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  1. Stage II Testicular Seminoma: Patterns of Care and Survival by Treatment Strategy.

    PubMed

    Glaser, S M; Vargo, J A; Balasubramani, G K; Beriwal, S

    2016-08-01

    Stage II testicular seminoma is highly curable with radiotherapy or multi-agent chemotherapy (MACT). These modalities have not been compared in a randomised manner. Using the US National Cancer Data Base, we identified 2437 stage II seminoma patients (IIA = 960, IIB = 812, IIC = 665) treated with orchiectomy and either radiotherapy or MACT from 1998 to 2012. Factors affecting treatment modality (radiotherapy versus MACT) were studied using multivariable logistic regression. Propensity scores for treatment selection were incorporated into multivariable Cox regression analyses of overall survival. The median follow-up was 65 months (interquartile range 34-106). Rates of radiotherapy utilisation were: IIA = 78.1%, IIB = 54.4%, IIC = 4.2%. Rates of MACT utilisation were: IIA = 21.9%, IIB = 45.6%, IIC = 95.8%. For both IIA and IIB patients, later year of diagnosis, academic treatment facility and pathological confirmation of lymph node positivity were associated with increased utilisation of MACT. Also predictive for preferential utilisation of MACT were comorbidity score ≥ 1 and non-private insurance for IIA patients and T stage ≥ 2 for IIB patients. For IIA patients, survival was improved with radiotherapy compared with MACT with a 5 year survival of 99.0% (95% confidence interval 98.2-99.8) versus 93.0% (95% confidence interval 89.0-97.0). This advantage persisted on propensity-adjusted multivariate analysis (hazard ratio 0.28; 95% confidence interval 0.09-0.86; P = 0.027). For IIB patients, 5 year survival was 95.2% (95% confidence interval 92.8-97.6) for radiotherapy and 92.4% (95% confidence interval 89.2-95.6) for MACT (Log-rank P = 0.041), with no significant difference on multivariable analysis. Radiotherapy is associated with improved survival over MACT for IIA patients, with no significant survival difference for IIB patients. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  2. Type II Migration and Giant Planet Survival

    NASA Technical Reports Server (NTRS)

    Ward, William R.

    2003-01-01

    Type II migration, in which a newly formed large planet opens a gap in its precursor circumstellar nebula and subsequently evolves with it, has been implicated as a delivery mechanism responsible for close stellar companions. Large scale migration is possible in a viscously spreading disk of surface density sigma (r,t) when most of it is sacrificed to the primary in order to promote a small portion of the disk to much higher angular momentum orbits. Embedded planets generally follow its evolution unless their own angular momentum is comparable to that of the disk. The fraction of the starting disk mass, M (sub d) = 2pi integral rsigma(r,0)dr, that is consumed by the star depends on the distance at which material escapes the disk's outer boundary. If the disk is allowed to expand indefinitely, virtually all of the disk will fall into the primary in order to send a vanishingly small portion to infinity. For such a case, it is difficult to explain the survival of any giant planets, including Jupiter and Saturn. Realistically, however, there are processes that could truncate a disk at a finite distance, r(sub d). Recent numerical modeling has illustrated that planets can survive in this case. We show here that much of these results can be understood by simple conservation arguments.

  3. DO GIANT PLANETS SURVIVE TYPE II MIGRATION?

    SciTech Connect

    Hasegawa, Yasuhiro; Ida, Shigeru E-mail: ida@geo.titech.ac.jp

    2013-09-10

    Planetary migration is one of the most serious problems to systematically understand the observations of exoplanets. We clarify that the theoretically predicted type II, migration (like type I migration) is too fast, by developing detailed analytical arguments in which the timescale of type II migration is compared with the disk lifetime. In the disk-dominated regime, the type II migration timescale is characterized by a local viscous diffusion timescale, while the disk lifetime is characterized by a global diffusion timescale that is much longer than the local one. Even in the planet-dominated regime where the inertia of the planet mass reduces the migration speed, the timescale is still shorter than the disk lifetime except in the final disk evolution stage where the total disk mass decays below the planet mass. This suggests that most giant planets plunge into the central stars within the disk lifetime, and it contradicts the exoplanet observations that gas giants are piled up at r {approx}> 1 AU. We examine additional processes that may arise in protoplanetary disks: dead zones, photoevaporation of gas, and gas flow across a gap formed by a type II migrator. Although they make the type II migration timescale closer to the disk lifetime, we show that none of them can act as an effective barrier for rapid type II migration with the current knowledge of these processes. We point out that gas flow across a gap and the fraction of the flow accreted onto the planets are uncertain and they may have the potential to solve the problem. Much more detailed investigation for each process may be needed to explain the observed distribution of gas giants in extrasolar planetary systems.

  4. Mechanism of histone survival during transcription by RNA polymerase II.

    PubMed

    Kulaeva, Olga I; Studitsky, Vasily M

    2010-01-01

    This work is related to and stems from our recent NSMB paper, "Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II" (December 2009). Synopsis. Recent genomic studies from many laboratories have suggested that nucleosomes are not displaced from moderately transcribed genes. Furthermore, histones H3/H4 carrying the primary epigenetic marks are not displaced or exchanged (in contrast to H2A/H2B histones) during moderate transcription by RNA polymerase II (Pol II) in vivo. These exciting observations suggest that the large molecule of Pol II passes through chromatin structure without even transient displacement of H3/H4 histones. The most recent analysis of the RNA polymerase II (Pol II)-type mechanism of chromatin remodeling in vitro (described in our NSMB 2009 paper) suggests that nucleosome survival is tightly coupled with formation of a novel intermediate: a very small intranucleosomal DNA loop (Ø-loop) containing transcribing Pol II. In the submitted manuscript we critically evaluate one of the key predictions of this model: the lack of even transient displacement of histones H3/H4 during Pol II transcription in vitro. The data suggest that, indeed, histones H3/H4 are not displaced during Pol II transcription in vitro. These studies are directly connected with the observation in vivo on the lack of exchange of histones H3/H4 during Pol II transcription.

  5. Single-arm Phase II cancer survival trial designs.

    PubMed

    Wu, Jianrong

    2016-01-01

    The current practice for designing single-arm Phase II trials with time-to-event endpoints is limited to using either a maximum likelihood estimate test under the exponential model or a naive approach based on dichotomizing the event time at a landmark time point. A trial designed under the exponential model may not be reliable, and the naive approach is inefficient. The modified one-sample log-rank test statistic proposed in this article fills the void. In general, the proposed test can be used to design single-arm Phase II survival trials under any parametric survival distribution. Simulation results showed that it preserves type I error well and provides adequate power for Phase II cancer trial designs with time-to-event endpoints.

  6. Comparison of avalanche survival patterns in Canada and Switzerland

    PubMed Central

    Haegeli, Pascal; Falk, Markus; Brugger, Hermann; Etter, Hans-Jürg; Boyd, Jeff

    2011-01-01

    Background Current recommendations for rescue and resuscitation of people buried in avalanches are based on Swiss avalanche survival data. We analyzed Canadian survival patterns and compared them with those from Switzerland. Methods We extracted relevant data for survivors and nonsurvivors of complete avalanche burials from Oct. 1, 1980, to Sept. 30, 2005, from Canadian and Swiss databases. We calculated survival curves for Canada with and without trauma-related deaths as well as for different outdoor activities and snow climates. We compared these curves with the Swiss survival curve. Results A total of 301 people in the Canadian database and 946 in the Swiss database met the inclusion criteria. The overall proportion of people who survived did not differ significantly between the two countries (46.2% [139/301] v. 46.9% [444/946]; p = 0.87). Significant differences were observed between the overall survival curves for the two countries (p = 0.001): compared with the Swiss curve, the Canadian curve showed a quicker drop at the early stages of burial and poorer survival associated with prolonged burial. The probability of survival fell quicker with trauma-related deaths and in denser snow climates. Poorer survival probabilities in the Canadian sample were offset by significantly quicker extrication (median duration of burial 18 minutes v. 35 minutes in the Swiss sample; p < 0.001). Interpretation Observed differences in avalanche survival curves between the Canadian and Swiss samples were associated with the prevalence of trauma and differences in snow climate. Although avoidance of avalanches remains paramount for survival, the earlier onset of asphyxia, especially in maritime snow climates, emphasizes the importance of prompt extrication, ideally within 10 minutes. Protective devices against trauma and better clinical skills in organized rescue may further improve survival. PMID:21422139

  7. Modelling survival: exposure pattern, species sensitivity and uncertainty

    NASA Astrophysics Data System (ADS)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

    2016-07-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

  8. Modelling survival: exposure pattern, species sensitivity and uncertainty

    PubMed Central

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; Van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans. PMID:27381500

  9. Child survival and changing fertility patterns in Pakistan.

    PubMed

    Sathar, Z A

    1992-01-01

    Pakistan is a country with high fertility and high infant and child mortality, and declines in total mortality and substantial development initiatives. The discussion considers whether fertility patterns in Pakistan can be related to changes in child mortality, and whether current and future changes in fertility influence child survival favorably. Omran's study linked large family size to child survival. Resources, which are divided, become more important deficits in households below the poverty line: a situation common in Pakistan. High fertility is associated with short birth intervals, which are related to higher infant and child mortality. In Pakistan, the spacing and mortality link was found among both poverty and higher socioeconomic households. There is some support for the notion that it is birth weight and general health that are linked to survival rather than competition for resources. Other studies link the maternal age at birth and birth order with child mortality (Alam and Cleland). Trussel argues for limiting births in high risk ages of under 20 years and over 35 years. The exact casual link is not well documented. Institutional and community factors are also considered important in influencing child survival: sanitation, potable water, access to roads, electricity, health and family planning services, and sewage. Young infants are more vulnerable to these factors. Bangladesh and some Indian states have shown that population programs and raising per captia incomes are necessary to fertility decline. In India, female autonomy, access to education, and more equal income distribution were considered more important than economic development to child survival. In Pakistan, Sathar and Kazi have linked at least 2 years of elementary, maternal education with reductions in child mortality. The pervasiveness of female illiteracy hinders the chances of child survival. Sex preferences also impact on female children. The probably impacts of declines in breast

  10. Starvation-Survival Patterns of Sixteen Freshly Isolated Open-Ocean Bacteria †

    PubMed Central

    Amy, Penny S.; Morita, Richard Y.

    1983-01-01

    Sixteen marine isolates from a NORPAX cruise, which were transferred once on medium after initial isolation, survived nutrient deprivation for at least 8 months (longest period test). All but one isolate remained cellularly intact, although their sizes and shapes changed greatly, and all became smaller, decreasing in size from 40 to 79%. Three starvation-survival patterns were demonstrated, namely (i) an initial increase in viable cells followed by a decrease until a constant number was reached, (ii) an increase in viable cells until a constant number was reached, and (iii) a decrease in viable cells until a constant number was reached. One isolate from each starvation-survival pattern was starved for 8 months and then was tested in comparison with 4-month-starved Ant-300 for [14C]glutamic acid uptake, respiration, and incorporation. The response to glutamic acid was rapid and linear in each case. The data indicate that the starvation-survival of Ant-300 is not an anomalous situation and that open ocean bacteria can withstand nutrient deprivation for long periods of time and still retain the capacity for active metabolism, if the nutrients become available. Images PMID:16346231

  11. Patterns of recurrence and survival in neuroendocrine cervical cancer.

    PubMed

    Stecklein, Shane R; Jhingran, Anuja; Burzawa, Jennifer; Ramalingam, Preetha; Klopp, Ann H; Eifel, Patricia J; Frumovitz, Michael

    2016-12-01

    To analyze patterns of recurrence and survival and identify prognostic factors in women with neuroendocrine cervical cancer (NECC). We reviewed patients with International Federation of Gynecology and Obstetrics stage I-IVA NECC who were enrolled in the Neuroendocrine Cervical Tumor Registry and treated with curative intent. Event-free survival (EFS) and overall survival (OS) according to disease and treatment characteristics were analyzed using the Kaplan-Meier method. Among 40 patients with NECC, 25 (62%) had small cell NECC, eight (20%) had large cell NECC, and seven (18%) had unspecified neuroendocrine histology. With a median follow-up of 21.5months, 32 patients (80%) experienced progression, and 28 (70%) died. For all patients, the 5-year EFS rate was 20%, and the 5-year OS rate was 27%. Patients with large cell NECC had significantly better median EFS (median not reached vs. 10.0months, p=0.02) and showed a trend toward better median OS (153months vs. 21months, p=0.08) than patients with other histologic types. In patients with early-stage clinically node-negative disease, chemoradiation was associated with significantly better median EFS than surgery (median not reached vs. 18.0months, p=0.04). Patients with large cell NECC have better outcomes than patients with other subtypes of NECC. In early-stage node-negative NECC, chemoradiation yields better EFS than surgery. Most patients with NECC, even those with no evidence of nodal disease at diagnosis, rapidly develop widespread hematogenous metastases and die of their disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Effects of Rosmarinus officinalis on the survivability of random-patterned skin flaps: an experimental study.

    PubMed

    Ince, Bilsev; Yildirim, Alpagan Mustafa; Okur, Mehmet Ihsan; Dadaci, Mehmet; Yoruk, Ebru

    2015-04-01

    Improving survival of skin flaps used in soft-tissue reconstruction is clinically an important goal, and several systemic and local agents have been used for this purpose. However, a substance that prevents the flap necrosis has not yet been defined. This study aimed to investigate whether a Rosmarinus officinalis extract could improve the skin flap survival. In this study, 21 Wistar albino rats were divided into three groups. Rectangular 8 × 2 cm random-pattern flaps were elevated from the back of the rats. Group I was considered the control group. In Group II, a 0.5-cc of Rosmarinus officinalis oil was applied with an ear bud to the flap area 30 minutes before the flap elevation. After suturing the flaps to their location, the oil was administered twice a day for a week. In Group III, 0.5 cc of the oil was applied twice a day to the area that was elevated for a week until surgery. At the end of the week, the flaps were sutured to their location, and wiped postoperatively twice a day for a week with the oil. Mean percentage of these areas was found to be 29.81%, 58.99%, and 67.68% in Group I, Group II, and Group III, respectively. The mean percentage of the flap survival areas and vessel diameters were significantly greater in the Groups II and III than in the control group (p < 0.05). The results revealed that the topical use of the Rosmarinus officinalis extract can increase the flap survivability.

  13. Topoisomerase II{alpha} expression correlates with diminished disease-free survival in invasive breast cancer

    SciTech Connect

    O'Connor, John K. . E-mail: joconno@yahoo.com; Hazard, Lisa J.; Lee, R. Jeffrey; Fischbach, Jennifer; Gaffney, David K.

    2006-08-01

    Purpose: Topoisomerase II{alpha} (Topo II{alpha}) plays a role in DNA replication and is the molecular target for anthracyline-based chemotherapy. The purpose of this study was to evaluate the relationship between Topo II{alpha} expression and survival in patients with invasive breast cancer. Methods and Materials: Formalin-fixed, paraffin-embedded tumor specimens from 24 women with invasive breast cancer were stained for Topo II{alpha} expression. All women underwent mastectomy. Radiotherapy was given at University of Utah Department of Radiation Oncology. Of the patients, 23 (96%) received chemotherapy. The level of Topo II{alpha} expression within tumor cells was compared with clinical factors and overall survival. Results: The median percentage of tumor cells expressing Topo II{alpha} was 70%. Increased Topo II{alpha} tumor expression significantly correlated with diminished disease-free survival. Five-year disease-free survival was 100% for patients with <70% of breast cancer cells expressing Topo II{alpha} compared with 42% for patients with {>=}70% Topo II{alpha} expression (p 0.008). The level of Topo II{alpha} expression within tumor cells correlated with T stage (p = 0.008) but not with other pathologic factors. Conclusions: Increased Topo II{alpha} expression significantly correlated with diminished disease-free survival in patients with invasive breast cancer. These findings may indicate a role for Topo II{alpha} expression as a prognostic factor in breast cancer.

  14. Survival patterns of Dekkera bruxellensis in wines and inhibitory effect of sulphur dioxide.

    PubMed

    Barata, A; Caldeira, J; Botelheiro, R; Pagliara, D; Malfeito-Ferreira, M; Loureiro, V

    2008-01-31

    The wine spoilage yeast species Dekkera bruxellensis, after inoculation in red wines, displayed three survival patterns characterized by: i) initial lag phase followed by growth and sequential death; ii) initial death phase leading to reduced viable counts followed by growth and sequential death; and iii) death phase leading to complete loss of viability. These survival patterns were observed for the same strain in different dry red wine blends with 12% (v/v) ethanol and pH 3.50, in the absence of free sulphur dioxide. For the same wine blend, these patterns also varied with the tested strain. Under laboratory conditions the addition of 150 mg/l of potassium metabisulphite (PMB) to dry red wine with 12% (v/v) ethanol and pH 3.50 reduced initial cell counts by more than 6 logarithmic cycles, inducing full death within less than 24 h. Winery trials showed that D. bruxellensis blooms were only prevented in the presence of about 40 mg/l of free sulphur dioxide in dry red wine, with 13.8% (v/v) ethanol and pH 3.42, matured in oak barrels. These different amounts of PMB and sulphur dioxide corresponded to about 1 mg/l of molecular sulphur dioxide. Our results therefore demonstrate that the control of populations of D. bruxellensis growing in red wine can only be achieved under the presence of relatively high doses of molecular sulphur dioxide.

  15. Time-specific patterns of nest survival for ducks and passerines breeding in North Dakota

    USGS Publications Warehouse

    Shaffer, Terry L.; Grant, Todd A.

    2012-01-01

    In many bird species, survival can vary with the age of the nest, with the date a nest was initiated, or among years within the same nesting area. A literature review showed that patterns of survival vary in relation to nest age and date and are often contradictory. Inconsistencies could be a result of temporal variation in the environment or life-history differences among species. We examined patterns of nest survival in relation to nest age, date, and year for several duck and passerine species nesting at a single location in North Dakota during 1998–2003. We predicted that if environment shaped nest survival patterns, then temporal patterns in survival might be similar among three species of upland nesting ducks, and also among three species of grassland passerines nesting at the same site. We expected that survival patterns would differ between ducks and passerines because of relatively disparate life histories and differences in predators that prey on their nests. Nest survival was rarely constant among years, seasonally, or with age of the nest for species that we studied. As predicted, the pattern of survival was similar among duck species, driven mainly by differences in nest survival associated with nest initiation date. The pattern of survival also was similar among passerine species, but nest survival was more influenced by nest age than by date. Our findings suggest that some but not all variation in temporal patterns of nest survival in grassland birds reported in the literature can be explained on the basis of temporal environmental variation. Because patterns of survival were dissimilar among ducks and passerines, it is likely that mechanisms such as predation or brood parasitism have variable influences on productivity of ducks and passerines nesting in the same area. Our results indicate that biologists and managers should not assume that temporal environmental variations, especially factors that affect nest survival, act similarly on all

  16. On structural patterns in H II regions

    SciTech Connect

    Feibelman, W.A. )

    1989-05-01

    High-resolution photographs of H II regions show that a large number of stars embedded in the nebulosities appear to be surrounded by emply spaces. This phenomenon seems to be quite common but has escaped attention up to now. The effect is not a photographic one, nor does it arise in the half-tone reproduction processes employed in publications, but no satisfactory explanation is apparent. 9 refs.

  17. User Identification Using Gait Patterns on UbiFloorII

    PubMed Central

    Yun, Jaeseok

    2011-01-01

    This paper presents a system of identifying individuals by their gait patterns. We take into account various distinguishable features that can be extracted from a user’s gait and then divide them into two classes: walking pattern and stepping pattern. The conditions we assume are that our target environments are domestic areas, the number of users is smaller than 10, and all users ambulate with bare feet considering the everyday lifestyle of the Korean home. Under these conditions, we have developed a system that identifies individuals’ gait patterns using our biometric sensor, UbiFloorII. We have created UbiFloorII to collect walking samples and created software modules to extract the user’s gait pattern. To identify the users based on the gait patterns extracted from walking samples over UbiFloorII, we have deployed multilayer perceptron network, a feedforward artificial neural network model. The results show that both walking pattern and stepping pattern extracted from users’ gait over the UbiFloorII are distinguishable enough to identify the users and that fusing two classifiers at the matching score level improves the recognition accuracy. Therefore, our proposed system may provide unobtrusive and automatic user identification methods in ubiquitous computing environments, particularly in domestic areas. PMID:22163758

  18. Incidence and Survival Patterns of Sinonasal Undifferentiated Carcinoma in the United States

    PubMed Central

    Chambers, Kyle J.; Lehmann, Ashton E.; Remenschneider, Aaron; Dedmon, Matthew; Meier, Josh; Gray, Stacey T.; Lin, Derrick T.

    2014-01-01

    Objective To determine trends in sinonasal undifferentiated carcinoma (SNUC) survival patterns in the United States. Design Retrospective review of national database. Participants All cases of SNUC in the National Cancer Institute's Surveillance Epidemiology and End Results program from 1973 to 2010 were examined. Main Outcome Measures Age-adjusted incidence and survival rates were calculated and stratified by demographic information and treatment modality. Cohort analysis was performed to analyze survival patterns over time. Results A total of 318 SNUC cases were identified. Age-adjusted incidence rate (IR) was 0.02 per 100,000. Incidence was greater in males (IR: 0.03) than females (IR: 0.01; p = 0.03). Overall 5- and 10-year relative survival rate was 34.9% and 31.3%, respectively. Overall median survival was 22.1 months. Median survival following surgery combined with radiation was 41.9 months. Five-year relative survival rate following surgery, radiation, or surgery combined with radiation was 38.7%, 36.0%, and 39.1%, respectively. Median survival from 1973–1986 and 1987–2010 was 14.5 and 23.5 months, respectively. Conclusions This study provides new data regarding survival patterns of SNUC in the United States, confirming survival benefit with surgery and radiation as well as identifying a trend toward improved survival in recent decades. PMID:25844294

  19. Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins.

    PubMed

    Sallaberry-Pincheira, Nicole; González-Acuña, Daniel; Padilla, Pamela; Dantas, Gisele P M; Luna-Jorquera, Guillermo; Frere, Esteban; Valdés-Velásquez, Armando; Vianna, Juliana A

    2016-10-01

    The evolutionary and adaptive potential of populations or species facing an emerging infectious disease depends on their genetic diversity in genes, such as the major histocompatibility complex (MHC). In birds, MHC class I deals predominantly with intracellular infections (e.g., viruses) and MHC class II with extracellular infections (e.g., bacteria). Therefore, patterns of MHC I and II diversity may differ between species and across populations of species depending on the relative effect of local and global environmental selective pressures, genetic drift, and gene flow. We hypothesize that high gene flow among populations of Humboldt and Magellanic penguins limits local adaptation in MHC I and MHC II, and signatures of selection differ between markers, locations, and species. We evaluated the MHC I and II diversity using 454 next-generation sequencing of 100 Humboldt and 75 Magellanic penguins from seven different breeding colonies. Higher genetic diversity was observed in MHC I than MHC II for both species, explained by more than one MHC I loci identified. Large population sizes, high gene flow, and/or similar selection pressures maintain diversity but limit local adaptation in MHC I. A pattern of isolation by distance was observed for MHC II for Humboldt penguin suggesting local adaptation, mainly on the northernmost studied locality. Furthermore, trans-species alleles were found due to a recent speciation for the genus or convergent evolution. High MHC I and MHC II gene diversity described is extremely advantageous for the long-term survival of the species.

  20. Bioconvective patterns, synchrony, and survival. [in light-limited growth model of motile algae culture

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1990-01-01

    With and without bioconvective pattern formation, a theoretical model predicts growth in light-limited cultures of motile algae. At the critical density for pattern formation, the resulting doubly exponential population curves show an inflection. Such growth corresponds quantitatively to experiments in mechanically unstirred cultures. This attaches survival value to synchronized pattern formation.

  1. Bioconvective patterns, synchrony, and survival. [in light-limited growth model of motile algae culture

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1990-01-01

    With and without bioconvective pattern formation, a theoretical model predicts growth in light-limited cultures of motile algae. At the critical density for pattern formation, the resulting doubly exponential population curves show an inflection. Such growth corresponds quantitatively to experiments in mechanically unstirred cultures. This attaches survival value to synchronized pattern formation.

  2. Use of Systemic Rosmarinus Officinalis to Enhance the Survival of Random-Pattern Skin Flaps

    PubMed Central

    İnce, Bilsev; Bilgen, Fatma; Gündeşlioğlu, Ayşe Özlem; Dadacı, Mehmet; Kozacıoğlu, Sümeyye

    2016-01-01

    Background Skin flaps are commonly used in soft-tissue reconstruction; however, necrosis can be a frequent complication. Several systemic and local agents have been used in attempts to improve skin flap survival, but none that can prevent flap necrosis have been identified. Aims This study aims to determine whether the use of systemic Rosmarinus officinalis (R. officinalis) extract can prevent flap necrosis and improve skin flap recovery. Study Design Animal experimentation. Methods Thirty-five Wistar albino rats were divided in five groups. A rectangular random-pattern flaps measuring 8×2 cm was elevated from the back of each rat. Group I was the control group. In Group II, 0.2 ml of R. officinalis oil was given orally 2h before surgery. R. officinalis oil was then applied orally twice a day for a week. In Group III, R. officinalis oil was given orally twice a day for one week before surgery. At the end of the week, 0.2 mL of R. officinalis oil was given orally 2 h before surgery. In Group IV, 0.2 mL of R. officinalis oil was injected subcutaneously 2 h before surgery. After the surgery, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week. In Group V, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week prior to surgery. At the end of the week, one last 0.2 mL R. officinalis oil injection was administered subcutaneously 2 h before surgery. After the surgery, 0.2 mL R. officinalis oil was injected subcutaneously twice a day for one week. Results The mean percentage of viable surface area was significantly greater (p<0.05) in Groups II, III, IV, and V as compared to Group I. Mean vessel diameter was significantly greater (p<0.05) in Groups II, III, IV, and V as compared to Group I. Conclusion We have determined that, in addition to its anti-inflammatory and anti-oxidant effects, R. officinalis has vasodilatory effects that contribute to increased skin flap survival. PMID:27994918

  3. Protein kinase C beta II suppresses colorectal cancer by regulating IGF-1 mediated cell survival

    PubMed Central

    Dowling, Catríona M.; Phelan, James; Callender, Julia A.; Cathcart, Mary Clare; Mehigan, Brian; McCormick, Paul; Dalton, Tara; Coffey, John C.; Newton, Alexandra C.; O'sullivan, Jacintha; Kiely, Patrick A.

    2016-01-01

    Despite extensive efforts, cancer therapies directed at the Protein Kinase C (PKC) family of serine/threonine kinases have failed in clinical trials. These therapies have been directed at inhibiting PKC and have, in some cases, worsened disease outcome. Here we examine colon cancer patients and show not only that PKC Beta II is a tumour suppressor, but patients with low levels of this isozyme have significantly decreased disease free survival. Specifically, analysis of gene expression levels of all PKC genes in matched normal and cancer tissue samples from colon cancer patients revealed a striking down-regulation of the gene coding PKC Beta in the cancer tissue (n = 21). Tissue microarray analysis revealed a dramatic down-regulation of PKC Beta II protein levels in both the epithelial and stromal diseased tissue (n = 166). Of clinical significance, low levels of the protein in the normal tissue of patients is associated with a low (10%) 10 year survival compared with a much higher (60%) survival in patients with relatively high levels of the protein. Consistent with PKC Beta II levels protecting against colon cancer, overexpression of PKC Beta II in colon cancer cell lines reveals that PKC Beta II reverses transformation in cell based assays. Further to this, activation of PKC Beta II results in a dramatic downregulation of IGF-I-induced AKT, indicating a role for PKCs in regulating IGF-1 mediated cell survival. Thus, PKC Beta II is a tumour suppressor in colon cancer and low levels serve as a predictor for poor survival outcome. PMID:26989024

  4. Childhood cancer survival in Ireland: temporal, regional and deprivation-related patterns.

    PubMed

    Walsh, Paul M; Byrne, Julianne; Capra, Michael; Comber, Harry

    2011-08-01

    Survival after childhood cancer varies across Europe, but national or regional studies have so far shown no survival differences related to socio-economic disparity. The relationship of childhood cancer survival to disparity has not been studied in Ireland. We assessed observed survival for Irish children (ages 0-14 years) diagnosed with cancer during the period 1994-2005, overall (for all cancers included in the 3rd edition of the International Classification of Childhood Cancer) and for three main diagnostic groups - leukaemias, lymphomas, and central nervous system tumours. Comparisons were made between two diagnosis periods (1994-1999 and 2000-2005), between four regions of residence, and between five area-based deprivation categories. Regional patterns of treatment were examined to help assess the impact of centralisation of services. There was only limited evidence of improvements in survival over time. No clear evidence was found of deprivation-related influences on childhood cancer survival in Ireland, overall or for the three main diagnostic groups examined, although a weak trend was apparent for lymphoid leukaemias. Regional variation in survival was likewise not clear-cut, with the possible exception of CNS tumours (significantly higher survival amongst patients resident in the Western region). The absence of clear trends or patterns for regional or deprivation-related variation in survival may reflect a high degree of coordination and uniformity of treatment (and perhaps diagnostic) services, and application of standard treatment protocols nationally. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Incorporating movement patterns to improve survival estimates for juvenile bull trout

    USGS Publications Warehouse

    Bowerman, Tracy; Budy, Phaedra

    2012-01-01

    Populations of many fish species are sensitive to changes in vital rates during early life stages, but our understanding of the factors affecting growth, survival, and movement patterns is often extremely limited for juvenile fish. These critical information gaps are particularly evident for bull trout Salvelinus confluentus, a threatened Pacific Northwest char. We combined several active and passive mark–recapture and resight techniques to assess migration rates and estimate survival for juvenile bull trout (70–170 mm total length). We evaluated the relative performance of multiple survival estimation techniques by comparing results from a common Cormack–Jolly–Seber (CJS) model, the less widely used Barker model, and a simple return rate (an index of survival). Juvenile bull trout of all sizes emigrated from their natal habitat throughout the year, and thereafter migrated up to 50 km downstream. With the CJS model, high emigration rates led to an extreme underestimate of apparent survival, a combined estimate of site fidelity and survival. In contrast, the Barker model, which allows survival and emigration to be modeled as separate parameters, produced estimates of survival that were much less biased than the return rate. Estimates of age-class-specific annual survival from the Barker model based on all available data were 0.218±0.028 (estimate±SE) for age-1 bull trout and 0.231±0.065 for age-2 bull trout. This research demonstrates the importance of incorporating movement patterns into survival analyses, and we provide one of the first field-based estimates of juvenile bull trout annual survival in relatively pristine rearing conditions. These estimates can provide a baseline for comparison with future studies in more impacted systems and will help managers develop reliable stage-structured population models to evaluate future recovery strategies.

