lived clones have value of Tisserand parameter with respect to Neptune smaller than 3 during the whole 1 Gyr forward and backward integrations. This implies that there are several clones of the asteroid (463368) 2012 VU85 that cross the orbits of Neptune and Uranus. We find many orbital mean motion resonances lasting up to several Myr in the motion of the asteroid (463368) 2012 VU85. According to our computations the presence of the Kozai resonance protects the asteroid from the close approaches with Uranus and Neptune. The Lyapunov time for the asteroid (463368) 2012 VU85 is equal to 4260 years.

Visual Impairment Screening at the Geriatric Frailty Clinic for Assessment of Frailty and Prevention of Disability at the Gérontopôle.

PubMed

Soler, V; Sourdet, S; Balardy, L; Abellan van Kan, G; Brechemier, D; Rougé-Bugat, M E; Tavassoli, N; Cassagne, M; Malecaze, F; Nourhashémi, F; Vellas, B

2016-01-01

To evaluate visual performance and factors associated with abnormal vision in patients screened for frailty at the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability at Toulouse University Hospital. Retrospective, observational cross-sectional, single-centre study. Institutional practice. Patients were screened for frailty during a single-day hospital stay between October 2011 and October 2014 (n = 1648). Collected medical records included sociodemographic data (including living environment and educational level), anthropometric data, and clinical data. The general evaluation included the patient's functional status using the Activities of Daily Living (ADL) scale and the Instrumental Activity of Daily Living (IADL) scale, the Mini-Mental State Examination (MMSE) for cognition testing, and the Short Physical Performance Battery (SPPB) for physical performance. We also examined Body Mass Index (BMI), the Mini-Nutritional Assessment (MNA), and the Hearing Handicap Inventory for the Elderly Screening (HHIE-S) tool. The ophthalmologic evaluation included assessing visual acuity using the Snellen decimal chart for distant vision, and the Parinaud chart for near vision. Patients were divided into groups based on normal distant/near vision (NDV and NNV groups) and abnormal distant/near vision (ADV and ANV groups). Abnormal distant or near vision was defined as visual acuity inferior to 20/40 or superior to a Parinaud score of 2, in at least one eye. Associations with frailty-associated factors were evaluated in both groups. The mean age of the population was 82.6 ± 6.2 years. The gender distribution was 1,061 females (64.4%) and 587 males (35.6%). According to the Fried criteria, 619 patients (41.1%) were pre-frail and 771 (51.1%) were frail. Distant and near vision data were available for 1425 and 1426 patients, respectively. Distant vision was abnormal for 437 patients (30.7%). Near vision was abnormal for 199 patients (14%). Multiple regression analysis showed that abnormal distant vision as well as abnormal near vision were independently associated with greater age (P < 0.01), lower educational level (P < 0.05), lower performance on the MMSE (P < 0.001), and lower autonomy (P < 0.02), after controlling for age, gender, educational level, Fried criteria, and MMSE score. The high prevalence of visual disorders observed in the study population and their association with lower autonomy and cognitive impairment emphasises the need for systematic screening of visual impairments in the elderly. Frailty was not found to be independently associated with abnormal vision.

Algorithm to find distant repeats in a single protein sequence

PubMed Central

Banerjee, Nirjhar; Sarani, Rangarajan; Ranjani, Chellamuthu Vasuki; Sowmiya, Govindaraj; Michael, Daliah; Balakrishnan, Narayanasamy; Sekar, Kanagaraj

2008-01-01

Distant repeats in protein sequence play an important role in various aspects of protein analysis. A keen analysis of the distant repeats would enable to establish a firm relation of the repeats with respect to their function and three-dimensional structure during the evolutionary process. Further, it enlightens the diversity of duplication during the evolution. To this end, an algorithm has been developed to find all distant repeats in a protein sequence. The scores from Point Accepted Mutation (PAM) matrix has been deployed for the identification of amino acid substitutions while detecting the distant repeats. Due to the biological importance of distant repeats, the proposed algorithm will be of importance to structural biologists, molecular biologists, biochemists and researchers involved in phylogenetic and evolutionary studies. PMID:19052663

The Influence of Diabetes Mellitus and Metformin on Distant Metastases in Oropharyngeal Cancer: A Multicenter Study

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

Spratt, Daniel E.; Beadle, Beth M.; Zumsteg, Zachary S., E-mail: zachary.zumsteg@cshs.org

Purpose: Local control in oropharyngeal cancer has improved to unprecedented rates with combined modality therapy; as a result, distant metastases are becoming a principal challenge. We aimed to determine the impact of diabetes mellitus and metformin use on clinical outcomes in a large population of oropharyngeal cancer patients treated in the modern era. Methods and Materials: We identified 1745 consecutive patients with oropharyngeal cancer treated at 2 large cancer centers with external beam radiation therapy from 1998 to 2011. A total of 184 patients had diabetes mellitus at the time of diagnosis, of whom 102 were taking metformin. The outcomesmore » assessed included local failure-free survival (LFFS), regional failure-free survival (RFFS), distant metastasis-free survival (DMFS), and overall survival (OS). Results: The median follow-up time was 4.3 years. The 5-year actuarial rates of DMFS were 89.6% for nondiabetic patients and 78.7% for diabetic nonmetformin users (P=.011) and of OS were 83.0% for nondiabetic patients and 70.7% for diabetic nonmetformin users (P=.048). Diabetic metformin users had 5-year DMFS (90.1%) and OS (89.6%) similar to those of nondiabetic patients. Multivariate analysis (diabetic nonmetformin users as reference) demonstrated improved DMFS for nondiabetic patients (adjusted hazard ratio 0.54; 95% confidence interval 0.32-0.93; P=.03) and a trend toward improved DMFS with metformin use (adjusted hazard ratio 0.46; 95% confidence interval 0.20-1.04; P=.06). LFFS and RFFS were high in all groups and were not significantly different by diabetic status or metformin use. Conclusions: Diabetic patients not using metformin independently have significantly higher rates of distant metastases than do nondiabetic patients, whereas metformin users have rates of distant metastases similar to those of nondiabetic patients. Further prospective investigation is warranted to validate the benefit of metformin in oropharyngeal cancer.« less

A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

PubMed

Yuan, Xi; Liu, Wen-Jie; Li, Bing; Shen, Ze-Tian; Shen, Jun-Shu; Zhu, Xi-Xu

2017-08-01

This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks-Gelman-Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

Bidirectional Controlled Quantum Teleportation in the Three-dimension System

NASA Astrophysics Data System (ADS)

Ma, Peng-Cheng; Chen, Gui-Bin; Li, Xiao-Wei; Zhan, You-Bang

2018-04-01

We present a scheme for bidirectional controlled quantum teleportation (BCQT) via a five-qutrit entangled state as the quantum channel. In this scheme, two distant parties, Alice and Bob, are not only senders but also receivers, and Alice wants to teleport an unknown single-qutrit state to Bob, at the same time, Bob wishes to teleport another arbitrary single-qutrit state, respectively. It is shown that, only if the two senders and the controller collaborate with each other, the BCQT can be completed successfully.

Bidirectional Controlled Joint Remote State Preparation via a Seven-Qubit Entangled State

NASA Astrophysics Data System (ADS)

Wang, Xiao-yu; Mo, Zhi-wen

2017-04-01

A new protocol for implementing five-party bidirectional controlled joint remote state preparation is proposed by using a seven-qubit entangled state as the quantum channel. It can be shown that two distant senders can simultaneously and deterministically exchange their states with the other senders under the control of the supervisor, and it cannot be succeed without permission of the controller. Only pauli operation and single-qubit measurement are used in our scheme, so the scheme with five-party is feasible within the reach of current technologies.

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

PubMed

Hansen, Eric; Panwala, Kathryn; Holland, John

2002-11-01

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

Low joining efficiency and non-conservative repair of two distant double-strand breaks in mouse embryonic stem cells.

PubMed

Boubakour-Azzouz, Imenne; Ricchetti, Miria

2008-02-01

Efficient and faithful repair of DNA double-strand breaks (DSBs) is critical for genome stability. To understand whether cells carrying a functional repair apparatus are able to efficiently heal two distant chromosome ends and whether this DNA lesion might result in genome rearrangements, we induced DSBs in genetically modified mouse embryonic stem cells carrying two I-SceI sites in cis separated by a distance of 9 kbp. We show that in this context non-homologous end-joining (NHEJ) can repair using standard DNA pairing of the broken ends, but it also joins 3' non-complementary overhangs that require unusual joining intermediates. The repair efficiency of this lesion appears to be dramatically low and the extent of genome alterations was high in striking contrast with the spectra of repair events reported for two collinear DSBs in other experimental systems. The dramatic decline in accuracy suggests that significant constraints operate in the repair process of these distant DSBs, which may also control the low efficiency of this process. These findings provide important insights into the mechanism of repair by NHEJ and how this process may protect the genome from large rearrangements.

Phyllodes tumours

PubMed Central

Parker, S; Harries, S

2001-01-01

Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasms. With the non-operative management of fibroadenomas widely adopted, the importance of phyllodes tumours today lies in the need to differentiate them from other benign breast lesions. All breast lumps should be triple assessed and the diagnosis of a phyllodes tumour considered in women, particularly over the age of 35 years, who present with a rapidly growing "benign" breast lump. Treatment can be by either wide excision or mastectomy provided histologically clear specimen margins are ensured. Nodal metastases are rare and routine axillary dissection is not recommended. Few reliable clinical and histological prognostic factors have been identified. Local recurrence occurs in approximately 15% of patients and is more common after incomplete excision. It can usually be controlled by further surgery. Repeated local recurrence has been reported without the development of distant metastases or reduced survival. Approximately 20% of patients with malignant phyllodes tumours develop distant metastases. Long term survival with distant metastases is rare. The role of chemotherapy, radiotherapy, and hormonal manipulation in both the adjuvant and palliative settings remain to be defined.


Keywords: benign breast disease; fibroadenoma; phyllodes tumour PMID:11423590

Mechanisms of Vowel Variation in African American English

ERIC Educational Resources Information Center

Holt, Yolanda Feimster

2018-01-01

Purpose: This research explored mechanisms of vowel variation in African American English by comparing 2 geographically distant groups of African American and White American English speakers for participation in the African American Shift and the Southern Vowel Shift. Method: Thirty-two male (African American: n = 16, White American controls: n =…

Speech Motor Development: Integrating Muscles, Movements, and Linguistic Units

ERIC Educational Resources Information Center

Smith, Anne

2006-01-01

A fundamental problem for those interested in human communication is to determine how ideas and the various units of language structure are communicated through speaking. The physiological concepts involved in the control of muscle contraction and movement are theoretically distant from the processing levels and units postulated to exist in…

Merlino-Perkins Father-Daughter Relationship Inventory (MP-FDI): Construction, Reliability, Validity, and Implications for Counseling and Research

ERIC Educational Resources Information Center

Merlino Perkins, Rose J.

2008-01-01

The Merlino-Perkins Father-Daughter Relationship Inventory, a self-report instrument, assesses women's childhood interactions with supportive, doting, distant, controlling, tyrannical, physically abusive, absent, and seductive fathers. Item and scale development, psychometric findings drawn from factor analyses, reliability assessments, and…

Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

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

Farris, Michael, E-mail: mfarris@wakehealth.edu; McTyre, Emory R.; Cramer, Christina K.

Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 newmore » metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.« less

Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

PubMed

Miyoshi, Yuichiro; Shien, Tadahiko; Ogiya, Akiko; Ishida, Naoko; Yamazaki, Kieko; Horii, Rie; Horimoto, Yoshiya; Masuda, Norikazu; Yasojima, Hiroyuki; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Tomioka, Nobumoto; Endo, Yumi; Hosoda, Mitsuchika; Doihara, Hiroyoshi; Miyoshi, Shinichiro; Yamashita, Hiroko

2016-07-02

The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

A statewide investigation of geographic lung cancer incidence patterns and radon exposure in a low-smoking population.

PubMed

Ou, Judy Y; Fowler, Brynn; Ding, Qian; Kirchhoff, Anne C; Pappas, Lisa; Boucher, Kenneth; Akerley, Wallace; Wu, Yelena; Kaphingst, Kimberly; Harding, Garrett; Kepka, Deanna

2018-01-31

Lung cancer is the leading cause of cancer-related mortality in Utah despite having the nation's lowest smoking rate. Radon exposure and differences in lung cancer incidence between nonmetropolitan and metropolitan areas may explain this phenomenon. We compared smoking-adjusted lung cancer incidence rates between nonmetropolitan and metropolitan counties by predicted indoor radon level, sex, and cancer stage. We also compared lung cancer incidence by county classification between Utah and all SEER sites. SEER*Stat provided annual age-adjusted rates per 100,000 from 1991 to 2010 for each Utah county and all other SEER sites. County classification, stage, and sex were obtained from SEER*Stat. Smoking was obtained from Environmental Public Health Tracking estimates by Ortega et al. EPA provided low (< 2 pCi/L), moderate (2-4 pCi/L), and high (> 4 pCi/L) indoor radon levels for each county. Poisson models calculated overall, cancer stage, and sex-specific rates and p-values for smoking-adjusted and unadjusted models. LOESS smoothed trend lines compared incidence rates between Utah and all SEER sites by county classification. All metropolitan counties had moderate radon levels; 12 (63%) of the 19 nonmetropolitan counties had moderate predicted radon levels and 7 (37%) had high predicted radon levels. Lung cancer incidence rates were higher in nonmetropolitan counties than metropolitan counties (34.8 vs 29.7 per 100,000, respectively). Incidence of distant stage cancers was significantly higher in nonmetropolitan counties after controlling for smoking (16.7 vs 15.4, p = 0.02*). Incidence rates in metropolitan, moderate radon and nonmetropolitan, moderate radon counties were similar. Nonmetropolitan, high radon counties had a significantly higher incidence of lung cancer compared to nonmetropolitan, moderate radon counties after adjustment for smoking (41.7 vs 29.2, p < 0.0001*). Lung cancer incidence patterns in Utah were opposite of metropolitan/nonmetropolitan trends in other SEER sites. Lung cancer incidence and distant stage incidence rates were consistently higher in nonmetropolitan Utah counties than metropolitan counties, suggesting that limited access to preventative screenings may play a role in this disparity. Smoking-adjusted incidence rates in nonmetropolitan, high radon counties were significantly higher than moderate radon counties, suggesting that radon was also major contributor to lung cancer in these regions. National studies should account for geographic and environmental factors when examining nonmetropolitan/metropolitan differences in lung cancer.

Nucleoli and stress granules: connecting distant relatives.

PubMed

Mahboubi, Hicham; Stochaj, Ursula

2014-10-01

Nucleoli and cytoplasmic stress granules (SGs) are subcellular compartments that modulate the response to endogenous and environmental signals to control cell survival. In our opinion, nucleoli and SGs are functionally linked; they are distant relatives that combine forces when cellular homeostasis is threatened. Several lines of evidence support this idea; nucleoli and SGs share molecular building blocks, are regulated by common signaling pathways and communicate when vital cellular functions become compromised. Together, nucleoli and SGs orchestrate physiological responses that are directly relevant to stress and human health. As both compartments have established roles in neurodegenerative diseases, cancer and virus infections, we propose that these conditions will benefit from therapeutic interventions that target simultaneously nucleoli and SGs. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Teleportation of a Toffoli gate among distant solid-state qubits with quantum dots embedded in optical microcavities

PubMed Central

Hu, Shi; Cui, Wen-Xue; Wang, Dong-Yang; Bai, Cheng-Hua; Guo, Qi; Wang, Hong-Fu; Zhu, Ai-Dong; Zhang, Shou

2015-01-01

Teleportation of unitary operations can be viewed as a quantum remote control. The remote realization of robust multiqubit logic gates among distant long-lived qubit registers is a key challenge for quantum computation and quantum information processing. Here we propose a simple and deterministic scheme for teleportation of a Toffoli gate among three spatially separated electron spin qubits in optical microcavities by using local linear optical operations, an auxiliary electron spin, two circularly-polarized entangled photon pairs, photon measurements, and classical communication. We assess the feasibility of the scheme and show that the scheme can be achieved with high average fidelity under the current technology. The scheme opens promising perspectives for constructing long-distance quantum communication and quantum computation networks with solid-state qubits. PMID:26225781

Teleportation of a Toffoli gate among distant solid-state qubits with quantum dots embedded in optical microcavities.

PubMed

Hu, Shi; Cui, Wen-Xue; Wang, Dong-Yang; Bai, Cheng-Hua; Guo, Qi; Wang, Hong-Fu; Zhu, Ai-Dong; Zhang, Shou

2015-07-30

Teleportation of unitary operations can be viewed as a quantum remote control. The remote realization of robust multiqubit logic gates among distant long-lived qubit registers is a key challenge for quantum computation and quantum information processing. Here we propose a simple and deterministic scheme for teleportation of a Toffoli gate among three spatially separated electron spin qubits in optical microcavities by using local linear optical operations, an auxiliary electron spin, two circularly-polarized entangled photon pairs, photon measurements, and classical communication. We assess the feasibility of the scheme and show that the scheme can be achieved with high average fidelity under the current technology. The scheme opens promising perspectives for constructing long-distance quantum communication and quantum computation networks with solid-state qubits.

Interaction of Intense Short Laser Pulses with Air and Dielectric Materials

NASA Astrophysics Data System (ADS)

Eisenmann, S.; Katzir, Y.; Zigler, A.; Fibich, G.; Louzon, E.; Ehrlich, Y.; Henis, Z.; Pecker, S.; Fisher, D.; Fraenkel, M.

A study of the propagation of intense short laser pulses in air and the interaction of these pulses with distant targets is described. It is shown that the beam filamentation pattern can be controlled by introducing beam astigmatism. In addition, it is demonstrated that the collapse distance of intense femtosecond laser beams scales as P-1/2 for input powers that are moderately above the critical power for self focusing, and that at higher powers the collapse distance scales as P-1. Related to the interaction of intense short pulses with distant targets, it is measured that the threshold fluence for optical damage in wide gap materials is lower by up to 20% for negatively chirped pulses than for positively chirped, at pulse durations ranging from 60 fs to 1 ps.

Chandra Finds Most Distant X-ray Galaxy Cluster

NASA Astrophysics Data System (ADS)

2001-02-01

The most distant X-ray cluster of galaxies yet has been found by astronomers using NASA’s Chandra X-ray Observatory. Approximately 10 billion light years from Earth, the cluster 3C294 is 40 percent farther than the next most distant X-ray galaxy cluster. The existence of such a distant galaxy cluster is important for understanding how the universe evolved. "Distant objects like 3C294 provide snapshots to how these galaxy clusters looked billions of years ago," said Andrew Fabian of the Institute of Astronomy, Cambridge, England and lead author of the paper accepted for publication in the Monthly Notices of Britain’s Royal Astronomical Society. "These latest results help us better understand what the universe was like when it was only 20 percent of its current age." Chandra’s image reveals an hourglass-shaped region of X-ray emission centered on the previously known central radio source. This X-ray emission extends outward from the central galaxy for at least 300,000 light years and shows that the known radio source is in the central galaxy of a massive cluster. Scientists have long suspected that distant radio-emitting galaxies like 3C294 are part of larger groups of galaxies known as "clusters." However, radio data provides astronomers with only a partial picture of these distant objects. Confirmation of the existence of clusters at great distances - and, hence, at early stages of the universe - requires information from other wavelengths. Optical observations can be used to pinpoint individual galaxies, but X-ray data are needed to detect the hot gas that fills the space within the cluster. "Galaxy clusters are the largest gravitationally bound structures in the universe," said Fabian. "We do not expect to find many massive objects, such as the 3C294 cluster, in early times because structure is thought to grow from small scales to large scales." The vast clouds of hot gas that envelope galaxies in clusters are thought to be heated by collapse toward the center of the cluster. Until Chandra, X-ray telescopes have not had the needed sensitivity to identify and measure hot gas clouds in distant clusters. Carolin Crawford, Stefano Ettori and Jeremy Sanders of the Institute of Astronomy were also members of the team that observed 3C294 for 5.4 hours on October 29, 2000 with the Advanced CCD Imaging Spectrometer (ACIS). The ACIS X-ray camera was developed for NASA by Pennsylvania State University and Massachusetts Institute of Technology. NASA's Marshall Space Flight Center in Huntsville, AL, manages the Chandra program for the Office of Space Science in Washington, DC. The Smithsonian's Chandra X-ray Center controls science and flight operations from Cambridge, MA. Images associated with this release are available on the World Wide Web at: http://chandra.harvard.edu AND http://chandra.nasa.gov

Genetic influences on functional connectivity associated with feedback processing and prediction error: Phase coupling of theta-band oscillations in twins.

PubMed

Demiral, Şükrü Barış; Golosheykin, Simon; Anokhin, Andrey P

2017-05-01

Detection and evaluation of the mismatch between the intended and actually obtained result of an action (reward prediction error) is an integral component of adaptive self-regulation of behavior. Extensive human and animal research has shown that evaluation of action outcome is supported by a distributed network of brain regions in which the anterior cingulate cortex (ACC) plays a central role, and the integration of distant brain regions into a unified feedback-processing network is enabled by long-range phase synchronization of cortical oscillations in the theta band. Neural correlates of feedback processing are associated with individual differences in normal and abnormal behavior, however, little is known about the role of genetic factors in the cerebral mechanisms of feedback processing. Here we examined genetic influences on functional cortical connectivity related to prediction error in young adult twins (age 18, n=399) using event-related EEG phase coherence analysis in a monetary gambling task. To identify prediction error-specific connectivity pattern, we compared responses to loss and gain feedback. Monetary loss produced a significant increase of theta-band synchronization between the frontal midline region and widespread areas of the scalp, particularly parietal areas, whereas gain resulted in increased synchrony primarily within the posterior regions. Genetic analyses showed significant heritability of frontoparietal theta phase synchronization (24 to 46%), suggesting that individual differences in large-scale network dynamics are under substantial genetic control. We conclude that theta-band synchronization of brain oscillations related to negative feedback reflects genetically transmitted differences in the neural mechanisms of feedback processing. To our knowledge, this is the first evidence for genetic influences on task-related functional brain connectivity assessed using direct real-time measures of neuronal synchronization. Copyright © 2016 Elsevier B.V. All rights reserved.

NGC 3516: Disk Diagnostics from a Windy BLSy1 in a High-State

NASA Astrophysics Data System (ADS)

Turner, Tracey Jane

2005-10-01

Recent advances have shown X-ray flux to be simply correlated with reflection-signatures from the disk and an associated wind. It appears two things are essential to observe the disk/wind: 1) catch the Seyfert in a high-state where disk/wind features show up strongly and 2) separate out reprocessing from distant gas to allow isolation of disk/wind features. NGC 3516 provides the ideal source for further study in this regard. The source is currently in a very high state, which we predict will lead to observable features from the disk and its wind. We request 210 ks XMM exposure on NGC 3156 with supporting Chandra time to test our prediction of flux-linked disk reflection and wind.

The Distant Sodium Tail of Mercury

NASA Technical Reports Server (NTRS)

Potter, A. E.; Killen, R. M.; Morgan, T. H.

2001-01-01

Models of the sodium atmosphere of Mercury predict the possible existence of a cornet-like sodium tail. Detection and mapping of the predicted sodium tail would provide quantitative data on the energy of the process that produces sodium atoms from the planetary surface. Previous efforts to detect the sodium tail by means of observations done during daylight hours have been only partially successful because scattered sunlight obscured the weak sodium emissions in the tail. However, at greatest eastern elongation around the March equinox in the northern hemisphere, Mercury can be seen as an evening star in astronomical twilight. At this time, the intensity of scattered sunlight is low enough that sodium emissions as low as 500 Rayleighs can be detected. Additional information is contained in the original extended abstract.

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

Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities weremore » estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton therapy in the treatment of sinonasal malignancy.« less

Phagonaute: A web-based interface for phage synteny browsing and protein function prediction.

PubMed

Delattre, Hadrien; Souiai, Oussema; Fagoonee, Khema; Guerois, Raphaël; Petit, Marie-Agnès

2016-09-01

Distant homology search tools are of great help to predict viral protein functions. However, due to the lack of profile databases dedicated to viruses, they can lack sensitivity. We constructed HMM profiles for more than 80,000 proteins from both phages and archaeal viruses, and performed all pairwise comparisons with HHsearch program. The whole resulting database can be explored through a user-friendly "Phagonaute" interface to help predict functions. Results are displayed together with their genetic context, to strengthen inferences based on remote homology. Beyond function prediction, this tool permits detections of co-occurrences, often indicative of proteins completing a task together, and observation of conserved patterns across large evolutionary distances. As a test, Herpes simplex virus I was added to Phagonaute, and 25% of its proteome matched to bacterial or archaeal viral protein counterparts. Phagonaute should therefore help virologists in their quest for protein functions and evolutionary relationships. Copyright © 2016 Elsevier Inc. All rights reserved.

Testing Feedback Models with Nearby Star Forming Regions

NASA Astrophysics Data System (ADS)

Doran, E.; Crowther, P.

2012-12-01

The feedback from massive stars plays a crucial role in the evolution of galaxies. Accurate modelling of this feedback is essential in understanding distant star forming regions. Young nearby, high mass (> 104 M⊙) clusters such as R136 (in the 30 Doradus region) are ideal test beds for population synthesis since they host large numbers of spatially resolved massive stars at a pre-supernovae stage. We present a quantitative comparison of empirical calibrations of radiative and mechanical feedback from individual stars in R136, with instantaneous burst predictions from the popular Starburst99 evolution synthesis code. We find that empirical results exceed predictions by factors of ˜3-9, as a result of limiting simulations to an upper limit of 100 M⊙. 100-300 M⊙ stars should to be incorporated in population synthesis models for high mass clusters to bring predictions into close agreement with empirical results.

Cardiovascular and Postural Control Interactions during Hypergravity: Effects on Cerebral Autoregulation in Males and Females

NASA Astrophysics Data System (ADS)

Goswami, Nandu; Blaber, Andrew; Bareille, Marie-Pierre; Beck, Arnaud; Avan, Paul; Bruner, Michelle; Hinghofer-Szalkay, Helmut

2012-07-01

Orthostatic intolerance remains a problem upon return to Earth from the microgravity environment of spaceflight. A variety of conditions including hypovolemia, cerebral vasoconstriction, cerebral or peripheral vascular disease, or cardiac arrhythmias may result in syncope if the person remains upright. Current research indicates that there is a greater dependence on visual and somatosensory information at the beginning of space flight with a decreased otolith gain during prolonged space flight (Herault et al., 2002). The goal of the research is to further our understanding of the fundamental adaptive homeostatic mechanisms involved in gravity related changes in cardiovascular and postural function. Cardiovascular, cerebrovascular, and postural sensory motor control systems in male and female participants before, during, and after exposure to graded levels of hyper-G were investigated. Hypotheses: 1) Activation of skeletal muscle pump will be directly related to the degree of orthostatic stress. 2) Simultaneous measurement of heart rate, blood pressure and postural sway will predict cardio-postural stability. Blood pressure and heart rate (means and variability), postural sway, center of pressure (COP), baroreflex function, calf blood flow, middle cerebral artery blood flow, non-invasive intracranial pressure measurements, and two-breath CO2 were measured. Results from the study will be used to provide an integrated insight into mechanisms of cardio-postural control and cerebral autoregulation, which are important aspects of human health in flights to Moon, Mars and distant planets.

Differences in patterns of survival in metastatic adenoid cystic carcinoma of the head and neck.

PubMed

van Weert, Stijn; Reinhard, Rinze; Bloemena, Elisabeth; Buter, Jan; Witte, Birgit I; Vergeer, Marije R; Leemans, C René

2017-03-01

We examined the assumption in conventional teaching about metastatic adenoid cystic carcinoma (ACC) being an indolent type of disease. A single center analysis of 105 cases of ACC was performed. Radiographs were reviewed and tumor response to chemotherapy was measured. Distant disease-free survival (DDFS) and time to death since distant metastases diagnosis were analyzed. Forty-two percent of the patients were diagnosed with distant metastases. DDFS showed significant negative associations with advanced T classification, N+ classification, solid type tumor, and positive surgical margins. Distant metastases (91%) developed in the first 5 years after presentation. Median distant metastatic survival was 13.8 months. The most frequent organ sited was the lung. Solid type ACC showed a preponderance for multiorgan metastases (17/28; 61%). Distant metastases seemed not to occur in case of clear surgical margins. Solid type ACC had a significant poorer survival after development of distant metastases. Metastatic ACC is not always an indolent disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 456-463, 2017. © 2016 Wiley Periodicals, Inc.