  6. Adjuvant chemotherapy is associated with improved survival in patients with stage II colon cancer.

    PubMed

    Casadaban, Leigh; Rauscher, Garth; Aklilu, Mebea; Villenes, Dana; Freels, Sally; Maker, Ajay V

    2016-11-15

    The role of adjuvant chemotherapy in patients with stage II colon cancer remains to be elucidated and its use varies between patients and institutions. Currently, clinical guidelines suggest discussing adjuvant chemotherapy for patients with high-risk stage II disease in the absence of conclusive randomized controlled trial data. To further investigate this relationship, the objective of the current study was to determine whether an association exists between overall survival (OS) and adjuvant chemotherapy in patients stratified by age and pathological risk features. Data from the National Cancer Data Base were analyzed for demographics, tumor characteristics, management, and survival of patients with stage II colon cancer who were diagnosed from 1998 to 2006 with survival information through 2011. Pearson Chi-square tests and binary logistic regression were used to analyze disease and demographic data. Survival analysis was performed with the log-rank test and Cox proportional hazards regression modeling. Propensity score weighting was used to match cohorts. Among 153,110 patients with stage II colon cancer, predictors of receiving chemotherapy included age <65 years, male sex, nonwhite race, use of a community treatment facility, non-Medicare insurance, and diagnosis before 2004. Improved and clinically relevant OS was associated with the receipt of adjuvant chemotherapy in all patient subgroups regardless of high-risk tumor pathologic features (poor or undifferentiated histology, <12 lymph nodes evaluated, positive resection margins, or T4 histology), age, or chemotherapy regimen, even after adjustment for covariates and propensity score weighting (hazard ratio, 0.76; P<.001). There was no difference in survival noted between single and multiagent adjuvant chemotherapy regimens. In what to the authors' knowledge is the largest group of patients with stage II colon cancer evaluated to date, improved OS was found to be associated with adjuvant chemotherapy

  7. Stage II Adenocarcinoma of the Endometrium: Adjuvant Radiotherapy and Recurrence Patterns

    SciTech Connect

    Cozad, Scott C.

    2008-05-01

    Purpose: Review patterns of recurrence for Stage II endometrial cancer in a community practice. Methods and Materials: A retrospective review of patients with endometrial cancer diagnosed between 1985-2002. Patients were excluded for Stages I, III, or IV or treatment with preoperative pelvic radiation (external beam radiation therapy [EBRT]). Results: Eighty-six patients with a mean follow-up of 70 months are reported. Higher risk patients were selected for adjuvant radiation with no apparent differences for those receiving only EBRT compared with EBRT with brachytherapy. Five-year actuarial vaginal, pelvic sidewall/nodal, and metastatic control rates were 100% and 100%, 96.9% and 100%, and 79% and 84.2% for patients receiving EBRT or EBRT with brachytherapy. Overall survival rates were 70.5% and 75.8%, and cause-specific survival rates were 78.8% and 82.9% for those receiving EBRT or EBRT with brachytherapy. A select group was observed and experienced one vaginal recurrence with overall and cause-specific survival rates of 100%. Conclusion: In higher risk patients with Stage II, adjuvant EBRT achieves excellent vaginal and pelvic sidewall/nodal control without apparent benefit from additional brachytherapy. Select patients may not require adjuvant treatment.

  8. Intra-annual patterns in adult band-tailed pigeon survival estimates

    USGS Publications Warehouse

    Casazza, Michael L.; Coates, Peter S.; Overton, Cory T.; Howe, Kristy H.

    2015-01-01

    Implications: We present the first inter-seasonal analysis of survival probability of the Pacific coast race of band-tailed pigeons and illustrate important temporal patterns that may influence future species management including harvest strategies and disease monitoring.

  9. The status of HBV infection influences metastatic pattern and survival in Chinese patients with pancreatic cancer

    PubMed Central

    2013-01-01

    Background It has been proved that hepatitis B virus (HBV) infection alters the metastatic pattern and affects survival in colorectal cancer (CRC) and hepatocellular carcinoma (HCC), while the influence of HBV infection on metastatic pattern and survival in patients with pancreatic cancer (PC) has not been investigated yet. Methods We conducted an investigation to evaluate the impact of HBV infection on metastatic pattern and overall survival in PC. We collected the data of 460 PC patients treated in our hospital from 1999 to 2010. Serum HBV markers were tested with enzyme-linked immunosorbent assay. The impact of HBV infection on metastatic pattern and overall survival was analyzed. Results We found that the incidence of synchronous liver metastasis was significantly higher in patients with HBsAg positive than those with HBsAg negative (46.0% vs 32.0%, P < 0.05), and higher in chronic HBV infection (CHB) group than both non HBV infection and resolved HBV infection group (61.1% vs 33.9%, P < 0.05, and 61.1% vs 28.7%, P < 0.05, respectively). What’s more, Kaplan-Meier analysis showed that CHB, resolved HBV infection and non HBV infection group had significant longer overall survival (OS) compared with inactive HBsAg carriers (IC) group (P=0.037, P=0.009, and P=0.019 respectively). But, in the multivariate analysis, only the CHB and non HBV infection group had significant better overall survival compared with IC group (P=0.010 and P=0.018 respectively). Conclusions Our study found that HBV infection increased synchronous liver metastasis rate, and HBV infection status was an independent prognostic factor in PC patients. PMID:24099678

  10. Management and Survival Patterns of Patients with Gliomatosis Cerebri: A SEER-Based Analysis.

    PubMed

    Carroll, Kate T; Hirshman, Brian; Ali, Mir Amaan; Alattar, Ali A; Brandel, Michael G; Lochte, Bryson; Lanman, Tyler; Carter, Bob; Chen, Clark C

    2017-07-01

    We used the SEER (Surveillance Epidemiology and End Results) database (1999-2010) to analyze the clinical practice patterns and overall survival in patients with gliomatosis cerebri (GC), or glioma involving 3 or more lobes of the cerebrum. We identified 111 patients (age ≥18 years) with clinically or microscopically diagnosed GC in the SEER database. Analyses were performed to determine clinical practice patterns for these patients and whether these practices were associated with survival. Fifty-eight percent of the 111 patients with GC received microscopic confirmation of their diagnosis. Of the remaining patients, 40% were diagnosed via imaging or laboratory tests, and 2% had unknown methods of diagnosis. Seven percent of patients who did not have microscopic confirmation of their diagnosis received radiation therapy. Radiation therapy and surgery were not associated with survival. The only variable significantly associated with overall survival was age at diagnosis. Patients aged 18-50 years showed improved survival relative to patients aged >50 years (median survival, 11 and 6 months, respectively; P = 0.03). For patients aged >50 years, improved overall survival was observed in the post-temozolomide era (2005-2010) relative to those treated in the pre-temozolomide era (1999-2004) (median survival, 9 and 4 months, respectively; P = 0.005). In the SEER database, ∼40% of the patients with glioma with imaging findings of GC do not receive microscopic confirmation of their diagnosis. We propose that tissue confirmation is warranted in patients with GC, because genomic analysis of these specimens may provide insights that will contribute to meaningful therapeutic intervention. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Contrasting nest survival patterns for ducks and songbirds in northern mixed-grass prairie

    USGS Publications Warehouse

    Grant, Todd; Shaffer, Terry L.; Madden, Elizabeth M.; Nenneman, Melvin P.

    2017-01-01

    Management actions intended to protect or improve habitat for ducks may benefit grassland-nesting passerines, but scant information is available to explore this assumption. During 1998–2003, we examined nest survival of ducks and songbirds to determine whether effects of prescribed fire and other habitat features (e.g., shrub cover and distance to habitat edges) were similar for ducks and passerines breeding in North Dakota. We used the logistic-exposure method to estimate survival of duck and songbird nests (n = 3,171). We used an information-theoretic approach to identify factors that most influenced nest survival. Patterns of nest survival were markedly different between taxonomic groups. For ducks, nest survival was greater during the first postfire nesting season (daily survival rate [DSR] = 0.957, 85% CI = 0.951–0.963), relative to later postfire nesting seasons (DSR = 0.946, 85% CI = 0.942–0.950). Furthermore duck nest survival and nest densities were inversely related. Duck nest survival also was greater as shrub cover decreased and as distance from cropland and wetland edges increased. Passerines had lower nest survival during the first postfire nesting season (DSR = 0.934, 85% CI = 0.924–0.944), when densities also were low compared to subsequent postfire nesting seasons (DSR = 0.947, 85% CI = 0.944–0.950). Parasitism by brown-headed cowbirds (Molothrus ater) reduced passerine nest survival and this effect was more pronounced during the first postfire nesting season compared to subsequent nesting seasons. Passerine nest survival was greater as shrub cover decreased and perhaps for more concealed nests. Duck and songbird nest survival rates were not correlated during this study and for associated studies that examined additional variables using the same dataset, suggesting that different mechanisms influenced their survival. Based on our results, ducks should not be considered direct surrogates for passerines

  12. Dietary patterns and colorectal cancer recurrence and survival: a cohort study

    PubMed Central

    Zhu, Yun; Wu, Hao; Wang, Peizhong Peter; Savas, Sevtap; Woodrow, Jennifer; Wish, Tyler; Jin, Rong; Green, Roger; Woods, Michael; Roebothan, Barbara; Buehler, Sharon; Dicks, Elizabeth; Mclaughlin, John R; Campbell, Peter T; Parfrey, Patrick S

    2013-01-01

    Objective To examine the association between dietary patterns and colorectal cancer (CRC) survival. Design Cohort study. Setting A familial CRC registry in Newfoundland. Participants 529 newly diagnosed CRC patients from Newfoundland. They were recruited from 1999 to 2003 and followed up until April 2010. Outcome measure Participants reported their dietary intake using a food frequency questionnaire. Dietary patterns were identified with factor analysis. Multivariable Cox proportional hazards models were employed to estimate HR and 95% CI for association of dietary patterns with CRC recurrence and death from all causes, after controlling for covariates. Results Disease-free survival (DFS) among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest vs the lowest quartile HR 1.82, 95% CI 1.07 to 3.09). No associations were observed with the prudent vegetable or the high-sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest vs the lowest quartile: HR 2.29, 95% CI 1.19 to 4.40) whereas the relationship between overall survival (OS) and this pattern was observed among patients with colon cancer only (the highest vs the lowest quartile: HR 2.13, 95% CI 1.03 to 4.43). Potential effect modification was noted for sex (p value for interaction 0.04, HR 3.85 for women and 1.22 for men). Conclusions The processed meat dietary pattern prior to diagnosis is associated with higher risk of tumour recurrence, metastasis and death among patients with CRC. PMID:23396503

  13. Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival.

    PubMed

    Geles, Abidin; Gruber-Moesenbacher, Ulrike; Quehenberger, Franz; Manzl, Claudia; Al Effah, Mohamed; Grygar, Elisabeth; Juettner-Smolle, Freyja; Popper, Helmut H

    2015-12-01

    Of pulmonary adenocarcinomas, about 25-30 % of cases is of a mucinous type. Mucinous adenocarcinomas are regarded as more aggressive compared to their non-mucinous counterparts. Invasive mucinous adenocarcinoma, colloid, and enteric adenocarcinomas are variants within adenocarcinomas. We investigated 76 invasive mucinous adenocarcinomas, including colloid variants, for predominant and secondary patterns, their different form of mucin storage and release, expression of cytokeratin 7 and 20, TTF1 and CDX2, MUC1, 2, and 5AC proteins, p14 and p16 proteins, possible rearrangements for EML4ALK and ROS1, as well as KRAS mutational status, and correlated this with survival. For comparison, 259 non-mucinous adenocarcinomas were selected. Overall survival for invasive mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. Most were of an acinar pattern. Neither pattern, nor type of mucin storage and release, such as luminal, extracellular, or goblet cell type had any influence on survival. Of adenocarcinomas expressing CK20, all but one expressed TTF1 either strongly or at least focally, and 8 co-expressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, but rarely MUC2, while a few cases co-expressed both or all three. Loss of p16 expression correlated with worse outcome. KRAS mutation was found in 56 % of mucinous adenocarcinomas. Mutational status was neither correlated with architectural pattern nor survival. Codon 12 mutations were most frequent, and one case presented with KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations, while all colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged; ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similar to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.

  14. Tumour Budding and Survival in Stage II Colorectal Cancer: a Systematic Review and Pooled Analysis.

    PubMed

    Petrelli, F; Pezzica, E; Cabiddu, M; Coinu, A; Borgonovo, K; Ghilardi, M; Lonati, V; Corti, D; Barni, S

    2015-09-01

    Tumour budding is defined as the presence of isolated or small clusters of malignant cells at the invasive edge of the tumour. It is considered a negative prognostic factor in colorectal cancer (CRC) and is associated with a poor outcome and adverse pathological features. Here, we report a meta-analysis of the association of tumour budding and survival in stage II CRC patients. PubMed, EMBASE, Web of Science and SCOPUS were searched for studies that assessed the relationship between tumour budding and 5-year overall survival (OS) in stage II CRC patients. Published data were extracted and used to compute odds ratios (ORs) for death at 5 years and hazard ratios (HRs) for survival amongst patients with respect to the extent of tumour budding, using multivariate analysis. Data were pooled using the Mantel-Haenszel random effect model. We analysed 12 studies that included a total of 1652 patients. High-grade budding was associated with worse OS at 5 years (OR for death, 6.25; 95 % confidence interval [CI], 4.04-9.67; P < 0.00001). The absolute difference in 5-year OS was -25 % (95 % CI, -18- - 33 %, P < 0.00001). It was particularly noteworthy that the presence of high-grade budding was associated with an increased risk of death (HR for death, 3.68; 95 % CI, 2.16-6.28, P < 0.00001). Tumour budding is associated with worse survival in stage II CRC, in particular in pT3N0M0 patients. It could therefore potentially be used when deciding whether to administer adjuvant chemotherapy in high-risk node negative CRC patients.

  15. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer

    PubMed Central

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A.; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J. H.; Kuppen, Peter J. K.

    2016-01-01

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated. PMID:28035987

  16. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer.

    PubMed

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J H; Kuppen, Peter J K

    2016-12-27

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03-2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13-3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated.

  17. Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques.

    PubMed

    Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L; Bilello, Michel; O'Rourke, Donald M; Davatzikos, Christos

    2016-03-01

    MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood-brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Imaging patterns predict patient survival and molecular subtype in glioblastoma via machine learning techniques

    PubMed Central

    Macyszyn, Luke; Akbari, Hamed; Pisapia, Jared M.; Da, Xiao; Attiah, Mark; Pigrish, Vadim; Bi, Yingtao; Pal, Sharmistha; Davuluri, Ramana V.; Roccograndi, Laura; Dahmane, Nadia; Martinez-Lage, Maria; Biros, George; Wolf, Ronald L.; Bilello, Michel; O'Rourke, Donald M.; Davatzikos, Christos

    2016-01-01

    Background MRI characteristics of brain gliomas have been used to predict clinical outcome and molecular tumor characteristics. However, previously reported imaging biomarkers have not been sufficiently accurate or reproducible to enter routine clinical practice and often rely on relatively simple MRI measures. The current study leverages advanced image analysis and machine learning algorithms to identify complex and reproducible imaging patterns predictive of overall survival and molecular subtype in glioblastoma (GB). Methods One hundred five patients with GB were first used to extract approximately 60 diverse features from preoperative multiparametric MRIs. These imaging features were used by a machine learning algorithm to derive imaging predictors of patient survival and molecular subtype. Cross-validation ensured generalizability of these predictors to new patients. Subsequently, the predictors were evaluated in a prospective cohort of 29 new patients. Results Survival curves yielded a hazard ratio of 10.64 for predicted long versus short survivors. The overall, 3-way (long/medium/short survival) accuracy in the prospective cohort approached 80%. Classification of patients into the 4 molecular subtypes of GB achieved 76% accuracy. Conclusions By employing machine learning techniques, we were able to demonstrate that imaging patterns are highly predictive of patient survival. Additionally, we found that GB subtypes have distinctive imaging phenotypes. These results reveal that when imaging markers related to infiltration, cell density, microvascularity, and blood–brain barrier compromise are integrated via advanced pattern analysis methods, they form very accurate predictive biomarkers. These predictive markers used solely preoperative images, hence they can significantly augment diagnosis and treatment of GB patients. PMID:26188015

  19. Gallbladder cancer in the Netherlands: incidence, treatment and survival patterns since 1989.

    PubMed

    Witjes, Caroline D M; van den Akker, Sanne A W; Visser, Otto; Karim-Kos, Henrike E; de Vries, Esther; Ijzermans, Jan N M; de Man, Robert A; Coebergh, Jan Willem W; Verhoef, Cornelis

    2012-01-01

    To examine recent trends in gallbladder cancer (GBC) in the general population in the Western world, cancer registration data on GBC in the Netherlands were analyzed. Trends in incidence, treatment and survival, according to gender, age and stage of disease, between 1989 and 2008 for 3,917 patients were studied. Rates were age-standardized to the European standard population (European Standardized Rates - ESR). The incidence rate for GBC in the Netherlands decreased rapidly during the period of 1989-2008, except for males younger than 60 years. Overall survival remained stable, short-term (3-month) and long-term (5-year) relative survival among surgically treated patients increased significantly. Treatment patterns for GBC changed. Surgery decreased from 55% in 1989 to 38% in 2008 (p < 0.001). Chemotherapy and/or irradiation increased from 1.0 to 5.8% (p < 0.001). Receiving best supportive care increased from 44% in 1989 to 57% in 2008 (p < 0.001). The incidence rate for GBC in the Netherlands has decreased rapidly. Treatment patterns for GBC have changed and survival among surgically treated patients has increased. Copyright © 2012 S. Karger AG, Basel.

  20. Resistance patterns between cis-diamminedichloroplatinum(II) and ionizing radiation

    SciTech Connect

    De Pooter, C.M.; Scalliet, P.G.; Elst, H.J.; Huybrechts, J.J.; Gheuens, E.E.; Van Oosterom, A.T.; Fichtinger-Schepman, A.M.; De Bruijn, E.A. )

    1991-09-01

    Cross-resistance between cis-diamminedichloroplatinum(II) (CDDP) and radiation resistance has been suggested from clinical and experimental data. To determine whether cross-resistance patterns between both cytotoxic approaches exist, resistance against CDDP and ionizing radiation was induced separately in human ovarian cancer cells in a cross-over design. Subsequently sensitivity changes were determined for both treatment modalities. CDDP resistance was induced previously, and resistant cells were grown at three different levels of CDDP:0 ng/ml; 250 ng/ml; and 500 ng/ml. Resistance with resistance factor (RF) 3.4 to 5.1 proved to be stable, since withdrawal of CDDP pressure for at least 6 mo did not alter resistance patterns. CDDP-resistant cells also demonstrated stable resistance against ionizing radiation, with RF ranging from 1.7 to 2.0. The resistance patterns could not be explained by differences in growth kinetics and DNA content. Resistance to ionizing radiation was induced in the same human ovarian cancer cells as used for CDDP resistance studies. Exposure with 1.5 Gy of intermittent irradiation during 6 mo, at time intervals of 48 h, resulted in cells which were able to grow under chronic ionizing radiation pressure. RF was 2.0; the resistance was lost after 6 mo of culturing without ionizing radiation pressure. With intermittent radiation doses of 0.5 and 1.0 Gy, no significant resistance could be induced. Cells intermittently exposed to 0.5, 1.0, and 1.5 Gy during 6 mo demonstrated increased sensitivity to CDDP, with 0.22 less than RF less than 0.43. Increased sensitivity was associated with proportionally increased formation of the platinum-DNA adducts.

  1. Negative synergism of rainfall patterns and predators affects frog egg survival.

    PubMed

    Touchon, Justin Charles; Warkentin, Karen Michelle

    2009-07-01

    1. The importance of rainfall is recognized in arid habitats, but has rarely been explored in ecosystems not viewed as rainfall limited. In addition, most attempts to study how rainfall affects organismal survival have focused on long-term rainfall metrics (e.g. monthly or seasonal patterns) instead of short-term measures. For organisms that are short lived or are sensitive to desiccation, short-term patterns of rainfall may provide insight to understanding what determines survival in particular habitats. 2. We monitored daily rainfall and survival of arboreal eggs of the treefrog Dendropsophus ebraccatus at two ponds during the rainy season in central Panama. Desiccation and predation were the primary sources of egg mortality and their effects were not independent. Rainfall directly reduced desiccation mortality by hydrating and thickening the jelly surrounding eggs. In addition, rainfall reduced predation on egg clutches. 3. To elucidate the mechanism by which rainfall alters predation, we exposed experimentally hydrated and dehydrated egg clutches to the two D. ebraccatus egg predators most common at our site, ants and social wasps. Ants and wasps preferentially preyed on dehydrated clutches and ants consumed dehydrated eggs three times faster than hydrated eggs. 4. Rainfall patterns are expected to change and the responses of organisms that use rainfall as a reliable cue to reproduce may prove maladaptive. If rainfall becomes more sporadic, as is predicted to happen during this century, it may have negative consequences for desiccation-sensitive organisms.

  2. Sporulation and Germination patterns - hedging a bet on long term microbial survivability in dry soil

    NASA Astrophysics Data System (ADS)

    Claes, N.; Or, D.

    2012-04-01

    Soil hosts unparalleled diversity of microbial life that is constantly challenged by the vagaries of fluctuating ambient conditions. Desiccation stresses play a key role not only by directly affecting individual bacterial cells, but also by shaping diffusion pathways and cell dispersion. The gradual thinning and fragmentation of the aqueous environment during drying have led to different survival mechanisms including dormancy and sporulation, resulting in a highly resistive state capable of surviving extreme and prolonged environmental stresses until conditions improve in the future. Our aim is to investigate how temporal changes in hydration status shape microbial communities over time, based on simple survival strategy rules for each individual bacterium. The two survival strategies considered are dormancy and sporulation. Dormancy is the state in which bacterial cells significantly reduce their metabolism with minor morphological adaptations. The required energy and time for attaining this state are low relative to sporulation costs. Sporulation involves several morphological and biochemical changes that result in a resistive capsule that endures extreme stresses over long periods of time. The working hypothesis is that different micro-ecological conditions and community compositions would result from temporal patterns and magnitude of desiccation stresses. An Individual Based Model (IBM) considering habitats on rough soil surfaces and local effects of micro-hydrological conditions on dispersion and nutrient diffusion would enable systematic study of emerging communities over extended periods. Different population compositions are expected to emerge based on low and high frequency, duration and amplitudes of wetting-drying cycles reflecting relative success or failure of survival strategy.

  3. Movement patterns, habitat use, and survival of Lahontan cutthroat trout in the Truckee River

    USGS Publications Warehouse

    Alexiades, Alexander V.; Peacock, Mary M.; Al-Chokhachy, Robert K.

    2012-01-01

    Habitat fragmentation, hybridization, and competition with nonnative salmonids are viewed as major threats to Lahontan cutthroat trout Oncorhynchus clarkii henshawi. Understanding Lahontan cutthroat trout behavior and survival is a necessary step in the reintroduction and establishment of naturally reproducing populations of Lahontan cutthroat trout. We used weekly radiotelemetry monitoring to examine movement patterns, habitat use, and apparent survival of 42 hatchery-reared Lahontan cutthroat trout in a 16.5-km stretch of the Truckee River, Nevada, across three reaches separated by barriers to upstream movement. We found differences in total movement distances and home range sizes of fish in different reaches within our study area. Fish used pool habitats more than fast water habitats in all reaches. Time of year, stream temperature, and fish standard length covariates had the strongest relationship with apparent survival. Monthly apparent survival was lowest in January, which coincided with the lowest flows and temperatures during the study period. Our results verify the mobility of Lahontan cutthroat trout and indicate that conditions during winter may limit the survival and reintroduction success in the portions of the Truckee River evaluated in this study.

  4. Influence of native microbiota on survival of Ralstonia solanacearum phylotype II in river water microcosms.

    PubMed

    Alvarez, Belén; López, María M; Biosca, Elena G

    2007-11-01

    Ralstonia solanacearum phylotype II biovar 2 causes bacterial wilt in solanaceous hosts, producing severe economic losses worldwide. Waterways can be major dissemination routes of this pathogen, which is able to survive for long periods in sterilized water. However, little is known about its survival in natural water when other microorganisms, such as bacteriophages, other bacteria, and protozoa, are present. This study looks into the fate of a Spanish strain of R. solanacearum inoculated in water microcosms from a Spanish river, containing different microbiota fractions, at 24 degrees C and 14 degrees C, for a month. At both temperatures, R. solanacearum densities remained constant at the initial levels in control microcosms of sterile river water while, by contrast, declines in the populations of the introduced strain were observed in the nonsterile microcosms. These decreases were less marked at 14 degrees C. Lytic bacteriophages present in this river water were involved in the declines of the pathogen populations, but indigenous protozoa and bacteria also contributed to the reduced persistence in water. R. solanacearum variants displaying resistance to phage infection were observed, but only in microcosms without protozoa and native bacteria. In water microcosms, the temperature of 14 degrees C was more favorable for the survival of this pathogen than 24 degrees C, since biotic interactions were slower at the lower temperature. Similar trends were observed in microcosms inoculated with a Dutch strain. This is the first study demonstrating the influence of different fractions of water microorganisms on the survival of R. solanacearum phylotype II released into river water microcosms.