RULES OF COMPETITIVE STIMULUS SELECTION IN A CHOLINERGIC ISTHMIC NUCLEUS OF THE OWL MIDBRAIN

PubMed Central

Asadollahi, Ali; Mysore, Shreesh P.; Knudsen, Eric I.

2011-01-01

In a natural scene, multiple stimuli compete for the control of gaze direction and attention. The nucleus isthmi pars parvocellularis (Ipc) is a cholinergic, midbrain nucleus that is reciprocally interconnected to the optic tectum, a structure known to be involved in the control of gaze and attention. Previous research has shown that the responses of many Ipc units to a visual stimulus presented inside the classical receptive field (RF) can be powerfully inhibited when the strength of a distant, competing stimulus becomes the stronger stimulus. This study investigated further the nature of competitive interactions in the Ipc of owls by employing two complementary protocols: in the first protocol, we measured the effects of a distant stimulus on responses to an RF stimulus located at different positions inside the RF; in the second protocol, we measured the effects of a distant stimulus on responses to RF stimuli of different strengths. The first protocol demonstrated that the effect of a competing stimulus is purely divisive: the competitor caused a proportional reduction in responses to the RF stimulus that did not alter either the location or sharpness of spatial tuning. The second protocol demonstrated that, for most units, the strength of this divisive inhibition is regulated powerfully by the relative strengths of the competing stimuli: inhibition was strong when the competitor was the stronger stimulus and weak when the competitor was the weaker stimulus. The data indicate that competitive interactions in the Ipc depend on feedback and a globally divisive inhibitory network. PMID:21508234

Decoding the Dopamine Signal in Macaque Prefrontal Cortex: A Simulation Study Using the Cx3Dp Simulator

PubMed Central

Spühler, Isabelle Ayumi; Hauri, Andreas

2013-01-01

Dopamine transmission in the prefrontal cortex plays an important role in reward based learning, working memory and attention. Dopamine is thought to be released non-synaptically into the extracellular space and to reach distant receptors through diffusion. This simulation study examines how the dopamine signal might be decoded by the recipient neuron. The simulation was based on parameters from the literature and on our own quantified, structural data from macaque prefrontal area 10. The change in extracellular dopamine concentration was estimated at different distances from release sites and related to the affinity of the dopamine receptors. Due to the sparse and random distribution of release sites, a transient heterogeneous pattern of dopamine concentration emerges. Our simulation predicts, however, that at any point in the simulation volume there is sufficient dopamine to bind and activate high-affinity dopamine receptors. We propose that dopamine is broadcast to its distant receptors and any change from the local baseline concentration might be decoded by a transient change in the binding probability of dopamine receptors. Dopamine could thus provide a graduated ‘teaching’ signal to reinforce concurrently active synapses and cell assemblies. In conditions of highly reduced or highly elevated dopamine levels the simulations predict that relative changes in the dopamine signal can no longer be decoded, which might explain why cognitive deficits are observed in patients with Parkinson’s disease, or induced through drugs blocking dopamine reuptake. PMID:23951205

Statistical potential-based amino acid similarity matrices for aligning distantly related protein sequences.

PubMed

Tan, Yen Hock; Huang, He; Kihara, Daisuke

2006-08-15

Aligning distantly related protein sequences is a long-standing problem in bioinformatics, and a key for successful protein structure prediction. Its importance is increasing recently in the context of structural genomics projects because more and more experimentally solved structures are available as templates for protein structure modeling. Toward this end, recent structure prediction methods employ profile-profile alignments, and various ways of aligning two profiles have been developed. More fundamentally, a better amino acid similarity matrix can improve a profile itself; thereby resulting in more accurate profile-profile alignments. Here we have developed novel amino acid similarity matrices from knowledge-based amino acid contact potentials. Contact potentials are used because the contact propensity to the other amino acids would be one of the most conserved features of each position of a protein structure. The derived amino acid similarity matrices are tested on benchmark alignments at three different levels, namely, the family, the superfamily, and the fold level. Compared to BLOSUM45 and the other existing matrices, the contact potential-based matrices perform comparably in the family level alignments, but clearly outperform in the fold level alignments. The contact potential-based matrices perform even better when suboptimal alignments are considered. Comparing the matrices themselves with each other revealed that the contact potential-based matrices are very different from BLOSUM45 and the other matrices, indicating that they are located in a different basin in the amino acid similarity matrix space.

Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.

PubMed

Zeestraten, E C M; Maak, M; Shibayama, M; Schuster, T; Nitsche, U; Matsushima, T; Nakayama, S; Gohda, K; Friess, H; van de Velde, C J H; Ishihara, H; Rosenberg, R; Kuppen, P J K; Janssen, K-P

2012-01-03

There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer. In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples. Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours. Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.

ELEVEN NEW HEAVILY REDDENED FIELD WOLF-RAYET STARS

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

Smith, J. D. T.; Cushing, Michael; Barletta, Anthony

We report the results of a medium-narrowband 2 {mu}m line survey covering 5.8 deg{sup 2} near the Galactic plane. We confirm 11 new field Wolf-Rayet stars along three lines of sight probing the inner Galaxy, demonstrating the capability to uncover distant and highly reddened populations of Galactic wind-borne emission-line stars suffering extinction as high as A{sub V} {approx} 40 and as distant as 9 kpc down to modest magnitude limits of K{sub s} {approx} 12.5. All stars are of subtype WC7-8, with median distance d = 6 kpc and median extinction A{sub K{sub s}} = 2.5. Over the fields surveyed,more » the density of Wolf-Rayet stars to limiting magnitude K{sub s} {approx} 12.5 was found to be 1.9 deg{sup -2}. We compare this to models which predict their distribution within the Galaxy and find that, even neglecting survey and subtype incompleteness, they consistently underpredict the number of newly discovered stars along the surveyed lines of sight.« less

Recent advances in metastasis research.

PubMed

Molloy, Tim; van 't Veer, Laura J

2008-02-01

Advances in the early prediction, detection, and treatment of metastatic disease has improved the outlook in cancer patients in recent decades, however, metastasis remains the major cause of death in affected individuals. Metastasis occurs in a series of discreet biological steps in which a single, frequently clinically occult micrometastatic cell travels from the primary tumor to a distant location, where it lodges, grows, and ultimately results in the patient's death. Recent work has provided many new insights in the mechanisms and biology behind metastatic spread. This short review surveys some of the most important recent developments that have helped increase our understanding of the three broad phases of metastasis - the genesis of the metastatic cell through the loss of local constraints in the primary tumor microenvironment, dissemination of the cell to a distant organ while avoiding immune surveillance, and finally lodging and growth of the overt metastasis. These studies are providing mounting evidence that the interactions between tumor and normal cells and tissues are critical for disease progression - a paradigm that will provide a fertile area for future research.

CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design

PubMed Central

Rose, Timothy M.; Henikoff, Jorja G.; Henikoff, Steven

2003-01-01

We have developed a new primer design strategy for PCR amplification of distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). An interactive program has been written to design CODEHOP PCR primers from conserved blocks of amino acids within multiply-aligned protein sequences. Each CODEHOP consists of a pool of related primers containing all possible nucleotide sequences encoding 3–4 highly conserved amino acids within a 3′ degenerate core. A longer 5′ non-degenerate clamp region contains the most probable nucleotide predicted for each flanking codon. CODEHOPs are used in PCR amplification to isolate distantly related sequences encoding the conserved amino acid sequence. The primer design software and the CODEHOP PCR strategy have been utilized for the identification and characterization of new gene orthologs and paralogs in different plant, animal and bacterial species. In addition, this approach has been successful in identifying new pathogen species. The CODEHOP designer (http://blocks.fhcrc.org/codehop.html) is linked to BlockMaker and the Multiple Alignment Processor within the Blocks Database World Wide Web (http://blocks.fhcrc.org). PMID:12824413

A mediation model linking dispatcher leadership and work ownership with safety climate as predictors of truck driver safety performance.

PubMed

Zohar, Dov; Huang, Yueng-hsiang; Lee, Jin; Robertson, Michelle

2014-01-01

The study was designed to test the effect of safety climate on safety behavior among lone employees whose work environment promotes individual rather than consensual or shared climate perceptions. The paper presents a mediation path model linking psychological (individual-level) safety climate antecedents and consequences as predictors of driving safety of long-haul truck drivers. Climate antecedents included dispatcher (distant) leadership and driver work ownership, two contextual attributes of lone work, whereas its proximal consequence included driving safety. Using a prospective design, safety outcomes, consisting of hard-braking frequency (i.e. traffic near-miss events) were collected six months after survey completion, using GPS-based truck deceleration data. Results supported the hypothesized model, indicating that distant leadership style and work ownership promote psychological safety climate perceptions, with subsequent prediction of hard-braking events mediated by driving safety. Theoretical and practical implications for studying safety climate among lone workers in general and professional drivers in particular are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predictive protocol of flocks with small-world connection pattern.

PubMed

Zhang, Hai-Tao; Chen, Michael Z Q; Zhou, Tao

2009-01-01

By introducing a predictive mechanism with small-world connections, we propose a new motion protocol for self-driven flocks. The small-world connections are implemented by randomly adding long-range interactions from the leader to a few distant agents, namely, pseudoleaders. The leader can directly affect the pseudoleaders, thereby influencing all the other agents through them efficiently. Moreover, these pseudoleaders are able to predict the leader's motion several steps ahead and use this information in decision making towards coherent flocking with more stable formation. It is shown that drastic improvement can be achieved in terms of both the consensus performance and the communication cost. From the engineering point of view, the current protocol allows for a significant improvement in the cohesion and rigidity of the formation at a fairly low cost of adding a few long-range links embedded with predictive capabilities. Significantly, this work uncovers an important feature of flocks that predictive capability and long-range links can compensate for the insufficiency of each other. These conclusions are valid for both the attractive and repulsive swarm model and the Vicsek model.

Residual {sup 18}F-FDG-PET Uptake 12 Weeks After Stereotactic Ablative Radiotherapy for Stage I Non-Small-Cell Lung Cancer Predicts Local Control

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

Bollineni, Vikram Rao, E-mail: v.r.bollineni@umcg.nl; Widder, Joachim; Pruim, Jan

2012-07-15

Purpose: To investigate the prognostic value of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake at 12 weeks after stereotactic ablative radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC). Methods and Materials: From November 2006 to February 2010, 132 medically inoperable patients with proven Stage I NSCLC or FDG-PET-positive primary lung tumors were analyzed retrospectively. SABR consisted of 60 Gy delivered in 3 to 8 fractions. Maximum standardized uptake value (SUV{sub max}) of the treated lesion was assessed 12 weeks after SABR, using FDG-PET. Patients were subsequently followed at regular intervals using computed tomography (CT) scans. Association between post-SABR SUV{submore » max} and local control (LC), mediastinal failure, distant failure, overall survival (OS), and disease-specific survival (DSS) was examined. Results: Median follow-up time was 17 months (range, 3-40 months). Median lesion size was 25 mm (range, 9-70 mm). There were 6 local failures: 15 mediastinal failures, 15 distant failures, 13 disease-related deaths, and 16 deaths from intercurrent diseases. Glucose corrected post-SABR median SUV{sub max} was 3.0 (range, 0.55-14.50). Using SUV{sub max} 5.0 as a cutoff, the 2-year LC was 80% versus 97.7% for high versus low SUV{sub max}, yielding an adjusted subhazard ratio (SHR) for high post-SABR SUV{sub max} of 7.3 (95% confidence interval [CI], 1.4-38.5; p = 0.019). Two-year DSS rates were 74% versus 91%, respectively, for high and low SUV{sub max} values (SHR, 2.2; 95% CI, 0.8-6.3; p = 0.113). Two-year OS was 62% versus 81% (hazard ratio [HR], 1.6; 95% CI, 0.7-3.7; p = 0.268). Conclusions: Residual FDG uptake (SUV{sub max} {>=}5.0) 12 weeks after SABR signifies increased risk of local failure. A single FDG-PET scan at 12 weeks could be used to tailor further follow-up according to the risk of failure, especially in patients potentially eligible for salvage surgery.« less

Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

PubMed

Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

2014-01-01

Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating hepatocellular carcinoma cells, which might predict hematogenous spreading metastasis in patients with hepatocellular carcinoma and may be a poor prognostic factor for hepatocellular carcinoma patients.

Stereotactic Ablative Radiation Therapy for Centrally Located Early Stage or Isolated Parenchymal Recurrences of Non-Small Cell Lung Cancer: How to Fly in a “No Fly Zone”

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

Chang, Joe Y., E-mail: jychang@mdanderson.org; Li, Qiao-Qiao; Xu, Qing-Yong

2014-04-01

Purpose: We extended our previous experience with stereotactic ablative radiation therapy (SABR; 50 Gy in 4 fractions) for centrally located non-small cell lung cancer (NSCLC); explored the use of 70 Gy in 10 fractions for cases in which dose-volume constraints could not be met with the previous regimen; and suggested modified dose-volume constraints. Methods and Materials: Four-dimensional computed tomography (4DCT)-based volumetric image-guided SABR was used for 100 patients with biopsy-proven, central T1-T2N0M0 (n=81) or isolated parenchymal recurrence of NSCLC (n=19). All disease was staged with positron emission tomography/CT; all tumors were within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart,more » pericardium, brachial plexus, or vertebral body. Endpoints were toxicity, overall survival (OS), local and regional control, and distant metastasis. Results: At a median follow-up time of 30.6 months, median OS time was 55.6 months, and the 3-year OS rate was 70.5%. Three-year cumulative actuarial local, regional, and distant control rates were 96.5%, 87.9%, and 77.2%, respectively. The most common toxicities were chest-wall pain (18% grade 1, 13% grade 2) and radiation pneumonitis (11% grade 2 and 1% grade 3). No patient experienced grade 4 or 5 toxicity. Among the 82 patients receiving 50 Gy in 4 fractions, multivariate analyses showed mean total lung dose >6 Gy, V{sub 20} >12%, or ipsilateral lung V{sub 30} >15% to independently predict radiation pneumonitis; and 3 of 9 patients with brachial plexus D{sub max} >35 Gy experienced brachial neuropathy versus none of 73 patients with brachial D{sub max} <35 Gy (P=.001). Other toxicities were analyzed and new dose-volume constraints are proposed. Conclusions: SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected.« less

Relative Positions of Distant Spacecraft

NASA Image and Video Library

2011-04-29

This graphic shows the relative positions of NASA most distant spacecraft in early 2011, looking at the solar system from the side. Voyager 1 is the most distant spacecraft, 10.9 billion miles away from the sun at a northward angle.

Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

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

Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca; Aoyama, Hidefumi; Kocher, Martin

Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRSmore » alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.« less

Behind the Periscope: Leadership in China’s Navy

DTIC Science & Technology

2013-12-01

Spring Festival Distant Sea Voyage: A Complete Account of the North Sea Fleet’s Distant Seas Training Vessel Formation” (zhongguo haijun de ‘chunjie...staff VADM Du Jingchen.596 During the expedition, Yin convened a political working group which created a musical piece called “Song of the Gulf of Aden...Spring Festival Distant Sea Voyage: A Complete Account of the North Sea Fleet’s Distant Seas Training Vessel Formation” (zhongguo haijun de ‘chunjie

Galaxy Clusters, Near and Far, Have a Lot in Common

NASA Astrophysics Data System (ADS)

2005-04-01

Using two orbiting X-ray telescopes, a team of international astronomers has examined distant galaxy clusters in order to compare them with their counterparts that are relatively close by. Speaking today at the RAS National Astronomy Meeting in Birmingham, Dr. Ben Maughan (Harvard-Smithsonian Center for Astrophysics), presented the results of this new analysis. The observations indicate that, despite the great expansion that the Universe has undergone since the Big Bang, galaxy clusters both local and distant have a great deal in common. This discovery could eventually lead to a better understanding of how to "weigh" these enormous structures, and, in so doing, answer important questions about the nature and structure of the Universe. Clusters of galaxies, the largest known gravitationally-bound objects, are the knots in the cosmic web of structure that permeates the Universe. Theoretical models make predictions about the number, distribution and properties of these clusters. Scientists can test and improve models of the Universe by comparing these predictions with observations. The most powerful way of doing this is to measure the masses of galaxy clusters, particularly those in the distant Universe. However, weighing galaxy clusters is extremely difficult. One relatively easy way to weigh a galaxy cluster is to use simple laws ("scaling relations") to estimate its weight from properties that are easy to observe, like its luminosity (brightness) or temperature. This is like estimating someone's weight from their height if you didn't have any scales. Over the last 3 years, a team of researchers, led by Ben Maughan, has observed 11 distant galaxy clusters with ESA's XMM-Newton and NASA's Chandra X-ray Observatory. The clusters have redshifts of z = 0.6-1.0, which corresponds to distances of 6 to 8 billion light years. This means that we see them as they were when the Universe was half its present age. The survey included two unusual systems, one in which two massive clusters are merging and another extremely massive cluster which appears very "relaxed" and undisturbed. The X-ray data allowed the scientists to measure the temperatures and luminosities of the gas in the clusters. They were then able to infer their total masses, which varied between 200 and 1,100 times the mass of our Milky Way galaxy. These measurements were then used to test whether galaxy clusters of different sizes and located at different distances from us are simply scaled versions of each other -- a condition known as being "self-similar." This is an important characteristic for astronomers to identify if they hope to get the true weights of galaxy clusters. "For example, chocolate bars are strongly self-similar," said Maughan. "If you shrank a king-size bar to a fun-size bar, they would be identical versions of each other but just different sizes." "However, if you shrank a castle to the size of a bungalow, they would be very different structures, despite being the same size. This means that they are not strongly self-similar objects." Another possible type of relationship between clusters is what scientists call "weakly self-similar." In this case, galaxy clusters in the distant universe and those nearby are almost identical to each other, but not exactly the same. (The only differences between them can be accounted for by the expansion of the Universe since the Big Bang.) Although astronomers have known for some time that galaxy clusters are not strongly self-similar, the question of whether or not they are weakly self-similar has remained open. The new results show that as long as astronomers take into account the continuous expansion of the Universe, then galaxy clusters are, in fact, weakly self-similar. This means that the same scaling relations used to weigh nearby galaxy clusters hold true for these very distant clusters. "Our results mean that weighing distant galaxy clusters could become as easy as converting from Fahrenheit to Celsius," said Maughan. "This will help to answer important questions about the nature and structure of the Universe." The other members of the team were: Laurence Jones (University of Birmingham, UK) Harald Ebeling (Institute for Astronomy, HI, USA), and Caleb Scharf (Columbia Astrophysics Laboratory, NY, USA). The observations were made with the European Photon Imaging Camera (EPIC) on XMM and the Advanced Camera for Imaging and Spectroscopy (ACIS) on Chandra. They were part of the WARPS survey of distant galaxy clusters detected by chance in observations made with the UK-US-Dutch ROSAT X-ray satellite. Additional information and images are available at: http://www.sr.bham.ac.uk/~habib/nampr/

Mapping quantitative trait loci controlling seed and grain production traits of intermediate wheatgrass (Thinopyrum intermedium)

USDA-ARS?s Scientific Manuscript database

Intermediate wheatgrass (Thinopyrum intermedium) is a cool-season perennial grass cultivated for seed used in forage production, conservation plantings, and consumable grain products such as flour. Intermediate wheatgrass (2n=6x=42) has a large, allohexploid genome (~13 GB) and is a distant relativ...

Culture, Identity, and Structure in Social Exchange: A Web-Based Trust Experiment in the United States and Japan

ERIC Educational Resources Information Center

Kuwabara, Ko; Willer, Robb; Macy, Michael W.; Mashima, Rie; Terai, Shigeru; Yamagishi, Toshio

2007-01-01

Cross-cultural trust and cooperation are important concerns for international markets, political cooperation, and cultural exchange. Until recently, this problem was difficult to study under controlled conditions due to the inability to conduct experiments involving interaction between participants located in physically distant locations. We…

Localized sinonasal mucosal melanoma: Outcomes and associations with stage, radiotherapy, and positron emission tomography response.

PubMed

Samstein, Robert M; Carvajal, Richard D; Postow, Michael A; Callahan, Margaret K; Shoushtari, Alexander N; Patel, Snehal G; Lee, Nancy Y; Barker, Christopher A

2016-09-01

Sinonasal mucosal melanoma is a rare neoplasm with a poor prognosis. Retrospective analysis was conducted on 78 patients with localized sinonasal mucosal melanoma treated at Memorial Sloan Kettering Cancer Center (MSKCC from 1998-2013). Demographic, tumor, imaging, and treatment factors were recorded and survival and disease-control outcomes were analyzed. Median overall survival (OS) and disease-specific survival (DSS) were 32 and 50 months, respectively. Median locoregional recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were 43 and 12 months, respectively. Multivariate analysis demonstrated greater OS in nasal cavity tumors and earlier T classification. Radiotherapy (RT) was associated with significantly greater LRFS (5-years; 35% vs 59%; p = .01), but no difference in OS. Post-RT positron emission tomography (PET) response was associated with greater OS. Distant metastasis is the predominant mode of recurrence in sinonasal mucosal melanoma, but local recurrence remains common. RT is associated with improved local control, but no survival benefit. The prognostic value of post-RT PET imaging warrants further investigation. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1310-1317, 2016. © 2016 Wiley Periodicals, Inc.

Diverse Forms of RPS9 Splicing Are Part of an Evolving Autoregulatory Circuit

PubMed Central

Plocik, Alex M.; Guthrie, Christine

2012-01-01

Ribosomal proteins are essential to life. While the functions of ribosomal protein-encoding genes (RPGs) are highly conserved, the evolution of their regulatory mechanisms is remarkably dynamic. In Saccharomyces cerevisiae, RPGs are unusual in that they are commonly present as two highly similar gene copies and in that they are over-represented among intron-containing genes. To investigate the role of introns in the regulation of RPG expression, we constructed 16 S. cerevisiae strains with precise deletions of RPG introns. We found that several yeast introns function to repress rather than to increase steady-state mRNA levels. Among these, the RPS9A and RPS9B introns were required for cross-regulation of the two paralogous gene copies, which is consistent with the duplication of an autoregulatory circuit. To test for similar intron function in animals, we performed an experimental test and comparative analyses for autoregulation among distantly related animal RPS9 orthologs. Overexpression of an exogenous RpS9 copy in Drosophila melanogaster S2 cells induced alternative splicing and degradation of the endogenous copy by nonsense-mediated decay (NMD). Also, analysis of expressed sequence tag data from distantly related animals, including Homo sapiens and Ciona intestinalis, revealed diverse alternatively-spliced RPS9 isoforms predicted to elicit NMD. We propose that multiple forms of splicing regulation among RPS9 orthologs from various eukaryotes operate analogously to translational repression of the alpha operon by S4, the distant prokaryotic ortholog. Thus, RPS9 orthologs appear to have independently evolved variations on a fundamental autoregulatory circuit. PMID:22479208

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

PubMed

Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2006-08-10

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

First Job Search of Residents in the United States: A Survey of Anesthesiology Trainees' Interest in Academic Positions in Cities Distant from Previous Residences.

PubMed

Dexter, Franklin; De Oliveira, Gildasio S; McCarthy, Robert J

2016-01-15

We surveyed anesthesiology residents to evaluate the predictive effect of prior residence on desired location for future practice opportunities. One thousand five hundred United States anesthesiology residents were invited to participate. One question asked whether they intend to enter academic practice when they graduate from their residency/fellowship training. The analysis categorized the responses into "surely yes" and "probably" versus "even," "probably not," and "surely no." "After finishing your residency/fellowship training, are you planning to look seriously (e.g., interview) at jobs located more than a 2-hour drive from a location where you or your family (e.g., spouse or partner/significant other) have lived previously?" Responses were categorized into "very probably" and "somewhat probably" versus "somewhat improbably" and "not probable." Other questions explored predictors of the relationships quantified using the area under the receiver operating characteristic curve (area under the curve) ± its standard error. Among the 696 respondents, 36.9% (N = 256) would "probably" consider an academic practice. Fewer than half of those (P < 0.0001) would "very probably" consider a distant location (31.6%, 99% CI 24.4%-39.6%). Respondents with prior formal research training (e.g., PhD or Master's) had greater interest in academic practice at a distant location (AUC 0.63 ± 0.03, P = 0.0002). Except among respondents with formal research training, a good question to ask a job applicant is whether the applicant or the applicant's family has previously lived in the area.

Phytoplankton growth rate modelling: can spectroscopic cell chemotyping be superior to physiological predictors?

PubMed

Fanesi, Andrea; Wagner, Heiko; Wilhelm, Christian

2017-02-08

Climate change has a strong impact on phytoplankton communities and water quality. However, the development of robust techniques to assess phytoplankton growth is still in progress. In this study, the growth rate of phytoplankton cells grown at different temperatures was modelled based on conventional physiological traits (e.g. chlorophyll, carbon and photosynthetic parameters) using the partial least square regression (PLSR) algorithm and compared with a new approach combining Fourier transform infrared-spectroscopy and PLSR. In this second model, it is assumed that the macromolecular composition of phytoplankton cells represents an intracellular marker for growth. The models have comparable high predictive power (R 2 > 0.8) and low error in predicting new observations. Interestingly, not all of the predictors present the same weight in the modelling of growth rate. A set of specific parameters, such as non-photochemical fluorescence quenching (NPQ) and the quantum yield of carbon production in the first model, and lipid, protein and carbohydrate contents for the second one, strongly covary with cell growth rate regardless of the taxonomic position of the phytoplankton species investigated. This reflects a set of specific physiological adjustments covarying with growth rate, conserved among taxonomically distant algal species that might be used as guidelines for the improvement of modern primary production models. The high predictive power of both sets of cellular traits for growth rate is of great importance for applied phycological studies. Our approach may find application as a quality control tool for the monitoring of phytoplankton populations in natural communities or in photobioreactors. © 2017 The Author(s).

Transcriptional Coupling of Neighboring Genes and Gene Expression Noise: Evidence that Gene Orientation and Noncoding Transcripts Are Modulators of Noise

PubMed Central

Wang, Guang-Zhong; Lercher, Martin J.; Hurst, Laurence D.

2011-01-01

Abstract How is noise in gene expression modulated? Do mechanisms of noise control impact genome organization? In yeast, the expression of one gene can affect that of a very close neighbor. As the effect is highly regionalized, we hypothesize that genes in different orientations will have differing degrees of coupled expression and, in turn, different noise levels. Divergently organized gene pairs, in particular those with bidirectional promoters, have close promoters, maximizing the likelihood that expression of one gene affects the neighbor. With more distant promoters, the same is less likely to hold for gene pairs in nondivergent orientation. Stochastic models suggest that coupled chromatin dynamics will typically result in low abundance-corrected noise (ACN). Transcription of noncoding RNA (ncRNA) from a bidirectional promoter, we thus hypothesize to be a noise-reduction, expression-priming, mechanism. The hypothesis correctly predicts that protein-coding genes with a bidirectional promoter, including those with a ncRNA partner, have lower ACN than other genes and divergent gene pairs uniquely have correlated ACN. Moreover, as predicted, ACN increases with the distance between promoters. The model also correctly predicts ncRNA transcripts to be often divergently transcribed from genes that a priori would be under selection for low noise (essential genes, protein complex genes) and that the latter genes should commonly reside in divergent orientation. Likewise, that genes with bidirectional promoters are rare subtelomerically, cluster together, and are enriched in essential gene clusters is expected and observed. We conclude that gene orientation and transcription of ncRNAs are candidate modulators of noise. PMID:21402863

Usefulness of predictive tests for cancer treatment.

PubMed

Rosell, R; Cuello, M; Cecere, F; Santarpia, M; Reguart, N; Felip, E; Taron, M

2006-08-01

This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. At least six lines of research have recently emerged as potential contributors to changes in clinical practice. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. Secondly, single nucleotide polymorphisms in the ERCC1 gene influence survival and toxicity with cisplatin-based chemotherapy. The main core of recent research has centered on EGFR mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine kinase inhibitors. In contrast, K-ras mutations confer a negative effect in these patients. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine kinase inhibitors plus aromatase inhibitors. microRNAs control the expression of cognate target genes, and downregulation of Dicer has been shown to be a strong predictor of relapse in surgically resected non-small-cell lung cancer patients. Finally, overexpression of the Wingless-type (Wnt) genes and methylation of Wnt antagonists like WIF and secreted frizzled related proteins have been documented in non-small-cell lung cancer and are believed to be an important mechanism of cancer stem cell maintenance.