  5. Microsatellite instability & survival in patients with stage II/III colorectal carcinoma

    PubMed Central

    Srdjan, Markovic; Jadranka, Antic; Ivan, Dimitrijevic; Branimir, Zogovic; Daniela, Bojic; Petar, Svorcan; Velimir, Markovic; Zoran, Krivokapic

    2016-01-01

    Background & objectives: The two key aspects associated with the microsatellite instability (MSI) as genetic phenomenon in colorectal cancer (CRC) are better survival prognosis, and the varying response to 5-fluorouracil (5-FU)-based chemotherapy. This study was undertaken to measure the survival of surgically treated patients with stages II and III CRC based on the MSI status, the postoperative 5-FU treatment as well as clinical and histological data. Methods: A total of 125 consecutive patients with stages II and III (American Joint Committee on Cancer, AJCC staging) primary CRCs, were followed prospectively for a median time of 31 months (January 2006 to December 2009). All patients were assessed, operated and clinically followed. Tumour samples were obtained for cytopathological verification and MSI grading. Results: Of the 125 patients, 21 (20%) had high MSI (MSI-H), and 101 patients (80%) had MSI-L or MSS (low frequency MSI or stable MSI). Patients with MSS CRC were more likely to have recurrent disease (P=0.03; OR=3.2; CI 95% 1-10.2) compared to those with MSI-H CRC. Multi- and univariate Cox regression analysis failed to show a difference between MSI-H and MSS groups with respect to disease-free, disease-specific and overall survival. However, the disease-free survival was significantly lower in patients with MSI-H CRC treated by adjuvant 5-FU therapy (P=0.03). Interpretation & conclusions: MSI-H CRCs had a lower recurrence rate, but the prognosis was worse following adjuvant 5-FU therapy. PMID:27748284

  6. Enhanced Cell Survival and Yield of Rat Small Hepatocytes by Honeycomb-Patterned Films

    NASA Astrophysics Data System (ADS)

    Tsukiyama, Shusaku; Matsushita, Michiaki; Tanaka, Masaru; Tamura, Hitoshi; Todo, Satoru; Yamamoto, Sadaaki; Shimomura, Masatsugu

    2008-02-01

    Surface designing of substrate to regulate cell adhesion and function in nano and micro scale is a critical issue in biomaterial science. In this study, we describe the fabrication of highly regular patterned porous films (honeycomb-patterned film) formed by a simply casting technique, and the culture of mature hepatocytes and small hepatocytes on the films. The pore size of the honeycomb-patterned films used was 6, 12, and 16 µm. We evaluated the effect of the honeycomb-patterned films on the morphology, cell yield, survival and the differentiated hepatic function (albumin production) of the both hepatocytes. Both hepatocytes attached on the flat films appeared to spread well, showing a typical monolayer morphology. They peeled off from the films at 7 days in culture on the flat films. On the other hand, spreading of the each hepatocytes was restricted on the honeycomb-patterned films at 3 and 7 days in culture. The cell yield and survival of the each hepatocytes increased with increasing culture time. Small hepatocyte on the pore sizes of 16 µm showed the highest cell yield (approximately 3 times). Albumin production of mature hepatocyte on the pore sizes of 16 µm (224.1.3 ±157 ng ml-1 well-1 at 1 day in culture, 369.5 ±222 ng ml-1 well-1 at 3 days in culture) was higher than that of the hepatocytes on the flat films (119.3 ±9.3 ng ml-1 well-1 at 1 day in culture, 262.8 ±47.3 ng ml-1 well-1 at 3 days in culture), although that of small hepatocytes on the honeycomb-patterned films (pore size: 16 µm) was similar on the flat film. These results indicated that both the surface topography and the pore size of the honeycomb-patterned film affected the hepatic metabolic function.

  7. Vaginal and pelvic recurrences in stage I and II endometrial carcinoma--survival and prognostic factors.

    PubMed

    Blecharz, P; Brandys, P; Urbański, K; Reinfuss, M; Patla, A

    2011-01-01

    The analysis of prognostic factors and treatment outcomes in 106 patients with Stage I and II endometrial carcinoma (EC) treated between 1980 and 2005 in the Center of Oncology, Maria Skłodowska-Curie Memorial Institute, Kracow, Poland, who developed vaginal or pelvic recurrences. The median age of patients was 61. Stage IB and IC of EC was diagnosed in 48 (45.3%) patients and Stage IIA and IIB in 58 (54.7%) patients. All patients were treated previously with surgery (TAH-BSO) and postoperative radiotherapy. There were 17 (16%) patients with vaginal vault recurrences, 30 (28.3%) with lower one-third vaginal recurrences, and 59 (55.7%) with pelvic recurrences. Palliative treatment (chemo- or hormonotherapy) or best supportive care only was undertaken in 53 (50.0%) patients. Radical treatment was conducted in 70.6% (12/17) of vault recurrences, 86.7% (26/30) of lower one-third vagina recurrences, and 25.4% (15/59) of pelvic recurrences, with surgery (4 patients), brachytherapy +/- chemotherapy (34 patients), and teleradiotherapy +/- chemotherapy (15 patients). The 5-year overall survival rate in the observed group was 17%. Five-year survival was 23.3% (14/60) for patients with KPS 60-70 vs 8.7% (4/46) with KPS 40-50, 25% (12/48) patients with Stage I EC vs 10.3% (6/58) with Stage II EC, and 34% (16/47) patients with vaginal recurrence vs 3.4% (2/59) with pelvic recurrences. In the analyzed group of 106 patients with Stage I and II EC, treated previously with surgery and postoperative radiotherapy, 5-year overall survival rate was low; in radically treated patients it was 42.1%, and 13.3% for vaginal and pelvis recurrences, respectively. Univariate analysis showed a statistically significant, unfavorable impact of KPS < 60, Stage II and recurrence pelvic. Cox multivariate analysis demonstrated that the only independent prognostic factor for 5-year overall survival was the site of recurrence.

  8. Seed deposition patterns and the survival of seeds and seedlings of the palm Euterpe edulis

    NASA Astrophysics Data System (ADS)

    Pizo, Marco A.; Simão, Isaac

    2001-08-01

    The seed deposition pattern created by a seed disperser is one of the components of the efficiency of a species as seed disperser, and ultimately may influence the recruitment of a plant species. In this study, we used the seeds of a bird-dispersed forest palm, Euterpe edulis, to investigate the effects of two distinct seed deposition patterns created by birds that defecate (clumped pattern) and regurgitate seeds (loose-clumped pattern) on the survival of seeds experimentally set in an E. edulis-rich site, and of seedlings grown under shade-house conditions. The study was conducted in the lowland forest of Parque Estadual Intervales, SE Brazil. Clumped and loose-clumped seeds were equally preyed upon by rodents and insects. Although clumped and isolated seedlings had the same root weight after 1 year, the isolated seedlings survived better and presented more developed shoots, suggesting intraspecific competition among clumped seedlings. Our results indicate that animals that deposit E. edulis seeds in faecal clumps (e.g. cracids, tapirs) are less efficient seed dispersers than those that regurgitate seeds individually (e.g. trogons, toucans). Intraspecific competition among seedlings growing from faecal clumps is a likely process preventing the occurrence of clumps of adult palms.

  9. The Impact of Delayed Chemotherapy on Its Completion and Survival Outcomes in Stage II Colon Cancer Patients

    PubMed Central

    Xu, Fang; Rimm, Alfred A.; Fu, Pingfu; Krishnamurthi, Smitha S.; Cooper, Gregory S.

    2014-01-01

    Background Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients. Patients and Methods Patients (age ≥66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER–Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples. Results 4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2–3 months), and 12.3% had delayed chemotherapy (≥3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival). Conclusion Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation. PMID:25238395

  10. Association of tRNA methyltransferase NSUN2/IGF-II molecular signature with ovarian cancer survival.

    PubMed

    Yang, Jia-Cheng; Risch, Eric; Zhang, Meiqin; Huang, Chan; Huang, Huatian; Lu, Lingeng

    2017-08-22

    To investigate the association between NSUN2/IGF-II signature and ovarian cancer survival. Using a publicly accessible dataset of RNA sequencing and clinical follow-up data, we performed Classification and Regression Tree and survival analyses. Patients with NSUN2 (high) IGF-II (low) had significantly superior overall and disease progression-free survival, followed by NSUN2 (low) IGF-II (low), NSUN2 (high) IGF-II (high) and NSUN2 (low) IGF-II (high) (p < 0.0001 for overall, p = 0.0024 for progression-free survival, respectively). The associations of NSUN2/IGF-II signature with the risks of death and relapse remained significant in multivariate Cox regression models. Random-effects meta-analyses show the upregulated NSUN2 and IGF-II expression in ovarian cancer versus normal tissues. The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

  11. Movement patterns and study area boundaries: Influences on survival estimation in capture-mark-recapture studies

    USGS Publications Warehouse

    Horton, G.E.; Letcher, B.H.

    2008-01-01

    The inability to account for the availability of individuals in the study area during capture-mark-recapture (CMR) studies and the resultant confounding of parameter estimates can make correct interpretation of CMR model parameter estimates difficult. Although important advances based on the Cormack-Jolly-Seber (CJS) model have resulted in estimators of true survival that work by unconfounding either death or recapture probability from availability for capture in the study area, these methods rely on the researcher's ability to select a method that is correctly matched to emigration patterns in the population. If incorrect assumptions regarding site fidelity (non-movement) are made, it may be difficult or impossible as well as costly to change the study design once the incorrect assumption is discovered. Subtleties in characteristics of movement (e.g. life history-dependent emigration, nomads vs territory holders) can lead to mixtures in the probability of being available for capture among members of the same population. The result of these mixtures may be only a partial unconfounding of emigration from other CMR model parameters. Biologically-based differences in individual movement can combine with constraints on study design to further complicate the problem. Because of the intricacies of movement and its interaction with other parameters in CMR models, quantification of and solutions to these problems are needed. Based on our work with stream-dwelling populations of Atlantic salmon Salmo salar, we used a simulation approach to evaluate existing CMR models under various mixtures of movement probabilities. The Barker joint data model provided unbiased estimates of true survival under all conditions tested. The CJS and robust design models provided similarly unbiased estimates of true survival but only when emigration information could be incorporated directly into individual encounter histories. For the robust design model, Markovian emigration (future

  12. cN-II expression predicts survival in patients receiving gemcitabine for advanced non-small cell lung cancer.

    PubMed

    Sève, Pascal; Mackey, John R; Isaac, Sylvie; Trédan, Olivier; Souquet, Pierre Jean; Pérol, Maurice; Cass, Carol; Dumontet, Charles

    2005-09-01

    Resistance to gemcitabine is likely to be multifactorial and could involve a number of mechanisms involved in drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human equilibrative nucleoside transporter 1 (hENT1)-deficient cells display resistance to gemcitabine. Overexpression of certain nucleotidases, such as cN-II, has also been frequently shown in gemcitabine-resistant models. In this study, we applied immunohistochemical methods to assess the protein abundance of cN-II, hENT1, human concentrative nucleoside transporter 3 (hCNT3) and deoxycitidine kinase (dCK) in malignant cells in from 43 patients with treatment-naïve locally advanced or metastatic non-small cell lung cancer (NSCLC). All patients subsequently received gemcitabine-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival (OS) were correlated with abundance of these proteins. Among the 43 samples, only 7 (16%) expressed detectable hENT1, with a low percentage of positive cells, 18 expressed hCNT3 (42%), 36 (86%) expressed cN-II and 28 (66%) expressed dCK. In univariate analysis, only cN-II expression levels were correlated with overall survival. None of the parameters were correlated with freedom from progression survival nor with response. Patients with low levels of expression of cN-II (less than 40% positively stained cells) had worse overall survival than patients with higher levels of cN-II expression (6 months and 11 months, respectively). In a multivariate analysis taking into account age, sex, weight loss, stage and immunohistochemical results, cN-II was the only predictive factor associated with overall survival. This study suggests that cN-II nucleotidase expression levels identify subgroups of NSCLC patients with different outcomes under gemcitabine-based therapy. Larger prospective studies are warranted to confirm the predictive value of cN-II in these patients.

  13. One-stage and two-stage designs for phase II clinical trials with survival endpoints.

    PubMed

    Whitehead, John

    2014-09-28

    This work is motivated by trials in rapidly lethal cancers or cancers for which measuring shrinkage of tumours is infeasible. In either case, traditional phase II designs focussing on tumour response are unsuitable. Usually, tumour response is considered as a substitute for the more relevant but longer-term endpoint of death. In rapidly lethal cancers such as pancreatic cancer, there is no need to use a surrogate, as the definitive endpoint is (sadly) available so soon. In uveal cancer, there is no counterpart to tumour response, and so, mortality is the only realistic response available. Cytostatic cancer treatments do not seek to kill tumours, but to mitigate their effects. Trials of such therapy might also be based on survival times to death or progression, rather than on tumour shrinkage. Phase II oncology trials are often conducted with all study patients receiving the experimental therapy, and this approach is considered here. Simple extensions of one-stage and two-stage designs based on binary responses are presented. Outcomes based on survival past a small number of landmark times are considered: here, the case of three such times is explored in examples. This approach allows exact calculations to be made for both design and analysis purposes. Simulations presented here show that calculations based on normal approximations can lead to loss of power when sample sizes are small. Two-stage versions of the procedure are also suggested.

  14. Multiple births in sub-saharan Africa: epidemiology, postnatal survival, and growth pattern.

    PubMed

    Gebremedhin, Samson

    2015-02-01

    The study endeavored to assess the epidemiology, postnatal survival, and growth pattern of multiple births in Sub-Saharan Africa (SSA). It was based on the data of 25 demographic health surveys conducted in the subcontinent since 2008. The records of 213,889 children born in the preceding 59 months of the surveys were included. The multiple birth rate was computed as the number of multiple confinements per 1,000 births. Factors associated with multiple births were identified using logistic regression and their survival pattern was assessed using the Kaplan-Meier method. The multiple birth rate was 17.1 (95% confidence interval: 17.7-16.6) and showed considerable variation across the 25 countries included in the study. Odds of multiple births were significantly increased with advanced maternal age, parity, and maternal height but not with wealth index, age at first birth, and month of birth. At the end of the fourth year of age, the cumulative survival probability was as low as 0.77 in multiple births as compared to 0.93 in their counterparts. The odds of neonatal, infant and under-five mortality were 5.55, 4.39, and 3.72 times increased in multiple births, respectively. Multiple births tend to be malnourished than singletons and the odds of wasting, stunting, and underweight were 1.31, 1.83, and 1.73 times raised, consecutively. Nevertheless, multiple births regain their weight-for-age (WFA) and height-for-age (HFA) deficits by the end of the fourth year of age. Counseling pregnant mothers with multiple gestation to give birth at a health institution and providing close medical follow-up during and after the neonatal period can improve the survival of multiple births.

  15. Frequency and survival pattern of in-hospital cardiac arrests: The impacts of etiology and timing.

    PubMed

    Tran, Sheri; Deacon, Naomi; Minokadeh, Anushirvan; Malhotra, Atul; Davis, Daniel P; Villanueva, Sheri; Sell, Rebecca E

    2016-10-01

    Define the frequency and survival pattern of cardiac arrests in relation to the hospital day of event and etiology of arrest. Retrospective cohort study of adult in-hospital cardiac arrests between July 1, 2005, and June 30, 2013, that were classified by etiology of deterioration. Arrests were divided based on hospital day (HD) of event (HD1, HD2-7, HD>7 days), and analysis of frequency was performed. The primary outcome of survival to discharge and secondary outcomes of return of spontaneous circulation (ROSC) and favorable neurological outcomes were compared using multivariable logistic regression analysis. A total of 627 cases were included, 193 (30.8%) cases in group HD1, 206 (32.9%) in HD2-7, and 228 (36.4%) in HD>7. Etiology of arrest demonstrated variability across the groups (p<0.001). Arrests due to ventilation issues increased in frequency with longer hospitalization (p<0.001) while arrests due to dysrhythmia had the opposite trend (p=0.014). Rates of survival to discharge (p=0.038) and favorable neurological outcomes (p=0.002) were lower with increasing hospital days while ROSC was not different among the groups (p=0.183). Survival was highest for HD1 (HD1: 38.9% [95% CI, 32.0-45.7%], p=0.002 vs HD2-7: 34.0% [95% CI, 27.5-40.4%], p<0.001 vs HD>7: 27.2% [95% CI, 21.4-33.0%], p<0.001). The etiology of cardiac arrests varies in frequency as length of hospitalization increases. Survival rates and favorable neurological outcomes are lower for in-hospital arrests occurring later in the hospitalization, even when adjusted for age, sex, and location of event. Understanding these issues may help with focusing therapies and accurate prognostication. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Contrasting patterns of nest survival and postfledging survival in ovenbirds and Acadian flycatchers in Missouri forest fragments

    Treesearch

    Julianna M. A. Jenkins; Frank R. Thompson; John Faaborg

    2016-01-01

    We can improve our ability to assess population viability and forecast population growth under different scenarios by understanding factors that limit population parameters in each stage of the annual cycle. Postfledging mortality rates may be as variable as nest survival across regions and fragmentation gradients, although factors that negatively impact nest survival...

  17. Early rheumatoid disease. II. Patterns of joint involvement.

    PubMed Central

    Fleming, A; Benn, R T; Corbett, M; Wood, P H

    1976-01-01

    Data from the first research clinic visit (Fleming and others, 1976) have been subjected to factor analysis to identify early patterns of joint involvement. Nine patterns emerged. Two patterns, if present early, were found to have prognostic significance. An eventually more severe disease was associated with a pattern of large joint involvement (shoulder, elbow, wrist, knee) and a pattern based on metatarsophalangeal joints I and III. PMID:970995

  18. Effect of side-stream smoking on random-pattern skin flap survival in rats.

    PubMed

    Gazzalle, Anajara; Teixeira, Lourenço Frigeri; Pellizzari, Alice Cardoso; Cocolichio, Fernanda; Zampieri, Juliana Tonietto; Rauber, Daniel; Pezzin, Luíse S; Zago, Vanessa D; Braga-Silva, Jefferson Luis

    2014-04-01

    The secondhand exposure to cigarette smoke is being considered evil, and damage caused by this passive exposure has been proven by several studies. To investigate the effects of sidestream smoke exposure on random-pattern skin flap survival, 20 female rats were separated into 2 groups: group A (n = 10) was exposed 6 weeks to the smoke from the burning cigarette (passive smoking) and group B (n = 10) was the control group. After 6 weeks of exposition, a dorsal McFarlane flap of 4 × 10 cm was performed in all rats. Two weeks after this procedure, the ratio of necrotic and total areas was calculated using computer programs. The median area of necrosis in group A was 29.5%, significantly higher than that in group B with 17.5% (P < 0.024). In conclusion, this study suggests increased risk of random-pattern skin flap necrosis after sidestream exposure to cigarette smoke.

  19. The ability to survive intracellular freezing in nematodes is related to the pattern and distribution of ice formed.

    PubMed

    Raymond, Méliane R; Wharton, David A

    2016-07-01

    A few species of nematodes can survive extensive intracellular freezing throughout all their tissues, an event that is usually thought to be fatal to cells. How are they able to survive in this remarkable way? The pattern and distribution of ice formed, after freezing at -10°C, can be observed using freeze substitution and transmission electron microscopy, which preserves the former position of ice as white spaces. We compared the pattern and distribution of ice formed in a nematode that survives intracellular freezing well (Panagrolaimus sp. DAW1), one that survives poorly (Panagrellus redivivus) and one with intermediate levels of survival (Plectus murrayi). We also examined Panagrolaimus sp. in which the survival of freezing had been compromised by starvation. Levels of survival were as expected and the use of vital dyes indicated cellular damage in those that survived poorly (starved Panagrolaimus sp. and P. murrayi). In fed Panagrolaimus sp. the intracellular ice spaces were small and uniform, whereas in P. redivivus and starved Panagrolaimus sp. there were some large spaces that may be causing cellular damage. The pattern and distribution of ice formed was different in P. murrayi, with a greater number of individuals having no ice or only small intracellular ice spaces. Control of the size of the ice formed is thus important for the survival of intracellular freezing in nematodes. © 2016. Published by The Company of Biologists Ltd.

  20. Morbidity and survival patterns in patients after radical hysterectomy and postoperative adjuvant pelvic radiotherapy

    SciTech Connect

    Fiorica, J.V.; Roberts, W.S.; Greenberg, H.; Hoffman, M.S.; LaPolla, J.P.; Cavanagh, D. )

    1990-03-01

    Morbidity and survival patterns were reviewed in 50 patients who underwent radical hysterectomy, pelvic lymphadenectomy, and adjuvant postoperative pelvic radiotherapy for invasive cervical cancer. Ninety percent of the patients were FIGO stage IB, and 10% were clinical stage IIA or IIB. Indications for adjuvant radiotherapy included pelvic lymph node metastasis, large volume, deep stromal penetration, lower uterine segment involvement, or capillary space involvement. Seventy-two percent of the patients had multiple high-risk factors. An average of 4700 cGy of whole-pelvis radiotherapy was administered. Ten percent of the patients suffered major gastrointestinal complications, 14% minor gastrointestinal morbidity, 12% minor genitourinary complications, one patient a lymphocyst, and one patient lymphedema. Of the five patients with major gastrointestinal morbidity, all occurred within 12 months of treatment. Three patients required intestinal bypass surgery for distal ileal obstructions and all are currently doing well and free of disease. All of the patients who developed recurrent disease had multiple, high-risk factors. The median time of recurrence was 12 months. All patients recurred within the radiated field. Actuarial survival was 90% and disease-free survival 87% at 70 months. It is our opinion that the morbidity of postoperative pelvic radiotherapy is acceptable, and benefit may be gained in such a high-risk patient population.

  1. Comparing population patterns to processes: abundance and survival of a forest salamander following habitat degradation.

    PubMed

    Otto, Clint R V; Roloff, Gary J; Thames, Rachael E

    2014-01-01

    Habitat degradation resulting from anthropogenic activities poses immediate and prolonged threats to biodiversity, particularly among declining amphibians. Many studies infer amphibian response to habitat degradation by correlating patterns in species occupancy or abundance with environmental effects, often without regard to the demographic processes underlying these patterns. We evaluated how retention of vertical green trees (CANOPY) and coarse woody debris (CWD) influenced terrestrial salamander abundance and apparent survival in recently clearcut forests. Estimated abundance of unmarked salamanders was positively related to CANOPY (β Canopy  = 0.21 (0.02-1.19; 95% CI), but not CWD (β CWD  = 0.11 (-0.13-0.35) within 3,600 m2 sites, whereas estimated abundance of unmarked salamanders was not related to CANOPY (β Canopy  = -0.01 (-0.21-0.18) or CWD (β CWD  = -0.02 (-0.23-0.19) for 9 m2 enclosures. In contrast, apparent survival of marked salamanders within our enclosures over 1 month was positively influenced by both CANOPY and CWD retention (β Canopy  = 0.73 (0.27-1.19; 95% CI) and β CWD  = 1.01 (0.53-1.50). Our results indicate that environmental correlates to abundance are scale dependent reflecting habitat selection processes and organism movements after a habitat disturbance event. Our study also provides a cautionary example of how scientific inference is conditional on the response variable(s), and scale(s) of measure chosen by the investigator, which can have important implications for species conservation and management. Our research highlights the need for joint evaluation of population state variables, such as abundance, and population-level process, such as survival, when assessing anthropogenic impacts on forest biodiversity.

  2. Racial Patterns of Peripheral T-Cell Lymphoma Incidence and Survival in the United States

    PubMed Central

    Adams, Scott V.; Newcomb, Polly A.

    2016-01-01

    Purpose To compare incidence and survival of peripheral T-cell lymphoma (PTCL) subtypes among US racial/ethnic groups. Methods Patients with PTCL (age ≥ 15 years; 2000 to 2012) were identified in the Surveillance, Epidemiology, and End Results (SEER) registries. Race/ethnicity was categorized as non-Hispanic white, black, Asian/Pacific Islander, Hispanic white, or American Indian/Alaskan native. Age-standardized annual incidence rates and incidence rate ratios were estimated with 95% CIs, and case-case odds ratios were estimated by race/ethnicity using polytomous regression. Survival was estimated from SEER follow-up data with Cox regression. Results Thirteen thousand one hundred seven patients with PTCL were identified. Annual PTCL incidence was highest in blacks and lowest in Native Americans. Compared with non-Hispanic whites, blacks had a higher incidence of PTCL not otherwise specified (PTCL-NOS), anaplastic large-cell lymphoma, and adult T-cell leukemia/lymphoma (ATLL) and a lower incidence of angioimmunoblastic T-cell lymphoma (AITL); Asians/Pacific Islanders had a higher incidence of AITL, extranodal nasal-type natural killer/T-cell lymphoma and NK-cell leukemia (ENKCL), and ATLL and a lower incidence of anaplastic large-cell lymphoma; Hispanics had a higher incidence of AITL and ENKCL; and Native Americans had a lower incidence of PTCL-NOS (all P < .05). The ratio of ENKCL to PCTL-NOS among Native Americans, Asians/Pacific Islanders, and Hispanic whites was approximately three- to four-fold the same ratio among non-Hispanic whites. Survival varied significantly by race/ethnicity (P < .001), with blacks in particular experiencing shorter survival for most subtypes. Conclusion Striking variation in incidence, proportions of PTCL subtypes, and survival was observed. Aspects of these PTCL subtype patterns, such as for ENKCL and ATLL, were similar to corresponding global populations. Despite the small population size and limited number of Native American

  3. Lymphoma development and survival in refractory coeliac disease type II: Histological response as prognostic factor

    PubMed Central

    van Wanrooij, RLJ; van Gils, T; Wierdsma, NJ; Tack, GJ; Witte, BI; Bontkes, HJ; Visser, O; Mulder, CJJ; Bouma, G

    2016-01-01

    Background Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). Objective The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies. Methods A total of 45 patients were retrospectively analysed. All patients received 2-CdA, after which they were either closely monitored (monotherapy, n = 30) or a step-up approach was used including auSCT (step-up therapy, n = 15). Results Ten patients (22%) ultimately developed EATL; nine of these had received monotherapy. Absence of histological remission after monotherapy was associated with EATL development (p = 0.010). Overall, 20 patients (44%) died with a median survival of 84 months. Overall survival (OS) within the monotherapy group was significantly worse in those without histological remission compared to those with complete histological remission(p = 0.030). The monotherapy group who achieved complete histological remission showed comparable EATL occurrence and OS as compared to the step-up therapy group (p = 0.80 and p = 0.14 respectively). Conclusion Histological response is an accurate parameter to evaluate the effect of 2-CdA therapy and this parameter should be leading in the decisions whether or not to perform a step-up treatment approach in RCDII. PMID:28344788

  4. Lymphoma development and survival in refractory coeliac disease type II: Histological response as prognostic factor.

    PubMed

    Nijeboer, P; van Wanrooij, Rlj; van Gils, T; Wierdsma, N J; Tack, G J; Witte, B I; Bontkes, H J; Visser, O; Mulder, Cjj; Bouma, G

    2017-03-01

    Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies. A total of 45 patients were retrospectively analysed. All patients received 2-CdA, after which they were either closely monitored (monotherapy, n = 30) or a step-up approach was used including auSCT (step-up therapy, n = 15). Ten patients (22%) ultimately developed EATL; nine of these had received monotherapy. Absence of histological remission after monotherapy was associated with EATL development (p = 0.010). Overall, 20 patients (44%) died with a median survival of 84 months. Overall survival (OS) within the monotherapy group was significantly worse in those without histological remission compared to those with complete histological remission(p = 0.030). The monotherapy group who achieved complete histological remission showed comparable EATL occurrence and OS as compared to the step-up therapy group (p = 0.80 and p = 0.14 respectively). Histological response is an accurate parameter to evaluate the effect of 2-CdA therapy and this parameter should be leading in the decisions whether or not to perform a step-up treatment approach in RCDII.

  5. Primary intracranial haemangiopericytoma: comparison of survival outcomes and metastatic potential in WHO grade II and III variants.

    PubMed

    Damodaran, Omprakash; Robbins, Peter; Knuckey, Neville; Bynevelt, Michael; Wong, George; Lee, Gabriel

    2014-08-01

    Primary intracranial haemangiopericytomas (HPC) are rare, highly vascular tumours with a high propensity for local recurrence and distant metastasis. Optimal treatment includes maximal surgical resection followed by adjuvant radiotherapy. In 2007, new histopathological grading criteria were introduced to differentiate between high grade (World Health Organization [WHO] grade III) and low grade (WHO grade II) tumours. Given the rarity of this tumour, there is a paucity of information regarding the prognostic significance of histological grade. We conducted a retrospective review of our 20 year experience in treating 27 patients with HPC at our institution. Statistical analysis to compare overall survival, local recurrence rate and metastatic potential between the two grades were conducted using Kaplan-Meier analysis. The estimated median survival for grade II HPC was 216 months and for grade III tumours was 142 months. On multivariate analysis, grade II tumours were associated with better survival than grade III lesions (hazard ratio=0.16, 95% confidence interval 0.26-0.95; p=0.044). During the study period, 33% of grade III tumours developed local recurrence compared to 21% of grade II tumours. Metastases were found in 36% of grade II patients and 25% of grade III patients. There was no significant statistical difference in local recurrence rate and metastasis between the two grades. Higher histological grading in HPC is associated with worse overall survival. However based on our series higher histological grading is not associated with higher local recurrence or distant metastatic rates. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

    SciTech Connect

    Karam, Irene; Lesperance, Maria F.; Berrang, Tanya; Speers, Caroline; Tyldesley, Scott; Truong, Pauline T.

    2013-11-15

    Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examined outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal

  7. The effects of vasonatrin peptide on random pattern skin flap survival.

    PubMed

    Wang, Shi-Ping; Lan, Zhi-Yong; Xia, Wei; Zhao, Xi; Ma, Ge-Jia; Liu, Bei; Pan, Bao-Hua; Guo, Shu-Zhong

    2014-01-01

    < 0.05). This study found that VNP, which could elevate the tissue blood perfusion and mitigate the tissue damage and inflammatory reaction, is associated with a higher percentage of survival random pattern skin flap area.

  8. Mucinous and Signet Ring Cell Differentiation Affect Patterns of Metastasis in Colorectal Carcinoma and Influence Survival.