Cooperative vocal control in marmoset monkeys via vocal feedback

PubMed Central

Choi, Jung Yoon; Takahashi, Daniel Y.

2015-01-01

Humans adjust speech amplitude as a function of distance from a listener; we do so in a manner that would compensate for such distance. This ability is presumed to be the product of high-level sociocognitive skills. Nonhuman primates are thought to lack such socially related flexibility in vocal production. Using predictions from a simple arousal-based model whereby vocal feedback from a conspecific modulates the drive to produce a vocalization, we tested whether another primate exhibits this type of cooperative vocal control. We conducted a playback experiment with marmoset monkeys and simulated “far-away” and “nearby” conspecifics using contact calls that differed in sound intensity. We found that marmoset monkeys increased the amplitude of their contact calls and produced such calls with shorter response latencies toward more distant conspecifics. The same was not true in response to changing levels of background noise. To account for how simulated conspecific distance can change both the amplitude and timing of vocal responses, we developed a model that incorporates dynamic interactions between the auditory system and limbic “drive” systems. Overall, our data show that, like humans, marmoset monkeys cooperatively control the acoustics of their vocalizations according to changes in listener distance, increasing the likelihood that a conspecific will hear their call. However, we propose that such cooperative vocal control is a system property that does not necessitate any particularly advanced sociocognitive skill. At least in marmosets, this vocal control can be parsimoniously explained by the regulation of arousal states across two interacting individuals via vocal feedback. PMID:25925323

Method and apparatus for determining return stroke polarity of distant lightning

NASA Technical Reports Server (NTRS)

Blakeslee, Richard J. (Inventor); Brook, Marx (Inventor)

1992-01-01

A method is described for determining the return stroke polarity of distant lightning for distances beyond 600 km by detecting the electric field associated with a return stroke of distant lightning, and processing the electric field signal to determine the polarity of the slow tail of the VLF waveform signal associated with the detected electric field. The polarity of the return stroke of distant lightning is determined based upon the polarity of the slow tail portion of the waveform.

Method and apparatus for determining return stroke polarity of distant lightning

NASA Technical Reports Server (NTRS)

Blakeslee, Richard J. (Inventor); Brook, Marx (Inventor)

1990-01-01

A method is described for determining the return stroke polarity of distant lightning for distances beyond 600 km by detecting the electric field associated with a return stroke of distant lightning, and processing the electric field signal to determine the polarity of the slow tail of the VLF waveform signal associated with the detected electric field. The polarity of the return stroke of distant lightning is determined based upon the polarity of the slow tail portion of the waveform.

Paradoxical choice in rats: Subjective valuation and mechanism of choice.

PubMed

Ojeda, Andrés; Murphy, Robin A; Kacelnik, Alex

2018-07-01

Decision-makers benefit from information only when they can use it to guide behavior. However, recent experiments found that pigeons and starlings value information that they cannot use. Here we show that this paradox is also present in rats, and explore the underlying decision process. Subjects chose between two options that delivered food probabilistically after a fixed delay. In one option ("info"), outcomes (food/no-food) were signaled immediately after choice, whereas in the alternative ("non-info") the outcome was uncertain until the delay lapsed. Rats sacrificed up to 20% potential rewards by preferring the info option, but reversed preference when the cost was 60%. This reversal contrasts with the results found with pigeons and starlings and may reflect species' differences worth of further investigation. Results are consistent with predictions of the Sequential Choice Model (SCM), that proposes that choices are driven by the mechanisms that control action in sequential encounters. As expected from the SCM, latencies to respond in single-option trials predicted preferences in choice trials, and latencies in choice trials were the same or shorter than in single-option trials. We argue that the congruence of results in distant vertebrates probably reflects evolved adaptations to shared fundamental challenges in nature, and that the apparently paradoxical overvaluing of information is not sub-optimal as has been claimed, even though its functional significance is not yet understood. Copyright © 2018 Elsevier B.V. All rights reserved.

An Intelligent Catheter System Robotic Controlled Catheter System

PubMed Central

Negoro, M.; Tanimoto, M.; Arai, F.; Fukuda, T.; Fukasaku, K.; Takahashi, I.; Miyachi, S.

2001-01-01

Summary We have developed a novel catheter system, an intelligent catheter system, which is able to control a catheter by an externally-placed controller. This system has made from master-slave mechanism and has following three components; 1) a joy stick as a master (for operators) 2)a catheter controller as a slave (for a patient),3)a micro force sensor as a sensing device. This catheter tele-guiding system has abilities to perform intravascular procedures from the distant places. It may help to reduce the radiation exposures to the operators and also to help train young doctors. PMID:20663387

Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis.

PubMed

Huang, Xiongfeng; Wang, Jianmin; Chen, Qiao; Jiang, Jielin

2014-01-01

This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients. A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration's Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI). We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups. Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II-IIIA remains to be determined.

Renal surgery in the new millennium.

PubMed

Delvecchio, F C; Preminger, G M

2000-11-01

In the not too distant future, the minimally invasive renal surgeon will be able to practice an operation on a difficult case on a three-dimensional virtual reality simulator, providing all attributes of the real procedure. The patient's imaging studies will be imported into the simulator to better mimic particular anatomy. When confident enough of his or her skills, the surgeon will start operating on the patient using the same virtual reality simulator/telepresence surgery console system, which will permit the live surgery to be conducted by robots hundreds of miles away. The robots will manipulate miniature endoscopes or control minimally or noninvasive ablative technologies. Endoscopic/laparoscopic footage of the surgical procedure will be stored digitally in optical disks to be used later in telementoring of a surgery resident. All this and more will be possible in the not so distant third millennium.

mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family

PubMed Central

Chen, Hua-Wei; Chen, Xiu; Oh, Su-Wan; Marinissen, Maria J.; Gutkind, J. Silvio; Hou, Steven X.

2002-01-01

The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development. Receptors for the pathway have yet to be identified. Here we have identified a Drosophila gene that shows embryonic mutant phenotypes identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e mutations. We named this gene master of marelle (mom). Genetic analyses place mom's function between upd (the ligand) and hop. We further show that cultured cells transfected with the mom gene bind UPD and activate the HOP/STAT92E signal transduction pathway. mom encodes a protein distantly related to the mammalian cytokine receptor family. These data show that mom functions as a receptor of the Drosophila JAK/STAT signal transduction pathway. PMID:11825879

Selective Listening Point Audio Based on Blind Signal Separation and Stereophonic Technology

NASA Astrophysics Data System (ADS)

Niwa, Kenta; Nishino, Takanori; Takeda, Kazuya

A sound field reproduction method is proposed that uses blind source separation and a head-related transfer function. In the proposed system, multichannel acoustic signals captured at distant microphones are decomposed to a set of location/signal pairs of virtual sound sources based on frequency-domain independent component analysis. After estimating the locations and the signals of the virtual sources by convolving the controlled acoustic transfer functions with each signal, the spatial sound is constructed at the selected point. In experiments, a sound field made by six sound sources is captured using 48 distant microphones and decomposed into sets of virtual sound sources. Since subjective evaluation shows no significant difference between natural and reconstructed sound when six virtual sources and are used, the effectiveness of the decomposing algorithm as well as the virtual source representation are confirmed.

Low-Thrust Transfers from Distant Retrograde Orbits to L2 Halo Orbits in the Earth-Moon System

NASA Technical Reports Server (NTRS)

Parrish, Nathan L.; Parker, Jeffrey S.; Hughes, Steven P.; Heiligers, Jeannette

2016-01-01

This paper presents a study of transfers between distant retrograde orbits (DROs) and L2 halo orbits in the Earth-Moon system that could be flown by a spacecraft with solar electric propulsion (SEP). Two collocation-based optimal control methods are used to optimize these highly-nonlinear transfers: Legendre pseudospectral and Hermite-Simpson. Transfers between DROs and halo orbits using low-thrust propulsion have not been studied previously. This paper offers a study of several families of trajectories, parameterized by the number of orbital revolutions in a synodic frame. Even with a poor initial guess, a method is described to reliably generate families of solutions. The circular restricted 3-body problem (CRTBP) is used throughout the paper so that the results are autonomous and simpler to understand.

Using the structure-function linkage database to characterize functional domains in enzymes.

PubMed

Brown, Shoshana; Babbitt, Patricia

2014-12-12

The Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu/) is a Web-accessible database designed to link enzyme sequence, structure, and functional information. This unit describes the protocols by which a user may query the database to predict the function of uncharacterized enzymes and to correct misannotated functional assignments. The information in this unit is especially useful in helping a user discriminate functional capabilities of a sequence that is only distantly related to characterized sequences in publicly available databases. Copyright © 2014 John Wiley & Sons, Inc.

Impact of relationships between test and training animals and among training animals on reliability of genomic prediction.

PubMed

Wu, X; Lund, M S; Sun, D; Zhang, Q; Su, G

2015-10-01

One of the factors affecting the reliability of genomic prediction is the relationship among the animals of interest. This study investigated the reliability of genomic prediction in various scenarios with regard to the relationship between test and training animals, and among animals within the training data set. Different training data sets were generated from EuroGenomics data and a group of Nordic Holstein bulls (born in 2005 and afterwards) as a common test data set. Genomic breeding values were predicted using a genomic best linear unbiased prediction model and a Bayesian mixture model. The results showed that a closer relationship between test and training animals led to a higher reliability of genomic predictions for the test animals, while a closer relationship among training animals resulted in a lower reliability. In addition, the Bayesian mixture model in general led to a slightly higher reliability of genomic prediction, especially for the scenario of distant relationships between training and test animals. Therefore, to prevent a decrease in reliability, constant updates of the training population with animals from more recent generations are required. Moreover, a training population consisting of less-related animals is favourable for reliability of genomic prediction. © 2015 Blackwell Verlag GmbH.

An Approach for Predicting Essential Genes Using Multiple Homology Mapping and Machine Learning Algorithms.

PubMed

Hua, Hong-Li; Zhang, Fa-Zhan; Labena, Abraham Alemayehu; Dong, Chuan; Jin, Yan-Ting; Guo, Feng-Biao

Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset from Synechococcus elongatus , which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge.

Genome-Wide Prediction and Validation of Intergenic Enhancers in Arabidopsis Using Open Chromatin Signatures[OPEN

PubMed Central

Zhu, Bo; Zhang, Wenli; Jiang, Jiming

2015-01-01

Enhancers are important regulators of gene expression in eukaryotes. Enhancers function independently of their distance and orientation to the promoters of target genes. Thus, enhancers have been difficult to identify. Only a few enhancers, especially distant intergenic enhancers, have been identified in plants. We developed an enhancer prediction system based exclusively on the DNase I hypersensitive sites (DHSs) in the Arabidopsis thaliana genome. A set of 10,044 DHSs located in intergenic regions, which are away from any gene promoters, were predicted to be putative enhancers. We examined the functions of 14 predicted enhancers using the β-glucuronidase gene reporter. Ten of the 14 (71%) candidates were validated by the reporter assay. We also designed 10 constructs using intergenic sequences that are not associated with DHSs, and none of these constructs showed enhancer activities in reporter assays. In addition, the tissue specificity of the putative enhancers can be precisely predicted based on DNase I hypersensitivity data sets developed from different plant tissues. These results suggest that the open chromatin signature-based enhancer prediction system developed in Arabidopsis may serve as a universal system for enhancer identification in plants. PMID:26373455

Pretreatment subcutaneous adipose tissue predicts the outcomes of patients with head and neck cancer receiving definitive radiation and chemoradiation in Taiwan.

PubMed

Pai, Ping Ching; Chuang, Chi Cheng; Chuang, Wen Ching; Tsang, Ngan Ming; Tseng, Chen Kan; Chen, Kuan Hung; Yen, Tzu Chen; Lin, Chien Yu; Chang, Kai Ping; Lei, Kin Fong

2018-05-01

We aimed to determine whether body composition assessment before treatment can predict outcomes in patients with head and neck cancer (HNC). All 881 patients with locoregional head and neck cancer treated with curative intent radiotherapy (RT) between 2005 and 2012 were retrospectively investigated. Body composition was analyzed via pre-RT planning computed tomography (CT) images. Subcutaneous adipose tissue (SAT) and skeletal muscle (SM) indices were measured cross-sectionally at the level of the third thoracic vertebra. Overall survival (OS), locoregional control (LRC), and distant metastasis-free survival (MFS) were analyzed by body composition index and body mass index (BMI). Survivors were followed up for a median of 4.68 years. The SAT indices in female patients were significantly higher than those in males (P < 0.001). The median SAT and muscle indices were 18.6 and 34.3 cm 2 /m 2 for women and 6.19 and 51.74 cm 2 /m 2 for men, respectively. The 5- and 10-year MFS, LRC, and OS rates were 83% and 82.1%, 73.4% and 71.4%, and 66.4 and 57.6%, respectively. Higher pretreatment SAT index was associated with MFS (hazard ratio [HR]: 0.65; P = 0.015), LRC (HR: 0.758; P = 0.047), and OS (HR: 0.604; P < 0.001). Higher pretreatment BMI was associated with MFS (HR: 0.642; P = 0.031) and OS (HR: 0.615; P < 0.001). The pretreatment SM index had no significant effect on MFS, LRC, and OS. Multivariate analysis revealed that T-stage, N-stage, lesion sites, age, and RT treatment days are independent factors associated with OS; T-stage, N-stage, and lesion sites are independent factors associated with MFS; and N-stage, smoking history, and betel quid chewing history are independent factors associated with LRC. A higher CT-assessed SAT index predicts superior MSF, LCR, and OS in patients with curative HNC, whereas SM does not predict survival or locoregional control. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Sunitinib efficacy in the treatment of metastatic skin adnexal carcinomas: report of two patients with hidradenocarcinoma and trichoblastic carcinoma.

PubMed

Battistella, M; Mateus, C; Lassau, N; Chami, L; Boukoucha, M; Duvillard, P; Cribier, B; Robert, C

2010-02-01

Adnexal carcinomas are rare and diverse cutaneous tumours. They are locally aggressive and have the potential for distant metastasis. Metastatic adnexal carcinomas are very resistant to conventional chemotherapies. Sunitinib, an oral tyrosine kinase inhibitor, is reportedly effective for the treatment of various solid cancers. Its use in adnexal carcinomas has never been reported. The first patient had metastatic clear cell hidradenocarcinoma and was stabilized over 8 months with sunitinib, before she relapsed. The second patient had a metastatic malignant hair follicle tumour (trichoblastic carcinoma) and achieved a partial remission with sunitinib, and disease stabilized after 10 months. Dynamic contrast-enhanced ultrasound (DCE-US) performed to evaluate tumour vascularization during treatment depicted a dramatic and early decrease in the tumour blood volume. Sunitinib was effective in controlling the disease in our two patients. DCE-US using linear raw data may have an early predictive value for tumour response to sunitinib. Further studies involving larger cohorts of patients are warranted in order to confirm the efficacy of sunitinib in these rare tumours.

Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

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

Tsuji, Hiroshi; Ishikawa, Hitoshi; Yanagi, Takeshi

2007-03-01

Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascularmore » glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.« less

Electric coupling between distant nitrate reduction and sulfide oxidation in marine sediment

PubMed Central

Marzocchi, Ugo; Trojan, Daniela; Larsen, Steffen; Louise Meyer, Rikke; Peter Revsbech, Niels; Schramm, Andreas; Peter Nielsen, Lars; Risgaard-Petersen, Nils

2014-01-01

Filamentous bacteria of the Desulfobulbaceae family can conduct electrons over centimeter-long distances thereby coupling oxygen reduction at the surface of marine sediment to sulfide oxidation in deeper anoxic layers. The ability of these cable bacteria to use alternative electron acceptors is currently unknown. Here we show that these organisms can use also nitrate or nitrite as an electron acceptor thereby coupling the reduction of nitrate to distant oxidation of sulfide. Sulfidic marine sediment was incubated with overlying nitrate-amended anoxic seawater. Within 2 months, electric coupling of spatially segregated nitrate reduction and sulfide oxidation was evident from: (1) the formation of a 4–6-mm-deep zone separating sulfide oxidation from the associated nitrate reduction, and (2) the presence of pH signatures consistent with proton consumption by cathodic nitrate reduction, and proton production by anodic sulfide oxidation. Filamentous Desulfobulbaceae with the longitudinal structures characteristic of cable bacteria were detected in anoxic, nitrate-amended incubations but not in anoxic, nitrate-free controls. Nitrate reduction by cable bacteria using long-distance electron transport to get privileged access to distant electron donors is a hitherto unknown mechanism in nitrogen and sulfur transformations, and the quantitative importance for elements cycling remains to be addressed. PMID:24577351

Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

PubMed

Li, Duo-Jie; Li, Hong-Wei; He, Bin; Wang, Geng-Ming; Cai, Han-Fei; Duan, Shi-Miao; Liu, Jing-Jing; Zhang, Ya-Jun; Cui, Zhen; Jiang, Hao

2016-01-01

To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

Probing the gravitational Faraday rotation using quasar X-ray microlensing.

PubMed

Chen, Bin

2015-11-17

The effect of gravitational Faraday rotation was predicted in the 1950s, but there is currently no practical method for measuring this effect. Measuring this effect is important because it will provide new evidence for correctness of general relativity, in particular, in the strong field limit. We predict that the observed degree and angle of the X-ray polarization of a cosmologically distant quasar microlensed by the random star field in a foreground galaxy or cluster lens vary rapidly and concurrently with flux during caustic-crossing events using the first simulation of quasar X-ray microlensing polarization light curves. Therefore, it is possible to detect gravitational Faraday rotation by monitoring the X-ray polarization of gravitationally microlensed quasars. Detecting this effect will also confirm the strong gravity nature of quasar X-ray emission.

Science, Medicine, and Intercessory Prayer

PubMed Central

Sloan, Richard P.; Ramakrishnan, Rajasekhar

2012-01-01

Among the many recent attempts to demonstrate the medical benefits of religious activity, the methodologically strongest seem to be studies of the effects of distant intercessory prayer (IP). In these studies, patients are randomly assigned to receive standard care or standard care plus the prayers or “healing intentions” of distant intercessors. Most of the scientific community has dismissed such research, but cavalier rejection of studies of IP is unwise, because IP studies appear to conform to the standards of randomized controlled trials (RCTs) and, as such, would have a significant advantage over observational investigations of associations between religious variables and health outcomes. As we demonstrate, however, studies of IP fail to meet the standards of RCTs in several critical respects. They fail to adequately measure and control exposure to prayer from others, which is likely to exceed IP and to vary widely from subject to subject, and whose magnitude is unknown. This supplemental prayer so greatly attenuates the differences between the treatment and control groups that sample sizes are too large to justify studies of IP. Further, IP studies generally do not specify the outcome variables, raising problems of multiple comparisons and Type 1 errors. Finally, these studies claim findings incompatible with current views of the physical universe and consciousness. Unless these problems are solved, studies of IP should not be conducted. PMID:17146135

Patterns of inpatient care for immigrants in Switzerland: a case control study.

PubMed

Lay, Barbara; Lauber, Christoph; Nordt, Carlos; Rössler, Wulf

2006-03-01

Migration has become a major political and social concern in West European societies. A case-control method was used to analyse the utilisation of inpatient mental health services by immigrants from a catchment area in Switzerland over a 7-year period. Compared to natives, immigrants had fewer psychiatric hospitalisations, but more emergency and compulsory admissions. During inpatient treatment, they received less psycho-, ergo- and physiotherapy. Other therapies as well as compulsory measures were at comparable rates, as was the frequency of irregular discharge. They spent shorter periods as inpatients and the rate of psychiatric readmissions was significantly lower. Comparison of different countries of origin revealed that only patients from West and North Europe were comparable to natives regarding type of referral, inpatient treatment, and longitudinal measures of service utilisation. Even after accounting for effects of social class, immigrants from South Europe, former Yugoslavia, Turkey, East Europe and more distant countries spent significantly shorter time in inpatient treatment, compared to Swiss control patients. Results of this study clearly point to an underutilisation of inpatient facilities among immigrants with mental disorders, and to disadvantages in psychiatric inpatient care. This, however, does not pertain to all foreign patients to the same extent: inequalities of mental health service use are particularly pronounced in immigrants from more distant countries.

Distant and Distributed Learners Are Two Sides of the Same Coin.

ERIC Educational Resources Information Center

Barron, Brette Barclay

2002-01-01

An academic librarian at the University of South Carolina, faced with providing online resources for distant and distributed learners, examines whether there is any difference between distant and distributed learners. Illustrates changes brought on by implementation of information technologies. Discusses seeking a new definition, meeting…

Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

PubMed

Stemmer, Salomon M; Steiner, Mariana; Rizel, Shulamith; Soussan-Gutman, Lior; Ben-Baruch, Noa; Bareket-Samish, Avital; Geffen, David B; Nisenbaum, Bella; Isaacs, Kevin; Fried, Georgeta; Rosengarten, Ora; Uziely, Beatrice; Svedman, Christer; McCullough, Debbie; Maddala, Tara; Klang, Shmuel H; Zidan, Jamal; Ryvo, Larisa; Kaufman, Bella; Evron, Ella; Karminsky, Natalya; Goldberg, Hadassah; Shak, Steven; Liebermann, Nicky

2017-01-01

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 ( n  = 304) and 11-25 ( n  = 1037) (TAILORx categorizatio n ) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

PREDICTORS OF INFLAMMATORY LOCAL RECURRENCE AFTER BREAST-CONSERVING THERAPY FOR BREAST CANCER: MATCHED CASE-CONTROL STUDY.

PubMed

Akoum, Riad; Abdalla, Eddie K; Saade, Michel; Awdeh, Adnan; Abi-Aad, Fouad; Bejjani, Noha; Ghossain, Antoine; Brihi, Emile; Audi, Akram

2015-01-01

Inflammatory local recurrence (ILR) after breast-conserving surgery for noninflammatory breast cancer (BC) is associated with dismal prognosis. Risk factors for ILR are not well defined. Between 2001 and 2010, twelve patients at our hospital developed ILR after breast-conserving surgery, adjuvant chemotherapy, and radiotherapy for BC. We compared their clinico-pathological characteristics to those of 24 patients with noninflammatory local recurrence (non-ILR), 24 patients with distant metastases, and 48 disease-free controls, matched for age and observation period. The median time to ILR was 10 months. In univariate analysis, extent of lymph node involvement (p < 0.05), multifocality (p < 0.05), c-erbB2 overexpression (p < 0.05), and lymphovascular invasion (LVI) (p < 0.001) affected the risk of ILR. Conditional logistic regression analysis showed a significant association between ILR and combined LVI and high histopathological grade. The odds ratio (OR) for ILR versus non-ILR was 6.14 (95% confidence interval [CI] 1.48-25.38) and for ILR versus distant metastases it was 3.05 (95% CI 0.09-97.83) when both LVI and high histopathological grade were present. Patients with family history of BC were more likely to present with ILR than non-ILR (OR 5.47; 95% CI 1.55-19.31) or distant relapse (OR 5.62; 95% CI 0.26-119.95). Pre- and postmenopausal women with high-grade BC and LVI are at increased risk to develop ILR, especially in the presence of family history of BC. Identification of risk factors for this lethal form of recurrent BC may lead to more effective preventive treatment strategies in properly selected patients.

Microseismic Monitoring of Stimulating Shale Gas Reservoir in SW China: 2. Spatial Clustering Controlled by the Preexisting Faults and Fractures

NASA Astrophysics Data System (ADS)

Chen, Haichao; Meng, Xiaobo; Niu, Fenglin; Tang, Youcai; Yin, Chen; Wu, Furong

2018-02-01

Microseismic monitoring is crucial to improving stimulation efficiency of hydraulic fracturing treatment, as well as to mitigating potential induced seismic hazard. We applied an improved matching and locating technique to the downhole microseismic data set during one treatment stage along a horizontal well within the Weiyuan shale gas play inside Sichuan Basin in SW China, resulting in 3,052 well-located microseismic events. We employed this expanded catalog to investigate the spatiotemporal evolution of the microseismicity in order to constrain migration of the injected fluids and the associated dynamic processes. The microseismicity is generally characterized by two distinctly different clusters, both of which are highly correlated with the injection activity spatially and temporarily. The distant and well-confined cluster (cluster A) is featured by relatively large-magnitude events, with 40 events of M -1 or greater, whereas the cluster in the immediate vicinity of the wellbore (cluster B) includes two apparent lineations of seismicity with a NE-SW trending, consistent with the predominant orientation of natural fractures. We calculated the b-value and D-value, an index of fracture complexity, and found significant differences between the two seismicity clusters. Particularly, the distant cluster showed an extremely low b-value ( 0.47) and D-value ( 1.35). We speculate that the distant cluster is triggered by reactivation of a preexisting critically stressed fault, whereas the two lineations are induced by shear failures of optimally oriented natural fractures associated with fluid diffusion. In both cases, the spatially clustered microseismicity related to hydraulic stimulation is strongly controlled by the preexisting faults and fractures.

Widespread Pressure Pain Hypersensitivity Is Similar in Women With Frequent Episodic and Chronic Tension-Type Headache: A Blinded Case-Control Study.

PubMed

Palacios Ceña, María; Castaldo, Matteo; Kelun Wang; Torelli, Paola; Pillastrini, Paolo; Fernández-de-Las-Peñas, César; Arendt-Nielsen, Lars

2017-02-01

To investigate differences in widespread pressure pain hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with frequent episodic (FETTH) and chronic (CTTH) tension-type headache. It seems that people with tension-type headache exhibit central sensitization. No study has investigated differences between FETTH and CTTH in terms of widespread pressure pain hypersensitivity. Forty-three women with FETTH, 42 with CTTH, and 45 women without headache diagnosis were recruited. Pressure pain thresholds (PPTs) were bilaterally assessed over trigeminal area (ie, temporalis muscle), extra-trigeminal (ie, C5/C6 zygapophyseal joint), and two distant points (ie, second metacarpal and tibialis anterior muscle) by a blinded assessor. Clinical features of the headache were collected with a 4-week headache diary. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The ANCOVA revealed that PPTs were significantly decreased bilaterally over trigeminal (mean differences ranging from 97.5 to 101.5 kPa), extra-trigeminal (from 94.3 to 114.5 kPa), and distant points (from 99.4 to 208.6 kPa) in both FETTH and CTTH groups compared with controls (all, P < .001). No differences between FETTH and CTTH were observed (all points, P > .217). Anxiety (all, P > .803) or depression (P > .206) did not influence pressure pain hyperalgesia. No associations between widespread pressure hypersensitivity and headache features were observed (all, P > .110). Current results suggest the presence of similar local and widespread pressure hyperalgesia, not associated with anxiety or depression, in women with FETTH and CTTH supporting that localized and central manifestations are involved in both the episodic and chronic forms of tension-type headache. © 2016 American Headache Society.

Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary?

PubMed

Zhao, Kuai-le; Ma, Jin-bo; Liu, Guang; Wu, Kai-liang; Shi, Xue-hui; Jiang, Guo-liang

2010-02-01

To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. Copyright 2010 Elsevier Inc. All rights reserved.

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Perceptual attraction in tool use: evidence for a reliability-based weighting mechanism.

PubMed

Debats, Nienke B; Ernst, Marc O; Heuer, Herbert

2017-04-01

Humans are well able to operate tools whereby their hand movement is linked, via a kinematic transformation, to a spatially distant object moving in a separate plane of motion. An everyday example is controlling a cursor on a computer monitor. Despite these separate reference frames, the perceived positions of the hand and the object were found to be biased toward each other. We propose that this perceptual attraction is based on the principles by which the brain integrates redundant sensory information of single objects or events, known as optimal multisensory integration. That is, 1 ) sensory information about the hand and the tool are weighted according to their relative reliability (i.e., inverse variances), and 2 ) the unisensory reliabilities sum up in the integrated estimate. We assessed whether perceptual attraction is consistent with optimal multisensory integration model predictions. We used a cursor-control tool-use task in which we manipulated the relative reliability of the unisensory hand and cursor position estimates. The perceptual biases shifted according to these relative reliabilities, with an additional bias due to contextual factors that were present in experiment 1 but not in experiment 2 The biased position judgments' variances were, however, systematically larger than the predicted optimal variances. Our findings suggest that the perceptual attraction in tool use results from a reliability-based weighting mechanism similar to optimal multisensory integration, but that certain boundary conditions for optimality might not be satisfied. NEW & NOTEWORTHY Kinematic tool use is associated with a perceptual attraction between the spatially separated hand and the effective part of the tool. We provide a formal account for this phenomenon, thereby showing that the process behind it is similar to optimal integration of sensory information relating to single objects. Copyright © 2017 the American Physiological Society.

Remote Photoregulated Ring Gliding in a [2]Rotaxane via a Molecular Effector.

PubMed

Tron, Arnaud; Pianet, Isabelle; Martinez-Cuezva, Alberto; Tucker, James H R; Pisciottani, Luca; Alajarin, Mateo; Berna, Jose; McClenaghan, Nathan D

2017-01-06

A molecular barbiturate messenger, which is reversibly released/captured by a photoswitchable artificial molecular receptor, is shown to act as an effector to control ring gliding on a distant hydrogen-bonding [2]rotaxane. Thus, light-driven chemical communication governing the operation of a remote molecular machine is demonstrated using an information-rich neutral molecule.

MIGRATION OF SMALL MOONS IN SATURN's RINGS

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

Bromley, Benjamin C.; Kenyon, Scott J., E-mail: bromley@physics.utah.edu, E-mail: skenyon@cfa.harvard.edu

2013-02-20

The motions of small moons through Saturn's rings provide excellent tests of radial migration models. In theory, torque exchange between these moons and ring particles leads to radial drift. We predict that moons with Hill radii r {sub H} {approx} 2-24 km should migrate through the A ring in 1000 yr. In this size range, moons orbiting in an empty gap or in a full ring eventually migrate at the same rate. Smaller moons or moonlets-such as the propellers-are trapped by diffusion of disk material into corotating orbits, creating inertial drag. Larger moons-such as Pan or Atlas-do not migrate becausemore » of their own inertia. Fast migration of 2-24 km moons should eliminate intermediate-size bodies from the A ring and may be responsible for the observed large-radius cutoff of r {sub H} {approx} 1-2 km in the size distribution of the A ring's propeller moonlets. Although the presence of Daphnis (r {sub H} Almost-Equal-To 5 km) inside the Keeler gap challenges this scenario, numerical simulations demonstrate that orbital resonances and stirring by distant, larger moons (e.g., Mimas) may be important factors. For Daphnis, stirring by distant moons seems the most promising mechanism to halt fast migration. Alternatively, Daphnis may be a recent addition to the ring that is settling into a low inclination orbit in {approx}10{sup 3} yr prior to a phase of rapid migration. We provide predictions of observational constraints required to discriminate among possible scenarios for Daphnis.« less

Evidence that Magnetic Navigation and Geomagnetic Imprinting Shape Spatial Genetic Variation in Sea Turtles.

PubMed

Brothers, J Roger; Lohmann, Kenneth J

2018-04-23

The canonical drivers of population genetic structure, or spatial genetic variation, are isolation by distance and isolation by environment. Isolation by distance predicts that neighboring populations will be genetically similar and geographically distant populations will be genetically distinct [1]. Numerous examples also exist of isolation by environment, a phenomenon in which populations that inhabit similar environments (e.g., same elevation, temperature, or vegetation) are genetically similar even if they are distant, whereas populations that inhabit different environments are genetically distinct even when geographically close [2-4]. These dual models provide a widely accepted conceptual framework for understanding population structure [5-8]. Here, we present evidence for an additional, novel process that we call isolation by navigation, in which the navigational mechanism used by a long-distance migrant influences population structure independently of isolation by either distance or environment. Specifically, we investigated the population structure of loggerhead sea turtles (Caretta caretta) [9], which return to nest on their natal beaches by seeking out unique magnetic signatures along the coast-a behavior known as geomagnetic imprinting [10-12]. Results reveal that spatial variation in Earth's magnetic field strongly predicts genetic differentiation between nesting beaches, even when environmental similarities and geographic proximity are taken into account. The findings provide genetic corroboration of geomagnetic imprinting [10, 13]. Moreover, they provide strong evidence that geomagnetic imprinting and magnetic navigation help shape the population structure of sea turtles and perhaps numerous other long-distance migrants that return to their natal areas to reproduce [13-17]. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolutionary relationships among pollinators and repeated pollinator sharing in sexually deceptive orchids.

PubMed

Phillips, R D; Brown, G R; Dixon, K W; Hayes, C; Linde, C C; Peakall, R

2017-09-01

The mechanism of pollinator attraction is predicted to strongly influence both plant diversification and the extent of pollinator sharing between species. Sexually deceptive orchids rely on mimicry of species-specific sex pheromones to attract their insect pollinators. Given that sex pheromones tend to be conserved among related species, we predicted that in sexually deceptive orchids, (i) pollinator sharing is rare, (ii) closely related orchids use closely related pollinators and (iii) there is strong bias in the wasp lineages exploited by orchids. We focused on species that are pollinated by sexual deception of thynnine wasps in the distantly related genera Caladenia and Drakaea, including new field observations for 45 species of Caladenia. Specialization was extreme with most orchids using a single pollinator species. Unexpectedly, seven cases of pollinator sharing were found, including two between Caladenia and Drakaea, which exhibit strikingly different floral morphology. Phylogenetic analysis of pollinators using four nuclear sequence loci demonstrated that although orchids within major clades primarily use closely related pollinator species, up to 17% of orchids within these clades are pollinated by a member of a phylogenetically distant wasp genus. Further, compared to the total diversity of thynnine wasps within the study region, orchids show a strong bias towards exploiting certain genera. Although these patterns may arise through conservatism in the chemical classes used in sex pheromones, apparent switches between wasp clades suggest unexpected flexibility in floral semiochemical production. Alternatively, wasp sex pheromones within lineages may exhibit greater chemical diversity than currently appreciated. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

75 FR 29479 - Medicare and Medicaid Programs: Proposed Changes Affecting Hospital and Critical Access Hospital...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... have to include all adverse events that may result from telemedicine services provided by the distant... adverse events that result from the telemedicine services provided by the distant-site physician or... include all adverse events that result from the telemedicine services provided by the distant-site...

A review of the cicada genus Kosemia Matsumura (Hemiptera: Cicadidae).

PubMed

Qi, Shengping; Hayashi, Masami; Wei, Cong

2015-01-21

The genus Kosemia Matsumura is reviewed based on investigation of the described species and the descriptions of two new species, Kosemia castanea sp. n. and Kosemia guanzhongensis sp. n., from Shaanxi Province, China. Two species formerly belonging to the genus Cicadetta Kolenati, C. chinensis (Distant) and C. mogannia (Distant), are transferred to Kosemia Matsumura to become K. chinensis (Distant), comb. n. and K. mogannia (Distant), comb. n.. The male of K. chinensis (Distant), comb. n. is discovered and described for the first time. Melampsalta bifuscata Liu, 1940 is recognized to be a junior synonym of K. chinensis. Leptopsalta rubicosta Chou & Lei, 1997 and Lycurgus sinensis Jacobi, 1944 are recognized to be junior synonyms of K. mogannia. Kosemia radiator (Uhler, 1896) is removed from the Chinese cicada fauna. A key to species of Kosemia is provided. 

WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning

PubMed Central

Sutphin, George L.; Mahoney, J. Matthew; Sheppard, Keith; Walton, David O.; Korstanje, Ron

2016-01-01

The rapid advancement of technology in genomics and targeted genetic manipulation has made comparative biology an increasingly prominent strategy to model human disease processes. Predicting orthology relationships between species is a vital component of comparative biology. Dozens of strategies for predicting orthologs have been developed using combinations of gene and protein sequence, phylogenetic history, and functional interaction with progressively increasing accuracy. A relatively new class of orthology prediction strategies combines aspects of multiple methods into meta-tools, resulting in improved prediction performance. Here we present WORMHOLE, a novel ortholog prediction meta-tool that applies machine learning to integrate 17 distinct ortholog prediction algorithms to identify novel least diverged orthologs (LDOs) between 6 eukaryotic species—humans, mice, zebrafish, fruit flies, nematodes, and budding yeast. Machine learning allows WORMHOLE to intelligently incorporate predictions from a wide-spectrum of strategies in order to form aggregate predictions of LDOs with high confidence. In this study we demonstrate the performance of WORMHOLE across each combination of query and target species. We show that WORMHOLE is particularly adept at improving LDO prediction performance between distantly related species, expanding the pool of LDOs while maintaining low evolutionary distance and a high level of functional relatedness between genes in LDO pairs. We present extensive validation, including cross-validated prediction of PANTHER LDOs and evaluation of evolutionary divergence and functional similarity, and discuss future applications of machine learning in ortholog prediction. A WORMHOLE web tool has been developed and is available at http://wormhole.jax.org/. PMID:27812085

WORMHOLE: Novel Least Diverged Ortholog Prediction through Machine Learning.

PubMed

Sutphin, George L; Mahoney, J Matthew; Sheppard, Keith; Walton, David O; Korstanje, Ron

2016-11-01

The rapid advancement of technology in genomics and targeted genetic manipulation has made comparative biology an increasingly prominent strategy to model human disease processes. Predicting orthology relationships between species is a vital component of comparative biology. Dozens of strategies for predicting orthologs have been developed using combinations of gene and protein sequence, phylogenetic history, and functional interaction with progressively increasing accuracy. A relatively new class of orthology prediction strategies combines aspects of multiple methods into meta-tools, resulting in improved prediction performance. Here we present WORMHOLE, a novel ortholog prediction meta-tool that applies machine learning to integrate 17 distinct ortholog prediction algorithms to identify novel least diverged orthologs (LDOs) between 6 eukaryotic species-humans, mice, zebrafish, fruit flies, nematodes, and budding yeast. Machine learning allows WORMHOLE to intelligently incorporate predictions from a wide-spectrum of strategies in order to form aggregate predictions of LDOs with high confidence. In this study we demonstrate the performance of WORMHOLE across each combination of query and target species. We show that WORMHOLE is particularly adept at improving LDO prediction performance between distantly related species, expanding the pool of LDOs while maintaining low evolutionary distance and a high level of functional relatedness between genes in LDO pairs. We present extensive validation, including cross-validated prediction of PANTHER LDOs and evaluation of evolutionary divergence and functional similarity, and discuss future applications of machine learning in ortholog prediction. A WORMHOLE web tool has been developed and is available at http://wormhole.jax.org/.

Bioinformatic prediction and in vivo validation of residue-residue interactions in human proteins

NASA Astrophysics Data System (ADS)

Jordan, Daniel; Davis, Erica; Katsanis, Nicholas; Sunyaev, Shamil

2014-03-01

Identifying residue-residue interactions in protein molecules is important for understanding both protein structure and function in the context of evolutionary dynamics and medical genetics. Such interactions can be difficult to predict using existing empirical or physical potentials, especially when residues are far from each other in sequence space. Using a multiple sequence alignment of 46 diverse vertebrate species we explore the space of allowed sequences for orthologous protein families. Amino acid changes that are known to damage protein function allow us to identify specific changes that are likely to have interacting partners. We fit the parameters of the continuous-time Markov process used in the alignment to conclude that these interactions are primarily pairwise, rather than higher order. Candidates for sites under pairwise epistasis are predicted, which can then be tested by experiment. We report the results of an initial round of in vivo experiments in a zebrafish model that verify the presence of multiple pairwise interactions predicted by our model. These experimentally validated interactions are novel, distant in sequence, and are not readily explained by known biochemical or biophysical features.

Predicting Individual Characteristics from Digital Traces on Social Media: A Meta-Analysis.

PubMed

Settanni, Michele; Azucar, Danny; Marengo, Davide

2018-04-01

The increasing utilization of social media provides a vast and new source of user-generated ecological data (digital traces), which can be automatically collected for research purposes. The availability of these data sets, combined with the convergence between social and computer sciences, has led researchers to develop automated methods to extract digital traces from social media and use them to predict individual psychological characteristics and behaviors. In this article, we reviewed the literature on this topic and conducted a series of meta-analyses to determine the strength of associations between digital traces and specific individual characteristics; personality, psychological well-being, and intelligence. Potential moderator effects were analyzed with respect to type of social media platform, type of digital traces examined, and study quality. Our findings indicate that digital traces from social media can be studied to assess and predict theoretically distant psychosocial characteristics with remarkable accuracy. Analysis of moderators indicated that the collection of specific types of information (i.e., user demographics), and the inclusion of different types of digital traces, could help improve the accuracy of predictions.

Ab Initio structure prediction for Escherichia coli: towards genome-wide protein structure modeling and fold assignment

PubMed Central

Xu, Dong; Zhang, Yang

2013-01-01

Genome-wide protein structure prediction and structure-based function annotation have been a long-term goal in molecular biology but not yet become possible due to difficulties in modeling distant-homology targets. We developed a hybrid pipeline combining ab initio folding and template-based modeling for genome-wide structure prediction applied to the Escherichia coli genome. The pipeline was tested on 43 known sequences, where QUARK-based ab initio folding simulation generated models with TM-score 17% higher than that by traditional comparative modeling methods. For 495 unknown hard sequences, 72 are predicted to have a correct fold (TM-score > 0.5) and 321 have a substantial portion of structure correctly modeled (TM-score > 0.35). 317 sequences can be reliably assigned to a SCOP fold family based on structural analogy to existing proteins in PDB. The presented results, as a case study of E. coli, represent promising progress towards genome-wide structure modeling and fold family assignment using state-of-the-art ab initio folding algorithms. PMID:23719418

A comparison of different functions for predicted protein model quality assessment.

PubMed

Li, Juan; Fang, Huisheng

2016-07-01

In protein structure prediction, a considerable number of models are usually produced by either the Template-Based Method (TBM) or the ab initio prediction. The purpose of this study is to find the critical parameter in assessing the quality of the predicted models. A non-redundant template library was developed and 138 target sequences were modeled. The target sequences were all distant from the proteins in the template library and were aligned with template library proteins on the basis of the transformation matrix. The quality of each model was first assessed with QMEAN and its six parameters, which are C_β interaction energy (C_beta), all-atom pairwise energy (PE), solvation energy (SE), torsion angle energy (TAE), secondary structure agreement (SSA), and solvent accessibility agreement (SAE). Finally, the alignment score (score) was also used to assess the quality of model. Hence, a total of eight parameters (i.e., QMEAN, C_beta, PE, SE, TAE, SSA, SAE, score) were independently used to assess the quality of each model. The results indicate that SSA is the best parameter to estimate the quality of the model.

Recurrence and death from breast cancer after complete treatments: an experience from hospitals in Northern Thailand.

PubMed

Chairat, Rungnapa; Puttisri, Adisom; Pamarapa, Asani; Wongrach, Nongnoot; Tawichasri, Chamaiporn; Patumanond, Jayanton; Tantraworasin, Apichat; Charoentum, Chaiyut

2014-09-01

To describe the pattern of disease progression and to describe locoregional recurrence, distant recurrence, and death rates in breast cancer patients after complete treatment. Medical records of women diagnosed with breast cancer at two university affiliated tertiary care hospitals in the Northern Thailand that had complete treatments between 2006 and 2010 were traced. Extracted key information included patient clinical profiles and documented recurrence of cancer The causes of death were verified from breast cancer case registration database, death certificates through The Ministry of Internal Affairs'civil registration, by direct telephone contact, or by distributed prepaid postcards. Medical records of 829 women diagnosed with breast cancer without prior evidence ofdistant metastasis, and had complete recommended treatment were included. Six hundred thirty seven women had not experienced any events up to the end of the follow-up (76.8%). The first occurring events were focused and categorized into three distinct types, locoregional recurrence (n = 83, median follow-up time = 34.2 months), distant recurrence (n = 78, median follow-up time = 35.4 months), and death without any evidences of locoregional or distant recurrences (n = 12, median follow-up time = 36.7 months). Distant recurrence after locoregional recurrence was reported (n = 33). There were 109 patient who had died (breast cancer related death) up to the end of the follow-up (13.2%). The three types of consecutively occurring deaths were death after locoregional recurrence without any distant recurrences (n = 15), death after distant recurrence with locoregional recurrence (n = 21), and death after documenited distant recurrence without any locoregional recurrences (n = 61). The trend was that the rate of the first occurring locoregional recurrence was slightly higher than that of distant recurrence, The death rate in patients without any recurrences was much lower than in those experiencing prior recurrences. The rates of disease progression from local recurrence to distant recurrence and to death were approximately 5 to 7 times faster in patients who had experienced earlierprogressions.

CT-guided percutaneous fine-needle aspiration biopsy of the inferior vena cava wall: a posterior coaxial approach.

PubMed

Kos, Sebastian; Bilecen, Deniz; Baumhoer, Daniel; Guillaume, Nicolas; Jacob, Augustinus L

2010-02-01

A 72-year-old man was referred to our department with an incidentally diagnosed bronchogenic carcinoma of the right upper lobe. Positron emission tomography (PET) combined with computed tomography (PET-CT) revealed an unexpected hot spot in the ventral wall of the infrarenal segment of the inferior vena cava (IVC). Diagnostic biopsy of this lesion was performed under CT guidance with semiautomated 20G fine-needle aspiration (FNA) through a 19G coaxial needle. Cytology revealed few carcinoma cells, which led to the remarkable diagnosis of a distant metastasis to the IVC wall. Both the immediate postinterventional CT control and the further surveillance period of the patient were unremarkable; in particular, no signs of bleeding complications were detected. We conclude that coaxial FNA of an IVC wall lesion is technically feasible and may even help diagnose distant metastasis.

CT-Guided Percutaneous Fine-Needle Aspiration Biopsy of the Inferior Vena Cava Wall: A Posterior Coaxial Approach

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

Kos, Sebastian, E-mail: skos@gmx.de; Bilecen, Deniz; Baumhoer, Daniel

A 72-year-old man was referred to our department with an incidentally diagnosed bronchogenic carcinoma of the right upper lobe. Positron emission tomography (PET) combined with computed tomography (PET-CT) revealed an unexpected hot spot in the ventral wall of the infrarenal segment of the inferior vena cava (IVC). Diagnostic biopsy of this lesion was performed under CT guidance with semiautomated 20G fine-needle aspiration (FNA) through a 19G coaxial needle. Cytology revealed few carcinoma cells, which led to the remarkable diagnosis of a distant metastasis to the IVC wall. Both the immediate postinterventional CT control and the further surveillance period of themore » patient were unremarkable; in particular, no signs of bleeding complications were detected. We conclude that coaxial FNA of an IVC wall lesion is technically feasible and may even help diagnose distant metastasis.« less

Deregulated HOXB7 expression predicts poor prognosis of patients with malignancies of digestive system.

PubMed

Liu, Fang-Teng; Chen, Han-Min; Xiong, Ying; Zhu, Zheng-Ming

2017-07-26

Numerous studies have investigated the relationship between deregulated HOXB7 expression with the clinical outcome in patients with digestive stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed to comprehensively evaluate the prediction and prognostic value of HOXB7 in digestive stem cancers. Electronic databases updated to December 1, 2016 were retrieved to collect relevant eligible studies to quantitatively explore the potential roles of HOXB7 as a prognostic indicator in digestive system cancers. A total of 9 studies (n = 1298 patients) was included in this synthetical meta-analysis. The pooled hazard ratios suggested that high expression of HOXB7 protein was associated with poor prognosis of OS in patients with digestive system cancers (HR = 1.97, 95% CI: 1.65-2.28, p= 0.000), and HOXB7 protein could act as an independent prognostic factor for predicting OS of patients with digestive system cancers (HR: 2.02, 95% CI: 1.69-2.36, p = 0.000). Statistical significance was also observed in subgroup meta-analysis based on the cancer type, histology type, country, sample size and publication date. Furthermore, we examined the correlations between HOXB7 protein and clinicopathological features. It showed that altered expression of HOXB7 protein was correlated with tumor invasion (p = 0.000), lymph node status (p = 0.000), distant metastasis (p = 0.001) and TNM stage (p = 0.000). However, the expression of HOXB7 protein was not associated with age (p = 0.64), gender (p = 0.40) or levels of differentiation (p = 0.19). High expression of HOXB7 protein was associated with poor prognosis of patients with digestive system cancers, as well as clinicopathologic characteristics, including the tumor invasion, lymph node status, distant metastasis and TNM stage. The expression of HOXB7 protein was not associated with age, gender or levels of differentiation. HOXB7 protein expression level in tumor tissue might serve as a novel prognostic marker for digestive system cancers.

Prognostic importance of Gleason 7 disease among patients treated with external beam radiation therapy for prostate cancer: results of a detailed biopsy core analysis.

PubMed

Spratt, Daniel E; Zumsteg, Zach; Ghadjar, Pirus; Pangasa, Misha; Pei, Xin; Fine, Samson W; Yamada, Yoshiya; Kollmeier, Marisa; Zelefsky, Michael J

2013-04-01

To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used. Copyright © 2013 Elsevier Inc. All rights reserved.

Testing Fundamental Physics with Distant Star Clusters: Analysis of Observational Data on Palomar 14

NASA Astrophysics Data System (ADS)

Jordi, K.; Grebel, E. K.; Hilker, M.; Baumgardt, H.; Frank, M.; Kroupa, P.; Haghi, H.; Côté, P.; Djorgovski, S. G.

2009-06-01

We use the distant outer halo globular cluster Palomar 14 as a test case for classical versus modified Newtonian dynamics (MOND). Previous theoretical calculations have shown that the line-of-sight velocity dispersion predicted by these theories can differ by up to a factor of 3 for such sparse, remote clusters like Pal 14. We determine the line-of-sight velocity dispersion of Palomar 14 by measuring radial velocities of 17 red giant cluster members obtained using the Very Large Telescope and Keck telescope. The systemic velocity of Palomar 14 is (72.28 ± 0.12) km s-1. The derived velocity dispersion of (0.38 ± 0.12) km s-1 of the 16 definite member stars is in agreement with the theoretical prediction for the classical Newtonian case according to Baumgardt et al. In order to exclude the possibility that a peculiar mass function might have influenced our measurements, we derived the cluster's main-sequence mass function down to 0.53 M sun using archival images obtained with the Hubble Space Telescope. We found a mass function slope of α = 1.27 ± 0.44, which is, compared to the canonical mass function, a significantly shallower slope. The derived lower limit on the cluster's mass is higher than the theoretically predicted mass in the case of MOND. Our data are consistent with a central density of ρ0 = 0.1 M sun pc-3. We need no dark matter in Palomar 14. If the cluster is on a circular orbit, our spectroscopic and photometric results argue against MOND, unless the cluster experienced significant mass loss. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Prognostic Importance of Gleason 7 Disease Among Patients Treated With External Beam Radiation Therapy for Prostate Cancer: Results of a Detailed Biopsy Core Analysis

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

Spratt, Daniel E.; Zumsteg, Zach; Ghadjar, Pirus

2013-04-01

Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6more » years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used.« less

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

PubMed Central

Kwak, Yoonjin; Koh, Jiwon; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Woo Ho; Lee, Hye Seung

2016-01-01

Background The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases. Methods The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS. Result Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status. Conclusion IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC. PMID:27835889

Two E-selectin ligands, BST-2 and LGALS3BP, predict metastasis and poor survival of ER-negative breast cancer.

PubMed

Woodman, Natalie; Pinder, Sarah E; Tajadura, Virginia; Le Bourhis, Xuefen; Gillett, Cheryl; Delannoy, Philippe; Burchell, Joy M; Julien, Sylvain

2016-07-01

Distant metastases account for the majority of cancer-related deaths in breast cancer. The rate and site of metastasis differ between estrogen receptor (ER)-negative and ER-positive tumours, and metastatic fate can be very diverse even within the ER-negative group. Characterisation of new pro-metastatic markers may help to identify patients with higher risk and improve their care accordingly. Selectin ligands aberrantly expressed by cancer cells promote metastasis by enabling interaction between circulating tumour cells and endothelial cells in distant organs. These ligands consist in carbohydrate molecules, such as sialyl-Lewis x antigen (sLex), borne by glycoproteins or glycolipids on the cancer cell surface. We have previously demonstrated that the molecular scaffold presenting sLex to selectins (e.g. glycolipid vs. glycoproteins) was crucial for these interactions to occur. Moreover, we reported that detection of sLex alone in breast carcinomas was only of limited prognostic value. However, since sLex was found to be carried by several glycoproteins in cancer cells, we hypothesized that the combination of the carbohydrate with its carriers could be more relevant than each marker independently. In this study, we addressed this question by analysing sLex expression together with two glycoproteins (BST-2 and LGALS3BP), shown to interact with E-selectin in a carbohydrate-dependent manner, in a cohort of 249 invasive breast cancers. We found both glycoproteins to be associated with distant metastasis risk and poorer survival. Importantly, concomitant high expression of BST-2 with sLex defined a sub-group of patients with ER-negative tumours displaying higher risks of liver and brain metastasis and a 3-fold decreased survival rate.

Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

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

Yoo, Tae; Lee, Woo Jin; Woo, Sang Myung

2011-11-15

Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM{sup 3m}), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, andmore » CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM{sup 3m}, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2-31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM{sup 3m} occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level ({<=}400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM{sup 3m} (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p < 0.05 for all three parameters). Conclusion: For patients with localized and unresectable pancreatic cancer, pretreatment CA 19-9 level could be helpful in predicting tumor response, DM{sup 3m}, and overall survival and identifying patients who will benefit from CRT.« less

Essentiality Is a Strong Determinant of Protein Rates of Evolution during Mutation Accumulation Experiments in Escherichia coli

PubMed Central

Alvarez-Ponce, David; Sabater-Muñoz, Beatriz; Toft, Christina; Ruiz-González, Mario X.; Fares, Mario A.

2016-01-01

Abstract The Neutral Theory of Molecular Evolution is considered the most powerful theory to understand the evolutionary behavior of proteins. One of the main predictions of this theory is that essential proteins should evolve slower than dispensable ones owing to increased selective constraints. Comparison of genomes of different species, however, has revealed only small differences between the rates of evolution of essential and nonessential proteins. In some analyses, these differences vanish once confounding factors are controlled for, whereas in other cases essentiality seems to have an independent, albeit small, effect. It has been argued that comparing relatively distant genomes may entail a number of limitations. For instance, many of the genes that are dispensable in controlled lab conditions may be essential in some of the conditions faced in nature. Moreover, essentiality can change during evolution, and rates of protein evolution are simultaneously shaped by a variety of factors, whose individual effects are difficult to isolate. Here, we conducted two parallel mutation accumulation experiments in Escherichia coli, during 5,500–5,750 generations, and compared the genomes at different points of the experiments. Our approach (a short-term experiment, under highly controlled conditions) enabled us to overcome many of the limitations of previous studies. We observed that essential proteins evolved substantially slower than nonessential ones during our experiments. Strikingly, rates of protein evolution were only moderately affected by expression level and protein length. PMID:27566759

SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

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

Zhang, H; Wang, J; Chuong, M

2015-06-15

Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporalmore » PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or support vector machine model. Conclusion: Applying radiomics approach to either midtreatment or post-treatment PET/CT could achieve high accuracy in predicting anal cancer treatment outcomes. This work was supported in part by the National Cancer Institute Grant R01CA172638.« less

Verifying a computational method for predicting extreme ground motion

USGS Publications Warehouse

Harris, R.A.; Barall, M.; Andrews, D.J.; Duan, B.; Ma, S.; Dunham, E.M.; Gabriel, A.-A.; Kaneko, Y.; Kase, Y.; Aagaard, Brad T.; Oglesby, D.D.; Ampuero, J.-P.; Hanks, T.C.; Abrahamson, N.

2011-01-01

In situations where seismological data is rare or nonexistent, computer simulations may be used to predict ground motions caused by future earthquakes. This is particularly practical in the case of extreme ground motions, where engineers of special buildings may need to design for an event that has not been historically observed but which may occur in the far-distant future. Once the simulations have been performed, however, they still need to be tested. The SCEC-USGS dynamic rupture code verification exercise provides a testing mechanism for simulations that involve spontaneous earthquake rupture. We have performed this examination for the specific computer code that was used to predict maximum possible ground motion near Yucca Mountain. Our SCEC-USGS group exercises have demonstrated that the specific computer code that was used for the Yucca Mountain simulations produces similar results to those produced by other computer codes when tackling the same science problem. We also found that the 3D ground motion simulations produced smaller ground motions than the 2D simulations.

Why Is There a Glass Ceiling for Threading Based Protein Structure Prediction Methods?