    PubMed

    Kermanshahi, Taher Reza; Magge, Deepa; Choudry, Haroon; Ramalingam, Leksmi; Zhu, Benjamin; Pingpank, James; Ahrendt, Steven; Holtzman, Matthew; Zeh, Herbert; Bartlett, David; Zureikat, Amer; Pai, Reetesh K

    2017-04-01

    Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

  9. Neonatal Idiotypic Exposure Alters Subsequent Cytokine, Pathology, and Survival Patterns in Experimental Schistosoma mansoni Infections

    PubMed Central

    Angela Montesano, M.; Colley, Daniel G.; Eloi-Santos, Silvana; Freeman, George L.; Secor, W. Evan

    1999-01-01

    Exposure to maternal idiotypes (Ids) or antigens might predispose a child to develop an immunoregulated, asymptomatic clinical presentation of schistosomiasis. We have used an experimental murine system to address the role of Ids in this immunoregulation. Sera from mice with 8-wk Schistosoma mansoni infection, chronic (20-wk infection) moderate splenomegaly syndrome (MSS), or chronic hypersplenomegaly syndrome (HSS) were passed over an S. mansoni soluble egg antigen (SEA) immunoaffinity column to prepare Ids (8WkId, MSS Id, HSS Id). Newborn mice were injected with 8WkId, MSS Id, HSS Id, or normal mouse immunoglobulin (NoMoIgG) and infected with S. mansoni 8 wk later. Mice exposed to 8WkId or MSS Id as newborns had prolonged survival and decreased morbidity compared with mice that received HSS Id or NoMoIgG. When stimulated with SEA, 8WkId, or MSS Id, spleen cells from mice neonatally injected with 8WkId or MSS Id produced more interferon γ than spleen cells from mice neonatally injected with HSS Id or NoMoIgG. Furthermore, neonatal exposure to 8WkId or MSS Id, but not NoMoIgG or HSS Id, led to significantly smaller granuloma size and lower hepatic fibrosis levels in infected mice. Together, these results indicate that perinatal exposure to appropriate anti-SEA Ids induces long-term effects on survival, pathology, and immune response patterns in mice subsequently infected with S. mansoni. PMID:9989978

  10. The Effect of Thrombolytic, Anticoagulant, and Vasodilator Agents on the Survival of Random Pattern Skin Flap.

    PubMed

    Aral, Mübin; Tuncer, Serhan; Şencan, Ayşe; Elmas, Çiğdem; Ayhan, Sühan

    2015-09-01

    The aim of this study was to investigate the effect of subcutaneously applied thrombolytic, anticoagulant, and vasodilator agents on the survival of random-pattern skin flap. A caudally based dorsal flap model was used in 24 rats in four groups. In group 1 (n = 6), flap was elevated and sutured. In group 2 (n = 6), enoxaparin sodium was injected subcutaneously immediately after surgery, on days 1 and 2. In group 3 (n = 6), a transdermal nitroglycerin was applied directly following surgery, on days 1 and 2. In group 4 (n = 6), alteplase was injected subcutaneously immediately after surgery, on days 1 and 2. Blood flow was measured with laser Doppler flowmetry at the proximal and distal halves of flap before, immediately after surgery, and on days 3 and 7. Histologic samples were taken from the same locations on day 3 and day 7 postoperatively. Vessel and lymphocyte count was obtained. Photographs were taken to determine flap necrosis areas at day 7 postoperatively. Area of skin necrosis was found to be less in all medication groups. But only enoxaparin sodium group showed significant decrease in skin necrosis (p < 0.05). Laser Doppler flowmetry showed a gradual decrease in all groups over time, with no statistically significant result. The histologic findings revealed the induction of angiogenesis in all experimental groups. Subcutaneously applied thrombolytic, anticoagulant, and vasodilator agents increase random-pattern skin flap survival with only enoxaparin sodium showing significant decrease in flap necrosis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Mucin-1 correlates with survival, smoking status, and growth patterns in lung adenocarcinoma.

    PubMed

    Lappi-Blanco, Elisa; Mäkinen, Johanna M; Lehtonen, Siri; Karvonen, Henna; Sormunen, Raija; Laitakari, Kirsi; Johnson, Shirley; Mäkitaro, Riitta; Bloigu, Risto; Kaarteenaho, Riitta

    2016-10-01

    Mucin-1 (MUC1) affects cancer progression in lung adenocarcinoma, and its aberrant expression pattern has been correlated with poor tumor differentiation and impaired prognosis. In this study, the immunohistochemical expression of MUC1 and Mucin-4 (MUC4) was analyzed in a series of 106 surgically operated stage I-IV pulmonary adenocarcinomas. MUC1 immunohistochemistry was evaluated according to the Nagai classification, and the immunohistochemical profile of the tumors was correlated with detailed clinical and histological data. The effect of cigarette smoke on MUC1 expression in lung cancer cell lines was examined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoelectron microscopy (IEM). In contrast to the normal apical localization of MUC1, a basolateral and cytoplasmic (depolarized) MUC1 expression pattern was frequently encountered in the high-grade subtypes, i.e., solid predominant adenocarcinoma and the cribriform variant of acinar predominant adenocarcinoma (p < 0.001), and was rarely observed in tumors containing a non-predominant lepidic component (p < 0.001). Furthermore, the altered staining pattern of MUC1 correlated with stage (p = 0.002), reduced overall survival (p = 0.031), and was associated with smoking (p < 0.001). When H1650 adenocarcinoma cells were exposed to cigarette smoke and analyzed by RT-qPCR and IEM, the levels of the MUC1 transcript and protein were elevated (p = 0.042). In conclusion, MUC1 participates in the pathogenesis of lung adenocarcinoma and associates with smoking both in vitro and in vivo. In lung adenocarcinoma, depolarized MUC1 protein expression correlated with histological growth patterns, stage, and patient outcome.

  12. Effect of Mycobacterial Drug Resistance Patterns on Patients’ Survival: A Cohort Study in Thailand

    PubMed Central

    Anuwatnonthakate, Amornrat; Whitehead, Sara J.; Varma, Jay K.; Silachamroon, Udomsak; Kasetjaroen, Yuthichai; Moolphate, Saiyud; Limsomboon, Pranom; Inyaphong, Jiraphun; Suriyon, Narin; Kavinum, Suporn; Chiengson, Navarat; Tunteerapat, Phatchara; Kaewkungwal, Jaranit

    2013-01-01

    Background: Drug resistance substantially increases tuberculosis (TB) mortality. This study aimed to describe the prevalence of mycobacterial drug resistance pattern and association of common resistance patterns with TB mortality in Thailand. Method: A retrospective cohort study was conducted using TB surveillance data. A total of 9,518 culture-confirmed, pulmonary TB patients registered from 1 October 2004 to 31 December 2008 from the Thailand TB Active Surveillance Network were included in this study. Patients were followed up until TB treatment completion or death. Mycobacterial drug resistance patterns were categorized as pan-susceptible, rifampicin resistance, isoniazid monoresistance, and ethambutol/streptomycin resistance. Drug susceptibility testing (DST) was determined by Mycobacterial Growth Indicator Tube (MGIT) liquid culture systems. Survival analysis was applied. Result: Isoniazid monoresistance was the most common pattern, while rifampicin resistance had the largest impact on mortality. Cox regression analysis showed a significantly higher risk of death among patients with rifampicin resistance (adjusted hazard ratio (aHR) 1.9, 95% confident interval (CI), 1.5-2.5) and isoniazid monoresistance (aHR 1.4, 95% CI 1.1-1.7) than those with pan-susceptible group after adjustment for age, nationality, human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status, diabetes mellitus, cavitary disease on chest x-ray, treatment observation, and province. HIV co-infection was associated with higher mortality in patients both on ART (aHR 1.9, 95% CI 1.5-2.5) and not on ART (aHR 8.1, 95% CI 6.8-9.8). Conclusion: Rifampicin resistance and isoniazid monoresistance were associated with increased TB mortality. HIV-coinfection was associated with a higher risk of death including among those taking antiretroviral therapy. PMID:24171875

  13. The effect of TENS on random pattern flap survival in nicotinized rats.

    PubMed

    Özyazgan, İrfan; Baykan, Halit

    2015-03-01

    The adverse effects of cigarettes, due to their nicotine content, may cause important ischemic complications in flaps. Electrical stimulation increases blood flow in ischemic tissues, the level of vascular endothelial growth factor, capillary density, and angiogenesis while decreasing oxygen tension in tissues. Electrical stimulation is also known to increase survival rate in flaps. In this study, which tests the hypothesis that TENS (a type of electrical stimulation) contributes to enhancement of flap viability by eliminating the adverse effects of nicotine, 40 rats were divided into 4 groups of 10 rats. Nicotinization was achieved by subcutaneous administration of 2 mg/kg per day to the rats, other than those in the Control group, for 4 weeks. The rats in one of the nicotinized groups received 20 mA, 80 Hz TENS (TENS1 group) for 1 hour daily throughout the last week before McFarlane flaps of random pattern were made in the backs of all the rats. Another nicotinized group was subjected to TENS in a similar dose after flap elevation (TENS2 group). Flap blood flow was measured before and 48 hours after their construction, and their fluorescein perfusion was measured immediately after the flap elevation. The comparison of the survival rates of the flaps revealed that, although the blood flow in the Nicotine group was significantly lower than in the Control group, it was significantly higher in the TENS1 group than in both the Control and Nicotine groups. The proportion of the area stained with fluorescein, immediately after the elevation of flaps, was significantly reduced in the Nicotine group compared to the Control group. In the TENS1 group, however, it was greater than in the nicotine and TENS2 groups. Flap viability rates decreased significantly in the Nicotine group compared with the Control group. In the TENS2 group, however, an increase was observed compared with the Nicotine group.These findings suggest that although TENS performed before flap elevation does

  14. Class II correction in a growing patient with hyperdivergent growth patterns and severe overjet.

    PubMed

    Park, Jae Hyun

    2010-01-01

    In general, the success of Class II treatment depends as much on the skill of the orthodontist as it does on a favorable facial-growth pattern. Lack of sufficient favorable growth during treatment will make it difficult to correct the skeletal malrelationship or significantly improve the facial profile. The case report presents the treatment of a patient with a Class II, Division 1 malocclusion with severe overjet and a hyperdivergent growth pattern. © 2011 BY QUINTESSENCE PUBLISHING CO, INC.

  15. TEMOZOLOMIDE FOR RECURRENT INTRACRANIAL EPENDYMOMA OF THE ADULT: PATTERNS OF RESPONSE, SURVIVAL AND CORRELATIONS WITH MGMT PROMOTER METHYLATION

    PubMed Central

    Soffietti, Riccardo; Bosa, Chiara; Bertero, Luca; Trevisan, Elisa; Cassoni, Paola; Morra, Isabella; Rudà, Roberta

    2014-01-01

    BACKGROUND: A variety of agents have been investigated with modest results in recurrent grade II and III ependymomas failing surgery and/or radiotherapy. Few data are available on the role of temozolomide (TMZ). We investigated patterns of response, outcome and correlations with MGMT promoter methylation in a cohort of patients with recurrent ependymomas of the adult receiving temozolomide as salvage therapy. METHODS: We retrospectively studied all patients aged ≥18 years with recurrent intracranial ependymoma, who received as part of their treatment standard temozolomide between 1999 and 2011. Clinical information were retrieved from the database and follow-up visits, while MRI images were reviewd by an investigator blind to patients' outcome. Response to TMZ on MRI was evaluated according to Macdonald Criteria. An analysis of MGMT gene promoter methylation by PCR was performed. RESULTS: We found 18 evaluable patients of whom 12 were males and 6 females, and 10 (56%) were of grade III and 8 (44%) of grade II. Tumor location at initial surgery was supratentorial in 11 (61%) patients and infratentorial in 7 (39%), and type of progression before TMZ was local in 10 (56%), local and spinal in 6 (33%) and spinal alone in 2 (11%). Median age was 42 years (18-61) and median KPS 70 (60-90). Previous treatments consisted of radiotherapy (either adjuvant or at relapse) in 17/18 (94%) patients, and chemotherapy (cisplatin + VP16, PCV, BCNU) in 6/18 (33%). A median of 8 cycles of TMZ (1-24) were administered. Best response to TMZ was as follows: CR 1/18 (5%) and PR 3/18 (17%), with an overall RR of 22%; SD 7/18 (39%) and PD 7/18 (39%). Maximum reponse in 3 out of 4 patients was observed after 10, 14 and 15 cycles, respectively. All 4 responding patients were chemotherapy-naive. Responses occurred in both anaplastic (2) and low grade (2) tumors. Median PFS was 9 months (1 month-13 years), while PFS 6 and 12 were 72% and 39%, respectively. Median OS was 31 months (3 months-14

  16. Does seasonality drive spatial patterns in demography? Variation in survival in African reed warblers Acrocephalus baeticatus across southern Africa does not reflect global patterns

    PubMed Central

    Jansen, Dorine YM; Abadi, Fitsum; Harebottle, Doug; Altwegg, Res

    2014-01-01

    Among birds, northern temperate species generally have larger clutches, shorter development periods and lower adult survival than similarly-sized southern and tropical species. Even though this global pattern is well accepted, the driving mechanism is still not fully understood. The main theories are founded on the differing environmental seasonality of these zones (higher seasonality in the North). These patterns arise in cross-species comparisons, but we hypothesized that the same patterns should arise among populations within a species if different types of seasonality select for different life histories. Few studies have examined this. We estimated survival of an azonal habitat specialist, the African reed warbler, across the environmentally diverse African subcontinent, and related survival to latitude and to the seasonality of the different environments of their breeding habitats. Data (1998–2010) collected through a public ringing scheme were analyzed with hierarchical capture-mark-recapture models to determine resident adult survival and its spatial variance across sixteen vegetation units spread across four biomes. The models were defined as state-space multi-state models to account for transience and implemented in a Bayesian framework. We did not find a latitudinal trend in survival or a clear link between seasonality and survival. Spatial variation in survival was substantial across the sixteen sites (spatial standard deviation of the logit mean survival: 0.70, 95% credible interval (CRI): 0.33–1.27). Mean site survival ranged from 0.49 (95% CRI: 0.18–0.80) to 0.83 (95% CRI: 0.62–0.97) with an overall mean of 0.67 (95% CRI: 0.47–0.85). A hierarchical modeling approach enabled us to estimate spatial variation in survival of the African reed warbler across the African subcontinent from sparse data. Although we could not confirm the global pattern of higher survival in less seasonal environments, our findings from a poorly studied region

  17. An insulin-like growth factor-II intronic variant affects local DNA conformation and ovarian cancer survival.

    PubMed

    Lu, Lingeng; Risch, Evan; Deng, Qian; Biglia, Nicoletta; Picardo, Elisa; Katsaros, Dionyssios; Yu, Herbert

    2013-09-01

    Insulin-like growth factor-II (IGF-II) may be a prognostic marker in ovarian cancer, and its intronic single nucleotide polymorphism (SNP) rs4320932 has been associated with risk of the disease. We determined whether rs4320932 is associated with IGF-II expression and patient survival in ovarian cancer, and explored whether the SNP variation affects DNA conformation both in the absence of and presence of carboplatin. IGF-II genotype (rs4320932) and phenotype were analyzed in 212 primary invasive epithelial ovarian cancer tissue samples with Taqman® SNP genotyping assays, quantitative reverse transcription-polymerase chain reaction and commercial enzyme-linked immunosorbent assay. DNA conformation was evaluated by circular dichroism (CD) spectra. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to analyze the SNP associations with patient survival. The C allele of rs4320932, previously associated with decreased risk of ovarian cancer development, was here associated with significantly elevated risks of relapse (Ptrend = 0.0002) and death (Ptrend = 0.0006), remaining significant in multivariate analyses. The adjusted hazard ratios were 3.05 (95% confidence interval [CI]: 1.47-6.37) for relapse and 3.28 (95% CI: 1.64-6.57) for death, respectively. The variant was also significantly associated with chemotherapy response, but not with other clinicopathologic variables or with IGF-II expression. DNA with genotypes TT and CC had distinct CD spectra in both the absence of and presence of carboplatin. These findings suggest that the intronic SNP rs4320932 affects patient survival and chemotherapy response via alteration of DNA conformation, but not through regulation of IGF-II expression. This novel finding may have implications in individualized medicine for the design of specific molecules targeting DNA of specific conformations.

  18. [Chemical pattern recognition of traditional Chinese medicine kudingcha (II)].

    PubMed

    Su, W; Wu, Z; He, X; Chen, J

    1998-04-01

    In this paper, the HPLC data from 78 samples of Kudingcha were treated with back propagation algorithm of artifical neural network pattern recognition, and the computer-aided classification of Ilex cornuta Lindl., Ilex latifolia Thunb. and Ligustrum lucidum Ait. was accomplished. This paper provides a scientific, advanced and feasible method for identification of traditional Chinese medicine.

  19. Central role of Th2/Tc2 lymphocytes in pattern II multiple sclerosis lesions

    PubMed Central

    Planas, Raquel; Metz, Imke; Ortiz, Yaneth; Vilarrasa, Nuria; Jelčić, Ilijas; Salinas-Riester, Gabriela; Heesen, Christoph; Brück, Wolfgang; Martin, Roland; Sospedra, Mireia

    2015-01-01

    Objective Multiple sclerosis (MS) is a disease of the central nervous system with marked heterogeneity in several aspects including pathological processes. Based on infiltrating immune cells, deposition of humoral factors and loss of oligodendrocytes and/or myelin proteins, four lesion patterns have been described. Pattern II is characterized by antibody and complement deposition in addition to T-cell infiltration. MS is considered a T-cell-mediated disease, but until now the study of pathogenic T cells has encountered major challenges, most importantly the limited access of brain-infiltrating T cells. Our objective was to identify, isolate, and characterize brain-infiltrating clonally expanded T cells in pattern II MS lesions. Methods We used next-generation sequencing to identify clonally expanded T cells in demyelinating pattern II brain autopsy lesions, subsequently isolated these as T-cell clones from autologous cerebrospinal fluid and functionally characterized them. Results We identified clonally expanded CD8+ but also CD4+ T cells in demyelinating pattern II lesions and for the first time were able to isolate these as live T-cell clones. The functional characterization shows that T cells releasing Th2 cytokines and able to provide B cell help dominate the T-cell infiltrate in pattern II brain lesions. Interpretation Our data provide the first functional evidence for a putative role of Th2/Tc2 cells in pattern II MS supporting the existence of this pathogenic phenotype and questioning the protective role that is generally ascribed to Th2 cells. Our observations are important to consider for future treatments of pattern II MS patients. PMID:26401510

  20. Failure patterns and survival outcomes in triple negative breast cancer (TNBC): a 15 year comparison of 448 non-Hispanic black and white women.

    PubMed

    Prasad, Shreya; Efird, Jimmy T; James, Sarah E; Walker, Paul R; Zagar, Timothy M; Biswas, Tithi

    2016-01-01

    Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer with unique pathologic, molecular and clinical behavior. It occurs more frequently in young blacks and has been reported to have a shorter disease-free interval. We undertook this study to analyze the demographic characteristics, failure patterns, and survival outcomes in this disease. A total of 448 non-Hispanic black and white women were identified over a 15 year period from 1996 to 2011. Demographic and clinical information including age, race, menopausal status, stage, tumor characteristics, and treatments were collected. Fisher's exact test and multivariable Cox regression were used to compare failure patterns and survival outcomes between races. 49 % (n = 223) were black. 59 % patients were between 41 and 60 years, with 18 % ≤40 years. 57 % were premenopausal and 89 % had grade 3 tumors. Stage II (47 %) was most frequent stage at diagnosis followed by stage III (28 %). 32 % had lymphovascular invasion. Adjusting for age, stage, and grade, there was no difference in survival outcomes (OS, DFS, LFFS, and DFFS) between the two races. 62 (14 %) patients failed locally either in ipsilateral breast or chest wall, and 19 (4 %) failed in the regional lymphatics. Lung (18 %) was the most frequent distant failure site with <12 % each failing in brain, liver and bones. Failure patterns and survival outcomes did not differ by race in this large collection of TNBC cases. Lung was the predominate site of distant failure followed by brain, bone, and liver. Few patients failed in the regional lymphatics.

  1. Treatment patterns and survival outcomes in patients with cervical cancer complicated by complete uterine prolapse: a systematic review of literature.

    PubMed

    Matsuo, Koji; Fullerton, Morgan E; Moeini, Aida

    2016-01-01

    Cervical cancer complicated by complete uterine prolapse is a rare clinical entity and uniform management recommendations have yet to be determined. The aim of the current review was to examine the effects of management patterns on survival outcomes in cervical cancer patients with complete uterine prolapse. A systematic review of the literature was conducted using three public search engines. This included case reports with detailed descriptions of tumor characteristics, cancer management, and survival outcomes. Treatment patterns and tumor characteristics were correlated to survival outcomes. There were 78 patients with cervical cancer with complete uterine prolapse. Their mean age was 63.7 years. The median duration of prolapse was 147.9 months and 22.2% of the patients experienced persistent/recurrent prolapse after cancer treatment. The mean tumor size was 8.9 cm and squamous cell carcinoma (83.9%) was the most common histologic type. The majority of patients (56.2%) had stage I cancer. Tumor characteristics were similar across the treatment patterns. Survival outcomes were more favorable with surgery-based treatment (48 patients) than with radiation-based treatment (30 patients): 5-year recurrence-free survival rate 72.0% vs. 62.9% (p = 0.057), and 5-year disease-specific overall survival rate 77.0% vs. 68.2% (p = 0.017). After controlling for age and stage, surgery-based therapy remained an independent prognostic factor for better disease-specific overall survival outcome (hazard ratio 0.32, 95% confidence interval 0.11 - 0.94, adjusted p = 0.039). Although limited in study size, our results at least suggest that surgery-based treatment may have a positive effect on survival outcome in cervical cancer patients with complete uterine prolapse.

  2. Meniscal ossification. II. The normal pattern in the tiger knee.

    PubMed

    Ganey, T M; Ogden, J A; Abou-Madi, N; Colville, B; Zdyziarski, J M; Olsen, J H

    1994-04-01

    Examination of knee menisci of Bengal tigers revealed ossicles within the cartilaginous anterior horn of each medial meniscus. This ossification was not evident in the neonatal animal, but was present in animals aged 20 months or older. The ossicle appeared prior to the completion of skeletal maturation at the knee, and was composed of normal remodeling trabecular bone. While most animals had a single, variably sized ossicle, multiple ossicles also occurred. The meniscal cartilage apposed to the femoral articulation exhibited a distinct columnar pattern in the region of the ossicle, in contrast to the non-columnar pattern throughout the bulk of the meniscus, including the ossicle side apposed to the tibial plateau. In this particular large mammalian species medial meniscal ossification appears to be a normal anatomical variation that progressively develops following birth, and may serve as a model for the phylogenetic (developmental) theory of etiology.

  3. Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer

    PubMed Central

    Garrett, C R; Hassabo, H M; Bhadkamkar, N A; Wen, S; Baladandayuthapani, V; Kee, B K; Eng, C; Hassan, M M

    2012-01-01

    Background: Patients with type II diabetes mellitus (DM) have an increased risk of adenomatous colorectal (CRC) polyps and CRC cancer. The use of the anti-hyperglycemic agent metformin is associated with a reduced incidence of cancer-related deaths. Methods: We retrospectively evaluated the medical records of 4758 patients seen at a single institution and determined that 424 patients were identified by their physicians as having type II DM and CRC cancer. Data were subsequently acquired determining the subject's age, body mass index (BMI), and disease date of diagnosis, stage, site of cancer, treatment, and survival. Results: Patients with type II DM and CRC cancer treated with metformin as one of their diabetic medications had a survival of 76.9 months (95% CI=61.4–102.4) as compared with 56.9 months in those patients not treated with metformin (95% CI=44.8–68.8), P=0.048. By using a multivariable Cox regression model adjusted for age, sex, race, BMI, and initial stage of disease, we demonstrated that type II diabetic patients treated with metformin had a 30% improvement in overall survival (OS) when compared with diabetic patients treated with other diabetic agents. Conclusion: Colorectal cancer patients with DM treated with metformin as part of their diabetic therapy appear to have a superior OS. PMID:22421948

  4. Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma.

    PubMed

    Sozen, Hamdullah; Çiftçi, Rumeysa; Vatansever, Dogan; Topuz, Samet; Iyibozkurt, Ahmet Cem; Bozbey, Hamza Ugur; Yaşa, Cenk; Çali, Halime; Yavuz, Ekrem; Kucucuk, Seden; Aydiner, Adnan; Salihoglu, Yavuz

    2016-04-01

    The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92-95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  5. Expression patterns of three regulation enzymes in glycolysis in esophageal squamous cell carcinoma: association with survival.

    PubMed

    Li, Wenfeng; Xu, Zhengyang; Hong, Junfeng; Xu, Yunsheng

    2014-09-01

    Enhanced glycolysis is a common trait of many types of human cancers. This study was to detect the expression pattern of three regulatory enzymes during glycolysis in esophageal squamous cell carcinoma (ESCC) and to investigate their correlation with patients' outcome based on banked pathology material. A total of 141 surgically resected specimens of primary ESCC patients without prior treatments were retrospectively recruited from the First Affiliated Hospital of Wenzhou Medical College Hospital from 2007 to 2009. Expression of HK1, PFKB, and PKM2 in ESCC specimens was analyzed by immunohistochemical staining and Western blotting analysis. HK1-shRNA was used to knock down HK1 expression in ESCC cells, and the functional significance was assessed by CCK8 assay. It was found that the expression of two glycolytic enzymes, HK1 and PKM2, was associated with disease progression, invasion, and poor survival of patients with ESCC. Silence of HK1-inhibited cell proliferation in vitro and suppressed phospho-S6 kinase expression. Our findings suggest that activation of key enzymes in glycolysis might serve as potential therapeutic targets and/or prognostic factors for patients with ESCC.

  6. Ewing's sarcoma. Radiographic pattern of healing and bony complications in patients with long-term survival

    SciTech Connect

    Ehara, S.; Kattapuram, S.V.; Egglin, T.K. )

    1991-10-01

    The radiographic appearance of Ewing's sarcoma was studied retrospectively in 22 patients who survived 5 years or longer after diagnosis and treatment. Expected changes from treatment, including regression of the extraosseous soft tissue mass, periostitis, and reconstitution of the cortex, occurred in all patients. Local recurrence occurred in one patient 10 years after complete remission whereas secondary osteosarcoma occurred more than 5 years after complete remission in two other cases. Both recurrent and secondary tumors presented as new lytic foci at the site of the original primary lesion. Lytic changes from radiation (radiation osteitis) may develop more than 2 years after treatment and in this sample; such findings were widely distributed in the radiation port. The authors conclude that bone remodeling and postradiation changes occur slowly over 2 years after treatment, and that any localized lysis at the primary site is suspicious for recurrence or secondary neoplasm. Knowledge of the expected changes and patterns of local recurrence and secondary neoplasms helps one to detect any significant change in its early phase.

  7. Do age-specific survival patterns of wild boar fit current evolutionary theories of senescence?

    PubMed

    Gamelon, Marlène; Focardi, Stefano; Gaillard, Jean-Michel; Gimenez, Olivier; Bonenfant, Christophe; Franzetti, Barbara; Choquet, Rémi; Ronchi, Francesca; Baubet, Eric; Lemaître, Jean-François

    2014-12-01

    Actuarial senescence is widespread in age-structured populations. In growing populations, the progressive decline of Hamiltonian forces of selection with age leads to decreasing survival. As actuarial senescence is overcompensated by a high fertility, actuarial senescence should be more intense in species with high reproductive effort, a theoretical prediction that has not been yet explicitly tested across species. Wild boar (Sus scrofa) females have an unusual life-history strategy among large mammals by associating both early and high reproductive effort with potentially long lifespan. Therefore, wild boar females should show stronger actuarial senescence than similar-sized related mammals. Moreover, being polygynous and much larger than females, males should display higher senescence rates than females. Using a long-term monitoring (18 years) of a wild boar population, we tested these predictions. We provided clear evidence of actuarial senescence in both sexes. Wild boar females had earlier but not stronger actuarial senescence than similar-sized ungulates. Both sexes displayed similar senescence rates. Our study indicates that the timing of senescence, not the rate, is associated with the magnitude of fertility in ungulates. This demonstrates the importance of including the timing of senescence in addition to its rate to understand variation in senescence patterns in wild populations. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  8. Combined detection of the expression of Nm23-H1 and p53 is correlated with survival rates of patients with stage II and III colorectal cancer

    PubMed Central

    Wu, Yinying; Li, Yi; Zhao, Xiaoai; Dong, Danfeng; Tang, Chunhui; Li, Enxiao; Geng, Qianqian

    2017-01-01

    Molecular tumor markers hold considerable promise for accurately predicting the recurrence and progression of colorectal cancer (CRC) in patients. However, in the majority of cases, single marker analysis has been found to have low accuracy, and is of little practical use in clinical practice. The present study investigated the prognostic value of the combined detection of the protein expression of metastasis suppressor 23-H1 (Nm23-H1) and p53 using immunohistochemical analysis, and the mRNA expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction in 110 cases of stage II and III CRC. The results revealed that the expression levels of Nm23-H1 in CRC tissues were lower, compared with those in normal tissues (χ2=18.249; P<0.001), and the protein expression levels of p53 were higher in the CRC tissues (χ2=23.940; P<0.001); although the mRNA expression levels of Nm23-H1 and p53 presented with the same trend. The protein expression of Nm23-H1 was correlated with lymph node metastases (χ2=11.847; P=0.001) and pathological patterns (χ2=6.911; P=0.032). However, it did not correlate with patient gender or age, or with tumor World Health Organization classification or invasive depth (P>0.05). No significant correlation was observed between the expression of p53 and clinicopathological features (P>0.05). Patients with CRC with Nm23-H1(+)/p53(−) tumors had increased survival rates, with a five-year overall survival rate of 83.8% and a five-year disease-free survival rate of 70.2%. The five-year overall survival rates in other study cohorts were lower, compared with the Nm23-H1(+)/p53(−) group (P<0.0125), and this was the same for the five-year disease-free survival rate (P<0.0125). In conclusion, the present study demonstrated that the combined detection of the protein expression of Nm23-H1 and p53 was associated with the long term survival rates of patients with stage II and III CRC; and this may offer potential for use as a

  9. Calculation of the non-isothermal inactivation patterns of microbes having sigmoidal isothermal semi-logarithmic survival curves.