PubMed

Skolnick, Jeffrey; Zhou, Hongyi

2017-04-20

Despite their different implementations, comparison of the best threading approaches to the prediction of evolutionary distant protein structures reveals that they tend to succeed or fail on the same protein targets. This is true despite the fact that the structural template library has good templates for all cases. Thus, a key question is why are certain protein structures threadable while others are not. Comparison with threading results on a set of artificial sequences selected for stability further argues that the failure of threading is due to the nature of the protein structures themselves. Using a new contact map based alignment algorithm, we demonstrate that certain folds are highly degenerate in that they can have very similar coarse grained fractions of native contacts aligned and yet differ significantly from the native structure. For threadable proteins, this is not the case. Thus, contemporary threading approaches appear to have reached a plateau, and new approaches to structure prediction are required.

Identifiability, reducibility, and adaptability in allosteric macromolecules.

PubMed

Bohner, Gergő; Venkataraman, Gaurav

2017-05-01

The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed "allostery," is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca 2+ -activated K + (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. © 2017 Bohner and Venkataraman.

Identifiability, reducibility, and adaptability in allosteric macromolecules

PubMed Central

Bohner, Gergő

2017-01-01

The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed “allostery,” is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca2+-activated K+ (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. PMID:28416647

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

NASA Astrophysics Data System (ADS)

Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

2016-08-01

Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

PubMed Central

Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

2016-01-01

Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID:27561351

Ocean noise in the tropical and subtropical Pacific Ocean.

PubMed

Sirović, Ana; Wiggins, Sean M; Oleson, Erin M

2013-10-01

Ocean ambient noise is well studied in the North Pacific and North Atlantic but is poorly described for most of the worlds' oceans. Calibrated passive acoustic recordings were collected during 2009-2010 at seven locations in the central and western tropical and subtropical Pacific. Monthly and hourly mean power spectra (15-1000 Hz) were calculated in addition to their skewness, kurtosis, and percentile distributions. Overall, ambient noise at these seven sites was 10-20 dB lower than reported recently for most other locations in the North Pacific. At frequencies <100 Hz, spectrum levels were equivalent to those predicted for remote or light shipping. Noise levels in the 40 Hz band were compared to the presence of nearby and distant ships as reported to the World Meteorological Organization Voluntary Observing Ship Scheme (VOS) project. There was a positive, but nonsignificant correlation between distant shipping and low frequency noise (at 40 Hz). There was a seasonal variation in ambient noise at frequencies >200 Hz with higher levels recorded in the winter than in the summer. Several species of baleen whales, humpback (Megaptera novaeangliae), blue (Balaenoptera musculus), and fin (B. physalus) whales, also contributed seasonally to ambient noise in characteristic frequency bands.

The usability of the optical parametric amplification of light for high-angular-resolution imaging and fast astrometry

NASA Astrophysics Data System (ADS)

Kurek, A. R.; Stachowski, A.; Banaszek, K.; Pollo, A.

2018-05-01

High-angular-resolution imaging is crucial for many applications in modern astronomy and astrophysics. The fundamental diffraction limit constrains the resolving power of both ground-based and spaceborne telescopes. The recent idea of a quantum telescope based on the optical parametric amplification (OPA) of light aims to bypass this limit for the imaging of extended sources by an order of magnitude or more. We present an updated scheme of an OPA-based device and a more accurate model of the signal amplification by such a device. The semiclassical model that we present predicts that the noise in such a system will form so-called light speckles as a result of light interference in the optical path. Based on this model, we analysed the efficiency of OPA in increasing the angular resolution of the imaging of extended targets and the precise localization of a distant point source. According to our new model, OPA offers a gain in resolved imaging in comparison to classical optics. For a given time-span, we found that OPA can be more efficient in localizing a single distant point source than classical telescopes.

A molecular study of microbe transfer between distant environments.

PubMed

Hooper, Sean D; Raes, Jeroen; Foerstner, Konrad U; Harrington, Eoghan D; Dalevi, Daniel; Bork, Peer

2008-07-09

Environments and their organic content are generally not static and isolated, but in a constant state of exchange and interaction with each other. Through physical or biological processes, organisms, especially microbes, may be transferred between environments whose characteristics may be quite different. The transferred microbes may not survive in their new environment, but their DNA will be deposited. In this study, we compare two environmental sequencing projects to find molecular evidence of transfer of microbes over vast geographical distances. By studying synonymous nucleotide composition, oligomer frequency and orthology between predicted genes in metagenomics data from two environments, terrestrial and aquatic, and by correlating with phylogenetic mappings, we find that both environments are likely to contain trace amounts of microbes which have been far removed from their original habitat. We also suggest a bias in direction from soil to sea, which is consistent with the cycles of planetary wind and water. Our findings support the Baas-Becking hypothesis formulated in 1934, which states that due to dispersion and population sizes, microbes are likely to be found in widely disparate environments. Furthermore, the availability of genetic material from distant environments is a possible font of novel gene functions for lateral gene transfer.

A Molecular Study of Microbe Transfer between Distant Environments

PubMed Central

Hooper, Sean D.; Raes, Jeroen; Foerstner, Konrad U.; Harrington, Eoghan D.; Dalevi, Daniel; Bork, Peer

2008-01-01

Background Environments and their organic content are generally not static and isolated, but in a constant state of exchange and interaction with each other. Through physical or biological processes, organisms, especially microbes, may be transferred between environments whose characteristics may be quite different. The transferred microbes may not survive in their new environment, but their DNA will be deposited. In this study, we compare two environmental sequencing projects to find molecular evidence of transfer of microbes over vast geographical distances. Methodology By studying synonymous nucleotide composition, oligomer frequency and orthology between predicted genes in metagenomics data from two environments, terrestrial and aquatic, and by correlating with phylogenetic mappings, we find that both environments are likely to contain trace amounts of microbes which have been far removed from their original habitat. We also suggest a bias in direction from soil to sea, which is consistent with the cycles of planetary wind and water. Conclusions Our findings support the Baas-Becking hypothesis formulated in 1934, which states that due to dispersion and population sizes, microbes are likely to be found in widely disparate environments. Furthermore, the availability of genetic material from distant environments is a possible font of novel gene functions for lateral gene transfer. PMID:18612393

76 FR 31351 - Safety Requirements and Manning Exemption Eligibility on Distant Water Tuna Fleet Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-31

...The Coast Guard announces the availability of Office of Vessel Activities Policy Letter 11-05 regarding Distant Water Tuna Fleet vessels manning exemption eligibility and safety requirements. This final policy clarifies the requirements to allow a distant water tuna fleet vessel to engage foreign citizens under a temporary manning exemption.

76 FR 3646 - Safety Requirements and Manning Exemption Eligibility on Distant Water Tuna Fleet Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

...Pursuant to Section 904 of the 2010 Coast Guard Authorization Act, the Coast Guard announces the availability of a draft policy regarding distant water tuna fleet vessels manning exemption eligibility and safety requirements. We request your comments on the Safety Requirements and Manning Exemption Eligibility on Distant Water Tuna Fleet Vessels.

Saul Perlmutter, Distant Supernovae, Dark Energy, and the Accelerating

Science.gov Websites

, Distant Supernovae, Dark Energy, and the Accelerating Expansion of the Universe Resources with Additional nature of dark energy.'1 'The accelerating expansion means that the universe could expand forever until , in the distant future, it is cold and dark. The teams' discovery led to speculation that there is a

Estimation of genomic prediction accuracy from reference populations with varying degrees of relationship.

PubMed

Lee, S Hong; Clark, Sam; van der Werf, Julius H J

2017-01-01

Genomic prediction is emerging in a wide range of fields including animal and plant breeding, risk prediction in human precision medicine and forensic. It is desirable to establish a theoretical framework for genomic prediction accuracy when the reference data consists of information sources with varying degrees of relationship to the target individuals. A reference set can contain both close and distant relatives as well as 'unrelated' individuals from the wider population in the genomic prediction. The various sources of information were modeled as different populations with different effective population sizes (Ne). Both the effective number of chromosome segments (Me) and Ne are considered to be a function of the data used for prediction. We validate our theory with analyses of simulated as well as real data, and illustrate that the variation in genomic relationships with the target is a predictor of the information content of the reference set. With a similar amount of data available for each source, we show that close relatives can have a substantially larger effect on genomic prediction accuracy than lesser related individuals. We also illustrate that when prediction relies on closer relatives, there is less improvement in prediction accuracy with an increase in training data or marker panel density. We release software that can estimate the expected prediction accuracy and power when combining different reference sources with various degrees of relationship to the target, which is useful when planning genomic prediction (before or after collecting data) in animal, plant and human genetics.

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-diethylaminoethyl-dextran methyl methacrylate copolymer non-viral vector-p53.

PubMed

Baliaka, A; Zarogoulidis, P; Domvri, K; Hohenforst-Schmidt, W; Sakkas, A; Huang, H; Le Pivert, P; Koliakos, G; Koliakou, E; Kouzi-Koliakos, K; Tsakiridis, K; Chioti, A; Siotou, E; Cheva, A; Zarogoulidis, K; Sakkas, L

2014-02-01

Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes.

PubMed

Jia, Da; Gomez, Timothy S; Metlagel, Zoltan; Umetani, Junko; Otwinowski, Zbyszek; Rosen, Michael K; Billadeau, Daniel D

2010-06-08

We recently showed that the Wiskott-Aldrich syndrome protein (WASP) family member, WASH, localizes to endosomal subdomains and regulates endocytic vesicle scission in an Arp2/3-dependent manner. Mechanisms regulating WASH activity are unknown. Here we show that WASH functions in cells within a 500 kDa core complex containing Strumpellin, FAM21, KIAA1033 (SWIP), and CCDC53. Although recombinant WASH is constitutively active toward the Arp2/3 complex, the reconstituted core assembly is inhibited, suggesting that it functions in cells to regulate actin dynamics through WASH. FAM21 interacts directly with CAPZ and inhibits its actin-capping activity. Four of the five core components show distant (approximately 15% amino acid sequence identify) but significant structural homology to components of a complex that negatively regulates the WASP family member, WAVE. Moreover, biochemical and electron microscopic analyses show that the WASH and WAVE complexes are structurally similar. Thus, these two distantly related WASP family members are controlled by analogous structurally related mechanisms. Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder.

Parallel genetic origins of pelvic reduction in vertebrates

PubMed Central

Shapiro, Michael D.; Bell, Michael A.; Kingsley, David M.

2006-01-01

Despite longstanding interest in parallel evolution, little is known about the genes that control similar traits in different lineages of vertebrates. Pelvic reduction in stickleback fish (family Gasterosteidae) provides a striking example of parallel evolution in a genetically tractable system. Previous studies suggest that cis-acting regulatory changes at the Pitx1 locus control pelvic reduction in a population of threespine sticklebacks (Gasterosteus aculeatus). In this study, progeny from intergeneric crosses between pelvic-reduced threespine and ninespine (Pungitius pungitius) sticklebacks also showed severe pelvic reduction, implicating a similar genetic origin for this trait in both genera. Comparative sequencing studies in complete and pelvic-reduced Pungitius revealed no differences in the Pitx1 coding sequences, but Pitx1 expression was absent from the prospective pelvic region of larvae from pelvic-reduced parents. A much more phylogenetically distant example of pelvic reduction, loss of hindlimbs in manatees, shows a similar left–right size bias that is a morphological signature of Pitx1-mediated pelvic reduction in both sticklebacks and mice. These multiple lines of evidence suggest that changes in Pitx1 may represent a key mechanism of morphological evolution in multiple populations, species, and genera of sticklebacks, as well as in distantly related vertebrate lineages. PMID:16945911

SU-F-R-07: Radiomics of CT Features and Associations and Correlation with Outcomes Following Lung SBRT

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

Schreibmann, E; Iwinski Sutter, A; Whitaker, D

Objective: To investigate the prognostic significance of image gradients and in predicting clinical outcomes in a patients with non-small cell lung cancer treated with stereotactic body radiotherapy (SBRT) on 71 patients with 83 treated lesions. Methods: The records of patients treated with lung SBRT were retrospectively reviewed. When applicable, SBRT target volumes were modified to exclude any overlap with pleura, chestwall, or mediastinum. The ITK software package was utilized to generate quantitative measures of image intensity, inhomogeneity, shape morphology and first and second-order CT textures. Multivariate and univariate models containing CT features were generated to assess associations with clinicopathologic factors.more » Results: On univariate analysis, tumor size (HR 0.54, p=0.045) sumHU (HR 0.31, p=0.044) and short run grey level emphasis STD (HR 0.22, p=0.019) were associated with regional failure-free survival; meanHU (HR 0.30, p=0.035), long run emphasis (HR 0.21, p=0.011) and long run low grey level emphasis (HR 0.14, p=0.005) was associated with distant failure-free survival (DFFS). No features were significant on multivariate modeling however long run low grey level emphasis had a hazard ratio of 0.12 (p=0.061) for DFFS. Adenocarcinoma and squamous cell carcinoma differed with respect to long run emphasis STD (p=0.024), short run low grey level emphasis STD (p<0.001), and long run low grey level emphasis STD (p=0.024). Multivariate modeling of texture features associated with tumor histology was used to estimate histologies of 18 lesions treated without histologic confirmation. Of these, MVA suggested the same histology as a prior metachronous lung malignancy in 3/7 patients. Conclusion: Extracting radiomics features on clinical datasets was feasible with the ITK package with minimal effort to identify pre-treatment quantitative CT features with prognostic factors for distant control after lung SBRT.« less

Intensity-modulated salvage radiotherapy with simultaneous integrated boost for local recurrence of prostate carcinoma: a pilot study on the place of PET-choline for guiding target volume delineation.

PubMed

Wahart, Aurélien; Guy, Jean-Baptiste; Vallard, Alexis; Geissler, Benjamin; Ben Mrad, Majed; Falk, Alexander T; Prevot, Nathalie; de Laroche, Guy; Rancoule, Chloé; Chargari, Cyrus; Magné, Nicolas

2016-01-01

The aim of this study was to report the first cases of salvage radiotherapy (RT) using the intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) targeted on choline positron emission tomography (PET) uptake in a local recurrent prostate cancer, after a radical prostatectomy. Four patients received salvage irradiation for biochemical relapse that occurred after the initial radical prostatectomy. The relapse occurred from 10 months to 6 years with PSA levels ranging from 2.35 to 4.86 ng ml(-1). For each patient, an (18)F-choline PET-CT showed a focal choline uptake in prostatic fossa, with standardized uptake value calculated on the basis of predicted lean body mass (SUL) max of 3.3-6.8. No involved lymph node or distant metastases were diagnosed. IMRT doses were of 62.7 Gy (1.9 Gy/fraction, 33 fractions), with a SIB of 69.3 Gy (2.1 Gy/fraction, 33 fractions) to a PET-guided target volume. Acute toxicities were limited. We observed no gastrointestinal toxicity ≥grade 2 and only one grade 2 genitourinary toxicity. At 1-month follow-up evaluation, no complication and a decrease in PSA level (6.8-43.8% of the pre-therapeutic level) were reported. After 4 months, a decrease in PSA level was obtained for all the patients, ranging from 30% to 70%. At a median follow-up of 15 months, PSA level was controlled for all the patients, but one of them experienced a distant lymph node recurrence. Salvage irradiation to the prostate bed with SIB guided by PET-CT is feasible, with biological efficacy and no major acute toxicity. IMRT with PET-oriented SIB for salvage treatment of prostate cancer is possible, without major acute toxicity.

Analysis and results of Ku and XRCC4 expression in hypopharyngeal cancer tissues treated with chemoradiotherapy

PubMed Central

HAYASHI, JYUNICHI; SAKATA, KOH-ICHI; SOMEYA, MASANORI; MATSUMOTO, YOSHIHISA; SATOH, MASAAKI; NAKATA, KENSEI; HORI, MASAKAZU; TAKAGI, MASARU; KONDOH, ATSUSHI; HIMI, TETSUO; HAREYAMA, MASATO

2012-01-01

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation. Non-homologous end-joining (NHEJ) is a key mechanism of DNA DSB repair. The immunohistochemical analysis of proteins involved in NHEJ may have potential as a predictive assay for tumor radiosensitivity. We examined the correlation between the expression of proteins involved in DNA DSB in biopsy specimens and the results of chemoradiotherapy in hypopharyngeal cancers. Fifty-seven patients with previously untreated squamous cell carcinoma of the hypopharynx were treated between March 2002 and December 2009. Most patients (75%) had stage III or IV disease. The chemotherapy consisted of cisplatin plus 5FU or S-1. A tumor dose of 50 Gy was usually administered to the primary tumor and regional lymph nodes. Doses of 10–20 Gy were usually added to the primary tumor with reduced fields after 50 Gy. The 5-year disease-free survival rate was 100% for patients in stage I, 90% in stage II, 64% in stage III and 50% in stage IV. In stages I-III, patients with a lower expression of Ku70 or XRCC4 tended to have better locoregional control. These results indicated that a lower expression of Ku70 or XRCC4 may be correlated with higher radiosensitivity. Two patients had distant metastasis alone, of which one had 0% expression of Ku70 and the other had 0% expression of Ku86. The absence of Ku70 or Ku86 expression indicates low DNA-PK activity. Low DNA-PK activity due to a low expression of Ku may result in the genetic alteration of cancer cells, leading to a higher tendency of distant metastasis. This finding suggests that proteins involved in NHEJ may have an impact on the treatment results of chemoradiotherapy in hypopharyngeal cancer. PMID:22807979

Frontal lobe connectivity and cognitive impairment in pediatric frontal lobe epilepsy.

PubMed

Braakman, Hilde M H; Vaessen, Maarten J; Jansen, Jacobus F A; Debeij-van Hall, Mariette H J A; de Louw, Anton; Hofman, Paul A M; Vles, Johan S H; Aldenkamp, Albert P; Backes, Walter H

2013-03-01

Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Thirty-two children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired. Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad-range cognitive impairments in children with FLE. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Nested case–control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage

PubMed Central

Sharpe, C R; Collet, J-P; McNutt, M; Belzile, E; Boivin, J-F; Hanley, J A

2000-01-01

We carried out a nested case–control study to measure the rate ratio (RR) for invasive female breast cancer in relation to non-steroidal anti-inflammatory drug (NSAID) use. The source population consisted of the female beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970. Four controls/case, matched on age and sampling time, were randomly selected. Dispensing rates during successive time periods characterized NSAID exposure. RRs associated with exposure during each period were adjusted for exposure during the others. Confounding by other determinants was studied in analyses adjusted with data obtained by interviewing samples of subjects accrued from mid-1991 to mid-1995. We accrued 5882 cases and 23 517 controls. Increasing NSAID exposure 2–5 years preceding diagnosis was associated with a trend towards a decreasing RR (P -trend = 0.003); for the highest exposure level RR = 0.76, 95% confidence interval 0.63–0.92. This protective effect could not be attributed to confounding by other determinants. In analyses involving only the cases, NSAID exposure 2–5 and 6–10 years preceding diagnosis was associated with significantly reduced risks of presenting with a large tumour (> 5 cm diameter) or distant metastasis, but not regional lymph node metastasis. The use of NSAIDs may retard the growth of breast cancers and prevent distant metastasis. © 2000 Cancer Research Campaign PMID:10883678

Relationship of recalled parenting style to self-perception in Korean American college students.

PubMed

Kim, Hyesoo; Chung, Ruth H Gim

2003-12-01

The authors examined the relationship of authoritarian, authoritative, and permissive parenting styles and the number of years in the United States with self-perception (academic competence, morality, and self-reliance) as recalled by Korean American college students (N = 144). Authoritative parenting behaviors were most common in Korean American families, followed by authoritarian behaviors, with permissive behaviors a distant 3rd. Authoritative parenting styles and the number of years lived in the United States were predictive of higher academic competence. Authoritarian and permissive parenting styles were predictive of lower self-reliance, whereas number of years lived in the United States was related to higher self-reliance. Those findings provide partial support for generalizing D. Baumrind's (1971) model of parenting styles to Korean American families, and the findings demonstrate the importance of considering acculturation issues in parenting studies.

Rebelling for a Reason: Protein Structural “Outliers”

PubMed Central

Arumugam, Gandhimathi; Nair, Anu G.; Hariharaputran, Sridhar; Ramanathan, Sowdhamini

2013-01-01

Analysis of structural variation in domain superfamilies can reveal constraints in protein evolution which aids protein structure prediction and classification. Structure-based sequence alignment of distantly related proteins, organized in PASS2 database, provides clues about structurally conserved regions among different functional families. Some superfamily members show large structural differences which are functionally relevant. This paper analyses the impact of structural divergence on function for multi-member superfamilies, selected from the PASS2 superfamily alignment database. Functional annotations within superfamilies, with structural outliers or ‘rebels’, are discussed in the context of structural variations. Overall, these data reinforce the idea that functional similarities cannot be extrapolated from mere structural conservation. The implication for fold-function prediction is that the functional annotations can only be inherited with very careful consideration, especially at low sequence identities. PMID:24073209

NGC 3516: Disk Diagnostics from a Windy BLSy1 in a High-State

NASA Astrophysics Data System (ADS)

Turner, Tracey

2006-09-01

Recent advances have shown X-ray flux to be simply correlated with reflection-signatures from the disk and with an associated wind in AGN. It appears two things are essential to observe the disk/wind: 1) catch the Seyfert in a high-state where disk/wind features show up strongly and 2) separate out reprocessing from distant gas to allow isolation of disk/wind features. NGC 3516 is currently in a very high state, which we predict will lead to observable features from the disk and its wind. UV data indicate NGC 3516 is very likely to have an observable disk wind due to a favorable orientation. We request 210 ks XMM exposure on NGC 3156 with supporting 200 ks Chandra time to test our prediction of flux-linked disk reflection and wind.

Probing the gravitational Faraday rotation using quasar X-ray microlensing

PubMed Central

Chen, Bin

2015-01-01

The effect of gravitational Faraday rotation was predicted in the 1950s, but there is currently no practical method for measuring this effect. Measuring this effect is important because it will provide new evidence for correctness of general relativity, in particular, in the strong field limit. We predict that the observed degree and angle of the X-ray polarization of a cosmologically distant quasar microlensed by the random star field in a foreground galaxy or cluster lens vary rapidly and concurrently with flux during caustic-crossing events using the first simulation of quasar X-ray microlensing polarization light curves. Therefore, it is possible to detect gravitational Faraday rotation by monitoring the X-ray polarization of gravitationally microlensed quasars. Detecting this effect will also confirm the strong gravity nature of quasar X-ray emission. PMID:26574051

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients.

PubMed

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Dietrich, Dimo

2017-01-01

This study evaluates promoter methylation of the programmed cell death ligand 1 (PD-L1) as a biomarker in a cohort of 383 colorectal cancer patients. PD-L1 methylation (m PD-L1 ) was inversely correlated with PD-L1 mRNA expression ( p = 0.001) and was associated with significantly shorter overall survival (OS, p = 0.003) and recurrence-free survival (RFS, p < 0.001). In age-stratified multivariate Cox proportional hazards analyses including sex, tumor, nodal, distant metastasis categories, microsatellite instability (MSI)-status, and PD-L1 mRNA, m PD-L1 is classified as an independent prognostic factor (OS: p = 0.030; RFS: p < 0.001). Further studies are needed to evaluate PD-L1 methylation as a biomarker for response prediction of immunotherapies targeting the PD-1/PD-L1 axis.

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14

PubMed Central

Wolmark, Norman; Baehner, Frederick L.; Butler, Steven M.; Tang, Gong; Jamshidian, Farid; Sing, Amy P.; Shak, Steven; Paik, Soonmyung

2016-01-01

Purpose We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1–expressing groups. Patients and Methods RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) –positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Results Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). Conclusion For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. PMID:27217450

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.

PubMed

Wolmark, Norman; Mamounas, Eleftherios P; Baehner, Frederick L; Butler, Steven M; Tang, Gong; Jamshidian, Farid; Sing, Amy P; Shak, Steven; Paik, Soonmyung

2016-07-10

We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis. © 2016 by American Society of Clinical Oncology.

TU-D-207B-02: Delta-Radiomics: The Prognostic Value of Therapy-Induced Changes in Radiomics Features for Stage III Non-Small Cell Lung Cancer Patients

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

Fave, X; Court, L; UT Health Science Center, Graduate School of Biomedical Sciences, Houston, TX

Purpose: To determine how radiomics features change during radiation therapy and whether those changes (delta-radiomics features) can improve prognostic models built with clinical factors. Methods: 62 radiomics features, including histogram, co-occurrence, run-length, gray-tone difference, and shape features, were calculated from pretreatment and weekly intra-treatment CTs for 107 stage III NSCLC patients (5–9 images per patient). Image preprocessing for each feature was determined using the set of pretreatment images: bit-depth resample and/or a smoothing filter were tested for their impact on volume-correlation and significance of each feature in univariate cox regression models to maximize their information content. Next, the optimized featuresmore » were calculated from the intratreatment images and tested in linear mixed-effects models to determine which features changed significantly with dose-fraction. The slopes in these significant features were defined as delta-radiomics features. To test their prognostic potential multivariate cox regression models were fitted, first using only clinical features and then clinical+delta-radiomics features for overall-survival, local-recurrence, and distant-metastases. Leave-one-out cross validation was used for model-fitting and patient predictions. Concordance indices(c-index) and p-values for the log-rank test with patients stratified at the median were calculated. Results: Approximately one-half of the 62 optimized features required no preprocessing, one-fourth required smoothing, and one-fourth required smoothing and resampling. From these, 54 changed significantly during treatment. For overall-survival, the c-index improved from 0.52 for clinical factors alone to 0.62 for clinical+delta-radiomics features. For distant-metastases, the c-index improved from 0.53 to 0.58, while for local-recurrence it did not improve. Patient stratification significantly improved (p-value<0.05) for overallsurvival and distant-metastases when delta-radiomics features were included. The delta-radiomics versions of autocorrelation, kurtosis, and compactness were selected most frequently in leave-one-out iterations. Conclusion: Weekly changes in radiomics features can potentially be used to evaluate treatment response and predict patient outcomes. High-risk patients could be recommended for dose escalation or consolidation chemotherapy. This project was funded in part by grants from the National Cancer Institute (NCI) and the Cancer Prevention Research Institute of Texas (CPRIT).« less

Feasibility study of astronaut standardized career dose limits in LEO and the outlook for BLEO

NASA Astrophysics Data System (ADS)

McKenna-Lawlor, Susan; Bhardwaj, A.; Ferrari, Franco; Kuznetsov, Nikolay; Lal, A. K.; Li, Yinghui; Nagamatsu, Aiko; Nymmik, Rikho; Panasyuk, Michael; Petrov, Vladislav; Reitz, Guenther; Pinsky, Lawrence; Muszaphar Shukor, Sheikh; Singhvi, A. K.; Straube, Ulrich; Tomi, Leena; Townsend, Lawrence

2014-11-01

Cosmic Study Group SG 3.19/1.10 was established in February 2013 under the aegis of the International Academy of Astronautics to consider and compare the dose limits adopted by various space agencies for astronauts in Low Earth Orbit. A preliminary definition of the limits that might later be adopted by crews exploring Beyond Low Earth Orbit was, in addition, to be made. The present paper presents preliminary results of the study reported at a Symposium held in Turin by the Academy in July 2013. First, an account is provided of exposure limits assigned by various partner space agencies to those of their astronauts that work aboard the International Space Station. Then, gaps in the scientific and technical information required to safely implement human missions beyond the shielding provided by the geomagnetic field (to the Moon, Mars and beyond) are identified. Among many recommendations for actions to mitigate the health risks potentially posed to personnel Beyond Low Earth Orbit is the development of a preliminary concept for a Human Space Awareness System to: provide for crewed missions the means of prompt onboard detection of the ambient arrival of hazardous particles; develop a strategy for the implementation of onboard responses to hazardous radiation levels; support modeling/model validation that would enable reliable predictions to be made of the arrival of hazardous radiation at a distant spacecraft; provide for the timely transmission of particle alerts to a distant crewed vehicle at an emergency frequency using suitably located support spacecraft. Implementation of the various recommendations of the study can be realized based on a two pronged strategy whereby Space Agencies/Space Companies/Private Entrepreneurial Organizations etc. address the mastering of required key technologies (e.g. fast transportation; customized spacecraft design) while the International Academy of Astronautics, in a role of handling global international co-operation, organizes complementary studies aimed at harnessing the strengths and facilities of emerging nations in investigating/solving related problems (e.g. advanced space radiation modeling/model validation; predicting the arrivals of Solar Energetic Particles and shocks at a distant spacecraft). Ongoing progress in pursuing these complementary parallel programs could be jointly reviewed bi-annually by the Space Agencies and the International Academy of Astronautics so as to maintain momentum and direction in globally progressing towards feasible human exploration of interplanetary space.