    PubMed

    Peleg, Micha

    2003-01-01

    Sigmoidal isothermal semi-logarithmic survival curves are of two main types; starting with a downward and changing to upward concavity and vice versa. Both can be described by a variety of mathematical models having 3-4 adjustable parameters. The temperature dependence of these models' parameters can be described by empirical models, which account for the progressive change in the sigmoidal shape, including its disappearance at either high or low temperatures. If the temperature history of a heat-treated population of microbial cells or spores ('temperature profile') can be described algebraically, then there is a way to estimate the survival pattern under these non-isothermal conditions without invoking the traditional D and z values, which require forcing straight lines through the curved experimental data. The described method is based on the assumption that the local slope of the non-isothermal survival curve is that of the isothermal curve at the momentary temperature, at a time, which corresponds to the momentary survival ratio. It is similar to the method previously proposed for microbial populations with a 'power law' type isothermal survival curves, except that the time, which corresponds to the momentary survival ratio, is calculated either symbolically or numerically as a procedure incorporated in the governing differential equation. The method's capabilities are demonstrated with simulated survival curves under temperature histories that resemble thermal processing of foods. They include heating to different target temperatures and starting the cooling at different times.

  10. Survival of plant seeds, their UV screens, and nptII DNA for 18 months outside the International Space Station.

    PubMed

    Tepfer, David; Zalar, Andreja; Leach, Sydney

    2012-05-01

    The plausibility that life was imported to Earth from elsewhere can be tested by subjecting life-forms to space travel. Ultraviolet light is the major liability in short-term exposures (Horneck et al., 2001 ), and plant seeds, tardigrades, and lichens-but not microorganisms and their spores-are candidates for long-term survival (Anikeeva et al., 1990 ; Sancho et al., 2007 ; Jönsson et al., 2008 ; de la Torre et al., 2010 ). In the present study, plant seeds germinated after 1.5 years of exposure to solar UV, solar and galactic cosmic radiation, temperature fluctuations, and space vacuum outside the International Space Station. Of the 2100 exposed wild-type Arabidopsis thaliana and Nicotiana tabacum (tobacco) seeds, 23% produced viable plants after return to Earth. Survival was lower in the Arabidopsis Wassilewskija ecotype and in mutants (tt4-8 and fah1-2) lacking UV screens. The highest survival occurred in tobacco (44%). Germination was delayed in seeds shielded from solar light, yet full survival was attained, which indicates that longer space travel would be possible for seeds embedded in an opaque matrix. We conclude that a naked, seed-like entity could have survived exposure to solar UV radiation during a hypothetical transfer from Mars to Earth. Chemical samples of seed flavonoid UV screens were degraded by UV, but their overall capacity to absorb UV was retained. Naked DNA encoding the nptII gene (kanamycin resistance) was also degraded by UV. A fragment, however, was detected by the polymerase chain reaction, and the gene survived in space when protected from UV. Even if seeds do not survive, components (e.g., their DNA) might survive transfer over cosmic distances.

  11. Two years survival rate of Class II ART restorations in primary molars using two ways to avoid saliva contamination.

    PubMed

    Carvalho, Thiago Saads; Sampaio, Fábio Correia; Diniz, Alexandre; Bönecker, Marcelo; Van Amerongen, Willem Evert

    2010-11-01

    To compare the survival rates of Class II Atraumatic Restorative Treatment (ART) restorations placed in primary molars using cotton rolls or rubber dam as isolation methods. A total of 232 children, 6-7 years old, both genders, were selected having one primary molar with proximal dentine lesion. The children were randomly assigned into two groups: control group with Class II ART restoration made using cotton rolls and experimental group using rubber dam. The restorations were evaluated by eight calibrated evaluators (Kappa > 0.8) after 6, 12, 18 and 24 months. A total of 48 (20.7%) children were considered dropout, after 24 months. The cumulative survival rate after 6, 12, 18 and 24 months was 61.4%, 39.0%, 29.1% and 18.0%, respectively for the control group, and 64.1%, 55.1%, 40.1% and 32.1%, respectively for the rubber dam group. The log rank test for censored data showed no statistical significant difference between the groups (P = 0.07). The univariate Cox Regression showed no statistical significant difference after adjusting for independent variables (P > 0.05). Both groups had similar survival rates, and after 2 years, the use of rubber dam does not increase the success of Class II ART restorations significantly. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.

  12. Family patterns of development dyslexia, Part II: Behavioral phenotypes

    SciTech Connect

    Wolff, P.H.; Melngailis, I.; Bedrosian, M.

    1995-12-18

    The motor control of bimanual coordination and motor speech was compared between first degree relatives from families with at least 2 dyslexic family members, and families where probands were the only affected family members. Half of affected relatives had motor coordination deficits; and they came from families in which probands also showed impaired motor coordination. By contrast, affected relatives without motor deficits came from dyslexia families where probands did not have motor deficits. Motor coordination deficits were more common and more severe among affected offspring in families where both parents were affected than among affected offspring in families where only one parent was affected. However, motor coordination deficits were also more common and more severe in affected parents when both parents were affected than among affected parents in families where only one parent was affected. We conclude that impaired temporal resolution in motor action identifies a behavioral phenotype in some subtypes of developmental dyslexia. The observed pattern of transmission for motor deficits and reading impairment in about half of dyslexia families was most congruent with a genetic model of dyslexia in which 2 codominant major genes cosegregate in dyslexia pedigrees where the proband is also motorically impaired. 54 refs., 5 figs., 5 tabs.

  13. Recurrence Patterns and Survival for Patients With Intermediate- and High-Grade Myxofibrosarcoma

    SciTech Connect

    Haglund, Karl E.; Raut, Chandrajit P.; Nascimento, Alessandra F.; Wang, Qian; George, Suzanne; Baldini, Elizabeth H.

    2012-01-01

    Purpose: Myxofibrosarcoma (MFS) is a rare sarcoma with a predilection for multiple local recurrences (LR), for which optimal treatment has not been defined. We reviewed our experience to determine the impact of surgery and radiation therapy (RT) on pattern of recurrence, limb salvage, and overall survival (OS). Methods and Materials: Between 1995 and 2005, 36 patients with localized intermediate- or high-grade MFS were treated at our institution. Data on clinicopathologic features, treatments, and patient outcomes were reviewed and analyzed. Results: Median age was 72.5 years (range, 42-96 years). Median tumor size was 7.5 cm, and 34 tumors (94%) were high grade. All patients underwent surgery at our institution, including re-resections in 20 patients (56%) after initial surgery elsewhere. Margins were microscopically positive in 9 patients (25%). RT was given to 28 patients (78%) pre - and/or postoperatively. After a median follow-up of 3.5 years (range, 0.4-12.4 years), 11 patients (31%) developed LR. There were no significant predictors for LR on univariate analysis, including margin status or use of RT. Limb salvage was ultimately achieved in only 5 of 11 LRs (45%) because of multiple subsequent LRs. Distant recurrence (DR) occurred in 6 patients (17%). Median and 4-year OS were 96 months and 65%, respectively. Seven patients (19%) died of tumor-related causes, 6 of whom had DRs. On univariate analysis, tumor size was associated with OS. Conclusions: Despite aggressive surgery and RT, intermediate- and high-grade MFS are associated with a high rate of LR that adversely affects limb preservation. More aggressive local treatment strategies are necessary.

  14. CasExpress reveals widespread and diverse patterns of cell survival of caspase-3 activation during development in vivo

    PubMed Central

    Ding, Austin Xun; Sun, Gongping; Argaw, Yewubdar G; Wong, Jessica O; Easwaran, Sreesankar; Montell, Denise J

    2016-01-01

    Caspase-3 carries out the executioner phase of apoptosis, however under special circumstances, cells can survive its activity. To document systematically where and when cells survive caspase-3 activation in vivo, we designed a system, CasExpress, which drives fluorescent protein expression, transiently or permanently, in cells that survive caspase-3 activation in Drosophila. We discovered widespread survival of caspase-3 activity. Distinct spatial and temporal patterns emerged in different tissues. Some cells activated caspase-3 during their normal development in every cell and in every animal without evidence of apoptosis. In other tissues, such as the brain, expression was sporadic both temporally and spatially and overlapped with periods of apoptosis. In adults, reporter expression was evident in a large fraction of cells in most tissues of every animal; however the precise patterns varied. Inhibition of caspase activity in wing discs reduced wing size demonstrating functional significance. The implications of these patterns are discussed. DOI: http://dx.doi.org/10.7554/eLife.10936.001 PMID:27058168

  15. Inferring parturition and neonate survival from movement patterns of female ungulates: a case study using woodland caribou

    PubMed Central

    DeMars, Craig A; Auger-Méthé, Marie; Schlägel, Ulrike E; Boutin, Stan

    2013-01-01

    Analyses of animal movement data have primarily focused on understanding patterns of space use and the behavioural processes driving them. Here, we analyzed animal movement data to infer components of individual fitness, specifically parturition and neonate survival. We predicted that parturition and neonate loss events could be identified by sudden and marked changes in female movement patterns. Using GPS radio-telemetry data from female woodland caribou (Rangifer tarandus caribou), we developed and tested two novel movement-based methods for inferring parturition and neonate survival. The first method estimated movement thresholds indicative of parturition and neonate loss from population-level data then applied these thresholds in a moving-window analysis on individual time-series data. The second method used an individual-based approach that discriminated among three a priori models representing the movement patterns of non-parturient females, females with surviving offspring, and females losing offspring. The models assumed that step lengths (the distance between successive GPS locations) were exponentially distributed and that abrupt changes in the scale parameter of the exponential distribution were indicative of parturition and offspring loss. Both methods predicted parturition with near certainty (>97% accuracy) and produced appropriate predictions of parturition dates. Prediction of neonate survival was affected by data quality for both methods; however, when using high quality data (i.e., with few missing GPS locations), the individual-based method performed better, predicting neonate survival status with an accuracy rate of 87%. Understanding ungulate population dynamics often requires estimates of parturition and neonate survival rates. With GPS radio-collars increasingly being used in research and management of ungulates, our movement-based methods represent a viable approach for estimating rates of both parameters. PMID:24324866

  16. Differential pattern of semantic memory organization between bipolar I and II disorders.

    PubMed

    Chang, Jae Seung; Choi, Sungwon; Ha, Kyooseob; Ha, Tae Hyon; Cho, Hyun Sang; Choi, Jung Eun; Cha, Boseok; Moon, Eunsoo

    2011-06-01

    Semantic cognition is one of the key factors in psychosocial functioning. The aim of this study was to explore the differences in pattern of semantic memory organization between euthymic patients with bipolar I and II disorders using the category fluency task. Study participants included 23 euthymic subjects with bipolar I disorder, 23 matched euthymic subjects with bipolar II disorder and 23 matched control subjects. All participants were assessed for verbal learning, recall, learning strategies, and fluency. The combined methods of hierarchical clustering and multidimensional scaling were used to compare the pattern of semantic memory organization among the three groups. Quantitative measures of verbal learning, recall, learning strategies, and fluency did not differ between the three groups. A two-cluster structure of semantic memory organization was identified for the three groups. Semantic structure was more disorganized in the bipolar I disorder group compared to the bipolar II disorder. In addition, patients with bipolar II disorder used less elaborate strategies of semantic memory organization than those of controls. Compared to healthy controls, strategies for categorization in semantic memory appear to be less knowledge-based in patients with bipolar disorders. A differential pattern of semantic memory organization between bipolar I and II disorders indicates a higher risk of cognitive abnormalities in patients with bipolar I disorder compared to patients with bipolar II disorder. Exploring qualitative nature of neuropsychological domains may provide an explanatory insight into the characteristic behaviors of patients with bipolar disorders.

  17. Disease characteristics, patterns of care, and survival in very elderly patients with diffuse large B-cell lymphoma.

    PubMed

    Williams, Jessica N; Rai, Ashish; Lipscomb, Joseph; Koff, Jean L; Nastoupil, Loretta J; Flowers, Christopher R

    2015-06-01

    Although the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients aged >80 years are less clear. The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to characterize presentation, treatment, and survival patterns in patients with DLBCL who were diagnosed between 2002 and 2009. Chi-square tests compared characteristics and initial treatments among patients with DLBCL who were aged >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients aged >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. Among 4635 patients with DLBCL, 1156 (25%) were aged >80 years. Patients aged >80 years were less likely to receive R-CHOP and more likely to be observed or receive the combination of rituximab, cyclophosphamide, vincristine, and prednisone (P<.0001 for both). Marital status, stage of disease, disease site, performance status, radiotherapy, and growth factor support were associated with initial R-CHOP in patients aged >80 years. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen found to be associated with improved overall survival (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62) and lymphoma-related survival (hazard ratio, 0.58; 95% confidence interval, 0.38-0.88). Although patients with DLBCL who were aged >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of treatment of DLBCL on quality of life among patients in

  18. Cat hindlimb motoneurons during locomotion. II. Normal activity patterns.

    PubMed

    Hoffer, J A; Sugano, N; Loeb, G E; Marks, W B; O'Donovan, M J; Pratt, C A

    1987-02-01

    Activity patterns were recorded from 51 motoneurons in the fifth lumbar ventral root of cats walking on a motorized treadmill at a range of speeds between 0.1 and 1.3 m/s. The muscle of destination of recorded motoneurons was identified by spike-triggered averaging of EMG recordings from each of the anterior thigh muscles. Forty-three motoneurons projected to one of the quadriceps (vastus medialis, vastus lateralis, vastus intermedius, or rectus femoris) or sartorius (anterior or medial) muscles of the anterior thigh. Anterior thigh motoneurons always discharged a single burst of action potentials per step cycle, even in multifunctional muscles (e.g., sartorius anterior) that exhibited more than one burst of EMG activity per step cycle. The instantaneous firing rates of most motoneurons were lowest upon recruitment and increased progressively during a burst, as long as the EMG was still increasing. Firing rates peaked midway through each burst and tended to decline toward the end of the burst. The initial, mean, and peak firing rates of single motoneurons typically increased for faster walking speeds. At any given walking speed, early recruited motoneurons typically reached higher firing rates than late recruited motoneurons. In contrast to decerebrated cats, initial doublets at the beginning of bursts were seen only rarely. In the 4/51 motoneurons that showed initial doublets, both the instantaneous frequency of the doublet and the probability of starting a burst with a doublet decreased for faster walking speeds. The modulations in firing rate of every motoneuron were found to be closely correlated to the smoothed electromyogram of its target muscle. For 32 identified motoneurons, the unit's instantaneous frequencygram was scaled linearly by computer to the rectified smoothed EMG recorded from each of the anterior thigh muscles. The covariance between unitary frequencygram and muscle EMG was computed for each muscle. Typically, the EMG profile of the target

  19. Temporal and spatial patterns in emergence and early survival of perennial plants in the Sonoran Desert

    USGS Publications Warehouse

    Bowers, Janice E.; Turner, R.M.; Burgess, T.L.

    2004-01-01

    Seedling emergence and survival of 15 perennial species were studied for six years in a 557-m2 permanent plot at Tumamoc Hill, Arizona, USA, an ungrazed site in the northern Sonoran Desert. The minimum rain required for germination and emergence ranged from 17.5 to 35.6 mm. Few species emerged in every year of the study. First-year survival averaged across all 15 species was 3.7%; only 0.1% of seedlings lived as long as four years. The odds of survival in the first year improved with increased rain. About three times as many seedlings died from predation as desiccation. In 2-m2 subplots, mortality of three woody species in the first 30 days after emergence appeared to be independent of seedling density. Short-, moderate-, and long-lived species displayed distinct survival strategies. Long-lived species compensated for generally poor seedling survival by frequent germination and emergence. Moderate-lived species exhibited highly episodic germination and emergence, a potentially risky behavior that might have been offset to some extent by relatively good long-term survival. Short-lived species had the highest seedling survival. Because these species can bloom in their first year, good early survival meant that some individuals were able to reproduce before they died.

  20. Wolbachia Has Two Different Localization Patterns in Whitefly Bemisia tabaci AsiaII7 Species

    PubMed Central

    Shi, Peiqiong; He, Zhan; Li, Shaojian; An, Xuan; Lv, Ning; Ghanim, Murad; Cuthbertson, Andrew G. S.; Ren, Shun-Xiang

    2016-01-01

    The whitefly Bemisia tabaci is a cosmopolitan insect species complex that harbors the obligate primary symbiont Portiera aleyrodidarum and several facultative secondary symbionts including Wolbachia, which have diverse influences on the host biology. Here, for the first time, we revealed two different localization patterns of Wolbachia present in the immature and adult stages of B. tabaci AsiaII7 cryptic species. In the confined pattern, Wolbachia was restricted to the bacteriocytes, while in the scattered pattern Wolbachia localized in the bacteriocytes, haemolymph and other organs simultaneously. Our results further indicated that, the proportion of B. tabaci AsiaII7 individuals with scattered Wolbachia were significantly lower than that of confined Wolbachia, and the distribution patterns of Wolbachia were not associated with the developmental stage or sex of whitefly host. This study will provide a new insight into the various transmission routes of Wolbachia in different whitefly species. PMID:27611575

  1. Wolbachia Has Two Different Localization Patterns in Whitefly Bemisia tabaci AsiaII7 Species.

    PubMed

    Shi, Peiqiong; He, Zhan; Li, Shaojian; An, Xuan; Lv, Ning; Ghanim, Murad; Cuthbertson, Andrew G S; Ren, Shun-Xiang; Qiu, Bao-Li

    2016-01-01

    The whitefly Bemisia tabaci is a cosmopolitan insect species complex that harbors the obligate primary symbiont Portiera aleyrodidarum and several facultative secondary symbionts including Wolbachia, which have diverse influences on the host biology. Here, for the first time, we revealed two different localization patterns of Wolbachia present in the immature and adult stages of B. tabaci AsiaII7 cryptic species. In the confined pattern, Wolbachia was restricted to the bacteriocytes, while in the scattered pattern Wolbachia localized in the bacteriocytes, haemolymph and other organs simultaneously. Our results further indicated that, the proportion of B. tabaci AsiaII7 individuals with scattered Wolbachia were significantly lower than that of confined Wolbachia, and the distribution patterns of Wolbachia were not associated with the developmental stage or sex of whitefly host. This study will provide a new insight into the various transmission routes of Wolbachia in different whitefly species.

  2. Relationship between necrotic patterns in glioblastoma and patient survival: fractal dimension and lacunarity analyses using magnetic resonance imaging.

    PubMed

    Liu, Shuai; Wang, Yinyan; Xu, Kaibin; Wang, Zheng; Fan, Xing; Zhang, Chuanbao; Li, Shaowu; Qiu, Xiaoguang; Jiang, Tao

    2017-08-16

    Necrosis is a hallmark feature of glioblastoma (GBM). This study investigated the prognostic role of necrotic patterns in GBM using fractal dimension (FD) and lacunarity analyses of magnetic resonance imaging (MRI) data and evaluated the role of lacunarity in the biological processes leading to necrosis. We retrospectively reviewed clinical and MRI data of 95 patients with GBM. FD and lacunarity of the necrosis on MRI were calculated by fractal analysis and subjected to survival analysis. We also performed gene ontology analysis in 32 patients with available RNA-seq data. Univariate analysis revealed that FD < 1.56 and lacunarity > 0.46 significantly correlated with poor progression-free survival (p = 0.006 and p = 0.012, respectively) and overall survival (p = 0.008 and p = 0.005, respectively). Multivariate analysis revealed that both parameters were independent factors for unfavorable progression-free survival (p = 0.001 and p = 0.015, respectively) and overall survival (p = 0.002 and p = 0.007, respectively). Gene ontology analysis revealed that genes positively correlated with lacunarity were involved in the suppression of apoptosis and necrosis-associated biological processes. We demonstrate that the fractal parameters of necrosis in GBM can predict patient survival and are associated with the biological processes of tumor necrosis.

  3. Identification of Gene Expression Pattern Related to Breast Cancer Survival Using Integrated TCGA Datasets and Genomic Tools

    PubMed Central

    Huang, Zhenzhen; Duan, Huilong; Li, Haomin

    2015-01-01

    Several large-scale human cancer genomics projects such as TCGA offered huge genomic and clinical data for researchers to obtain meaningful genomics alterations which intervene in the development and metastasis of the tumor. A web-based TCGA data analysis platform called TCGA4U was developed in this study. TCGA4U provides a visualization solution for this study to illustrate the relationship of these genomics alternations with clinical data. A whole genome screening of the survival related gene expression patterns in breast cancer was studied. The gene list that impacts the breast cancer patient survival was divided into two patterns. Gene list of each of these patterns was separately analyzed on DAVID. The result showed that mitochondrial ribosomes play a more crucial role in the cancer development. We also reported that breast cancer patients with low HSPA2 expression level had shorter overall survival time. This is widely different to findings of HSPA2 expression pattern in other cancer types. TCGA4U provided a new perspective for the TCGA datasets. We believe it can inspire more biomedical researchers to study and explain the genomic alterations in cancer development and discover more targeted therapies to help more cancer patients. PMID:26576432

  4. Identification of Gene Expression Pattern Related to Breast Cancer Survival Using Integrated TCGA Datasets and Genomic Tools.

    PubMed

    Huang, Zhenzhen; Duan, Huilong; Li, Haomin

    2015-01-01

    Several large-scale human cancer genomics projects such as TCGA offered huge genomic and clinical data for researchers to obtain meaningful genomics alterations which intervene in the development and metastasis of the tumor. A web-based TCGA data analysis platform called TCGA4U was developed in this study. TCGA4U provides a visualization solution for this study to illustrate the relationship of these genomics alternations with clinical data. A whole genome screening of the survival related gene expression patterns in breast cancer was studied. The gene list that impacts the breast cancer patient survival was divided into two patterns. Gene list of each of these patterns was separately analyzed on DAVID. The result showed that mitochondrial ribosomes play a more crucial role in the cancer development. We also reported that breast cancer patients with low HSPA2 expression level had shorter overall survival time. This is widely different to findings of HSPA2 expression pattern in other cancer types. TCGA4U provided a new perspective for the TCGA datasets. We believe it can inspire more biomedical researchers to study and explain the genomic alterations in cancer development and discover more targeted therapies to help more cancer patients.

  5. Impact of Systemic Therapy and Recurrence Pattern on Survival Outcome after Radiofrequency Ablation for Colorectal Liver Metastases

    PubMed Central

    Stang, Axel; Donati, Marcello; Weilert, Hauke; Oldhafer, Karl Jürgen

    2016-01-01

    Background: Most patients undergoing radiofrequency ablation (RFA) of colorectal liver metastasases (CLM) develop disease recurrence, but little is known about the effect of recurrence patterns and/or systemic therapy on outcome. In this study, we examined the recurrence patterns and survival after systemic therapy plus RFA in patients with unresectable CLM without extrahepatic disease. The aims were to analyze the effect of recurrence patterns on survival and to assess the relative benefit contributed by systemic therapy and local ablation to disease control and patient outcome. Methods: From January 2002 to December 2012, 113 patients underwent RFA of liver-limited CLM after systemic therapy. Univariate and multivariate analyses for associations between clinical and/or treatment-related variables, recurrence-free survival (RFS), recurrence patterns, and overall survival (OS) were carried out. Results: Of 113 patients, 105 (92.8%) had disease recurrence (median RFS: 6.1 months). Lower post-recurrence OS was observed after early (≤6 months) than after late recurrence (8.5 versus 24.0 months, p < 0.001). Recurrence sites were RFA-sites only (4.8%), liver-only (57.1%), lung-only (10.5%), or multiple (27.6%); the corresponding post-recurrence OS was 21, 19, 39, and 7 months (p < 0.001), respectively. Response to pre-RFA systemic therapy was the strongest predictor for OS (hazard ratio [HR] 5.28), RFS (HR 3.30), early (odds ratio [OR] 6.34) and multiple-site recurrence (OR 3.83) (p < 0.01), respectively; only responders achieved 5-year OS and RFS (29% and 12% versus 0% and 0% for non-responders, p < 0.001, respectively). Conclusions: Survival after RFA for liver-limited CLM is strongly linked to the timing and pattern of non-local disease recurrence. Local ablation efficacy is necessary but not sufficient to obtain long-term disease control. Effective pre-RFA systemic therapy does favourably affect the incidence, timing and patterns of recurrence and long

  6. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns

    SciTech Connect

    Altman, R.; Harrich, D.; Garcia, J.A. ); Gaynor, R.B. Wadsworth Veterans Hospital, Los Angeles, CA )

    1988-04-01

    Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, the authors performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses.

  7. Causes of mortality and temporal patterns in breeding season survival of lesser prairie-chickens in shinnery oak prairies

    USGS Publications Warehouse

    Grisham, Blake A.; Boal, Clint W.

    2015-01-01

    Baseline survival and mortality data for lesser prairie-chickens (Tympanuchus pallidicinctus) are lacking for shinnery oak (Quercus havardii) prairies. An understanding of the causes and timing of mortalities and breeding season survival in this ecoregion is important because shinnery oak prairies have hotter and drier environmental conditions, as well as different predator communities compared with the northern distribution of the species. The need for this information has become more pressing given the recent listing of the species as threatened under the U.S. Endangered Species Act. We investigated causes of mortality and survival of lesser prairie-chickens during the 6-month breeding season (1 Mar–31 Aug) of 2008–2011 on the Texas Southern High Plains, USA. We recorded 42 deaths of radiotagged individuals, and our results indicated female mortalities were proportionate among avian and mammalian predation and other causes of mortality but survival was constant throughout the 6-month breeding season. Male mortalities were constant across avian and mammalian predation and other causes, but more mortalities occurred in June compared with other months. Male survival also varied by month, and survival probabilities were lower in June–August. We found predation on leks was rare, mortalities from fence collisions were rare, female survival did not decrease during incubation or brood-rearing, and survival was influenced by drought. Our study corroborated recent studies that suggested lesser prairie-chickens are living at the edge of their physiological tolerances to environmental conditions in shinnery oak prairies. As such, lesser prairie-chickens in our study experienced different patterns of mortality and survival that we attributed to hot, dry conditions during the breeding season. Specifically, and converse to other studies on lesser prairie-chicken survival and mortality, drought positively influenced female survival because females did not incubate eggs

  8. β-Catenin Expression Pattern in Stage I and II Ovarian Carcinomas

    PubMed Central

    Gamallo, Carlos; Palacios, José; Moreno, Gema; Calvo de Mora, Jorge; Suárez, Asunción; Armas, Alvaro

    1999-01-01

    The immunohistochemical expression pattern of β-catenin has been correlated with β-catenin gene mutations, clinicopathological features, and disease outcome in 69 stage I and II ovarian carcinomas. β-Catenin expression was localized in the nuclei, in addition to the cytoplasm and membrane, in 11 tumors (16%): nine endometrioid carcinomas with widespread nuclear expression and two serous carcinomas with focal nuclear expression. The remaining 58 carcinomas (84%) only had membranous β-catenin expression. All but one of the endometrioid carcinomas with nuclear β-catenin expression had considerable squamous metaplasia, and five of these cases had large areas of endometrioid tumor of low malignant potential. In addition, β-catenin nuclear expression was observed in atypical epithelial cells in endometriotic glands adjacent to an endometrioid carcinoma. Sequencing was performed on 25 tumors and corresponding normal tissue: all 13 endometrioid tumors as well as 12 carcinomas of other histological types (four serous, two clear cell, two mucinous, and two mixed). There were oncogenic mutations in the phosphorylation sequence for GSK-3β in exon 3 of the β-catenin gene in seven endometrioid carcinomas with β-catenin nuclear expression. Three mutations affected codon 32 (D32G, D32Y, and D32Y), one affected codon 33 (S33C), two affected codon 37 (S37C and S37F), and one affected codon 41 (T41A). No mutations were observed in the other 18 carcinomas analyzed, comprising two endometrioid and two serous carcinomas with β-catenin nuclear expression, and 14 carcinomas of different histological types with only membranous expression. In the univariate and multivariate survival analyses, β-catenin nuclear expression was selected as an indicator of good prognosis, because no patient whose tumor expressed β-catenin in the nuclei showed relapses or died, in contrast to the 19 relapses and deaths among patients with tumors that only had β-catenin membranous expression

  9. Unplanned hospital readmissions after HeartMate II implantation: frequency, risk factors, and impact on resource use and survival.

    PubMed

    Smedira, Nicholas G; Hoercher, Katherine J; Lima, Brian; Mountis, Maria M; Starling, Randall C; Thuita, Lucy; Schmuhl, Darlene M; Blackstone, Eugene H

    2013-02-01

    The purpose of this study was to identify potential areas for quality improvement and cost containment. We investigated readmissions after HeartMate II left ventricular assist device (LVAD) implantation by characterizing their type, temporal frequency, causative factors, and resource use and survival after readmission. The HeartMate II LVAD provides enhanced survival and quality of life to end-stage heart failure patients. Whether these improved outcomes are accompanied by a similar reduction in unplanned hospital readmissions is largely unknown. From October 2004 to January 2010, 118 patients received a HeartMate II, of whom 92 were discharged on device support. Subsequent readmissions were analyzed using prospectively maintained clinical and financial databases. Forty-eight patients (52%) had 177 unplanned hospital readmissions, 87 non-LVAD- and 90 LVAD-associated. Reasons for non-LVAD-associated readmissions included medical management of comorbidities and progression of cardiac pathology (n = 48), neuropsychiatric/psychosocial issues (n = 22), and infections (n = 17). Those for LVAD-associated readmissions included device component infection (n = 51), management of nontherapeutic anticoagulation or device malfunction (n = 22), and bleeding (n = 15). Cumulative incidence of unplanned readmissions was higher (p < 0.0001) for destination therapy than bridge-to-transplant patients (9/patient vs. 4/patient at 24 months). Cumulative hospital days overall were 25 and 42 at 12 and 18 months, respectively, and the costs were 18% and 29% of initial implantation costs. Increased number of unplanned readmissions was predictive of mortality. Unplanned readmissions are common during HeartMate II support and negatively affect resource use and survival. Refining patient selection, especially in destination therapy patients, reducing infectious and bleeding complications, and increasing awareness about these devices might reduce unnecessary readmissions. Copyright

  10. (1)H MRSI and progression-free survival in patients with WHO grades II and III gliomas.

    PubMed

    Hattingen, Elke; Delic, Oliver; Franz, Kea; Pilatus, Ulrich; Raab, Peter; Lanfermann, Heinrich; Gerlach, Rüdiger

    2010-07-01

    To evaluate if metabolic changes in WHO grades II and III gliomas measured in vivo with proton magnetic resonance spectroscopic imaging ((1)H-MRSI) correlate with progression-free survival (PFS). (1)H-MRSI and MRI were performed before surgery in 61 patients with histopathological proven WHO grades II and III gliomas. Averaged (av) and maximum (max) metabolite concentrations of creatine/phosphocreatine (tCr) and choline-containing compounds (tCho) from the tumor were normalized to contralateral brain tissue. In 50 patients with a median follow-up of 34 (WHO grade II) and 19.5 (WHO grade III) months, spectroscopic data as well as the extent of tumor resection, histopathological subtype, adjuvant therapy and patients' ages were analysed for PFS times with Cox regression analysis. Kaplan-Meier method was performed with categorized tCr values (cutoff: 0.93) to estimate the median PFS time. The normalized tCr(av) was prognostic for the PFS in patients with WHO grades II and III gliomas (p<0.0001 and p=0.034, respectively). For WHO grade II gliomas, tCr(max) (p=0.008) and the patients' ages (p=0.006) were also prognostic. The multivariate analysis provided tCr(av) (p=0.001) as single independent prognostic factor for the PFS of WHO grade II gliomas. Patients with WHO grades II and III gliomas revealing a normalized tCr(av) greater than 0.93 had a significant shorter PFS. Potential tumor progression in WHO grades II and III gliomas is best indicated by the normalized tCr(av). Normalized tCr(av) >0.93 seems to indicate gliomas with earlier progression.

  11. Molecules and dust in Cassiopeia A. II. Dust sputtering and diagnosis of supernova dust survival in remnants

    NASA Astrophysics Data System (ADS)

    Biscaro, Chiara; Cherchneff, Isabelle

    2016-05-01

    We study the dust evolution in the supernova remnant Cassiopeia A. We follow the processing of dust grains that formed in the Type II-b supernova ejecta by modelling the sputtering of grains. The dust is located in dense ejecta clumps that are crossed by the reverse shock. We also investigate further sputtering in the inter-clump medium gas once the clumps have been disrupted by the reverse shock. The dust evolution in the dense ejecta clumps of Type II-P supernovae and their remnants is also explored. We study oxygen-rich clumps that describe the oxygen core of the ejecta, and carbon-rich clumps that correspond to the outermost carbon-rich ejecta zone. We consider the various dust components that form in the supernova, several reverse shock velocities and inter-clump gas temperatures, and derive grain-size distributions and masses for the dust as a function of time. Both non-thermal sputtering within clumps and thermal sputtering in the inter-clump medium gas are studied. We find that non-thermal sputtering in the clumps is important for all supernova types and accounts for reducing the grain population by ~ 40% to 80% in mass, depending on the clump gas over-density, the grain type and size, and the shock velocity in the clump. A Type II-b SN forms small grains that are sputtered within the clumps and in the inter-clump medium. For Cas A, silicate grains do not survive thermal sputtering in the inter-clump medium, while alumina, silicon carbide, and carbon dust may survive in the remnant. Our derived masses of currently processed silicate, alumina and carbon grains agree well with the values derived from the observations of warm dust, and seem to indicate that the dust is currently being processed within clumps by non-thermal sputtering. Out of the ~ 0.03M⊙ of dust formed in the ejecta, between 30% and 60% of this mass is present today in Cas A, and only 6% to 11% of the initial mass will survive the remnant phase. Grains formed in Type II-P supernovae are

  12. Treatment Patterns, Survival, and Healthcare Costs of Patients with Malignant Gliomas in a Large US Commercially Insured Population

    PubMed Central

    Ray, Saurabh; Bonafede, Machaon M.; Mohile, Nimish A.

    2014-01-01

    Background Glioblastoma multiforme is the most common malignant primary brain tumor in adults and is associated with poor survival rates. Symptoms often include headaches; nausea and vomiting; and progressive memory, personality, or neurologic deficits. The treatment remains a challenge, and despite the approval of multiple new therapies in the past decade, survival has not improved. Objective To describe treatment patterns, survival, and healthcare costs of patients with incident glioblastoma in a large US population. Methods For this population-based study, adult patients (aged ≥18 years) with incident malignant brain neoplasm who had undergone brain surgery between January 1, 2006, and December 31, 2010, were identified in the Truven Health Analytics MarketScan Research Databases. The patients were stratified into 4 cohorts based on the use of temozolomide and/or external beam radiation therapy within 90 days after brain surgery (ie, the index event). Treatment patterns, survival, and healthcare costs were assessed until patient death, disenrollment, or the end-of-study period. Results A total of 2272 patients met the inclusion criteria; of these, 37% received temozolomide and radiation therapy, 13.8% received radiation alone, 3.9% received temozolomide alone, and 45.3% of patients received neither. The average patient age ranged from 55.3 years to 59.8 years across the study cohorts; between 29.8% and 44% of patients in each cohort were female. The duration of temozolomide use was similar between the temozolomide-only cohort and patients receiving temozolomide with external beam radiation; approximately 76% of patients received temozolomide at least 60 days, dropping to 48.1% and 23% at 180 days and 360 days of follow-up, respectively. The median survival was 456 days, ranging from 331 days in the temozolomide-only cohort to 529 days in the cohort that received neither temozolomide nor external beam radiation. The average total costs in the 6 months postindex

  13. Treatment patterns and survival analysis in 9014 patients with malignant pleural mesothelioma from Belgium, the Netherlands and England.

    PubMed

    Damhuis, R A; Khakwani, A; De Schutter, H; Rich, A L; Burgers, J A; van Meerbeeck, J P

    2015-08-01

    Pleural mesothelioma has a dismal prognosis and is refractory to local treatment. Combination chemotherapy can increase median survival by several months and was gradually introduced in the period 2003-2006. Elderly patients may be unfit for chemotherapy but little is known about age-related treatment practice. To determine treatment patterns and current survival outcome, three large population-based registries were queried in a uniform manner. Data from the Belgian Cancer Registry, the Netherlands Cancer Registry and the UK National Lung Cancer Audit were analyzed for patients diagnosed with pleural mesothelioma since 2007. Treatment patterns and survival rates were compared between countries and age-groups. The study included 900, 2306 and 5808 patients from Belgium, the Netherlands and England, respectively. Fifty-nine percent of patients were 70 years or older and 84% were men. Chemotherapy use decreased with advancing age and was used more often in Belgium (60%) than in the Netherlands (41%) and England (37%). For patients aged 70-79 years, chemotherapy use was 55%, 36% and 34% in the respective countries. Median survival was 10.7 months in Belgium versus 9.2 months for the Netherlands and 9.5 months for England. Survival rates decreased with advancing age. On average, median survival was 5.6 months longer for patients treated with chemotherapy, irrespective of age. Combined analysis of data from three countries with high mesothelioma rates demonstrates that chemotherapy has become standard treatment for younger patients. Elderly patients currently account for more than half of all cases and less toxic treatment options will be required to improve their prospects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Patterns of coho salmon size and survival within a stream network

    EPA Science Inventory

    Effective habitat restoration planning requires correctly anticipating demographic responses to altered habitats. Network-scale investigations of habitat-specific growth and survival of juvenile salmonids have provided critical insights that can now better inform and help priori...

  15. Patterns of coho salmon size and survival within a stream network

    EPA Science Inventory

    Effective habitat restoration planning requires correctly anticipating demographic responses to altered habitats. Network-scale investigations of habitat-specific growth and survival of juvenile salmonids have provided critical insights that can now better inform and help priori...

  16. Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival.

    PubMed

    Pfleger, J; He, M; Abdellatif, M

    2015-07-30

    The survival of a cell depends on its ability to meet its energy requirements. We hypothesized that the mitochondrial reserve respiratory capacity (RRC) of a cell is a critical component of its bioenergetics that can be utilized during an increase in energy demand, thereby, enhancing viability. Our goal was to identify the elements that regulate and contribute to the development of RRC and its involvement in cell survival. The results show that activation of metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism. Notably, we identified mitochondrial complex II (cII) as a target of these metabolic sensors and the main source of RRC. Moreover, we show that RRC, via cII, correlates with enhanced cell survival after hypoxia. Thus, for the first time, we show that metabolic sensors via Sirt3 maximize the cellular RRC through activating cII, which enhances cell survival after hypoxia.

  17. Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival

    PubMed Central

    Pfleger, J; He, M; Abdellatif, M

    2015-01-01

    The survival of a cell depends on its ability to meet its energy requirements. We hypothesized that the mitochondrial reserve respiratory capacity (RRC) of a cell is a critical component of its bioenergetics that can be utilized during an increase in energy demand, thereby, enhancing viability. Our goal was to identify the elements that regulate and contribute to the development of RRC and its involvement in cell survival. The results show that activation of metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism. Notably, we identified mitochondrial complex II (cII) as a target of these metabolic sensors and the main source of RRC. Moreover, we show that RRC, via cII, correlates with enhanced cell survival after hypoxia. Thus, for the first time, we show that metabolic sensors via Sirt3 maximize the cellular RRC through activating cII, which enhances cell survival after hypoxia. PMID:26225774

  18. Survival patterns in lung and pleural cancer in Europe 1999-2007: Results from the EUROCARE-5 study.

    PubMed

    Francisci, Silvia; Minicozzi, Pamela; Pierannunzio, Daniela; Ardanaz, Eva; Eberle, Andrea; Grimsrud, Tom K; Knijn, Arnold; Pastorino, Ugo; Salmerón, Diego; Trama, Annalisa; Sant, Milena

    2015-10-01

    Survival of patients diagnosed with lung and pleura cancer is a relevant health care indicator which is related to the availability and access to early diagnosis and treatment facilities. Aim of this paper is to update lung and pleural cancer survival patterns and time trends in Europe using the EUROCARE-5 database. Data on adults diagnosed with lung and pleural cancer from 87 European cancer registries in 28 countries were analysed. Relative survival (RS) in 2000-2007 by country/region, age and gender, and over time trends in 1999-2007 were estimated. Lung cancer survival is poor everywhere in Europe, with a RS of 39% and 13% at 1 and 5years since diagnosis, respectively. A geographical variability is present across European areas with a maximum regional difference of 12 and 5 percentage points in 1-year and 5-year RS respectively. Pleural cancer represents 4% of cases included in the present study with 7% 5-year RS overall in Europe. Most pleural cancers (83%) are microscopically verified mesotheliomas. Survival for both cancers decreases with advancing age at diagnosis for both cancers. Slight increasing trends are described for lung cancer. Survival over time is higher for squamous cell carcinoma and adenocarcinomas than for small and large cell carcinoma; and better among women than men. Despite the generalised although slight increase, survival of lung and pleural cancer patients still remains poor in European countries. Priority should be given to prevention, with tobacco control policies across Europe for lung cancer and banning asbestos exposure for pleural cancer, and in early diagnosis and better treatment. The management of mesothelioma needs a multidisciplinary team and standardised health care strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. The anatomic pattern of biliary atresia identified at time of Kasai hepatoportoenterostomy and early postoperative clearance of jaundice are significant predictors of transplant-free survival

    PubMed Central

    Superina, Riccardo; Magee, John C.; Brandt, Mary L.; Healey, Patrick J.; Tiao, Greg; Ryckman, Fred; Karrer, Frederick M; Iyer, Kishore; Fecteau, Annie; West, Karen; Burns, R. Cartland; Flake, Alan; Lee, Hanmin; Lowell, Jeff A.; Dillon, Pat; Colombani, Paul; Ricketts, Richard; Li, Yun; Moore, Jeffrey; Wang, Kasper S.

    2012-01-01

    Objective The goals of this study were to describe the clinical and anatomic features of infants undergoing Kasai portoenterostomy (KPE) for biliary atresia (BA), and to examine associations between these parameters and outcomes. Methods Infants enrolled in the prospective Childhood Liver Disease Research and Education Network, who underwent KPE were studied. Patients enrolled in a blinded, interventional trial were excluded from survival analysis. Primary end-points were successful surgical drainage (total bilirubin less than 2 mg/dL within the first three months), transplant-free survival (Kaplan-Meier), and time to transplant/death (Cox regression). Results KPE was performed in 244 infants (54% female; mean age 65± 29 days). Transplant-free survival was 53.7% and 46.7% at 1 and 2 years post-KPE. The risk of transplant/death was significantly lower in the 45.6% of patients who achieved successful bile drainage within 3 months post-KPE (HR 0.08, p<0.001). The risk of transplant/death was increased in patients with porta hepatis atresia (Ohi Type II and III vs. Type I; HR 2.03, p=0.030), non-patent common bile duct (Ohi Subtype b, c, and d vs. a; HR 4.31, p=0.022), BA splenic malformation syndrome (HR 1.92, p=0.025), ascites > 20 ml (HR=1.90, p=0.0230), nodular liver appearance compared to firm (HR=1.61, p=0.008), and age at KPE ≥ 75 days (HR 1.73, p<0.002). Outcome was not associated with gestational age, gender, race, ethnicity, or extent of porta hepatis dissection. Conclusion Anatomic pattern of BA, BASM, presence of ascites and nodular liver appearance at KPE, and early postoperative jaundice clearance are significant predictors of transplant-free survival. PMID:21869674

  20. Knockdown of cytosolic 5'-nucleotidase II (cN-II) reveals that its activity is essential for survival in astrocytoma cells.

    PubMed

    Careddu, Maria Giovanna; Allegrini, Simone; Pesi, Rossana; Camici, Marcella; Garcia-Gil, Mercedes; Tozzi, Maria Grazia

    2008-08-01

    IMP preferring cytosolic 5'-nucleotidase (cN-II) is an ubiquitous nucleotide hydrolysing enzyme. The enzyme is widely distributed and its amino acid sequence is highly conserved among vertebrates. Fluctuations of cN-II activity have been associated with the pathogenesis of neurological disorders. The enzyme appears to be involved in the regulation of the intracellular availability of the purine precursor IMP and also of GMP and AMP, but the contribution of this activity and of its regulation to cell metabolism and to CNS cell functions remains uncertain. To address this issue, we used a vector based short hairpin RNA (shRNA) strategy to knockdown cN-II activity in human astrocytoma cells. Our results demonstrated that 53 h after transduction, cN-II mRNA was reduced to 17.9+/-0.03% of control cells. 19 h later enzyme activity was decreased from 0.7+/-0.026 mU/mg in control ADF cells to 0.45+/-0.046 mU/mg, while cell viability (evaluated by the MTT reduction assay) decreased up to 0.59+/-0.01 (fold vs control) and caspase 3 activity increased from 136+/-5.8 pmol min(-1) mg(-1) in control cells to 639+/-37.5 pmol min(-1) mg(-1) in silenced cells, thus demonstrating that cN-II is essential for cell survival. The decrease of enzyme activity causes apoptosis of the cultured cells without altering intracellular nucleotide and nucleoside concentration or energy charge. Since cN-II is highly expressed in tumour cells, our finding offers a new possible therapeutical approach especially against primary brain tumours such as glioblastoma, and to ameliorate chemotherapy against leukemia.

  1. Squamous-cell carcinoma of the tongue: preoperative interstitial radium and external irradiation. Part II. Survival

    SciTech Connect

    Vermund, H.; Breenhovd, I.O.; Kaalhus, O.; Poppe, E.

    1984-05-01

    The authors evaluated 300 cases of squamous-cell carcinoma of the anterior two thirds of the tongue treated from 1958 through 1972. Effects of treament on absolute and relative survival were determined by the log rank method. Selection was non-random, based on the extent of the primary tumor, age and general condition. Surgery, irradiation, or a combination of preoperative interstitial high-intensity radium needles and resection gave similar results in patients with tumor smaller than 4 cm. In patients with larger tumor or mobile, unilateral neck metastases, irradiation plus surgery produced better survival than irradiation alone. Different radiation techniques are analyzed.

  2. Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.

    PubMed

    Salisbury, Margaret L; Tolle, Leslie B; Xia, Meng; Murray, Susan; Tayob, Nabihah; Nambiar, Anoop M; Schmidt, Shelley L; Lagstein, Amir; Myers, Jeffery L; Gross, Barry H; Kazerooni, Ella A; Sundaram, Baskaran; Chughtai, Aamer R; Martinez, Fernando J; Flaherty, Kevin R

    2017-10-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF. Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival. IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p = 0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR = 0.42, CI 95% 0.23-0.78, p = 0.006). Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

    SciTech Connect

    Koshy, Matthew; Rich, Shayna E.; Mahmood, Usama; Kwok, Young

    2012-02-01

    Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used to analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.

  4. Single-Arm Phase II Group Sequential Trial Design with Survival Endpoint at a Fixed Time Point.

    PubMed

    Wu, Jianrong; Xiong, Xiaoping

    2014-01-01

    In this paper, three non-parametric test statistics are proposed to design single-arm phase II group sequential trials for monitoring survival probability. The small-sample properties of these test statistics are studied through simulations. Sample size formulas are derived for the fixed sample test. The Brownian motion property of the test statistics allowed us to develop a flexible group sequential design using a sequential conditional probability ratio test procedure (Xiong, 1995). An example is given to illustrate the trial design by using the proposed method.

  5. Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

    PubMed Central

    Williams, Jessica N.; Rai, Ashish; Lipscomb, Joseph; Koff, Jean L.; Nastoupil, Loretta J.; Flowers, Christopher R.

    2015-01-01

    Background Although rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered standard therapy for diffuse large B-cell lymphoma (DLBCL), patterns of use and the impact of R-CHOP on survival in patients >80 years are less clear. Methods We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to characterize presentation, treatment, and survival patterns in DLBCL patients diagnosed from 2002–2009. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and ≤80 years. Multivariable logistic regression models examined factors associated with treatment selection in patients >80 years; standard and propensity score-adjusted multivariable Cox proportional hazards models examined relationships between treatment regimen, treatment duration, and survival. Results Among 4,635 patients with DLBCL, 1,156 (25%) were >80 years. Patients >80 were less likely to receive R-CHOP and more likely to be observed or receive rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); both p<0.0001. Marital status, stage, disease site, performance status, radiation therapy, and growth factor support were associated with initial R-CHOP in patients >80. In propensity score-matched multivariable Cox proportional hazards models examining relationships between treatment regimen and survival, R-CHOP was the only regimen associated with improved OS (hazard ratio (HR) = 0.45, 95% confidence interval (CI) = 0.33–0.62) and LRS (HR=0.58, 95% CI 0.38–0.88). Conclusions Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the longest survival and should be considered for this population. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in this age group. PMID:25675909

  6. [Biphasic effect of angiotensin II on conditioned reflectory reaction patterns in albino rats].

    PubMed

    Hecht, K; Hecht, T; Poppei, M; Treptow, K; Choinowski, S; Nitschkoff, S

    1975-01-01

    40 male albino rats were used to investigate the influence of one single i. v. dose of 10 ng/kg Angiotensin II upon established and stabilized conditional-reflectory response pattern (two-dimensional conditional-reflectory decision process and periodicities of conditional-reflectory processes). At normotonous blood-pressure values, Angiotensin II exerted a biphasic action on the conditional-reflectory response pattern. In the first phase of action (up to 30 min after injection) there prevailed centralnervous inhibition processes, while the second phase of action (30-70 min after injection) was marked by a general centralnervous excitation, which is reflected by extremely short times of response, and a pronounced sensitivity to optic, acoustic and tactile stimuli. The decision capacity of the animals was considerably reduced in both phases. The periodicities of conditional-reflectory processes (duration of periods in the minute range) are strongly disturbed in the first phase of action, and tend to normal in the second phase. Furthermore, Angiotensin II was found to have a selective, hierarchically ordered influence with regard to the duration and intensity of action. Thus, the information processing activity of the CNS underwent most pronounced changes. The centralnervous regulatory functions were less affected; the blood pressure regulation showed little and transient influence by Angiotensin II. In the discussion, the neurotropic and algogenic action of Angiotensin II, and the relation of the octapeptide effect with pathogenetic mechanisms of experimental neurotically induced hypertonia are dealt with.

  7. Population ecology of the mallard VIII: Winter distribution patterns and survival rates of winter-banded mallards

    USGS Publications Warehouse

    Nichols, James D.; Hines, James E.

    1987-01-01

    In the present report we address questions about winter distribution patterns and survival rates of North American mallards Anas platyrhynchos. Inferences are based on analyses of banding and recovery data from both winter and preseason banding period. The primary wintering range of the mallard was dividded into 45 minor reference areas and 15 major reference areas which were used to summarize winter banding data. Descriptive tables and figures on the recovery distributions of winter-banded mallards are presented. Using winter recoveries of preseason-banded mallards, we found apparent differences between recovery distribution of young versus adult birds from the same breeding ground reference areas. However, we found no sex-specific differences in winter recovery distribution patterns. Winter recovery distributions of preseason-banded birds also provided evidence that mallards exhibited some degree of year-to-year variation in wintering ground location. The age- and sex-specificity of such variation was tested using winter recoveries of winter-banded birds, and results indicated that subadult (first year) birds were less likely to return to the same wintering grounds the following year than adults. Winter recovery distributions of preseason-banded mallards during 1950-58 differed from distributions in 1966-76. These differences could have resulted from either true distributional shifts or geographic changes in hunting pressure. Survival and recovery rates were estimated from winter banding data. We found no evidence of differences in survival or recovery rates between subadult and adult mallards. Thus, the substantial difference between survival rates of preseason-banded young and adult mallards must result almost entirely from higher mortality of young birds during the approximate period, August-January. Male mallards showed higher survival than females, corroborating inferences based on preseason data. Tests with winter banding and band recovery data indicated

  8. Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast.

    PubMed

    Hills, Frank A; Mehmet, Huseyin; Sullivan, Mark H

    2012-07-01

    This study aimed to determine the effects of insulin-like growth factors (IGF-I and IGF-II), heparin, aspirin and vitamin C on the proliferation and apoptosis of human villous cytotrophoblast from first trimester and term placentae. Villous cytotrophoblast cells were isolated from uncomplicated first trimester (n=12) and term placental tissues (n=12) using negative immunoselection with an antibody to HLA class I antigens. Cells were incubated with IGF-I, IGF-II, heparin, aspirin and vitamin C either alone, or in combination with either TNF-α/IFN-γ or staurosporine. Proliferation was determined by measurement of Ki67 expression using immunocytochemistry. Trophoblast apoptosis was determined by TUNEL staining. Finally RT-PCR was carried out to identify IGF-binding insulin receptor isoforms. Data were expressed as means±SEM. One way analysis of variance (ANOVA) with Bonferroni correction was used to determine if differences between groups were statistically significant. Following negative immunoselection >98% of cells were positively stained for cytokeratin 7, a marker for cytotrophoblasts, and <1% were vimentin positive. First trimester and term trophoblasts underwent spontaneous apoptosis which was inhibited by approximately 50% in the presence of IGF-II or heparin. Apoptosis was significantly increased following incubation with a combination of TNF-α and IFN-γ or staurosporine. Apoptosis was decreased to basal levels following coincubation with IGF-II or heparin. Incubation with IGFs or heparin resulted in a small, but significant increase in Ki67 expression. Insulin receptor isoform A, which binds IGF-II with high affinity, was present in all trophoblast samples tested. These results suggest that heparin and IGF-II, but not IGF-I are important regulators of villous cytotrophoblast survival in early and late pregnancy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Treatment patterns and survival in patients with ALK-positive non-small-cell lung cancer: a Canadian retrospective study

    PubMed Central

    Kayaniyil, S.; Hurry, M.; Wilson, J.; Wheatley-Price, P.; Melosky, B.; Rothenstein, J.; Cohen, V.; Koch, C.; Zhang, J.; Osenenko, K.; Liu, G.

    2016-01-01

    Background Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase (ALK)–positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib. However, patients eventually progress or develop resistance to crizotinib. With limited real-world data available, the objective of the present work was to evaluate treatment patterns and survival after crizotinib in patients with locally advanced or metastatic ALK+ nsclc in Canada. Methods In this retrospective study at 6 oncology centres across Canada, medical records of patients with locally advanced or metastatic ALK+ nsclc were reviewed. Demographic and clinical characteristics, treatments, and outcomes data were abstracted. Analyses focused on patients who discontinued crizotinib treatment. Results Of the 97 patients included, 9 were crizotinib-naïve, and 39 were still receiving crizotinib at study end. The 49 patients who discontinued crizotinib treatment were included in the analysis. Of those 49 patients, 43% received ceritinib at any time, 20% subsequently received systemic chemotherapy only (but never ceritinib), and 37% received no further treatment or died before receiving additional treatment. Median overall survival from crizotinib discontinuation was shorter in patients who did not receive ceritinib than in those who received ceritinib (1.7 months vs. 20.4 months, p < 0.001). In a multivariable analysis, factors associated with poorer survival included lack of additional therapies (particularly ceritinib), male sex, and younger age, but not smoking status; patients of Asian ethnicity showed a nonsignificant trend toward improved survival. Conclusions A substantial proportion of patients with ALK+ nsclc received no further treatment or died before receiving additional treatment after crizotinib. Treatment with systemic agents was associated with improved survival, with ceritinib use being associated with the longest survival. PMID:28050149

  10. Effects of drought on western pond turtle survival and movement patterns

    Treesearch

    Kathryn L. Purcell; Eric L. McGregor; Kathryn Calderala

    2017-01-01

    Drought has the ability to affect the persistence of small animal populations, especially those tied to aquatic habitats. We studied the response of western pond turtles Actinemys marmorata to California's worst drought on record. From 2009 through 2015 we used telemetry to track movements and assess survival of 19 western...