Evaluation of the prognostic impact of postoperative adjuvant radiotherapy on head and neck mucosal melanoma: a meta-analysis.

PubMed

Li, Wei; Yu, Yalian; Wang, Hailong; Yan, Aihui; Jiang, Xuejun

2015-10-21

Head and neck mucosal melanoma (HNMM) is a rare type of malignant tumor that frequently exhibits postoperative recurrence and distant metastasis. Many clinicians administer postoperative adjuvant radiotherapy to improve patient prognosis and enhance quality of life; however, the effects of this treatment remain controversial. Therefore, in this study, a meta-analysis was performed to evaluate the practical value of postoperative adjuvant radiotherapy for head and neck mucosal melanoma. Articles in the PubMed, MEDLINE, Cochrane Library, Web of Science and EMBASE databases were systematically retrieved. Analyses were conducted to compare the impact of treatments involving postoperative radiotherapy with treatments entailing surgery alone on patient overall survival time, local recurrence and distant metastasis. The hazard ratio (HR) was used to evaluate the time-to-event data employing RevMan version 5.2 and Stata/SE version 13.0 software according to the principles specified for systematic reviews of interventions in the Cochrane handbook. Twelve cohort studies involving 1593 patients satisfied the desired conditions. In comparing surgery alone with postoperative radiotherapy, there was no significant difference regarding a decrease in the death risk in HNMM patients (HR, 1.07; 95 % CI, 0.95-1.2; p = 0.903; low heterogeneity, I(2) = 0); this was also the case for sinonasal melanoma after subgroup meta-analysis (HR, 1.04; 95 % CI, 0.8-1.36; p = 0.983; low heterogeneity, I(2) = 0 %). A sensitivity analysis and subgroup meta-analysis showed that disease progression was the main source of the instability in the results. Surgery combined with postoperative radiotherapy reduced the risk of local recurrence (HR, 0.51; 95 % CI, 0.35-0.76; p = 0.155) but did not reduce the risk of distant metastasis (HR, 2.26; 95 % CI, 1.01-5.05; p = 0.006). This study demonstrated that for HNMM patients surgery is recommended if indicated, and surgery combined with postoperative radiotherapy is also recommended for dramatically improved local control of the tumor bed. For patients not suitable for surgical treatment, radiotherapy is still advised. To control distant metastasis and finally lower the risk of death, immunological therapy is another potential option whose therapeutic effect needs to be proved with more data from clinical trials.

Focal shift and the axial optical coordinate for high-aperture systems of finite Fresnel number.

PubMed

Sheppard, Colin J R; Török, Peter

2003-11-01

Analytic expressions are given for the on-axis intensity predicted by the Rayleigh-Sommerfeld and Kirchhoff diffraction integrals for a scalar optical system of high numerical aperture and finite value of Fresnel number. A definition of the axial optical coordinate is introduced that is valid for finite values of Fresnel number, for high-aperture systems, and for observation points distant from the focus. The focal shift effect is reexamined. For the case when the focal shift is small, explicit expressions are given for the focal shift and the axial peak in intensity.

Synchronous, Alternating, and Phase-Locked Stridulation by a Tropical Katydid

NASA Astrophysics Data System (ADS)

Sismondo, Enrico

1990-07-01

In the field the chirps of neighboring Mecopoda sp. (Orthoptera, Tettigoniidae, and Mecopodinae) males are normally synchronized, but between more distant individuals the chirps are either synchronous or regularly alternating. The phase response to single-stimulus chirps depends on both the phase and the intensity of the stimulus. Iteration of the Poincare map of the phase response predicts a variety of phase-locked synchronization regimes, including period-doubling bifurcations, in close agreement with experimental observations. The versatile acoustic behavior of Mecopoda encompasses most of the phenomena found in other synchronizing insects and thus provides a general model of insect synchronization behavior.

Vacuum Decay via Lorentzian Wormholes

NASA Astrophysics Data System (ADS)

Rosales, J. L.

We speculate about the space-time description due to the presence of Lorentzian worm-holes (handles in space-time joining two distant regions or other universes) in quantum gravity. The semiclassical rate of production of these Lorentzian wormholes in Reissner-Nordström space-times is calculated as a result of the spontaneous decay of vacuum due to a real tunneling configuration. In the magnetic case it only depends on the value of the field theoretical fine structure constant. We predict that the quantum probability corresponding to the nucleation of such geodesically complete space-times should be acutally negligible in our physical Universe.

Serifs and font legibility

PubMed Central

Arditi, Aries; Cho, Jianna

2015-01-01

Using lower-case fonts varying only in serif size (0%, 5%, and 10% cap height), we assessed legibility using size thresholds and reading speed. Five percentage serif fonts were slightly more legible than sans serif, but the average inter-letter spacing increase that serifs themselves impose, predicts greater enhancement than we observed. RSVP and continuous reading speeds showed no effect of serifs. When text is small or distant, serifs may, then, produce a tiny legibility increase due to the concomitant increase in spacing. However, our data exhibited no difference in legibility between typefaces that differ only in the presence or absence of serifs. PMID:16099015

MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis.

PubMed

Shen, Shixuan; Chen, Xiaohui; Li, Hao; Sun, Liping; Yuan, Yuan

2018-01-01

Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC. Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval. The Newcastle-Ottawa scale was used for quantity assessment . Subgroup and sensitivity analysis were conducted to explore sources of heterogeneity. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed for bioinformatics analysis on the correlation between MLH1 methylation and GC risk, clinicopathological behavior as well as prognosis. Results: 2365 GC and 1563 controls were included in the meta-analysis. The pooled OR of MLH1 methylation in GC was 4.895 (95% CI: 3.149-7.611, P<0.001), which considerably associated with increased GC risk. No significant difference was found in relation to Lauren classification, tumor invasion, lymph node/distant metastasis and tumor stage in GC. Analysis based on GEO and TCGA showed that high MLH1 methylation enhanced GC risk but might not related with GC clinicopathological features and prognosis. Conclusion: MLH1 methylation is an alive biomarker for the prediction of GC and it might not affect GC behavior. Further study could be conducted to verify the impact of MLH1 methylation on GC prognosis.

MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis

PubMed Central

Shen, Shixuan; Chen, Xiaohui; Li, Hao; Sun, Liping; Yuan, Yuan

2018-01-01

Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC. Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval. The Newcastle-Ottawa scale was used for quantity assessment. Subgroup and sensitivity analysis were conducted to explore sources of heterogeneity. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed for bioinformatics analysis on the correlation between MLH1 methylation and GC risk, clinicopathological behavior as well as prognosis. Results: 2365 GC and 1563 controls were included in the meta-analysis. The pooled OR of MLH1 methylation in GC was 4.895 (95% CI: 3.149-7.611, P<0.001), which considerably associated with increased GC risk. No significant difference was found in relation to Lauren classification, tumor invasion, lymph node/distant metastasis and tumor stage in GC. Analysis based on GEO and TCGA showed that high MLH1 methylation enhanced GC risk but might not related with GC clinicopathological features and prognosis. Conclusion: MLH1 methylation is an alive biomarker for the prediction of GC and it might not affect GC behavior. Further study could be conducted to verify the impact of MLH1 methylation on GC prognosis. PMID:29896277

Activity in distant comets

NASA Technical Reports Server (NTRS)

Luu, Jane X.

1992-01-01

Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

Argentines' collective memories of the military Junta of 1976: differences and similarities across generations and ideology.

PubMed

Muller, Felipe; Bermejo, Federico; Hirst, William

2016-08-01

Although memories about a nation's past usually are semantic in nature, a distinction needs to be made between lived and distant semantic collective memories. The former refers to memories of community-relevant events occurring during the lifetime of the rememberer, whereas the latter to memories of distant events. Does the content of lived and distant semantic collective memories differ? Employing both free and cued recall, we examined the memories of younger and older Argentines of the Military Junta of 1976. We also examined the effects of political ideology. Content analysis indicated that (1) lived semantic collective memories were more likely to contain personal recollections than distant semantic collective memories, even though those with distant semantic collective memories could have incorporated memories of the parent's personal experience in their recollections, (2) lived semantic collective memories contained more causal statements, and (3) those on the Right with distant semantic collective memories were more likely to claim that they "Don't know" or offer positive accounts of the Junta, suggesting a need to "defend" the reputation of those on the Right. The results are discussed in terms of the goals and plans different generations might have when recollecting their nation's past.

Effects of Distant Green Space on Physical Activity in Sydney, Australia.

PubMed

Chong, Shanley; Byun, Roy; Mazumdar, Soumya; Bauman, Adrian; Jalaludin, Bin

2017-01-01

The aim was to investigate the association between distant green space and physical activity modified by local green space. Information about physical activity, demographic and socioeconomic background at the individual level was extracted from the New South Wales Population Health Survey. The proportion of a postcode that was parkland was used as a proxy measure for access to parklands and was calculated for each individual. There was a significant relationship between distant green space and engaging in moderate-to-vigorous physical activity (MVPA) at least once a week. No significant relationship was found between adequate physical activity and distant green space. No significant relationships were found between adequate physical activity, engaging in MVPA, and local green space. However, if respondents lived in greater local green space (≥25%), there was a significant relationship between engaging in MVPA at least once a week and distance green space of ≥20%. This study highlights the important effect of distant green space on physical activity. Our findings also suggest that moderate size of local green space together with moderate size of distant green space are important levers for participation of physical activity.

SVM-Prot 2016: A Web-Server for Machine Learning Prediction of Protein Functional Families from Sequence Irrespective of Similarity.

PubMed

Li, Ying Hong; Xu, Jing Yu; Tao, Lin; Li, Xiao Feng; Li, Shuang; Zeng, Xian; Chen, Shang Ying; Zhang, Peng; Qin, Chu; Zhang, Cheng; Chen, Zhe; Zhu, Feng; Chen, Yu Zong

2016-01-01

Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

Tumour Necrosis Factor-α Gene Polymorphism Is Associated with Metastasis in Patients with Triple Negative Breast Cancer.

PubMed

Li, Hui-Hui; Zhu, Hui; Liu, Li-Sheng; Huang, Yong; Guo, Jun; Li, Jie; Sun, Xin-Ping; Chang, Chun-Xiao; Wang, Zhe-Hai; Zhai, Kan

2015-07-13

Tumour necrosis factor-α (TNF-α) is critical in the regulation of inflammation and tumour progression. TNF-α-308G > A is associated with constitutively elevated TNF-α expression. The purpose of this study was to assess the association between TNF-α-308G > A and breast cancer (BC) risk by subtype and the connection between genotypes and clinical features of BC. A total of 768 patients and 565 controls were enrolled in this study, and genotypes were detected using the TaqMan assay. No effect on susceptibility for any BC subtype was found for the TNF-α-308 polymorphism in our study or in the pooled meta-analysis. This polymorphism was shown to be associated with age at menarche in all BC and in progesterone receptor-negative BC. Interestingly, triple negative breast cancer (TNBC) patients with TNF-α-308A had an increased risk of distant tumour metastasis (OR = 3.80, 95% CI: 1.31-11.02, P = 0.009). Multi-regression analysis showed that TNF-α-308A was also a risk factor for distant tumour metastasis after adjustment for tumour size and lymph node metastasis status (OR = 6.26, 95% CI: 1.88-20.87, P = 0.003). These findings indicate that TNF-α might play a distinct role in the progression of TNBC, especially in distant tumour metastasis of TNBC.

Study of matrix metalloproteinases and their inhibitors in breast cancer

PubMed Central

Vizoso, F J; González, L O; Corte, M D; Rodríguez, J C; Vázquez, J; Lamelas, M L; Junquera, S; Merino, A M; García-Muñiz, J L

2007-01-01

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases. PMID:17342087

Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

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

Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl; Stiphout, Ruud G.P.M. van; Nout, Remi A.

Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variablesmore » which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT after surgery. These models facilitate decision support in daily clinical practice and can be used for patient counseling and shared decision making, selecting patients who benefit most from adjuvant treatment, and generating new hypotheses.« less

Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: a comparative clinical and immunological study.

PubMed

Shaheen, Maha Adel; Salem, Samar Abdallah M; Fouad, Dina Adel; El-Fatah, Abeer Aly Abd

2015-01-01

Intralesional purified protein derivative (PPD) or mumps, measles, rubella (MMR) were not previously compared regarding their efficacy or mechanism of action in treatment of warts. We aimed to compare their efficacy in treatment of multiple warts and investigate their effect on serum interleukin (IL)-4 and IL-12. Thirty patients with multiple warts were included (10 treated with PPD, 10 with MMR, and 10 with normal saline (control)). Injection was done every 3 weeks until clearance or maximum of three treatments. Clinical response of target and distant warts was evaluated. Serum ILs-4 and -12 were assessed before and after treatment. A significantly higher rate of complete response was found in target and distant warts with PPD (60% each) and MMR (80%, 40%, respectively) compared with controls (0%), with no significant difference between both treatments. After treatment, the control group showed the lowest serum IL-12 and IL-4 levels compared with the MMR- and PPD-treated groups with statistically significant difference in between. MMR resulted in a significantly higher serum IL-12 than PPD. With PPD, IL-4 was increased with statistically significant change compared with pretreat-ment level. Intralesional PPD and MMR show comparable efficacy and safety in treatment of multiple warts. Serum ILs-4 and-12 increase following antigen injection. © 2015 Wiley Periodicals, Inc.

Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease

PubMed Central

2013-01-01

Background Group A streptococcus (GAS) is an etiological agent for the immune mediated sequela post streptococcal glomerulonephritis (PSGN). In some populations PSGN is recognized as a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). It was found that a significantly greater proportion of subjects with past history of PSGN than without the history exhibited seroreactions to streptococcal antigens called streptococcal inhibitor of complement (SIC) and to distantly related SIC (DRS). These antigens are expressed by major PSGN-associated GAS types. We therefore predicted that in populations such as India, which is endemic for streptococcal diseases and which has high prevalence of CKD and ESRD, greater proportions of CKD and ESRD patients exhibit seroreaction to SIC and DRS than healthy controls. Methods To test this we conducted a SIC and DRS seroprevalence study in subjects from Mumbai area. We recruited 100 CKD, 70 ESRD and 70 healthy individuals. Results Nineteen and 35.7% of CKD and ESRD subjects respectively were SIC antibody-positive, whereas only 7% of healthy cohort was seropositive to SIC. Furthermore, significantly greater proportion of the ESRD patients than the CKD patients is seropositive to SIC (p=0.02; odds ratio 2.37). No association was found between the renal diseases and DRS-antibody-positivity. Conclusions Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients. PMID:23642030

Critical Power: An Important Fatigue Threshold in Exercise Physiology

PubMed Central

Poole, David C.; Burnley, Mark; Vanhatalo, Anni; Rossiter, Harry B.; Jones, Andrew M.

2016-01-01

The hyperbolic form of the power-duration relationship is rigorous and highly conserved across species, forms of exercise and individual muscles/muscle groups. For modalities such as cycling, the relationship resolves to two parameters, the asymptote for power (critical power, CP) and the so-called W′ (work doable above CP), which together predict the tolerable duration of exercise above CP. Crucially, the CP concept integrates sentinel physiological profiles - respiratory, metabolic and contractile - within a coherent framework that has great scientific and practical utility. Rather than calibrating equivalent exercise intensities relative to metabolically distant parameters such as the lactate threshold or V̇O2 max, setting the exercise intensity relative to CP unifies the profile of systemic and intramuscular responses and, if greater than CP, predicts the tolerable duration of exercise until W′ is expended, V̇O2 max is attained, and intolerance is manifested. CP may be regarded as a ‘fatigue threshold’ in the sense that it separates exercise intensity domains within which the physiological responses to exercise can (CP) be stabilized. The CP concept therefore enables important insights into 1) the principal loci of fatigue development (central vs. peripheral) at different intensities of exercise, and 2) mechanisms of cardiovascular and metabolic control and their modulation by factors such as O2 delivery. Practically, the CP concept has great potential application in optimizing athletic training programs and performance as well as improving the life quality for individuals enduring chronic disease. PMID:27031742

Critical Power: An Important Fatigue Threshold in Exercise Physiology.

PubMed

Poole, David C; Burnley, Mark; Vanhatalo, Anni; Rossiter, Harry B; Jones, Andrew M

2016-11-01

: The hyperbolic form of the power-duration relationship is rigorous and highly conserved across species, forms of exercise, and individual muscles/muscle groups. For modalities such as cycling, the relationship resolves to two parameters, the asymptote for power (critical power [CP]) and the so-called W' (work doable above CP), which together predict the tolerable duration of exercise above CP. Crucially, the CP concept integrates sentinel physiological profiles-respiratory, metabolic, and contractile-within a coherent framework that has great scientific and practical utility. Rather than calibrating equivalent exercise intensities relative to metabolically distant parameters such as the lactate threshold or V˙O2max, setting the exercise intensity relative to CP unifies the profile of systemic and intramuscular responses and, if greater than CP, predicts the tolerable duration of exercise until W' is expended, V˙O2max is attained, and intolerance is manifested. CP may be regarded as a "fatigue threshold" in the sense that it separates exercise intensity domains within which the physiological responses to exercise can (CP) be stabilized. The CP concept therefore enables important insights into 1) the principal loci of fatigue development (central vs. peripheral) at different intensities of exercise and 2) mechanisms of cardiovascular and metabolic control and their modulation by factors such as O2 delivery. Practically, the CP concept has great potential application in optimizing athletic training programs and performance as well as improving the life quality for individuals enduring chronic disease.

Expressions of IGF-1, ERK, GLUT4, IRS-1 in metabolic syndrome complicated with colorectal cancer and their associations with the clinical characteristics of CRC.

PubMed

Hu, Jianxia; Liu, Xiaoyi; Chi, Jingwei; Che, Kui; Feng, Yan; Zhao, Shihua; Wang, Zhongchao; Wang, Yangang

2018-01-01

Epidemiological data have revealed that colorectal cancer (CRC) risk is increased in patients with Metabolic syndrome. To explore the expressions of IGF-1, ERK, GLUT4, IRS-1 in MS patients with CRC and their associations with the clinical characteristics of CRC. We investigated the expressions of IGF-1, ERK, GLUT4 and IRS-1 in greater omental adipose tissues of 168 MS patients with/without CRC, 85 CRC patients without MS and 98 healthy controls by RT-PCR, and analyzed the relationships between their expressions and clinical characteristics of CRC. The expression levels of IGF-1 and ERK in MS patients with/without CRC were higher while the expression levels of GLUT4 were lower compared with CRC patients without MS and healthy controls (P< 0.01). The expression levels of IGF-1 and ERK in MS patients with CRC were higher while expression levels of GLUT4 were lower compared to MS patients without CRC (P< 0.01). Expression levels of ERK, IGF-1, GLUT4 were associated with clinical characteristics of CRC, including tumor size, distant metastasis and advanced stages (III/IV) (P< 0.05). Expressions of IGF-1, ERK and GLUT4 in greater omental adipose tissues might be useful biomarkers and predictive targets in the diagnosis of CRC.

Double streams of protons in the distant geomagnetic tail

NASA Technical Reports Server (NTRS)

Villante, U.; Lazarus, A. J.

1975-01-01

Two intermingled streams of protons have been observed in the distant geomagnetic tail. The number densities of the two streams are comparable, and their velocity difference tends to lie along the field direction. The lower-velocity stream is probably composed of magnetosheath protons which have diffused through the boundary of the distant tail. The higher-velocity stream appears to originate in the field reversal region.

Gene Transfers Between Distantly Related Organisms

NASA Technical Reports Server (NTRS)

Doolittle, Russell F.

2003-01-01

With the completion of numerous microbial genome sequences, reports of individual gene transfers between distantly related prokaryotes have become commonplace. On the other hand, transfers between prokaryotes and eukaryotes still excite the imagination. Many of these claims may be premature, but some are certainly valid. In this chapter, the kinds of supporting data needed to propose transfers between distantly related organisms and cite some interesting examples are considered.

Flexible Wing Base Micro Aerial Vehicles: Micro Air Vehicles (MAVs) for Surveillance and Remote Sensor Delivery

NASA Technical Reports Server (NTRS)

Ifju, Peter

2002-01-01

Micro Air Vehicles (MAVs) will be developed for tracking individuals, locating terrorist threats, and delivering remote sensors, for surveillance and chemical/biological agent detection. The tasks are: (1) Develop robust MAV platform capable of carrying sensor payload. (2) Develop fully autonomous capabilities for delivery of sensors to remote and distant locations. The current capabilities and accomplishments are: (1) Operational electric (inaudible) 6-inch MAVs with novel flexible wing, providing superior aerodynamic efficiency and control. (2) Vision-based flight stability and control (from on-board cameras).

CisMiner: Genome-Wide In-Silico Cis-Regulatory Module Prediction by Fuzzy Itemset Mining

PubMed Central

Navarro, Carmen; Lopez, Francisco J.; Cano, Carlos; Garcia-Alcalde, Fernando; Blanco, Armando

2014-01-01

Eukaryotic gene control regions are known to be spread throughout non-coding DNA sequences which may appear distant from the gene promoter. Transcription factors are proteins that coordinately bind to these regions at transcription factor binding sites to regulate gene expression. Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). However, these tools present at least one of the following limitations: 1) scope limited to promoter or conserved regions of the genome; 2) do not allow to identify combinations involving more than two motifs; 3) require prior information about target motifs. In this work we present CisMiner, a novel methodology to detect putative CRMs by means of a fuzzy itemset mining approach able to operate at genome-wide scale. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs. CisMiner tackles the combinatorial complexity of genome-wide cis-regulatory module extraction using a natural representation of motif combinations as itemsets and applying the Top-Down Fuzzy Frequent- Pattern Tree algorithm to identify significant itemsets. Fuzzy technology allows CisMiner to better handle the imprecision and noise inherent to regulatory processes. Results obtained for a set of well-known binding sites in the S. cerevisiae genome show that our method yields highly reliable predictions. Furthermore, CisMiner was also applied to putative in-silico predicted transcription factor binding sites to identify significant combinations in S. cerevisiae and D. melanogaster, proving that our approach can be further applied genome-wide to more complex genomes. CisMiner is freely accesible at: http://genome2.ugr.es/cisminer. CisMiner can be queried for the results presented in this work and can also perform a customized cis-regulatory module prediction on a query set of transcription factor binding sites provided by the user. PMID:25268582

1. View top of warhead handling building (northwest to southeast) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. View top of warhead handling building (northwest to southeast) of missile launch area. Sprint silos are seen on the left; Spartan silos on the right; and the missile site control building in the distant background and to the right. Launch area antennae and launch chamber covers can be seen - Stanley R. Mickelsen Safeguard Complex, Missile Launch Area, Within Exclusion Area, Nekoma, Cavalier County, ND

Effects of transcutaneous electrical nerve stimulation on rats with the third lumbar vertebrae transverse process syndrome.

PubMed

Li, Huan; Shang, Xiao-Jun; Dong, Qi-Rong

2015-10-01

To investigate the analgesic and anti-inflammatory effects of transcutaneous electrical nerve stimulation (TENS) at local or distant acupuncture points in a rat model of the third lumbar vertebrae transverse process syndrome. Forty Sprague-Dawley rats were randomly divided into control, model, model plus local acupuncture point stimulation at BL23 (model+LAS) and model plus distant acupuncture point stimulation at ST36 (model+DAS) groups. All rats except controls underwent surgical third lumbar vertebrae transverse process syndrome modelling on day 2. Thereafter, rats in the model+LAS and model+DAS groups were treated daily with TENS for a total of six treatments (2/100 Hz, 30 min/day) from day 16 to day 29. Thermal pain thresholds were measured once a week during treatment and were continued until day 57, when local muscle tissue was sampled for RT-PCR and histopathological examination after haematoxylin and eosin staining. mRNA expression of interleukin-1 β (IL-1β), tumour necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) was determined. Thermal pain thresholds of all model rats decreased relative to the control group. Both LAS and DAS significantly increased the thermal pain threshold at all but one point during the treatment period. Histopathological assessment revealed that the local muscle tissues around the third lumbar vertebrae transverse process recovered to some degree in both the model+LAS and model+DAS groups; however, LAS appeared to have a greater effect. mRNA expression of IL-1β, TNF-α and iNOS in the local muscle tissues was increased after modelling and attenuated in both model+LAS and model+DAS groups. The beneficial effect was greater after LAS than after DAS. TENS at both local (BL23) and distant (ST36) acupuncture points had a pain-relieving effect in rats with the third lumbar vertebrae transverse process syndrome, and LAS appeared to have greater anti-inflammatory and analgesic effects than DAS. 09073. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

PubMed

Herrera, L; Leal, I; Lapi, F; Schuemie, M; Arcoraci, V; Cipriani, F; Sessa, E; Vaccheri, A; Piccinni, C; Staniscia, T; Vestri, A; Di Bari, M; Corrao, G; Zambon, A; Gregori, D; Carle, F; Sturkenboom, M; Mazzaglia, G; Trifiro, G

2015-05-01

Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

Rapidly deployable emergency communication system

DOEpatents

Gladden, Charles A.; Parelman, Martin H.

1979-01-01

A highly versatile, highly portable emergency communication system which permits deployment in a very short time to cover both wide areas and distant isolated areas depending upon mission requirements. The system employs a plurality of lightweight, fully self-contained repeaters which are deployed within the mission area to provide communication between field teams, and between each field team and a mobile communication control center. Each repeater contains a microcomputer controller, the program for which may be changed from the control center by the transmission of digital data within the audible range (300-3,000 Hz). Repeaters are accessed by portable/mobile transceivers, other repeaters, and the control center through the transmission and recognition of digital data code words in the subaudible range.

Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.

PubMed

McDonald, Oliver G; Li, Xin; Saunders, Tyler; Tryggvadottir, Rakel; Mentch, Samantha J; Warmoes, Marc O; Word, Anna E; Carrer, Alessandro; Salz, Tal H; Natsume, Sonoko; Stauffer, Kimberly M; Makohon-Moore, Alvin; Zhong, Yi; Wu, Hao; Wellen, Kathryn E; Locasale, Jason W; Iacobuzio-Donahue, Christine A; Feinberg, Andrew P

2017-03-01

During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis. Changes were targeted to thousands of large chromatin domains across the genome that collectively specified malignant traits, including euchromatin and large organized chromatin histone H3 lysine 9 (H3K9)-modified (LOCK) heterochromatin. Remarkably, distant metastases co-evolved a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP), and oxPPP inhibition selectively reversed reprogrammed chromatin, malignant gene expression programs, and tumorigenesis. These findings suggest a model whereby linked metabolic-epigenetic programs are selected for enhanced tumorigenic fitness during the evolution of distant metastasis.

Clinical significance of FDG-PET/CT at the postoperative surveillance in the breast cancer patients.

PubMed

Jung, Na Young; Yoo, Ie Ryung; Kang, Bong Joo; Kim, Sung Hun; Chae, Byung Joo; Seo, Ye Young

2016-01-01

We evaluated the clinical role of [(18)F]-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) compared with conventional imaging (CI) to detect locoregional recurrence or distant metastasis during postoperative surveillance of patients with breast cancer. We included 1,819 examinations of 1,161 patients, who underwent FDG-PET/CT and CI, including mammography, breast ultrasound, whole-body bone scintigraphy, and chest radiography for postoperative surveillance. All patients had a history of surgery with or without adjuvant treatment due to more than stage II breast cancer between November 2003 and November 2009. We evaluated the diagnostic performance of CI, FDG-PET/CT, and combined CI and FDG-PET/CT for detecting locoregional recurrence, distant metastasis, and incidental cancer. We also analyzed false-positive and false-negative results in both FDG-PET/CT and CI. Sensitivity, specificity, positive predictive value, and negative predictive value of CI were 75.4, 98.7, 93.4, and 94.3 %. Those of FDG-PET/CT were 97.5, 98.8, 95.4, and 99.4 %. Those of the combined results were 98.6, 98.2, 96.7, and 99.7 %. Sensitivity of FDG-PET/CT was significantly higher than that of CI (P < 0.05). Sensitivity of combined CI and FDG-PET/CT results improved, but they were not significantly different from those of FDG-PET/CT alone (P = 0.43). Seventeen false-positive and nine false-negative cases were detected with FDG-PET/CT, and 19 false-positive and 88 false-negative cases were detected with CI. FDG-PET/CT is considered as an acceptable diagnostic imaging modality for postoperative surveillance of patients with breast cancer.

Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer.

PubMed

Zeng, Wen; Sun, Hanying; Meng, Fankai; Liu, Zeming; Xiong, Jing; Zhou, Sheng; Li, Fan; Hu, Jia; Hu, Zhiquan; Liu, Zheng

2015-01-01

Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa. Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens. Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020). Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.

Novel Risk Stratification Score for Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

PubMed Central

Press, Robert H.; Prabhu, Roshan S.; Nickleach, Dana C.; Liu, Yuan; Shu, Hui-Kuo G.; Kandula, Shravan; Patel, Kirtesh R.; Curran, Walter J.; Crocker, Ian

2015-01-01

Background The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events. Methods We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk. Results No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001). Conclusion Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation. PMID:26242475

Use of local (111)in-capromab pendetide scan results to predict outcome after salvage radiotherapy for prostate cancer.

PubMed

Koontz, Bridget F; Mouraviev, Vladimir; Johnson, Jeffrey L; Mayes, Janice; Chen, Stephanie H; Wong, Terence Z; Anscher, Mitchell S; Sun, Leon; Moul, Judd; Polascik, Thomas J

2008-06-01

The (111)In-capromab pendetide scan (ProstaScint; Cytogen Corp., Princeton NJ) is approved by the Food and Drug Administration to evaluate increasing prostate-specific antigen (PSA) levels after radical prostatectomy. This study evaluated the role of prostate bed (111)In-capromab pendetide scan findings to predict response to salvage radiotherapy (RT). Forty patients who had PSA recurrence after radical prostatectomy and a (111)In-capromab pendetide scan immediately before salvage prostate bed RT (median, 66 Gy) were identified from the Duke Prostate Center database. Patients with distant uptake of capromab pendetide or long-term androgen deprivation therapy were excluded. Median follow-up after salvage RT was 2.7 years. Patient demographic, clinical, and pathologic characteristics; PSA values; and (111)In-capromab pendetide scan results were retrospectively analyzed. A PSA failure after salvage RT was defined as PSA level greater than 0.2 ng/ml. Data were combined with other published results in a secondary pooled analysis of 106 patients. (111)In-Capromab pendetide findings included 20 patients with negative scan results and 20 with locally positive scan results. Two-year progression-free survival rates were 60% for patients with a negative scan result and 74% for those with a locally positive scan result (p = 0.49). Combined analysis did not show a difference in outcome based on local (111)In-capromab pendetide scan result. For patients without distant signal detected by using (111)In-capromab pendetide scan, patients with locally positive scan findings did not have statistically different progression-free survival than those with a negative scan result, suggesting that salvage RT may be successful in patients with either a locally positive or negative (111)In-capromab pendetide scan result.

Oncofetal Protein IMP3: A Novel Molecular Marker That Predicts Metastasis of Papillary and Chromophobe Renal Cell Carcinomas

PubMed Central

Jiang, Zhong; Lohse, Christine M.; Chu, Peigou G.; Wu, Chin-Lee; Woda, Bruce A.; Rock, Kenneth L.; Kwon, Eugene D.

2009-01-01

BACKGROUND Whether an oncofetal protein, IMP3, can serve as a prognostic biomarker to predict metastasis for patients with localized papillary and chromophobe subtypes of renal cell carcinomas (RCCs) was investigated. METHODS The expression of IMP3 in 334 patients with primary papillary and chromophobe RCC from multiple medical centers was evaluated by immunohistochemistry. The 317 patients with localized papillary and chromophobe RCCs were further evaluated for outcome analyses. RESULTS IMP3 was significantly increased in a subset of localized papillary and chromophobe RCCs that subsequently metastasized. Patients with localized IMP3-positive tumors (n = 33; 10%) were over 10 times more likely to metastasize (risk ratio [RR], 11.38; 95% confidence interval [CI], 5.40–23.96; P <.001) and were nearly twice as likely to die (RR, 1.91; 95% CI, 1.13–3.22; P =.016) compared with patients with localized IMP3 negative tumors. The 5-year metastasis-free and overall survival rates were 64% and 58% for patients with IMP3-positive localized papillary and chromophobe RCCs compared with 98% and 85% for patients with IMP3 negative tumors, respectively. In multivariable analysis adjusting for the TNM stage and nuclear grade, patients with IMP3-positive tumors were still over 10 times more likely to progress to distant metastasis (RR, 13.45; 95% CI, 6.00–30.14; P <.001) and were still nearly twice as likely die (RR, 1.95; 95% CI, 1.15–3.31; P =.013) compared with patients with IMP3-negative tumors. CONCLUSIONS IMP3 is an independent prognostic biomarker that can be used to identify a subgroup of patients with localized papillary and chromophobe RCC who are at high risk for developing distant metastasis. PMID:18412154

The valine and lysine residues in the conserved FxVTxK motif are important for the function of phylogenetically distant plant cellulose synthases

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

Slabaugh, Erin; Scavuzzo-Duggan, Tess; Chaves, Arielle

2015-12-08

Cellulose synthases (CESAs) synthesize the β-1,4-glucan chains that coalesce to form cellulose microfibrils in plant cell walls. In addition to a large cytosolic (catalytic) domain, CESAs have eight predicted transmembrane helices (TMHs). However, analogous to the structure of BcsA, a bacterial CESA, predicted TMH5 in CESA may instead be an interfacial helix. This would place the conserved FxVTxK motif in the plant cell cytosol where it could function as a substrate-gating loop as occurs in BcsA. To define the functional importance of the CESA region containing FxVTxK, we tested five parallel mutations in Arabidopsis thaliana CESA1 and Physcomitrella patens CESA5more » in complementation assays of the relevant cesa mutants. In both organisms, the substitution of the valine or lysine residues in FxVTxK severely affected CESA function. In Arabidopsis roots, both changes were correlated with lower cellulose anisotropy, as revealed by Pontamine Fast Scarlet. Analysis of hypocotyl inner cell wall layers by atomic force microscopy showed that two altered versions of Atcesa1 could rescue cell wall phenotypes observed in the mutant background line. Overall, the data show that the FxVTxK motif is functionally important in two phylogenetically distant plant CESAs. The results show that Physcomitrella provides an efficient model for assessing the effects of engineered CESA mutations affecting primary cell wall synthesis and that diverse testing systems can lead to nuanced insights into CESA structure–function relationships. Although CESA membrane topology needs to be experimentally determined, the results support the possibility that the FxVTxK region functions similarly in CESA and BcsA.« less

Functionally conserved enhancers with divergent sequences in distant vertebrates

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

Yang, Song; Oksenberg, Nir; Takayama, Sachiko

To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. In conclusion, our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.

Functionally conserved enhancers with divergent sequences in distant vertebrates

DOE PAGES

Yang, Song; Oksenberg, Nir; Takayama, Sachiko; ...

2015-10-30

To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. In conclusion, our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.

The role of circulating tumor cells in evaluation of prognosis and treatment response in advanced non-small-cell lung cancer.

PubMed

Zhou, Jia; Dong, Fei; Cui, Fang; Xu, Rui; Tang, Xiaokui

2017-04-01

Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict the prognosis and treatment response. This study investigated whether circulating tumor cells (CTCs) detectable could reminder high risk of distant metastasis, provide prognostic information, and early indicate the response to the conventional therapy in patients with advanced NSCLC. In this single-center prospective study, blood samples for CTC analysis were obtained from 59 patients with previously untreated, stage III or IV NSCLC both before and after administration of two cycles of chemotherapy. CTCs took in peripheral blood were measured by Cell Search detect technique. Carcino-embryonic antigen and count of metastatic sites were positively related to CTC count analyzed by multiple linear regression (P < 0.05). The median overall survival was 11.2 months (95% CI: 10.37-12.03 months) for the baseline CTC ≥ 2 group compared with 8.3 months (95% CI: 7.72-8.88 months) for the CTC < 2 group (log-rank test P < 0.05). Similarly, patients with CTC ≥ 2 at baseline had a significantly shorter median PFS (4.3 months, 95% CI: 3.7-4.9 months) compared with patients with CTC < 2 (6.2 months, 95% CI: 5.59-6.82 months) (log-rank test P < 0.05). For the disease control (stable disease, partial response, or complete response), group CTC value before treatment did not present difference with that after therapy compared by pared-samples T test (t = 1.455, P = 0.154), similar to the result of progressed group (progressive disease) (t = -0.987, P = 0.335). The CTC value of progressed group was higher than that of disease control group either at baseline or post chemotherapy. These data provide an evidence of positive correlation between CTC counts with CEA, as well as count of metastatic sites. Meanwhile, CTCs could be an effective predictor of distant metastasis and poor prognosis. In this study, CTCs are poorly related to treatment response. Whether CTCs could be a predictor of curative effect in advanced NSCLC should be validated by more researches in the future.

[Correlations between cellular immunity and invasiveness in differentiated thyroid cancer].

PubMed

Han, Ting; Liang, Jun; Meng, Chao; Yang, Ke; Li, Xiao-yi; Lin, Yan-song

2014-02-01

To investigate the relationship between the immunity and invasiveness in differentiated thyroid cancer (DTC). Totally 74 DTC who were treated in Peking Union Medical College Hospital from September 2012 to December 2012 were enrolled in this study. These 74 patients were divided into membrane invasion group (n=36) and without membrane invasion group (n=38); also, they were divided into distant metastasis group (n=18) and without distant metastasis group (n=56). Natural killer (NK) cells and T-cell subsets were chosen as indicators for cellular immunity to investigate the correlation between cellular immunity and invasiveness in DTC. Univariate analysis showed that the membrane invasion (Χ(2)=12.175, P=0.000) and distant metastasis (Χ(2)=8.139, P=0.006) correlated with cell immunity, whereas distant metastasis correlated with lymphocytic thyroiditis (Χ(2)=7.094, P=0.008). Further investigation shows that distant metastasis was associated with the percentage of CD8+T cell subgroup (Χ(2)=5.429, P=0.020), and membrane invasion was significantly associated with NK cells (Χ(2)=2.445, P=0.018) and CD4/CD8 disorder subgroup (Χ(2)=8.079, P=0.002). Multivariate analysis showed that cell immunity disorder was a risk factor for membrane invasion [OR=5.701,95%CI(2.075~15.666), P=0.001] and distant metastasis [OR=5.063,95%CI (1.571~16.320), P=0.008]. Further analysis showed that CD8+T cell was a risk factor for metastasis [OR=2.236,95%CI( 1.084~4.613), P=0.029], and CD4/CD8 disorders were the risk factors for membrane invasion [OR=2.802,95%CI(1.257~6.244), P=0.012]. Cell immunity in thyroid cancer has close relationship with membrane invasion and distant metastasis, especially when the percentage of CD8+T cells decreases and when the NK cells and CD4/CD8 are abnormal, which may lead to membrane invasion and distant metastasis.

Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens.

PubMed

Sitaras, Ioannis; Rousou, Xanthoula; Peeters, Ben; de Jong, Mart C M

2016-11-04

Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field. In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose. We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity. Our results suggest that - for the antigenic distances we investigated - vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatic Radiofrequency Ablation–induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition

PubMed Central

Kumar, Gaurav; Moussa, Marwan; Wang, Yuanguo; Rozenblum, Nir; Galun, Eithan; Goldberg, S. Nahum

2016-01-01

Purpose To elucidate how hepatic radiofrequency (RF) ablation affects distant extrahepatic tumor growth by means of two key molecular pathways. Materials and Methods Rats were used in this institutional animal care and use committee–approved study. First, the effect of hepatic RF ablation on distant subcutaneous in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly assigned to standardized RF ablation, sham procedure, or no treatment. Tumor growth rate was measured for 3½ to 7 days. Then, tissue was harvested for Ki-67 proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation was performed for hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and c-Met receptor expression measurement in periablational rim, serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant tumor growth and growth factor levels. Finally, hepatic RF ablation was performed in rats with c-Met–negative R3230 tumors for comparison with the native c-Met–positive line. Tumor size and immunohistochemical quantification at day 0 and at sacrifice were compared with analysis of variance and the two-tailed Student t test. Tumor growth curves before and after treatment were analyzed with linear regression analysis to determine mean slopes of pre- and posttreatment growth curves on a per-tumor basis and were compared with analysis of variance and paired two-tailed t tests. Results After RF ablation of normal liver, distant R3230 tumors were substantially larger at 7 days compared with tumors treated with the sham procedure and untreated tumors, with higher growth rates and tumor cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF ablation predominantly increased periablational and serum HGF and downstream distant tumor VEGF levels. Compared with RF ablation alone, RF ablation combined with adjuvant PHA-665752 or semaxanib reduced distant tumor growth, proliferation, and microvascular density. For c-Met–negative tumors, hepatic RF ablation did not increase distant tumor growth, proliferation, or microvascular density compared with sham treatment. Conclusion RF ablation of normal liver can stimulate distant subcutaneous tumor growth mediated by HGF/c-Met pathway and VEGF activation. This effect was not observed in c-Met–negative tumors and can be blocked with adjuvant c-Met and VEGF inhibitors. © RSNA, 2015 PMID:26418615

Social distance and behavioral attributes of developmentally handicapped and normal children.

PubMed

Sherman, L W; Burgess, D E

1985-12-01

20 behavioral attributes predicting social distance were examined among 101 junior high school students in six classrooms. The sample included 8 developmentally handicapped students, of whom at least one of each was mainstreamed into each classroom. Subjects were predominantly white, middle-class, suburban midwesterners. A sociometric nomination measure was used to obtain behavioral attribute profiles of the students which were then used to predict a psychometric measure of social distance. Handicapped students were not more socially distant than their normal peers. Factor analysis of the 20 behavioral attributes yielded four factors, three of which were significant predictors of classroom social distance, accounting for better than half the variance in social distance. These were described as Incompetent/Unassertive, Positive/Active/Assertive, and Passive/Unassertive. Social rejection in mainstreamed classrooms is more a function of perceived behavioral attributes than the label developmentally handicapped.

Parenting and temperament prior to September 11, 2001, and parenting specific to 9/11 as predictors of children's posttraumatic stress symptoms following 9/11.

PubMed

Wilson, Anna C; Lengua, Liliana J; Meltzoff, Andrew N; Smith, Kimberly A

2010-01-01

Parenting is related to children's adjustment, but little research has examined the role of parenting in children's responses to disasters. This study describes parenting responses specific to the 9/11 terrorist attacks and examines pre-9/11 parenting, child temperament, and 9/11-specific parenting as predictors of children's posttraumatic stress (PTS) symptoms among children geographically distant from the attack locations. A community sample of children and parents (n = 137, ages 9-13 years) participating in an ongoing study were interviewed 1 month following 9/11. Parents reported engaging in a number of parenting responses following 9/11. Pre-9/11 acceptance and 9/11-specific, self-focused parental responses predicted PTS symptoms. Pre-9/11 parenting and temperament interacted to predict PTS symptoms, suggesting that parenting and temperament are important prospective predictors of children's responses to indirect exposure to disasters.

Modeling the NF-κB mediated inflammatory response predicts cytokine waves in tissue

PubMed Central

2011-01-01

Background Waves propagating in "excitable media" is a reliable way to transmit signals in space. A fascinating example where living cells comprise such a medium is Dictyostelium D. which propagates waves of chemoattractant to attract distant cells. While neutrophils chemotax in a similar fashion as Dictyostelium D., it is unclear if chemoattractant waves exist in mammalian tissues and what mechanisms could propagate them. Results We propose that chemoattractant cytokine waves may naturally develop as a result of NF-κB response. Using a heuristic mathematical model of NF-κB-like circuits coupled in space we show that the known characteristics of NF-κB response favor cytokine waves. Conclusions While the propagating wave of cytokines is generally beneficial for inflammation resolution, our model predicts that there exist special conditions that can cause chronic inflammation and re-occurrence of acute inflammatory response. PMID:21771307

Theta coupling between V4 and prefrontal cortex predicts visual short-term memory performance.

PubMed

Liebe, Stefanie; Hoerzer, Gregor M; Logothetis, Nikos K; Rainer, Gregor

2012-01-29

Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3-9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.

The Stellar Imager (SI) - A Mission to Resolve Stellar Surfaces, Interiors, and Magnetic Activity

NASA Technical Reports Server (NTRS)

Christensen-Dalsgaard, Jorgen; Carpenter, Kenneth G.; Schrijver, Carolus J.; Karovska, Margarita

2012-01-01

The Stellar Imager (SI) is a space-based, UV/Optical Interferometer (UVOI) designed to enable 0.1 milli-arcsecond (mas) spectral imaging of stellar surfaces and of the Universe in general. It will also probe via asteroseismology flows and structures in stellar interiors. SI will enable the development and testing of a predictive dynamo model for the Sun, by observing patterns of surface activity and imaging of the structure and differential rotation of stellar interiors in a population study of Sun-like stars to determine the dependence of dynamo action on mass, internal structure and flows, and time. SI's science focuses on the role of magnetism in the Universe and will revolutionize our understanding of the formation of planetary systems, of the habitability and climatology of distant planets, and of many magnetohydrodynamically controlled processes in the Universe. SI is a "LandmarklDiscovery Mission" in the 2005 Heliophysics Roadmap, an implementation of the UVOI in the 2006 Astrophysics Strategic Plan, and a NASA Vision Mission ("NASA Space Science Vision Missions" (2008), ed. M. Allen). We present here the science goals of the SI Mission, a mission architecture that could meet those goals, and the technology development needed to enable this mission

Research traditions and evolutionary explanations in medicine.

PubMed

Méthot, Pierre-Olivier

2011-02-01

In this article, I argue that distinguishing 'evolutionary' from 'Darwinian' medicine will help us assess the variety of roles that evolutionary explanations can play in a number of medical contexts. Because the boundaries of evolutionary and Darwinian medicine overlap to some extent, however, they are best described as distinct 'research traditions' rather than as competing paradigms. But while evolutionary medicine does not stand out as a new scientific field of its own, Darwinian medicine is united by a number of distinctive theoretical and methodological claims. For example, evolutionary medicine and Darwinian medicine can be distinguished with respect to the styles of evolutionary explanations they employ. While the former primarily involves 'forward looking' explanations, the latter depends mostly on 'backward looking' explanations. A forward looking explanation tries to predict the effects of ongoing evolutionary processes on human health and disease in contemporary environments (e.g., hospitals). In contrast, a backward looking explanation typically applies evolutionary principles from the vantage point of humans' distant biological past in order to assess present states of health and disease. Both approaches, however, are concerned with the prevention and control of human diseases. In conclusion, I raise some concerns about the claim that 'nothing in medicine makes sense except in the light of evolution'.

Leveraging genome-wide datasets to quantify the functional role of the anti-Shine-Dalgarno sequence in regulating translation efficiency.

PubMed

Hockenberry, Adam J; Pah, Adam R; Jewett, Michael C; Amaral, Luís A N

2017-01-01

Studies dating back to the 1970s established that sequence complementarity between the anti-Shine-Dalgarno (aSD) sequence on prokaryotic ribosomes and the 5' untranslated region of mRNAs helps to facilitate translation initiation. The optimal location of aSD sequence binding relative to the start codon, the full extents of the aSD sequence and the functional form of the relationship between aSD sequence complementarity and translation efficiency have not been fully resolved. Here, we investigate these relationships by leveraging the sequence diversity of endogenous genes and recently available genome-wide estimates of translation efficiency. We show that-after accounting for predicted mRNA structure-aSD sequence complementarity increases the translation of endogenous mRNAs by roughly 50%. Further, we observe that this relationship is nonlinear, with translation efficiency maximized for mRNAs with intermediate levels of aSD sequence complementarity. The mechanistic insights that we observe are highly robust: we find nearly identical results in multiple datasets spanning three distantly related bacteria. Further, we verify our main conclusions by re-analysing a controlled experimental dataset. © 2017 The Authors.

Inferring the annual migration patterns of fall armyworm (Lepidoptera: Noctuidae) in the United States from mitochondrial haplotypes

PubMed Central

Nagoshi, Rodney N; Meagher, Robert L; Hay-Roe, Mirian

2012-01-01

Spodoptera frugiperda (J. E. Smith) or fall armyworm is an important agricultural pest of a number of crops in the western hemisphere. In the United States, infestations in corn acreages extend from the Mexican to the Canadian border. Because fall armyworm does not survive prolonged freezing, the infestations annually affecting most of North America are migrants from southern Texas and Florida, where winter temperatures are mild and host plants are available. A haplotype method was developed that can distinguish between these two geographically distant overwintering populations, with the potential to delineate the associated migratory pathways. Several years of collections from major corn-producing areas in the southern, central, and eastern United States were used to map the geographical distribution of the fall armyworm haplotypes. From these haplotype profiles, it was possible to develop the most detailed description yet of the annual northward movements of fall armyworm. The consistency of these results with past studies and the implications on our understanding of fall armyworm biology are discussed. A better understanding of fall armyworm populations and their movement is critical for the development of strategies to predict infestation levels and eventually control this pest in the United States. PMID:22957154

High E6 Gene Expression Predicts for Distant Metastasis and Poor Survival in Patients With HPV-Positive Oropharyngeal Squamous Cell Carcinoma

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

Khwaja, Shariq S.; Baker, Callie; Haynes, Wesley

Purpose: Patients with human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC. Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM). Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 genemore » expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways. Conclusion: High E6 gene expression level identifies HPV-positive OPSCC patients with 5-fold greater risk of distant disease recurrence and worse cancer-specific survival. Validation in a multi-institutional prospective clinical trial is required to assess the utility of E6 gene expression as a clinically useful prognostic biomarker.« less

Recent Structural Evolution of Early-Type Galaxies: Size Growth from z = 1 to z = 0

NASA Astrophysics Data System (ADS)

van der Wel, Arjen; Holden, Bradford P.; Zirm, Andrew W.; Franx, Marijn; Rettura, Alessandro; Illingworth, Garth D.; Ford, Holland C.

2008-11-01

Strong size and internal density evolution of early-type galaxies between z ~ 2 and the present has been reported by several authors. Here we analyze samples of nearby and distant (z ~ 1) galaxies with dynamically measured masses in order to confirm the previous, model-dependent results and constrain the uncertainties that may play a role. Velocity dispersion (σ) measurements are taken from the literature for 50 morphologically selected 0.8 < z < 1.2 field and cluster early-type galaxies with typical masses Mdyn = 2 × 1011 M⊙. Sizes (Reff) are determined with Advanced Camera for Surveys imaging. We compare the distant sample with a large sample of nearby (0.04 < z < 0.08) early-type galaxies extracted from the Sloan Digital Sky Survey for which we determine sizes, masses, and densities in a consistent manner, using simulations to quantify systematic differences between the size measurements of nearby and distant galaxies. We find a highly significant difference between the σ - Reff distributions of the nearby and distant samples, regardless of sample selection effects. The implied evolution in Reff at fixed mass between z = 1 and the present is a factor of 1.97 +/- 0.15. This is in qualitative agreement with semianalytic models; however, the observed evolution is much faster than the predicted evolution. Our results reinforce and are quantitatively consistent with previous, photometric studies that found size evolution of up to a factor of 5 since z ~ 2. A combination of structural evolution of individual galaxies through the accretion of companions and the continuous formation of early-type galaxies through increasingly gas-poor mergers is one plausible explanation of the observations. Based on observations with the Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS5-26555, and observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under NASA contract 1407. Based on observations collected at the European Southern Observatory, Chile (169.A-0458). Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PubMed

Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

2017-03-01

Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Small bowel obstruction from distant metastasis of primary breast cancer: a case report.

PubMed

Oh, Seung Jae; Park, Seon Young; Kim, Ji Young; Yim, Hyunee; Jung, Yongsik; Han, Sae Hwan

2018-02-01

Gastrointestinal (GI) tract metastasis of primary breast cancer is very rare. We present a patient with small bowel obstruction from distant metastasis of primary breast cancer. Each characteristic features of concern of GI tract distant metastasis from many pervious studies has been reported differently. We should remember that GI tract metastasis may coexist when patients with breast cancer have intermittent or recurrent abdominal pain with or without obstructive symptoms.

A method of real-time detection for distant moving obstacles by monocular vision

NASA Astrophysics Data System (ADS)

Jia, Bao-zhi; Zhu, Ming

2013-12-01

In this paper, we propose an approach for detection of distant moving obstacles like cars and bicycles by a monocular camera to cooperate with ultrasonic sensors in low-cost condition. We are aiming at detecting distant obstacles that move toward our autonomous navigation car in order to give alarm and keep away from them. Method of frame differencing is applied to find obstacles after compensation of camera's ego-motion. Meanwhile, each obstacle is separated from others in an independent area and given a confidence level to indicate whether it is coming closer. The results on an open dataset and our own autonomous navigation car have proved that the method is effective for detection of distant moving obstacles in real-time.

Inference of Expanded Lrp-Like Feast/Famine Transcription Factor Targets in a Non-Model Organism Using Protein Structure-Based Prediction

PubMed Central

Ashworth, Justin; Plaisier, Christopher L.; Lo, Fang Yin; Reiss, David J.; Baliga, Nitin S.

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer. PMID:25255272

Inference of expanded Lrp-like feast/famine transcription factor targets in a non-model organism using protein structure-based prediction.

PubMed

Ashworth, Justin; Plaisier, Christopher L; Lo, Fang Yin; Reiss, David J; Baliga, Nitin S

2014-01-01

Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer.

Immediate reconstruction with implants in women with invasive breast cancer does not affect oncological safety in a matched cohort study.

PubMed

Eriksen, C; Frisell, J; Wickman, M; Lidbrink, E; Krawiec, K; Sandelin, K

2011-06-01

Physicians are still concerned about the oncological safety regarding immediate breast reconstruction (IBR) in breast cancer patients. This study aimed to evaluate possible differences between local, regional, and distant recurrences between women having implant-based reconstruction versus women operated with mastectomy alone. Secondary aims were to evaluate time to oncological treatment as well as disease-free and breast-cancer-specific survival. In a retrospective cohort designed study, 300 reconstructed patients with invasive breast cancer were matched with 300 patients from the population-based Regional Breast Cancer Register of the Stockholm-Gotland health-care region operated with mastectomy alone. They were matched for age, tumor size, nodal stage, and year of operation. Also included were patients treated with neoadjuvant chemotherapy and postoperative radiotherapy. The median follow-up for both the groups was 11.5 years (range 2-20). There were no significant differences in the local recurrence rate, 8.2% in the IBR group and 9.0% in the control group or in the regional recurrence rate, 8.2% versus 9.7%. Distant metastases occurred more frequently in the control group (27.1%) when compared to the IBR group (20.3%). There were no significant differences in time to treatment or in complications rate. Breast cancer mortality was 17% for the IBR group and 23% in the control group during follow-up. This long-term follow-up survey with a well-matched control group demonstrates that IBR with implants is safe to offer patients with invasive breast cancer without any negative effect on the oncological safety.

Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone.

PubMed

Patel, Kirtesh R; Prabhu, Roshan S; Kandula, Shravan; Oliver, Daniel E; Kim, Sungjin; Hadjipanayis, Constantinos; Olson, Jeffery J; Oyesiku, Nelson; Curran, Walter J; Khan, Mohammad K; Shu, Hui-Kuo; Crocker, Ian

2014-12-01

The aim of this study was to compare outcomes of postoperative whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) alone in patients with resected brain metastases (BM). We reviewed records of patients who underwent surgical resection of BM followed by WBRT or SRS alone between 2003 and 2013. Local control (LC) of the treated resected cavity, distant brain control (DBC), leptomeningeal disease (LMD), overall survival (OS), and radiographic leukoencephalopathy rates were estimated by the Kaplan-Meier method. One-hundred thirty-two patients underwent surgical resection for 141 intracranial metastases: 36 (27 %) patients received adjuvant WBRT and 96 (73 %) received SRS alone to the resection cavity. One-year OS (56 vs. 55 %, p = 0.64) and LC (83 vs. 74 %, p = 0.31) were similar between patients receiving WBRT and SRS. After controlling for number of BM, WBRT was associated with higher 1-year DBC compared with SRS (70 vs. 48 %, p = 0.03); single metastasis and WBRT were the only significant predictors for reduced distant brain recurrence in multi-variate analysis. Freedom from LMD was higher with WBRT at 18 months (87 vs. 69 %, p = 0.045), while incidence of radiographic leukoencephalopathy was higher with WBRT at 12 months (47 vs. 7 %, p = 0.001). One-year freedom from WBRT in the SRS alone group was 86 %. Compared with WBRT for patients with resected BM, SRS alone demonstrated similar LC, higher rates of LMD and inferior DBC, after controlling for the number of BM. However, OS was similar between groups. The results of ongoing clinical trials are needed to confirm these findings.