  11. Survival Patterns in Elderly Head and Neck Squamous Cell Carcinoma Patients Treated With Definitive Radiation Therapy.

    PubMed

    Sommers, Linda W; Steenbakkers, Roel J H M; Bijl, Henk P; Vemer-van den Hoek, Johanna G M; Roodenburg, Jan L N; Oosting, Sjoukje F; Halmos, Gyorgy B; de Rooij, Sophia E; Langendijk, Johannes A

    2017-07-15

    We sought to assess the effect of age on overall survival (OS), cancer-specific survival (CSS), and non-cancer-related death (NCRD) in elderly (aged ≥70 years) head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radiation therapy. The results were compared with those of younger patients, and the most important prognostic factors for survival endpoints were determined. Treatments may be better justified based on identification of the main differences in survival between young and elderly patients. Data were analyzed from all consecutive HNSCC patients treated with definitive radiation therapy (66-70 Gy) in our department between April 2007 and December 2014. A total of 674 patients, including 168 elderly patients (24.9%), were included in the study. Multivariate association models were constructed to assess the effect of age on survival endpoints. Multivariate analysis was performed to identify potential prognostic factors for survival in elderly patients. A total of 674 consecutive patients, including 168 elderly patients, were analyzed. The 5-year OS and NCRD rates were significantly worse for elderly patients than for young patients: 45.5% versus 58.2% (P=.007) and 39.0% versus 20.7% (P<.001), respectively. In the multivariate association analysis on the relationship between age and OS, lymph node involvement and worse World Health Organization (WHO) performance status were identified as significant confounders. Multivariate association analysis between age and NCRD identified Union for International Cancer Control stage as a significant confounder. After correction for confounders, the effect of age on OS and NCRD increased. Worse WHO performance status, lymph node involvement, and specific tumor site were independent prognostic factors for OS and CSS in the elderly patient group. Of the elderly patients, 80 (47%) died during follow-up; 45% of these deaths were ascribed to the index tumor. For elderly patients, radiation therapy

  12. Sex- and age-dependent patterns of survival and breeding success in a long-lived endangered avian scavenger

    NASA Astrophysics Data System (ADS)

    Sanz-Aguilar, Ana; Cortés-Avizanda, Ainara; Serrano, David; Blanco, Guillermo; Ceballos, Olga; Grande, Juan M.; Tella, José L.; Donázar, José A.

    2017-01-01

    In long-lived species, the age-, stage- and/or sex-dependent patterns of survival and reproduction determine the evolution of life history strategies, the shape of the reproductive value, and ultimately population dynamics. We evaluate the combined effects of age and sex in recruitment, breeder survival and breeding success of the globally endangered Egyptian vulture (Neophron percnopterus), using 31-years of exhaustive data on marked individuals in Spain. Mean age of first reproduction was 7-yrs for both sexes, but females showed an earlier median and a larger variance than males. We found an age-related improvement in breeding success at the population level responding to the selective appearance and disappearance of phenotypes of different quality but unrelated to within-individual aging effects. Old males (≥8 yrs) showed a higher survival than both young males (≤7 yrs) and females, these later in turn not showing aging effects. Evolutionary trade-offs between age of recruitment and fitness (probably related to costs of territory acquisition and defense) as well as human-related mortality may explain these findings. Sex- and age-related differences in foraging strategies and susceptibility to toxics could be behind the relatively low survival of females and young males, adding a new concern for the conservation of this endangered species.

  13. Sex- and age-dependent patterns of survival and breeding success in a long-lived endangered avian scavenger.

    PubMed

    Sanz-Aguilar, Ana; Cortés-Avizanda, Ainara; Serrano, David; Blanco, Guillermo; Ceballos, Olga; Grande, Juan M; Tella, José L; Donázar, José A

    2017-01-11

    In long-lived species, the age-, stage- and/or sex-dependent patterns of survival and reproduction determine the evolution of life history strategies, the shape of the reproductive value, and ultimately population dynamics. We evaluate the combined effects of age and sex in recruitment, breeder survival and breeding success of the globally endangered Egyptian vulture (Neophron percnopterus), using 31-years of exhaustive data on marked individuals in Spain. Mean age of first reproduction was 7-yrs for both sexes, but females showed an earlier median and a larger variance than males. We found an age-related improvement in breeding success at the population level responding to the selective appearance and disappearance of phenotypes of different quality but unrelated to within-individual aging effects. Old males (≥8 yrs) showed a higher survival than both young males (≤7 yrs) and females, these later in turn not showing aging effects. Evolutionary trade-offs between age of recruitment and fitness (probably related to costs of territory acquisition and defense) as well as human-related mortality may explain these findings. Sex- and age-related differences in foraging strategies and susceptibility to toxics could be behind the relatively low survival of females and young males, adding a new concern for the conservation of this endangered species.

  14. Sex- and age-dependent patterns of survival and breeding success in a long-lived endangered avian scavenger

    PubMed Central

    Sanz-Aguilar, Ana; Cortés-Avizanda, Ainara; Serrano, David; Blanco, Guillermo; Ceballos, Olga; Grande, Juan M.; Tella, José L.; Donázar, José A.

    2017-01-01

    In long-lived species, the age-, stage- and/or sex-dependent patterns of survival and reproduction determine the evolution of life history strategies, the shape of the reproductive value, and ultimately population dynamics. We evaluate the combined effects of age and sex in recruitment, breeder survival and breeding success of the globally endangered Egyptian vulture (Neophron percnopterus), using 31-years of exhaustive data on marked individuals in Spain. Mean age of first reproduction was 7-yrs for both sexes, but females showed an earlier median and a larger variance than males. We found an age-related improvement in breeding success at the population level responding to the selective appearance and disappearance of phenotypes of different quality but unrelated to within-individual aging effects. Old males (≥8 yrs) showed a higher survival than both young males (≤7 yrs) and females, these later in turn not showing aging effects. Evolutionary trade-offs between age of recruitment and fitness (probably related to costs of territory acquisition and defense) as well as human-related mortality may explain these findings. Sex- and age-related differences in foraging strategies and susceptibility to toxics could be behind the relatively low survival of females and young males, adding a new concern for the conservation of this endangered species. PMID:28074860

  15. Harsh social conditions and perinatal survival: an age-period-cohort analysis of the World War II occupation of Norway.

    PubMed

    Wilcox, A J; Skjaerven, R; Irgens, L M

    1994-09-01

    The hypothesis was tested that unfavorable social conditions are associated with poor perinatal survival through direct effects on pregnancy or, more indirectly, through effects on mothers born under such conditions. The occupation of Norway by Nazi Germany was used as a period of social hardship. Data from Norwegian vital statistics and the Medical Birth Registry were used to describe perinatal mortality during World War II and also a generation later, among babies born to mothers who had themselves been born during the war. Logistic regression was used to identify a possible cohort effect among mothers born in 1940 through 1944 compared with mothers born before or after that period. Harsh conditions in Norway during the occupation increased childhood mortality. However, perinatal mortality declined during that period. Likewise, no adverse effect was seen on the survival of babies born to mothers who had themselves been born during the war (odds ratio = 1.00; 95% confidence interval = 0.96, 1.04). We find no evidence that wartime conditions in Norway impaired perinatal survival, either directly or through an effect on women born during the war. These data underscore how little is known about the ways that social conditions influence perinatal mortality.

  16. Brief reports: Controlling the survival of human pluripotent stem cells by small molecule-based targeting of topoisomerase II alpha.

    PubMed

    Ben-David, Uri; Cowell, Ian G; Austin, Caroline A; Benvenisty, Nissim

    2015-03-01

    Pluripotent-specific inhibitors (PluriSIns) make a powerful tool to study the mechanisms controlling the survival of human pluripotent stem cells (hPSCs). Here, we characterize the mechanism of action of PluriSIn#2, a compound that selectively eliminates undifferentiated hPSCs, while sparing various other cell types derived from them. Toxicogenomic analysis predicts this compound to be a topoisomerase inhibitor. Gene expression analyses reveal that one of the human topoisomerase enzymes, topoisomerase II alpha (TOP2A), is uniquely expressed in hPSCs: TOP2A is highly expressed in undifferentiated cells, is downregulated during their differentiation, and its expression depends on the expression of core pluripotency transcription factors. Furthermore, siRNA-based knockdown of TOP2A in undifferentiated hPSCs results in their cell death, revealing that TOP2A expression is required for the survival of these cells. We find that PluriSIn#2 does not directly inhibit TOP2A enzymatic activity, but rather selectively represses its transcription, thereby significantly reducing TOP2A protein levels. As undifferentiated hPSCs require TOP2A activity for their survival, TOP2A inhibition by PluriSIn#2 thus causes their cell death. Therefore, TOP2A dependency can be harnessed for the selective elimination of tumorigenic hPSCs from culture. © 2014 AlphaMed Press.

  17. Technical considerations in the study of /sup 111/In-oxine labelled platelet survival patterns in dogs

    SciTech Connect

    Sharefkin, J.; Rich, N.M.

    1982-04-01

    A detailed technique for labelling canine platelets with /sup 111/In-oxine for the study of platelet survival patterns in four to six dogs at a time was developed. Useful modifications of earlier methods included splitting of the platelet rich plasma into multiple aliquots to improve pelleting efficiency at low gravity forces, use of saved platelet poor plasma to flush out injection syringes, and prompt use of commercial /sup 111/In-oxine sources 3 to 5 minutes after mixing with Ringer's Citrate Dextrose. Avoidable pitfalls of the method included excessive lengths of incubation time in plasma free medium and loss of labelling efficacy by exposure of the chelate to iron or other metal contaminants in glassware. The method was used to study changes in platelet survival time in dogs with large synthetic arterial prostheses, and gave results in good agreement with earlier studies using /sup 51/Cr labelled platelets.

  18. Tooth-wear patterns in subjects with Class II Division 1 malocclusion and normal occlusion.

    PubMed

    Janson, Guilherme; Oltramari-Navarro, Paula Vanessa Pedron; de Oliveira, Renata Biella Salles; Quaglio, Camila Leite; Sales-Peres, Sílvia Helena de Carvalho; Tompson, Bryan

    2010-01-01

    The aim of this study was to investigate the prevalence of tooth wear in adolescents with Class II malocclusion, compared with those with normal occlusion. The sample consisted of dental casts obtained from 310 subjects, divided into 3 groups: group 1, 110 subjects with normal occlusion (mean age, 13.51 years); group 2, 100 complete Class II Division 1 patients (mean age, 13.44 years); and group 3, 100 half-cusp Class II Division 1 patients (mean age, 13.17 years). Dental wear was assessed by using a modified version of the tooth-wear index. The 3 groups were compared by means of the Kruskal-Wallis and Dunn tests, considering the frequency and the severity of wear on each surface of each group of teeth. The level of statistical significance was set at 5%. The normal occlusion group had statistically greater tooth wear on the palatal surfaces of the maxillary central incisors and the incisal surfaces of the maxillary canines than the corresponding surfaces in both Class II malocclusion groups. The complete and half-cusp Class II Division 1 malocclusion groups had statistically greater tooth wear on the occlusal surfaces of the maxillary second premolar and first molar, the occlusal surfaces of the mandibular premolars, and the buccal surfaces of the mandibular posterior teeth compared with the normal occlusion group. The half-cusp Class II Division 1 malocclusion group had significantly greater tooth wear on the incisal surfaces of the mandibular incisors compared with the complete Class II Division 1 malocclusion group. Subjects with normal occlusion and complete or half-cusp Class II Division 1 malocclusions have different tooth-wear patterns. Tooth wear on the malocclusion subjects should not be considered pathologic but rather consequent to the different interocclusal tooth arrangement. Copyright 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  19. The Effect of Coenzyme Q10 (Ubiquinone) on Random Pattern Skin Flap Survival in Rat Model.

    PubMed

    Can, Asli; Temel, Metin; Dokuyucu, Recep; Mutaf, Mehmet

    2016-08-01

    In this study, the effect of coenzyme Q10 (CQ10) on flap survival was investigated. Fifty Wistar Albino rats were divided into 5 groups. The survival rates of the skin flaps were assessed 10 days after complete elevation of the flaps. Regions of survival and necrosis were drawn on transparent acetate sheets and scanned into a computer. Tissue samples were assessed histopathologically after staining with hematoxylin-eosin, vascular endothelial growth factor staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-Biotin Nick End-labeling staining. To evaluate the antioxidant effect of CQ10; malondialdehyde, nitric oxide levels were measured. Viable flaps area was found higher in groups 3 and 4 as compared to groups 1, 2, and 5. In terms of vascular proliferation, elevated angiogenesis was observed in pathological specimens of groups 3 and 4 as compared to groups 1, 2, and 5. Malondialdehyde levels in groups 3 and 4 were found to be significantly decreased as compared to groups 1, 2 and 5 (P < 0.05). Moreover, serum levels of CQ10 were found significantly increased in groups 3 and 4 (P < 0.05). In conclusion, CQ10 significantly improves flap viability in rat model, and the highest levels of serum CQ10 can be obtained by oral administration.

  20. Nest survival patterns in Eurasian Bittern: effect of nest age, time and habitat variables.

    PubMed

    Polak, Marcin

    2016-01-01

    Determining the key factors affecting the reproductive success of nesting birds is crucial in order to better understand the population dynamics of endangered species and to introduce effective conservation programmes for them. Inhabiting a variety of wetland habitats, aquatic birds actively select safe nesting sites so as to protect their nests against predators. The main aim of the present work was to assess the effect of temporal and habitat variables on the daily nest survival rate of Eurasian Bitterns colonizing semi-natural fishpond habitat in eastern Poland. MARK software was used for the modelling. Eurasian Bittern nests were most vulnerable to depredation at the beginning of the breeding season. This was probably because the reedbed vegetation at this time was not yet dense enough to effectively conceal the nests. There was a positive relationship between nest age and the daily survival rate. Two of the habitat variables analysed were of the greatest significance: water depth and vegetation density. In the Eurasian Bittern population studied here, nests built over deep water and in dense vegetation had the best chances of survival. The results of this work may be useful in the preparation of plans for the conservation and management of populations of this rare and endangered species. Conservation and restoration efforts that attempt to maintain high water levels will be especially beneficial to this avian species that is dependent on wetland ecosystems for breeding.

  1. Nest survival patterns in Eurasian Bittern: effect of nest age, time and habitat variables

    PubMed Central

    2016-01-01

    Determining the key factors affecting the reproductive success of nesting birds is crucial in order to better understand the population dynamics of endangered species and to introduce effective conservation programmes for them. Inhabiting a variety of wetland habitats, aquatic birds actively select safe nesting sites so as to protect their nests against predators. The main aim of the present work was to assess the effect of temporal and habitat variables on the daily nest survival rate of Eurasian Bitterns colonizing semi–natural fishpond habitat in eastern Poland. MARK software was used for the modelling. Eurasian Bittern nests were most vulnerable to depredation at the beginning of the breeding season. This was probably because the reedbed vegetation at this time was not yet dense enough to effectively conceal the nests. There was a positive relationship between nest age and the daily survival rate. Two of the habitat variables analysed were of the greatest significance: water depth and vegetation density. In the Eurasian Bittern population studied here, nests built over deep water and in dense vegetation had the best chances of survival. The results of this work may be useful in the preparation of plans for the conservation and management of populations of this rare and endangered species. Conservation and restoration efforts that attempt to maintain high water levels will be especially beneficial to this avian species that is dependent on wetland ecosystems for breeding. PMID:27350897

  2. 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.

  3. Patterns of common loon (Gavia immer) mercury exposure, reproduction, and survival in Wisconsin, USA

    SciTech Connect

    Meyer, M.W.; Evers, D.C.; Hartigan, J.J.; Rasmussen, P.S.

    1998-02-01

    A long-term study was initiated in 1992 to investigate whether elevated Hg exposure measured in Wisconsin common loons was associated with reduced reproductive performance or survival. Adults loons and chicks were captured on 45 lakes during 1992 and 1993, each was individually color-marked with plastic leg bands, and blood and feathers were collected for Hg analysis. Adult return rates and reproductive outcome were then recorded for the 45 lakes from 1993 to 1996. A significant linear relationship was observed between lake pH and log-transformed adult blood Hg and chick blood Hg concentrations. Egg Hg concentrations were within the range associated with reduced hatching success or reduced survival of embryos or hatchlings in other sensitive avian species. Chick production was lower at lakes where chick blood Hg concentrations were elevated. However, no relationship was observed between levels of adult Hg exposure and reproductive performance or annual adult return rates (an index of survival). Establishing a cause-and-effect relationship between Hg exposure and loon fitness is complicated by the negative correlation between lake pH and Hg exposure and potential confounding with other influences on productivity that may also be related to lake pH.

  4. Airway in Class I and Class II skeletal pattern: A computed tomography study

    PubMed Central

    Paul, Deepthi; Varma, Sapna; Ajith, V. V.

    2015-01-01

    Background and Objectives: A normal airway is required for the normal growth of the craniofacial structures. The present study was designed to evaluate and compare the airway in Class I and Class II skeletal pattern and to see if there is any association between the airway and maxillomandibular relationship. Materials and Methods: Peripheral nervous system computed tomography scans of 30 patients were divided into two groups as Class I (ANB ≤ 4.5°), Class II (ANB ≥ 4.5°). The Dolphin three-dimensional version 11 was used to assess the airway. Statistical Analysis: Correlations between the variables were tested with the Pearson correlation coefficient. Independent sample t-test was performed to compare the averages between the two groups. P < 0.05 was considered as statistically significant. Results: The ANB angle was negatively correlated with all the airway parameters. The airway area and volume was significantly reduced in Class II subjects compared to Class I. Conclusion: The results suggest a strong association between the airway and skeletal pattern showing a reduced airway in Class II patients with a high ANB angle. PMID:26321823

  5. Prevalence and patterns of tooth agenesis in Angle Class II Division 2 malocclusion in Japan.

    PubMed

    Ota, Kanako; Arai, Kazuhito

    2015-07-01

    The purpose of this study was to evaluate the prevalence and patterns of tooth agenesis in subjects with Angle Class II Division 2 malocclusion compared with general orthodontic patients in Japan. Panoramic radiographs, dental casts, and cephalograms of 76 patients with Class II Division 2 malocclusions (52 female, 24 male) and 270 orthodontic patients as the control group (168 female, 102 male) who were 14 years of age or older were selected. The prevalences of tooth agenesis in this cohort and in each tooth type were calculated and compared between the groups with the chi-square test. Odds ratios and corresponding 95% confidence intervals were also calculated. The prevalence of tooth agenesis excluding the third molars was significantly higher in the Class II Division 2 group (22.4%) than in the control group (11.9%) (P <0.05); the odds ratio was 2.14 (95% CI, 1.12-4.12). A higher prevalence of tooth agenesis excluding the third molars was observed in the Class II Division 2 group for the mandibular second premolar (P <0.05) and the maxillary lateral incisor (P <0.01). The prevalence of third molar agenesis was also significantly higher in the Class II Division 2 group (42.1%) compared with the control group (26.7%) (P <0.05); the odds ratio was 2.00 (95% CI, 1.18-3.40). Compared with the general orthodontic patient population, permanent tooth agenesis was observed approximately 2 times more frequently, and a distinctive agenesis pattern was found in the Class II Division 2 group in Japan. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  6. World leaders surviving serious illness: Franklin D. Roosevelt and Pope John Paul II.

    PubMed

    Kune, Gabriel

    2007-12-01

    The quality of medical care and the degree of transparency communicated to the world whilst President Franklin D. Roosevelt and Pope John Paul II were seriously ill, as well as the global consequences of critical decisions they made during this time, were examined from published studies and through personal communications. Franklin D. Roosevelt, in his last years, was secretive about his health and, with one exception, was probably given indifferent medical advice, arguably hung on to office too long which, at least for Europe, contributed to some negative outcomes. Pope John Paul II, when quite ill, was open and communicative about his illness, had high-quality medical and surgical care and, together with his spirited will, greatly contributed to favourable European political outcomes, and to European and world stability.

  7. Patterns of metastasis and survival in breast cancer patients: a preliminary study in an Iranian population.

    PubMed

    Ziaei, Jamal Eivazi; Pourzand, Ali; Bayat, Amrollah; Vaez, Jalil

    2012-01-01

    Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone

  8. Survival patterns of patients on maintenance hemodialysis for end stage renal disease in Ethiopia: summary of 91 cases.

    PubMed

    Shibiru, Tamiru; Gudina, Esayas Kebede; Habte, Belete; Derbew, Amare; Agonafer, Tewodros

    2013-06-19

    The increasing incidence and prevalence of chronic kidney disease is an important challenge for health systems around the world. Access for care of the disease in Ethiopia is extremely limited. The main purpose of the study was to investigate survival pattern and assess risk factors for poor outcome of patients on maintenance hemodialysis for end stage renal disease in Ethiopia. Medical records of patients on maintenance hemodialysis for end stage renal disease at Saint Gabriel General Hospital between 2002 and 2010 were reviewed. The data was collected by complete review of patient's clinical data. Descriptive statistics was used for most variables and Chi-square test, where necessary, was used to test the association among various variables. Kaplan-Meier survival analysis was done to assess both short and long term survival. P-values of <0.05 were considered as statistically significant. A total of 190 patients were registered for hemodialysis at the hospital 91 of which were included in the final assessment. Mean age at dialysis initiation was 58±15 years. Fifty-five (60.4%) of the patients had prior history of diabetes. Almost all of them had serum creatinine of >5mg/dl and some degree of anemia at dialysis initiation. Forty-one (45.1%) deaths occurred during dialysis treatment and 21 (23.1%) of patients died within the first 90 days of starting dialysis. Only 42.1% of them survived longer than a year. The frequently registered causes of death were septicemia (34.1%) and cardiovascular diseases (29.3%). Use of catheter as vascular access was associated with decreased short term and long term survival. Dialysis as treatment modality is extremely scarce in Ethiopia and affordable to only the rich. Survival pattern in those on the treatment is less satisfactory and short of usual standards in the developed world and needs further investigation. We thus recommend a large scale analysis of national dialysis registry at all dialysis centers in the country.

  9. Type III secretion and effectors shape the survival and growth pattern of Pseudomonas syringae on leaf surfaces.

    PubMed

    Lee, Jiyoung; Teitzel, Gail M; Munkvold, Kathy; del Pozo, Olga; Martin, Gregory B; Michelmore, Richard W; Greenberg, Jean T

    2012-04-01

    The bacterium Pseudomonas syringae pv syringae B728a (PsyB728a) uses a type III secretion system (T3SS) to inject effector proteins into plant cells, a process that modulates the susceptibility of different plants to infection. Analysis of GREEN FLUORESCENT PROTEIN-expressing PsyB728a after spray inoculation without additives under moderate relative humidity conditions permitted (1) a detailed analysis of this strain's survival and growth pattern on host (Nicotiana benthamiana) and nonhost (tomato [Solanum lycopersicum]) leaf surfaces, (2) an assessment of the role of plant defenses in affecting PsyB728a leaf surface (epiphytic) growth, and (3) the contribution of the T3SS and specific effectors to PsyB728a epiphytic survival and growth. On host leaf surfaces, PsyB728a cells initially persist without growing, and show an increased population only after 48 h, unless plants are pretreated with the defense-inducing chemical benzothiazole. During the persistence period, some PsyB728a cells induce a T3SS reporter, whereas a T3SS-deficient mutant shows reduced survival. By 72 h, rare invasion by PsyB728a to the mesophyll region of host leaves occurs, but endophytic and epiphytic bacterial growths are not correlated. The effectors HopZ3 and HopAA1 delay the onset of epiphytic growth of PsyB728a on N. benthamiana, whereas they promote epiphytic survival/growth on tomato. These effectors localize to distinct sites in plant cells and likely have different mechanisms of action. HopZ3 may enzymatically modify host targets, as it requires residues important for the catalytic activity of other proteins in its family of proteases. Thus, the T3SS, HopAA1, HopZ3, and plant defenses strongly influence epiphytic survival and/or growth of PsyB728a.

  10. Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes.

    PubMed

    Grover, Surbhi; Swisher-McClure, Samuel; Mitra, Nandita; Li, Jiaqi; Cohen, Roger B; Ahn, Peter H; Lukens, John N; Chalian, Ara A; Weinstein, Gregory S; O'Malley, Bert W; Lin, Alexander

    2015-07-01

    To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score-adjusted and inverse probability of treatment-weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders. A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment-weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not apply to T4a disease, and patients should be counseled

  11. Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

    SciTech Connect

    Grover, Surbhi; Swisher-McClure, Samuel; Mitra, Nandita; Li, Jiaqi; Cohen, Roger B.; Ahn, Peter H.; Lukens, John N.; Chalian, Ara A.; Weinstein, Gregory S.; O'Malley, Bert W.; Lin, Alexander

    2015-07-01

    Purpose: To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. Methods and Materials: Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score–adjusted and inverse probability of treatment–weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders. Results: A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment–weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. Conclusions: Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not

  12. Survival analysis of a critical resource for cavity-nesting communities: patterns of tree cavity longevity.

    PubMed

    Edworthy, Amanda B; Wiebe, Karen L; Martin, Kathy

    2012-09-01

    Tree cavities are a vital multi-annual resource used by cavity-nesting birds and mammals for nesting and shelter. The abundance of this resource will be influenced by the rates at which cavities are created and destroyed. We applied the demographic concepts of survival and longevity to populations of tree holes to investigate rates of loss for cavities in three tree species, as well as how characteristics of nest trees, habitat type, and species of excavator affected the persistence of tree cavities in trembling aspen, Populus tremuloides (95% of cavities were in aspen trees), in interior British Columbia, Canada. By modeling survival of 1635 nesting cavities in aspen over a time span of 16 years, we found that the decay stage of the nest tree was the most important factor determining cavity longevity. Cavities in trees with advanced decay had a relatively short median longevity of 7 years (95% CI 6-9 years), whereas those in living trees had a median longevity of more than 15 years. We found that cavity longevity was greater in continuous forest than in aspen grove habitat. Interestingly, cavities formed by weak excavators survived as long as those created by Northern Flickers (Colaptes auratus), despite occurring in more decayed tree stems. Thus, weak excavators may be selecting for characteristics that make a tree persistent, such as a broken top. Our results indicate that retention of cavities in large, live aspen trees is necessary to conserve persistent cavities, and that cavity longevity will have a large effect on the structure and function of cavity-using vertebrate communities.

  13. Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival

    SciTech Connect

    Loeffler, J.S.; Ervin, T.J.; Mauch, P.; Skarin, A.; Weinstein, H.J.; Canellos, G.; Cassady, J.R.

    1985-04-01

    Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkin's lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. A review of ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981 is presented. All patients had biopsy- proven CNS lymphomas without systemic disease at presentation. In this series, control of CNS lymphoma was seen only in patients receiving craniospinal radiation or CNS-penetrating chemotherapy.

  14. Hidden keys to survival: the type, density, pattern and functional role of emperor penguin body feathers.

    PubMed

    Williams, Cassondra L; Hagelin, Julie C; Kooyman, Gerald L

    2015-10-22

    Antarctic penguins survive some of the harshest conditions on the planet. Emperor penguins breed on the sea ice where temperatures drop below -40°C and forage in -1.8°C waters. Their ability to maintain 38°C body temperature in these conditions is due in large part to their feathered coat. Penguins have been reported to have the highest contour feather density of any bird, and both filoplumes and plumules (downy feathers) are reported absent in penguins. In studies modelling the heat transfer properties and the potential biomimetic applications of penguin plumage design, the insulative properties of penguin plumage have been attributed to the single afterfeather attached to contour feathers. This attribution of the afterfeather as the sole insulation component has been repeated in subsequent studies. Our results demonstrate the presence of both plumules and filoplumes in the penguin body plumage. The downy plumules are four times denser than afterfeathers and play a key, previously overlooked role in penguin survival. Our study also does not support the report that emperor penguins have the highest contour feather density. © 2015 The Author(s).

  15. Hidden keys to survival: the type, density, pattern and functional role of emperor penguin body feathers

    PubMed Central

    Williams, Cassondra L.; Hagelin, Julie C.; Kooyman, Gerald L.