Further Improvement in Outcomes of Nasopharyngeal Carcinoma With Optimized Radiotherapy and Induction Plus Concomitant Chemotherapy: An Update of the Milan Experience

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

Palazzi, Mauro; Orlandi, Ester; Bossi, Paolo

2009-07-01

Purpose: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Methods and Materials: Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. Results:more » With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Conclusions: Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.« less

Training for eye contact modulates gaze following in dogs.

PubMed

Wallis, Lisa J; Range, Friederike; Müller, Corsin A; Serisier, Samuel; Huber, Ludwig; Virányi, Zsófia

2015-08-01

Following human gaze in dogs and human infants can be considered a socially facilitated orientation response, which in object choice tasks is modulated by human-given ostensive cues. Despite their similarities to human infants, and extensive skills in reading human cues in foraging contexts, no evidence that dogs follow gaze into distant space has been found. We re-examined this question, and additionally whether dogs' propensity to follow gaze was affected by age and/or training to pay attention to humans. We tested a cross-sectional sample of 145 border collies aged 6 months to 14 years with different amounts of training over their lives. The dogs' gaze-following response in test and control conditions before and after training for initiating eye contact with the experimenter was compared with that of a second group of 13 border collies trained to touch a ball with their paw. Our results provide the first evidence that dogs can follow human gaze into distant space. Although we found no age effect on gaze following, the youngest and oldest age groups were more distractible, which resulted in a higher number of looks in the test and control conditions. Extensive lifelong formal training as well as short-term training for eye contact decreased dogs' tendency to follow gaze and increased their duration of gaze to the face. The reduction in gaze following after training for eye contact cannot be explained by fatigue or short-term habituation, as in the second group gaze following increased after a different training of the same length. Training for eye contact created a competing tendency to fixate the face, which prevented the dogs from following the directional cues. We conclude that following human gaze into distant space in dogs is modulated by training, which may explain why dogs perform poorly in comparison to other species in this task.

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

Tinkle, Christopher L.; Weinberg, Vivian; Chen, Lee-May

Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgicalmore » staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall survival continues to be limited by the high rates of distant metastasis.« less

Remote entanglement stabilization for modular quantum computing

NASA Astrophysics Data System (ADS)

Didier, Nicolas; Shankar, S.; Mirrahimi, M.

Quantum information processing in a modular architecture requires to distribute and stabilize entanglement in a qubit network. We present autonomous entanglement stabilization protocols between two qubits that are coupled to distant cavities. The cavities coupling is mediated and controlled via a three-wave mixing device that generates either a delocalized mode or a two-mode squeezed state between the remote cavities depending on the pump frequency. Local drives on the qubits and the cavities steer and maintain the system to the desired qubit Bell state. We show that these reservoir-engineering based protocols stabilize entanglement in presence of qubit-cavity asymmetries and losses. Most spectacularly, even a weakly-squeezed state can stabilize a maximally entangled Bell state of two distant qubits through entanglement accumulation. This research was supported by the Agence Nationale de la Recherche under Grant ANR-14-CE26-0018, by Inria's DPEI under the TAQUILLA associated team and by ARO under Grant No. W911NF-14-1-0011.

Biofeedback for Better Vision

NASA Technical Reports Server (NTRS)

1990-01-01

Biofeedtrac, Inc.'s Accommotrac Vision Trainer, invented by Dr. Joseph Trachtman, is based on vision research performed by Ames Research Center and a special optometer developed for the Ames program by Stanford Research Institute. In the United States, about 150 million people are myopes (nearsighted), who tend to overfocus when they look at distant objects causing blurry distant vision, or hyperopes (farsighted), whose vision blurs when they look at close objects because they tend to underfocus. The Accommotrac system is an optical/electronic system used by a doctor as an aid in teaching a patient how to contract and relax the ciliary body, the focusing muscle. The key is biofeedback, wherein the patient learns to control a bodily process or function he is not normally aware of. Trachtman claims a 90 percent success rate for correcting, improving or stopping focusing problems. The Vision Trainer has also proved effective in treating other eye problems such as eye oscillation, cross eyes, and lazy eye and in professional sports to improve athletes' peripheral vision and reaction time.

Essentiality Is a Strong Determinant of Protein Rates of Evolution during Mutation Accumulation Experiments in Escherichia coli.

PubMed

Alvarez-Ponce, David; Sabater-Muñoz, Beatriz; Toft, Christina; Ruiz-González, Mario X; Fares, Mario A

2016-09-26

The Neutral Theory of Molecular Evolution is considered the most powerful theory to understand the evolutionary behavior of proteins. One of the main predictions of this theory is that essential proteins should evolve slower than dispensable ones owing to increased selective constraints. Comparison of genomes of different species, however, has revealed only small differences between the rates of evolution of essential and nonessential proteins. In some analyses, these differences vanish once confounding factors are controlled for, whereas in other cases essentiality seems to have an independent, albeit small, effect. It has been argued that comparing relatively distant genomes may entail a number of limitations. For instance, many of the genes that are dispensable in controlled lab conditions may be essential in some of the conditions faced in nature. Moreover, essentiality can change during evolution, and rates of protein evolution are simultaneously shaped by a variety of factors, whose individual effects are difficult to isolate. Here, we conducted two parallel mutation accumulation experiments in Escherichia coli, during 5,500-5,750 generations, and compared the genomes at different points of the experiments. Our approach (a short-term experiment, under highly controlled conditions) enabled us to overcome many of the limitations of previous studies. We observed that essential proteins evolved substantially slower than nonessential ones during our experiments. Strikingly, rates of protein evolution were only moderately affected by expression level and protein length. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Bridging the Cyberspace Gap: Washington and Silicon Valley

DTIC Science & Technology

2017-12-21

distant concern, if not an outright impediment. Still, the two sides worked together to advocate for free speech and open access online, reduce...worked to control the destabilizing influence of the internet and the free flow of information through domestic laws and the deployment of filtering...renegotiating the North American Free Trade Agreement does include provisions to “secure commitments not to impose customs duties on digital products

Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation.

PubMed

Bae, Ja Seong; Kim, Yourha; Jeon, Sora; Kim, Se Hee; Kim, Tae Jung; Lee, Sohee; Kim, Min-Hee; Lim, Dong Jun; Lee, Youn Soo; Jung, Chan Kwon

2016-02-09

Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations. We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers. TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025). The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations.

Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship.

PubMed

Purushotham, A; Shamil, E; Cariati, M; Agbaje, O; Muhidin, A; Gillett, C; Mera, A; Sivanadiyan, K; Harries, M; Sullivan, R; Pinder, S E; Garmo, H; Holmberg, L

2014-07-01

Predictors for site of distant metastasis and impact on survival in breast cancer are incompletely understood. Clinico-pathological risk factors for site of distant metastasis and survival were analysed in patients with invasive breast cancer treated between 1986 and 2006. Of 3553 patients, with median follow-up 6.32years, 825 (23%) developed distant metastasis. The site of metastasis was bone in 196/825 (24%), viscera in 540/825 (65%) and unknown in 89 (11%). Larger primary invasive tumour size, higher tumour grade and axillary nodal positivity increased risk of metastasis to all sites. Lobular carcinoma was more likely to first metastasise to bone compared to invasive ductal carcinoma (NST). Oestrogen receptor (ER) negative, progesterone receptor (PgR) negative and/or Human epidermal growth factor (HER2) positive tumours were more likely to metastasise to viscera. A striking relationship between increasing age at diagnosis and a reduction in risk of distant metastasis to bone and viscera was observed. Median time to death from onset of metastatic disease was 1.52 (Interquartile range (IQR) 0.7-2.9)years for patients with bone metastasis and 0.7 (IQR 0.2-1.5)years for visceral metastasis. On multivariate analysis, despite the decrease in risk of distant metastasis with increasing age, there was an elevated hazard for death in patients >50years at diagnosis of metastasis if they developed bone metastasis, with a similar trend observed in the >70years age group if they developed visceral metastasis. These findings indicate that there are biological mechanisms underlying the impact of age on the development of distant metastasis and subsequent death. This may have important implications in the treatment of breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

"A Richness Study of 14 Distant X-Ray Clusters from the 160 Square Degree Survey"

NASA Technical Reports Server (NTRS)

Jones, Christine; West, Donald (Technical Monitor)

2001-01-01

We have measured the surface density of galaxies toward 14 X-ray-selected cluster candidates at redshifts z(sub i) 0.46, and we show that they are associated with rich galaxy concentrations. These clusters, having X-ray luminosities of Lx(0.5-2 keV) approx. (0.5 - 2.6) x 10(exp 44) ergs/ sec are among the most distant and luminous in our 160 deg(exp 2) ROSAT Position Sensitive Proportional Counter cluster survey. We find that the clusters range between Abell richness classes 0 and 2 and have a most probable richness class of 1. We compare the richness distribution of our distant clusters to those for three samples of nearby clusters with similar X-ray luminosities. We find that the nearby and distant samples have similar richness distributions, which shows that clusters have apparently not evolved substantially in richness since redshift z=0.5. There is, however, a marginal tendency for the distant clusters to be slightly poorer than nearby clusters, although deeper multicolor data for a large sample would be required to confirm this trend. We compare the distribution of distant X-ray clusters in the L(sub X)-richness plane to the distribution of optically selected clusters from the Palomar Distant Cluster Survey. The optically selected clusters appear overly rich for their X-ray luminosities, when compared to X-ray-selected clusters. Apparently, X-ray and optical surveys do not necessarily sample identical mass concentrations at large redshifts. This may indicate the existence of a population of optically rich clusters with anomalously low X-ray emission, More likely, however, it reflects the tendency for optical surveys to select unvirialized mass concentrations, as might be expected when peering along large-scale filaments.

Degree connectivity in body dysmorphic disorder and relationships with obsessive and compulsive symptoms.

PubMed

Beucke, Jan C; Sepulcre, Jorge; Buhlmann, Ulrike; Kathmann, Norbert; Moody, Teena; Feusner, Jamie D

2016-10-01

Individuals with body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) are categorized within the same major diagnostic group and both show regional brain hyperactivity in the orbitofrontal cortex (OFC) and the basal ganglia during symptom provocation. While recent studies revealed that degree connectivity of these areas is abnormally high in OCD and positively correlates with symptom severity, no study has investigated degree connectivity in BDD. We used functional magnetic resonance imaging (fMRI) to compare the local and distant degree of functional connectivity in all brain areas between 28 unmedicated BDD participants and 28 demographically matched healthy controls during a face-processing task. Correlational analyses tested for associations between degree connectivity and symptom severity assessed by the BDD version of the Yale-Brown obsessive-compulsive scale (BDD-Y-BOCS). Reduced local amygdalar connectivity was found in participants with BDD. No differences in distant connectivity were found. BDD-Y-BOCS scores significantly correlated with the local connectivity of the posterior-lateral OFC, and distant connectivity of the posterior-lateral and post-central OFC, respectively. These findings represent preliminary evidence that individuals with BDD exhibit brain-behavioral associations related to obsessive thoughts and compulsive behaviors that are highly similar to correlations previously found in OCD, further underscoring their related pathophysiology. This relationship could be further elucidated through investigation of resting-state functional connectivity in BDD, ideally in direct comparison with OCD and other obsessive-compulsive and related disorders. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Review: mucosal melanoma of the head and neck.

PubMed

Gavriel, Haim; McArthur, Grant; Sizeland, Andrew; Henderson, Michael

2011-08-01

Head and neck mucosal melanoma (MM) is a rare and aggressive neoplasm, with high rates of local, regional, and distant failure. Owing to the small size of most reported series and their retrospective nature, and the lack of uniform comprehensive staging system, the effect of various treatment strategies on disease control and survival has been difficult to assess. The optimal management of head and neck MM is not well defined. Surgical treatment has being advocated as the primary treatment modality, with growing consideration for postoperative radiotherapy, as wide surgical resection in the head and neck region is often difficult. Radiotherapy is recently reported as a beneficial management modality, regardless of the fact that MM has been considered to be radioresistant. As significant morbidity is expected in high doses of radiotherapy to the head and neck region, new radiographic modalities with better precision are required. Furthermore, high-energy radiotherapy was suggested as a better therapy to mucosal MM due to the suggested biology of the tumor. The high rates of locoregional recurrence and distant metastasis also suggest that a systemic treatment is needed. Currently, there is no role for adjuvant systemic therapy for patients who have been successfully resected, but recent developments in the understanding of the biology of melanoma and, in particular, specific growth pathways holds promise for the future. We strongly recommend further evaluation of the role of chemotherapy and immunotherapy to decrease the rates of distant metastasis and improve survival.

Bacteria may contribute to distant species recognition in ant-aphid mutualistic relationships.

PubMed

Fischer, Christophe Y; Detrain, Claire; Thonart, Philippe; Haubruge, Eric; Francis, Frédéric; Verheggen, François J; Lognay, Georges C

2017-04-01

Mutualistic interactions between ant and aphid species have been the subject of considerable historical and contemporary investigations, the primary benefits being cleaning and protection for the aphids and carbohydrate-rich honeydew for the ants. Questions remained, however, as to the volatile semiochemical factor influencing this relationship. A recent study highlighted the role of bacterial honeydew volatile compounds in ant attraction. Here, ant's ability to distantly discriminate 2 aphid species was investigated based on bacterial honeydew semiochemicals emissions using a two-way olfactometer. Both the mutualistic aphid Aphis fabae L. and the nonmyrmecophilous aphid Acyrthosiphon pisum Harris were found to be attractive for the ant Lasius niger L. The level of attraction was similar in both assays (control vs. one of the aphid species). However, when given a choice between these 2 aphid species, ants showed a significant preference for Aphis fabae. Honeydew volatiles, mostly from bacterial origins, are known to be a key element in ant attraction. Using the same olfactometry protocol, the relative attractiveness of volatiles emitted by honeydews collected from each aphid species and by bacteria isolated from each honeydew was investigated. Again, ants significantly preferred volatiles released by Aphis fabae honeydew and bacteria. This information suggests that microbial honeydew volatiles enable ants to distantly discriminate aphid species. These results strengthen the interest of studying the occurrence and potential impact of microorganisms in insect symbioses. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Genome-wide introgression among distantly related Heliconius butterfly species.

PubMed

Zhang, Wei; Dasmahapatra, Kanchon K; Mallet, James; Moreira, Gilson R P; Kronforst, Marcus R

2016-02-27

Although hybridization is thought to be relatively rare in animals, the raw genetic material introduced via introgression may play an important role in fueling adaptation and adaptive radiation. The butterfly genus Heliconius is an excellent system to study hybridization and introgression but most studies have focused on closely related species such as H. cydno and H. melpomene. Here we characterize genome-wide patterns of introgression between H. besckei, the only species with a red and yellow banded 'postman' wing pattern in the tiger-striped silvaniform clade, and co-mimetic H. melpomene nanna. We find a pronounced signature of putative introgression from H. melpomene into H. besckei in the genomic region upstream of the gene optix, known to control red wing patterning, suggesting adaptive introgression of wing pattern mimicry between these two distantly related species. At least 39 additional genomic regions show signals of introgression as strong or stronger than this mimicry locus. Gene flow has been on-going, with evidence of gene exchange at multiple time points, and bidirectional, moving from the melpomene to the silvaniform clade and vice versa. The history of gene exchange has also been complex, with contributions from multiple silvaniform species in addition to H. besckei. We also detect a signature of ancient introgression of the entire Z chromosome between the silvaniform and melpomene/cydno clades. Our study provides a genome-wide portrait of introgression between distantly related butterfly species. We further propose a comprehensive and efficient workflow for gene flow identification in genomic data sets.

Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

NASA Astrophysics Data System (ADS)

Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

2015-07-01

Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

PubMed

Finocchiaro, L M E; Glikin, G C

2008-02-01

We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

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

Baschnagel, Andrew M.; Williams, Lindsay; Hanna, Alaa

2014-03-01

Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16,more » and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status.« less

On the Einstein-Podolsky-Rosen Paradox

NASA Astrophysics Data System (ADS)

McWeeny, Roy

Central to the EPR paradox is a [`]thought experiment' in which two spins are initially coupled to a state with S = 0 and are then separated to a large distance, at which they can be separately observed. Quantum mechanics apparently predicts that the two spins remain forever coupled, but this conflicts with Einstein's principle of [`]locality' or [`]separability', according to which spatially well separated systems must be independent, no matter how strongly they have interacted in the past. It is now widely held that Einstein was wrong and that [`]non-locality' follows inevitably from quantum mechanics i.e. that even distant systems are never truly separable.

Effect of microgravity & space radiation on microbes.

PubMed

Senatore, Giuliana; Mastroleo, Felice; Leys, Natalie; Mauriello, Gianluigi

2018-06-01

One of the new challenges facing humanity is to reach increasingly further distant space targets. It is therefore of upmost importance to understand the behavior of microorganisms that will unavoidably reach the space environment together with the human body and equipment. Indeed, microorganisms could activate their stress defense mechanisms, modifying properties related to human pathogenesis. The host-microbe interactions, in fact, could be substantially affected under spaceflight conditions and the study of microorganisms' growth and activity is necessary for predicting these behaviors and assessing precautionary measures during spaceflight. This review gives an overview of the effects of microgravity and space radiation on microorganisms both in real and simulated conditions.

Building blocks for correlated superconductors and magnets

DOE PAGES

Sarrao, J. L.; Ronning, F.; Bauer, E. D.; ...

2015-04-01

Recent efforts at Los Alamos to discover strongly correlated superconductors and hard ferromagnets are reviewed. While serendipity remains a principal engine of materials discovery, design principles and structural building blocks are beginning to emerge that hold potential for predictive discovery. In addition, successes over the last decade with the so-called “115” strongly correlated superconductors are summarized, and more recent efforts to translate these insights and principles to novel hard magnets are discussed. While true “materials by design” remains a distant aspiration, progress is being made in coupling empirical design principles to electronic structure simulation to accelerate and guide materials designmore » and synthesis.« less

VLBI2020: From Reality to Vision

NASA Technical Reports Server (NTRS)

Titov, Oleg

2010-01-01

The individual apparent motions of distant radio sources are believed to be caused by the effect of intrinsic structure variations of the active galactic nuclei (AGN). However, some cosmological models of the expanded Universe predict that systematic astrometric proper motions of distant quasars do not vanish as the radial distance from the observer to the quasar grows. These systematic effects can even increase with the distance, making it possible to measure them with high-precision astrometric techniques like VLBI. The Galactocentric acceleration of the Solar System barycenter may cause a secular aberration drift with a magnitude of 4 uas/yr. The Solar System motion relative to the cosmic microwave background produces an additional dipole effect, proportional to red shift. We analyzed geodetic VLBI data spanning from 1979 until 2009 to estimate the vector spherical harmonics in the expansion of the vector field of the proper motion of 687 radio sources. The dipole and quadrupole vector spherical harmonics were estimated with an accuracy of 1-5 as/yr. We have shown that over the next decade the geodetic VLBI may approach the level of accuracy on which the cosmological models of the Universe could be tested. Hence, it is important to organize a dedicated observational program to increase the number of measured proper motions to 3000.

Validation of International Society of Urological Pathology (ISUP) grading for prostatic adenocarcinoma in thin core biopsies using TROG 03.04 'RADAR' trial clinical data.

PubMed

Delahunt, B; Egevad, L; Srigley, J R; Steigler, A; Murray, J D; Atkinson, C; Matthews, J; Duchesne, G; Spry, N A; Christie, D; Joseph, D; Attia, J; Denham, J W

2015-10-01

In 2014 a consensus conference convened by the International Society of Urological Pathology (ISUP) adopted amendments to the criteria for Gleason grading and scoring (GS) for prostatic adenocarcinoma. The meeting defined a modified grading system based on 5 grading categories (grade 1, GS 3+3; grade 2, GS 3+4; grade 3, GS 4+3; grade 4, GS 8; grade 5, GS 9-10). In this study we have evaluated the prognostic significance of ISUP grading in 496 patients enrolled in the TROG 03.04 RADAR Trial. There were 19 grade 1, 118 grade 2, 193 grade 3, 88 grade 4 and 79 grade 5 tumours in the series, with follow-up for a minimum of 6.5 years. On follow-up 76 patients experienced distant progression of disease, 171 prostate specific antigen (PSA) progression and 39 prostate cancer deaths. In contrast to the 2005 modified Gleason system (MGS), the hazards of the distant and PSA progression endpoints, relative to grade 2, were significantly greater for grades 3, 4 and 5 of the 2014 ISUP grading scheme. Comparison of predictive ability utilising Harrell's concordance index, showed 2014 ISUP grading to significantly out-perform 2005 MGS grading for each of the three clinical endpoints.

Racial Differences in the Effects of Neighborhood Disadvantage on Residential Mobility in Later Life

PubMed Central

Riley, Alicia; Cagney, Kathleen A.

2016-01-01

Objectives: Past research on the residential mobility of older adults has focused on individual-level factors and life course events. Less attention has been paid to the role of the residential environment in explaining residential mobility in older adults. We sought to understand whether neighborhood disadvantage had predictive utility in explaining residential relocation patterns, and whether associations differed between Whites and non-Whites. Method: Data are from the National Social Life, Health and Aging Project, a nationally representative sample of community-dwelling older adults. Neighborhoods were defined at the census tract level. Local movers (different census tract, same county) and distant movers (different county) were compared with stayers. Results: After adjusting for individual-level factors, neighborhood disadvantage increased the likelihood of a local move, regardless of race/ethnicity. For non-Whites, higher neighborhood disadvantage decreased the likelihood of a distant move. Among local movers, Blacks and Latinos were less likely to improve neighborhood quality than Whites. Discussion: Neighborhood disadvantage may promote local mobility by undermining person–environment fit. Racial differences in access to better neighborhoods persist in later life. Future research should explore how older adults optimize person–environment fit in the face of neighborhood disadvantage when the possibility of relocation to a better neighborhood may be restricted. PMID:27257227

Reduced ING1 levels in breast cancer promotes metastasis.

PubMed

Thakur, Satbir; Singla, Arvind K; Chen, Jie; Tran, Uyen; Yang, Yang; Salazar, Carolina; Magliocco, Anthony; Klimowicz, Alexander; Jirik, Frank; Riabowol, Karl

2014-06-30

INhibitor of Growth 1 (ING1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. ING1 levels were quantified in >500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering ING levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. ING1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in ER- or Her2+ patients. In these patients ING1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by ING1 was breast cancer (p = 0.0008). Decreasing levels of ING1 increased, and increasing levels decreased, migration and invasion of MDA-MB231 cells in vitro. ING1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that ING1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that ING1 may have a therapeutic role for inhibiting metastasis of breast cancer.

Metastases of malignant neoplasms: Historical, biological, & clinical considerations.

PubMed

Wick, Mark R

2018-03-01

The metastasis of neoplastic cells from their site of origin to distant anatomic locations continues to be the principal cause of death from malignant tumors, and that fact has been recognized by physicians for over a century. After the work done by Halsted in the treatment of breast cancer in the 1880s, accepted surgical canon held that metastasis occurred in a linear fashion, with centrifugal "growth in continuity" from the primary neoplasm that first involved regional lymph nodes. Those structures were considered to then be the sources of more distant, visceral metastases. With that premise in mind, radical and "ultra-radical" surgical procedures were devised to remove as many lymph nodes as possible in the treatment of carcinomas and melanomas. However, such interventions were ineffective in altering tumor-related mortality. This review considers the details of the historical material just mentioned. It also reviews currently-held concepts on biological mechanisms of metastasis, the "sentinel" lymph node biopsy technique, and the important topic of metastatic tumor "dormancy" as the cause of surgical treatment failure. Finally, predictive models of tumor behavior are discussed, which are based on gene signatures. These will likely be the key to identifying malignant lesions of low surgical stage that ultimately prove fatal through later manifestation of metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

The Biggest Loser Thinks Long-Term: Recency as a Predictor of Success in Weight Management.

PubMed

Koritzky, Gilly; Rice, Chantelle; Dieterle, Camille; Bechara, Antoine

2015-01-01

Only a minority of participants in behavioral weight management lose weight significantly. The ability to predict who is likely to benefit from weight management can improve the efficiency of obesity treatment. Identifying predictors of weight loss can also reveal potential ways to improve existing treatments. We propose a neuro-psychological model that is focused on recency: the reliance on recent information at the expense of time-distant information. Forty-four weight-management patients completed a decision-making task and their recency level was estimated by a mathematical model. Impulsivity and risk-taking were also measured for comparison. Weight loss was measured in the end of the 16-week intervention. Consistent with our hypothesis, successful dieters (n = 12) had lower recency scores than unsuccessful ones (n = 32; p = 0.006). Successful and unsuccessful dieters were similar in their demographics, intelligence, risk taking, impulsivity, and delay of gratification. We conclude that dieters who process time-distant information in their decision making are more likely to lose weight than those who are high in recency. We argue that having low recency facilitates future-oriented thinking, and thereby contributes to behavior change treatment adherence. Our findings underline the importance of choosing the right treatment for every individual, and outline a way to improve weight-management processes for more patients.

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

Liu, Jianguo; Hull, Vanessa; Batistella, Mateus

Interactions between distant places are increasingly widespread and influential, often leading to unexpected outcomes with profound implications for sustainability. Numerous sustainability studies have been conducted within a particular place with little attention to the impacts of distant interactions on sustainability in multiple places. Although distant forces have been studied, they are usually treated as exogenous variables and feedbacks have been rarely considered. To understand and integrate various distant interactions better, we propose an integrated framework based on telecoupling – an umbrella concept that refers to socioeconomic and environmental interactions over distances. The concept of telecoupling is a logical extension ofmore » research on coupled human and natural systems, in which human and natural systems interact within particular places. The telecoupling framework contains five major interrelated components (coupled human and natural systems, agents, flows, causes, and effects). We illustrate the framework using two examples of distant interactions, highlight the implications of the framework, and discuss research needs and approaches to move research on telecouplings forward. The framework can help better analyze system components and their interrelationships, identify research gaps, detect hidden costs and untapped benefits, provide a useful means to incorporate feedbacks as well as trade-offs and synergies across multiple places (sending, receiving, and spillover systems), and improve the understanding of distant interactions and the effectiveness of policies for socioeconomic and environmental sustainability from local to global levels.« less

Wet deposition monitoring and modelling in New Brunswick — An area dominated by wet deposition due to long-range transport

NASA Astrophysics Data System (ADS)

Davis, Claude S.

Two wet deposition monitoring networks, the Coleson Cove Precipitation Monitoring Network (CCPMN) (12 stations) located in the Coleson Cove-Saint John area of south New Brunswick, and the Expanded New Brunswick Precipitation Monitoring Network (ENBPMN) (6 stations) covering the remainder of the province, were established in May 1988. The monitoring networks and a complementary modelling study were implemented to assess the relative contributions of local and distant sources to wet deposition in New Brunswick. Quality assurance/quality control activities for the networks included independent external audits, collocated samplers at one site and comparisons of weekly measurements at the ENBPMN sampler and the Canadian Air and Precipitation Monitoring Network (CAPMoN) sampler which makes daily measurements. The intercomparisons provided reassurance that the networks provided high quality data. Analysis of 2 years (June 1988-May 1990) data from the networks included routine statistical analyses for acid rain chemistry as well as analysis of 1 year of daily back trajectory data from Harcourt, New Brunswick. Three-day back trajectories determined at 12-h intervals from Harcourt on days with precipitatio showed that air masses originate mainly from regions in Quebec, Ontario and northeast U.S.A. which are known to have high sulphur oxide emissions. Some 18 trajectories were associated with 50% of the wet sulphate deposition and over 200 trajectories with 75% of the deposition in the 1-year period ending 31 May 1989. The MESOPUFF model, applied to an 800 km by 800 km domain that included the entire province of New Brunswick, was used to make predictions of wet sulphate and nitrate deposition at each of the wet deposition monitoring stations for a 2-year period, 1 June 1988-31 May 1990. Model predictions averaged over all receptors due to all sources in the model domain accounted for 7-25% of the measured seasonal average wet sulphate deposition and less than 3% of the measured wet nitrate deposition at all monitoring stations. Wet deposition in New Brunswick is thus dominated by distant sources through long-range transport. The model estimated that the oil-fired Coleson Cove thermal generating station contributed between 7% and 16% to the seasonal wet sulphur deposition and less than 3% of the seasonal wet nitrogen deposition at monitoring stations in the Coleson Cove-Saint John area. The estimates for wet nitrogen deposition are limited by the NO χ emissions information which is considered less reliable than SO 2 emissions information.