    2015-01-01

    Antarctic penguins survive some of the harshest conditions on the planet. Emperor penguins breed on the sea ice where temperatures drop below −40°C and forage in −1.8°C waters. Their ability to maintain 38°C body temperature in these conditions is due in large part to their feathered coat. Penguins have been reported to have the highest contour feather density of any bird, and both filoplumes and plumules (downy feathers) are reported absent in penguins. In studies modelling the heat transfer properties and the potential biomimetic applications of penguin plumage design, the insulative properties of penguin plumage have been attributed to the single afterfeather attached to contour feathers. This attribution of the afterfeather as the sole insulation component has been repeated in subsequent studies. Our results demonstrate the presence of both plumules and filoplumes in the penguin body plumage. The downy plumules are four times denser than afterfeathers and play a key, previously overlooked role in penguin survival. Our study also does not support the report that emperor penguins have the highest contour feather density. PMID:26490794

  16. Platelets in blood stored in untreated and siliconed glass bottles and plastic bags. II. Survival studies.

    PubMed

    KISSMEYER-NIELSEN, F; MADSEN, C B

    1961-11-01

    Platelet survival was determined using untreated and siliconed glass bottles and plastic bags (Fenwal) for collecting and storing blood. The platelets were tagged in vivo with P(32) in six polycythaemic patients undergoing treatment with P(32). The results showed that fresh ACD blood collected in untreated glass, siliconed glass, and plastic gave the same recovery of platelets in the recipients. The use of EDTA (Fenwal formula) as anticoagulant gave results inferior to those obtained with blood using ACD as anticoagulant. Even after storage up to 24 hours in untreated glass bottles (ordinary bank blood) a satisfactory recovery of platelets was observed. After storage for 72 hours the recovery was less but not negligible.

  17. Clinical patterns in extremely preterm (22 to 24 weeks of gestation) infants in relation to survival time and prognosis.

    PubMed

    Iijima, Shigeo; Arai, Hiroko; Ozawa, Yuri; Kawase, Yasuhiro; Uga, Naoki

    2009-06-01

    We investigated time-related predictors of death or neurological sequelae in extremely preterm infants (EPI) born at 22 to 24 weeks' gestation by categorizing clinical patterns according to their survival time and morbidity. Data on 113 infants born at 22 to 24 weeks' gestation from January 1991 through April 2006 were analyzed by a case-control approach. Cesarean section, Apgar score survived >or= 24 hours, pulmonary hemorrhage and intraventricular hemorrhage (IVH) were significantly associated with death by day 6. Among those surviving >or= 7 days, sepsis and severe IVH were significantly associated with death. Assessment of survivors at a minimum follow-up period of 2 years revealed that protracted mechanical ventilation was significantly associated with a poor neurological outcome. There are various characteristic key events in relation to the outcome at different ages of life in EPI born at 22 to 24 weeks' gestation. Clinicians and parents should discuss management options for the infant on the basis of these findings.

  18. Survival Patterns in Patients With Hodgkin's Lymphoma With a Pre-Existing Hospital Discharge Diagnosis of Autoimmune Disease

    PubMed Central

    Landgren, Ola; Pfeiffer, Ruth M.; Kristinsson, Sigurdur Y.; Björkholm, Magnus

    2010-01-01

    Purpose Autoimmune diseases (AIs) are associated with elevated risk for Hodgkin's lymphoma (HL); however, information on the interplay of AIs and HL on survival is sparse. Patients and Methods We evaluated survival patterns for 7,414 patients with HL in relation to a pre-existing hospital discharge diagnosis of an AI. We also assessed survival patterns in relation to a prior AI diagnosis among 29,240 population-based matched controls. Results Among female patients with HL with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 46.0% (63.3%) and 41.0% (51.9%); for males, the corresponding numbers were 48.5% (59.2%) and 43.6% (51.5%), respectively (P < .001). Among female controls with (v those without) a pre-existing AI, the 5-year and 10-year overall survival was 79.1% (90.2%) and 67.2% (83.3%); for males, the corresponding numbers were 82.5% (90.3%) and 68.6% (81.6%), respectively (P < .001). Female patients with HL with (v those without) a pre-existing AI had a 1.8-fold (range, 1.3- to 2.4-fold) increased relative risk of dying at 5 years of follow-up; for males, the corresponding excess relative risk of dying was 1.7-fold (range, 1.3- to 2.2-fold). Conclusion Patients with HL have an overall excellent outcome from treatment but also pose some of the most complex challenges of cancer survivorship due to many late effects (eg, second malignancies, thyroid disease, cardiovascular disease, and altered reproductive and sexual function). Our finding that patients with HL with a hospital discharge diagnosis of an AI have a substantially higher risk of dying, emphasizes that underlying chronic diseases, such as AIs, should be high of the list of survivorship concerns for clinicians that treat HL. PMID:20940191

  19. BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study.

    PubMed

    Unni, Sudhir K; Schauerhamer, Marisa B; Deka, Rishi; Tyczynski, Jerzy E; Fernandes, Ancilla W; Stevens, Vanessa; Brixner, Diana I; Stenehjem, David D

    2016-03-22

    Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer. This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively. Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001). BRCAwt patients had similar outcomes to BRCAm patients, potentially

  20. The Activation Pattern of Blood Leukocytes in Head and Neck Squamous Cell Carcinoma Is Correlated to Survival

    PubMed Central

    Millrud, Camilla Rydberg; Månsson Kvarnhammar, Anne; Uddman, Rolf; Björnsson, Sven; Riesbeck, Kristian; Cardell, Lars Olaf

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) is known to cause substantial immunosuppression. The present study was designed to characterize blood leukocyte activation in HNSCC and to investigate if the individual activation pattern could be related to tumor progress and survival. The leukocyte activation profile of HNSCC patients and healthy controls was assessed with flow cytometry. HNSCC patients displayed increased numbers of monocytes, neutrophils and total leukocytes as well as an enhanced neutrophil/lymphocyte ratio. In addition, patients had a higher percentage of CD69+, CD71+ and CD98+ T cell subsets and NK cells, and a reduced expression of L-selectin in CD14highCD16+ monocytes and neutrophils, when compared to controls. These changes could be correlated to both tumor burden and spread to lymph nodes. Among the cancer patients an increased neutrophil/lymphocyte ratio, a low neutrophil and CD14high CD16+ monocyte activation state and an elevated CD4/CD8 ratio were related to poor survival. In contrast, a high percentage of CD98+ Th cells appeared to be associated with a better outcome. Taken together, the present data indicate that HNSCC causes activation of blood leukocytes and that the individual activation pattern can be linked to prognosis. PMID:23251433

  1. Dietary Patterns, Insulin Resistance, and Incidence of Type 2 Diabetes in the Whitehall II Study

    PubMed Central

    McNaughton, Sarah A.; Mishra, Gita D.; Brunner, Eric J.

    2008-01-01

    OBJECTIVE—The aim of this study was to identify a dietary pattern associated with insulin resistance and investigate whether this pattern was prospectively associated with type 2 diabetes. RESEARCH DESIGN AND METHODS—Analysis was based on 7,339 participants of the Whitehall II study. Dietary intake was measured using a 127-item food frequency questionnaire. We used the reduced rank regression method to determine dietary patterns using the homeostasis model assessment of insulin resistance as the intermediate or response variable. The association between the dietary pattern identified and incidence of type 2 diabetes was investigated using Cox proportional hazard regression models. RESULTS—We identified a dietary pattern characterized by high consumption of low-calorie/diet soft drinks, onions, sugar-sweetened beverages, burgers and sausages, crisps and other snacks, and white bread and low consumption of medium-/high-fiber breakfast cereals, jam, French dressing/vinaigrette, and wholemeal bread. Higher dietary pattern scores were associated with increased risk of type 2 diabetes (hazard ratio for top quartile 2.95 [95% CI 2.19–3.97]; adjusted for age, sex, and energy misreporting). This relationship was attenuated after adjustment for ethnicity, employment grade, health behaviors (smoking, alcohol use, and physical activity) but remained significant after further adjustment for blood pressure and BMI (1.51 [1.10–2.09]). CONCLUSIONS—A dietary pattern associated with insulin resistance predicts type 2 diabetes risk after adjustment for a range of confounders. This study adds to the evidence that dietary patterns are an important risk factor for type 2 diabetes. PMID:18390803

  2. A retrospective study of correlation of morphologic patterns, MIB1 proliferation index, and survival analysis in 134 cases of plasmacytoma.

    PubMed

    Ghodke, Kiran; Shet, Tanuja; Epari, Sridhar; Sengar, Manju; Menon, Hari; Gujral, Sumeet

    2015-06-01

    Plasmacytoma classified into solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) is characterized by infiltrate of plasma cells of diverse maturity and by their monoclonal immunoglobulin products. Both SPB and EMP represent different groups of neoplasm in terms of location, tumor progression, and overall survival rate. There is a need for features that indicate likelihood of myeloma in patients with plasmacytoma without other manifestations. This study was an attempt to study the morphologic patterns of plasmacytoma (SPB and EMP), MIB1 proliferation index, and correlation of these with clinicopathologic features and survival of the patients. The study group comprised of 134 cases of plasmacytoma (88 SPB and 46 EMP) over duration of 8 years and were graded as per Bartl's histologic grading system. Commonest site was vertebral body in SPB (36%) and upper aerodigestive tract in EMP (48%). On serum electrophoresis, overall M band was detected in 41% cases. Both SPB and EMP on histology revealed similar morphologic features. MIB1 proliferation index ranged from less than 1% to 80%. It was slightly higher in EMP in comparison with SPB (P value = .002). Seventy percent of cases, which progressed to multiple myeloma (MM) showed MIB1 labeling index more than 10%; however, it was not statistically significant in predicting the disease progression. With the median follow-up of 19 months (range, 1-99 months), 10 SPB had disease progression of which 7 converted to MM, and 3 developed EMP, with a median interval of 21 months (range, 8-75 months) for the development of MM and 3 months (range, 3-9 months) for the progression to EMP. Five-year survival for EMP varied by site, with poorest survival in brain/central nervous system EMP as compared with EMP at other sites. To conclude, grade and MIB1 proliferation index help in predicting aggressive course in plasmacytoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. DNA ploidy pattern in choroidal melanoma: correlation with survival. A flow cytometry study on archival material

    PubMed Central

    Toti, P.; Greco, G.; Mangiavacchi, P.; Bruni, A.; Palmeri, M. L.; Luzi, P.

    1998-01-01

    BACKGROUND/AIMS—Paraffin embedded samples have provided an important source of material for retrospective cytofluorimetric studies, useful in establishing the predictive value of DNA content measurements. The aim of this study was to investigate the incidence and type of aneuploidy in choroidal malignant melanomas (CMM) and the significance in the clinical outcome (median follow up 55 months).
METHODS—DNA content was quantified by flow cytometry in 61 CMM from archival material. Non-tumour ocular tissue was used as the reference diploid standard. Cases in which the coefficient of variation (CV) of the diploid peak was >8% were excluded. The CMM were classified as spindle A, spindle B, mixed spindle and epithelioid, epithelioid, and necrotic.
RESULTS—The frequency of the aneuploid DNA pattern was 38%. Necrotic tumours showed a worse clinical outcome independent of the ploidy pattern. Spindle A tumours were found to be diploid. Spindle B and mixed tumours showed a prevalent diploid and near diploid aneuploid pattern (DI <1.3), yet aneuploidy was not correlated with a worse prognosis. The epithelioid tumours were prevalently diploid. However, 83% of the aneuploid tumours were hypodiploid (DI <0.95), and showed the worst prognosis.
CONCLUSION—These results indicate that increasing DNA abnormalities in CMM, especially in the epithelioid histotype, were associated with an increasing mortality.

 Keywords: ocular melanoma; flow cytometry; DNA PMID:9930278

  4. Type II endometrial cancer in Hispanic women: tumor characteristics, treatment and survival compared to non-Hispanic white women.

    PubMed

    Mahdi, Haider; Hou, Huiying; Kowk, Li-Lian; Moslemi-Kebria, Mehdi; Michener, Chad

    2014-06-01

    To compare survival of Hispanic white (HW) and non-Hispanic white (NHW) women with type II endometrial adenocarcinoma (EC). Patients with serous, clear cell or grade 3 endometrioid EC were identified from the Surveillance, Epidemiology, and End Results (SEER) program 1988-2009 and were divided into HW and NHW. HW were subdivided into natives and immigrants. Of the 14,434 women, 13,012 (90.2%) were NHW and 1422 (9.8%) were HW. HW were younger than NHW (mean 63 vs. 68years, p<0.001). A higher proportion of HW presented with late stage disease than NHW (43.8% vs. 36.6%, p=0.04). Performing lymphadenectomy was not different but HW were more likely to have positive lymph nodes than NHW (27.6% vs. 23.1%, p=0.02). Further, HW were less likely to receive radiation than NHW (39.5% vs. 42.3%, p=0.04). No difference in clinicopathologic characteristics was found between immigrant and native HW. In multivariate models adjusting for age, stage, histology, surgical treatment, extent of lymphadenectomy, and radiation therapy, no difference in overall survival (OS) (HR 1.06, 95% CI 0.97-1.16, p=0.19) and cancer-specific survival (CSS) (HR 1.02, 95% CI 0.91-1.14, p=0.75) was found between HW and NHW. Interestingly, immigrant HW had better OS (HR 0.74, 95% CI 0.62-0.89, p<0.001) and CSS (HR 0.72, 95% CI 0.58-0.90, P=0.003) than native HW. Although they were more likely to present with advanced stage and positive nodal disease, no difference in outcome was noted between Hispanic and non-Hispanic whites with EC. Interestingly, immigrant HW had more favorable outcome compared to native HW. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A heavy particle comparative study. Part II: cell survival versus depth.

    PubMed

    Raju, M R; Bain, E; Carpenter, S G; Cox, R A; Robertson, J B

    1978-09-01

    Cell-survival measurements with depth of penetration were made for a series of incident doses of proton, helium, carbon, neon, argon, negative pion, neutron, and 60Co photon beams. Cultured human cells (T1) suspended in a gel-containing medium were used, and the measurements were found to be very useful in facilitating the design of ridge filters to produce iso-effects in the region of interest. Heavy charged particle beams (proton, helium, carbon, neon, and negative pion) were found to produce similar cell killing with depth of penetration. Because of saturation effects at higher LET, argon ions were less effective in killing aerated cells at depth, compared with other heavy charged-particle beams. Cell killing at depth in the region of interest, compared with that at the entrance, was not significantly different for single-field exposures when the Bragg peaks were broadened to cover a width of 10 cm. However, when two opposed fields with overlapping peaks were used, a large enhancement in killing was obtained in the peak region.

  6. The prevalence and significance of HTLV-I/II seroindeterminate Western blot patterns.

    PubMed

    Abrams, Anna; Akahata, Yoshimi; Jacobson, Steven

    2011-08-01

    Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15-20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.

  7. Survival of Listeria monocytogenes with different antibiotic resistance patterns to food-associated stresses.

    PubMed

    Komora, Norton; Bruschi, Carolina; Magalhães, Rui; Ferreira, Vânia; Teixeira, Paula

    2017-03-20

    The ongoing rise of antibiotic resistant microbial pathogens has become one of the major public health threats worldwide. Despite all the effort and actions taken so far, a proliferation of antibiotic resistant (AR) and multi-antibiotic resistant (MAR) strains is still observed, including in foodborne pathogens. This trend has been also noted recently for isolates of Listeria monocytogenes, a species that, although remaining largely sensitive to clinically relevant antimicrobials, has been reported to develop increased tolerance to antibiotics, particularly in isolates recovered from the food-chain. In this study we compared the ability of MAR (n=8), AR (n=18) and antibiotic susceptible (AS, n=11) L. monocytogenes strains from food and clinical origin to survive to different environmental stress conditions, including temperature (58°C), acidic stress (1% v/v lactic acid, pH3.5), and osmotic stress (37% w/v NaCl). The presence of antibiotic active efflux among MAR and AR strains, and its role on L. monocytogenes tolerance to different antimicrobial compounds was also investigated, namely; hydrogen peroxide; organic acids (acetic, citric and lactic); nisin; benzalkonium chloride (BC); and, sodium nitrite. While no significant differences were observed in the survival of the 37 strains exposed to high temperature (58°C), overall the mean logarithmic reduction of clinical strains was statistically lower after acid and salt exposure than that observed for strains of food origin; but both food and clinical strains resistant to two or three antibiotics were significantly less susceptible to acid (lactic acid 1% v/v) and osmotic stresses (37% w/v NaCl) when compared to AS strains. Using the EtBr-agar Cartwheel method, it was possible to detect efflux pumps in three of the 26 MAR and AR isolates, including one control strain; the active efflux in theses isolates was proven to be associated with fluoroquinolone resistance, and possible extrusion of BC and hydrogen peroxide

  8. Declining ring-necked pheasants in the Klamath Basin, California: II. Survival, productivity, and cover

    USGS Publications Warehouse

    Grove, Robert A.; Buhler, D.R.; Henny, Charles J.; Drew, A.D.

    2001-01-01

    Cover condition and its influence on nesting success, survival, and body condition of ring-necked pheasants (Phasianus colchicus) were evaluated at Tule Lake National Wildlife Refuge (TLNWR) and Lower Klamath National Wildlife Refuge (LKNWR). Inadequate nesting cover was responsible for extremely low nest success early in the nesting season at TLNWR. Later in the season at TLNWR, spring-planted crops provided cover to conceal nesting and renesting hens; however, only 0.07 young were produced (to 1 August) per hen during the study. The extremely low reproductive rates were well below those required to maintain a stable population. At TLNWR, most adult mortality during spring and early summer (before crops provided adequate cover) apparently resulted from predation by golden eagles (Aquila chrysaetos). This mortality occurred weeks before insecticide applications. Hard winters (cold temperatures and heavy snowfall) periodically reduce the pheasant population in the Klamath Basin and again greatly reduced numbers during the last year of this study. Unfortunately, pheasant populations declined under the conditions found during this study and were unable to recover from the hard winter of 1992 to 1993. Mean body mass and tarsal length of adult hen pheasants at TLNWR, which is intensively farmed, were less than those for hens at LKNWR, which is not intensively farmed. Results of our study suggest that TLNWR hens may have been nutritionally stressed, and that the amount and distribution of vegetative cover needs to be improved at TLNWR. Habitat management of edge cover along agricultural crops should feature perennial grasses and legumes with small tracts of land interspersed throughout the agricultural fields to provide alternative cover for wildlife in general including pheasants.

  9. Food patterns associated with blood lipids are predictive of coronary heart disease: the Whitehall II study

    PubMed Central

    McNaughton, Sarah A.; Mishra, Gita D.; Brunner, Eric J.

    2009-01-01

    Analysis of the epidemiological effects of overall dietary patterns offers an alternative approach to the investigation of the role of diet in coronary heart disease (CHD).We analyzed the role of blood lipid-related dietary patterns using a two-step method to confirm the prospective association of dietary pattern with incident CHD. Analysis is based on 7314 participants of the Whitehall II study. Dietary intake was measured using a 127-item food frequency questionnaire. Reduced rank regression (RRR) was used to derive dietary pattern scores using baseline serum total and HDL cholesterol, and triglyceride levels as dependent variables. Cox proportional hazard regression was used to confirm the association between dietary patterns and incident CHD (n=243) over 15 years of follow-up. Increased CHD risk (hazard ratio for top quartile:2.01, 95%CI 1.41-2.85, adjusted for age, sex, ethnicity and energy misreporting) was observed with a diet characterised by high consumption of white bread, fried potatoes, sugar in tea and coffee, burgers & sausages, soft drinks, and low consumption of French dressing and vegetables. The diet-CHD relationship was attenuated after adjustment for employment grade and health behaviors (HR for top quartile:1.81, 95%CI 1.26-2.62), and further adjustment for blood pressure and BMI (HR for top quartile:1.57, 95% CI 1.08-2.27). Dietary patterns are associated with serum lipids and predict CHD risk after adjustment for confounders. RRR identifies dietary patterns uses prior knowledge and focuses on the pathways through which diet may influence disease. This study adds to the evidence that diet is an important risk factor for CHD. PMID:19327192

  10. Two years survival rate of class II composite resin restorations prepared by ART with and without a chemomechanical caries removal gel in primary molars.

    PubMed

    Topaloglu-Ak, Asli; Eden, Ece; Frencken, Jo E; Oncag, Ozant

    2009-09-01

    The aim was to test the null hypotheses that there is no difference: (1) in carious lesion development at the restoration margin between class II composite resin restorations in primary molars produced through the atraumatic restorative treatment (ART) with and without a chemomechanical caries removal gel and (2) in the survival rate of class II composite resin restorations between two treatment groups after 2 years. Three hundred twenty-seven children with 568 class II cavitated lesions were included in a parallel mouth study design. Four operators placed resin composite (Filtek Z 250) restorations bonded with a self-etch adhesive (Adper prompt L pop). Two independent examiners evaluated the restorations after 0.5, 1, and 2 years using the modified Ryge criteria. The Kaplan-Meier survival method was applied to estimate survival percentages. A high proportion of restorations were lost during the study period. Therefore, the first hypothesis could not be tested. No statistically significant difference was observed between the cumulative survival percentages of restorations produced by the two treatment approaches over the 2-year period (ART, 54.1 +/- 3.4%; ART with Carisolv, 46.0 +/- 3.4%). This hypothesis was accepted. ART with chemomechanical gel might not provide an added benefit increasing the survival percentages of ART class II composite resin restorations in primary teeth.

  11. A phosphorylation pattern-recognizing antibody specifically reacts to RNA polymerase II bound to exons

    PubMed Central

    Han, Jungwon; Lee, Jong-Hyuk; Park, Sunyoung; Yoon, Soomin; Yoon, Aerin; Hwang, Do B; Lee, Hwa K; Kim, Min S; Lee, Yujean; Yang, Won J; Youn, Hong-Duk; Kim, Hyori; Chung, Junho

    2016-01-01

    The C-terminal domain of RNA polymerase II is an unusual series of repeated residues appended to the C-terminus of the largest subunit and serves as a flexible binding scaffold for numerous nuclear factors. The binding of these factors is determined by the phosphorylation patterns on the repeats in the domain. In this study, we generated a synthetic antibody library by replacing the third heavy chain complementarity-determining region of an anti-HER2 (human epidermal growth factor receptor 2) antibody (trastuzumab) with artificial sequences of 7–18 amino-acid residues. From this library, antibodies were selected that were specific to serine phosphopeptides that represent typical phosphorylation patterns on the functional unit (YSPTSPS)2 of the RNA polymerase II C-terminal domain (CTD). Antibody clones pCTD-1stS2 and pCTD-2ndS2 showed specificity for peptides with phosphoserine at the second residues of the first or second heptamer repeat, respectively. Additional clones specifically reacted to peptides with phosphoserine at the fifth serine of the first repeat (pCTD-1stS5), the seventh residue of the first repeat and fifth residue of the second repeat (pCTD-S7S5) or the seventh residue of either the first or second repeat (pCTD-S7). All of these antibody clones successfully reacted to RNA polymerase II in immunoblot analysis. Interestingly, pCTD-2ndS2 precipitated predominately RNA polymerase II from the exonic regions of genes in genome-wide chromatin immunoprecipitation sequencing analysis, which suggests that the phosphoserine at the second residue of the second repeat of the functional unit (YSPTSPS)2 is a mediator of exon definition. PMID:27857068

  12. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis

    PubMed Central

    Vannucchi, Alessandro M.; Kantarjian, Hagop M.; Kiladjian, Jean-Jacques; Gotlib, Jason; Cervantes, Francisco; Mesa, Ruben A.; Sarlis, Nicholas J.; Peng, Wei; Sandor, Victor; Gopalakrishna, Prashanth; Hmissi, Abdel; Stalbovskaya, Viktoriya; Gupta, Vikas; Harrison, Claire; Verstovsek, Srdan

    2015-01-01

    Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46–0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13–0.63). Both patients with intermediate-2– or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2–risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544) PMID:26069290

  13. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis.

    PubMed

    Vannucchi, Alessandro M; Kantarjian, Hagop M; Kiladjian, Jean-Jacques; Gotlib, Jason; Cervantes, Francisco; Mesa, Ruben A; Sarlis, Nicholas J; Peng, Wei; Sandor, Victor; Gopalakrishna, Prashanth; Hmissi, Abdel; Stalbovskaya, Viktoriya; Gupta, Vikas; Harrison, Claire; Verstovsek, Srdan

    2015-09-01

    Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46-0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13-0.63). Both patients with intermediate-2- or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544). Copyright© Ferrata Storti Foundation.

  14. Self-organized MBE growth of II VI epilayers on patterned GaSb substrates

    NASA Astrophysics Data System (ADS)

    Wissmann, H.; Tran Anh, T.; Rogaschewski, S.; von Ortenberg, M.

    1999-05-01

    We report on the self-organized MBE growth of II-VI epilayers on patterned and unpatterned GaSb substrates resulting in quantum wires and quantum wells, respectively. The HgSe : Fe quantum wires were grown on (0 0 1)GaSb substrates with a buffer of lattice-matched ZnTe 1- xSe x. Due to the anisotropic growth of HgSe on the A-oriented stripes roof-like overgrowth with a definite ridge was obtained. Additional Fe doping in the direct vicinity of the ridge results in a highly conductive quantum wire.

  15. Transport of Antarctic krill ( Euphausia superba) across the Scotia Sea. Part II: Krill growth and survival

    NASA Astrophysics Data System (ADS)

    Fach, Bettina A.; Hofmann, Eileen E.; Murphy, Eugene J.

    2006-06-01

    A time-dependent, size-structured, physiologically based krill growth model was used in conjunction with a circulation model to test the hypothesis that Antarctic krill ( Euphausia superba) populations at South Georgia are sustained by import of individuals from upstream regions. Surface phytoplankton concentrations along the simulated drifter trajectories were extracted from historical Coastal Zone Color Scanner (CZCS) measurements and sea ice biota concentrations were calculated from sea ice concentration and extent extracted along drifter trajectories from Special Sensor Microwave/Imager measurements. As additional food sources, a time series of heterotrophic food was constructed from historical data, and time series of detritus concentrations were calculated using phytoplankton concentrations extracted from CZCS measurements together with measured particulate organic carbon to chlorophyll a ratios. These food resources along specified drifter trajectories were then input to the krill growth model to determine the size and viability of krill during transport from the source region to South Georgia. The krill growth model simulations showed that no single food source can support continuous growth of krill during the 58-306 days needed for transport to South Georgia. However, under the current assumptions results indicate that combinations of food sources during the transport time enhanced krill survival, with heterotrophic food and detritus being particularly important during periods of low phytoplankton concentrations. The growth model simulations also showed that larval and juvenile krill originating along the western Antarctic Peninsula can grow to 1+ (14-36 mm) and 2+ (26-45 mm) age and size classes observed at South Georgia during the time needed for transport to this region. Krill originating in the Weddell Sea need 20 months for transport, which allows retention in a potentially high food environment, provided by sea ice, for almost 1 year. Krill then

  16. Treatment patterns and survival among low-income medicaid patients with head and neck cancer.

    PubMed

    Subramanian, Sujha; Chen, Amy

    2013-05-01

    Medicaid beneficiaries by definition are low income but they are not necessarily a homogeneous group. No study has assessed differences and disparities among Medicaid beneficiaries with head and neck cancers. To examine predictors of treatment receipt and mortality among Medicaid patients with head and neck cancer. Retrospective cohort study using Medicaid claims linked with cancer registry data for 2 states, California and Georgia, for the years 2002 through 2006. Inpatient and ambulatory care. Medicaid beneficiaries aged 18 to 64 years diagnosed as having head and neck cancer (N = 1308) were included. Descriptive statistics and multivariate regression models analyzed the likelihood of treatment receipt and survival. Receipt of treatment and 12- and 24-month mortality. Fewer than one-third of Medicaid patients with cancer received a diagnosis at an early stage. Overall, black patients were less likely to get surgical treatment and more likely to die than white patients, even after controlling for demographics, stage at diagnosis, and tumor site. Older age and disability status also increased 12-month mortality. Patients in California, who were alive for at least 12 months, have approximately half the odds of dying within 24 months compared with those in Georgia. Concrete steps should be taken to address the significant racial disparities observed in head and neck cancer outcomes among Medicaid beneficiaries. Further research is needed to explore the state-level policies and attributes to examine the startling differences in mortality among the state Medicaid programs analyzed in this study. Pooled comparisons of Medicaid beneficiaries with individuals covered by other types of insurance could mask important disparities among Medicaid beneficiaries, which need to be acknowledged and addressed to improve outcomes for these low-income patients with head and neck cancer.

  17. Pattern and Survival of Biliary Atresia Patients; Experience in Southern Nigeria

    PubMed Central

    Okoro, Philemon E; Igwe, Promise; Opara, Peace I

    2013-01-01

    Background: Biliary atresia (BA) has been a challenge to surgeons worldwide. Beyond the revolutionary surgical technique popularised by Kasai, liver transplantation has added renewed hope in the long-term outcome. In Nigeria, where late presentation is very common, there is need to assess the long-term results of the treatment options available to us. Aim: We aimed to evaluate the presentation and management outcome of BA and the long-term survival of BA patients seen in our practice. Materials and Methods: Cases of BA seen between January 2007 and December 2011 in three tertiary health facilities in South East Nigeria were included. Data obtained included age at presentation, clinical features, treatment offered and age at the time of death. Analysis was with the SPSS 17.0. Results: Twenty four patients comprising 10 (41.7%) males and 14 (58.3%) females were included in the study. The mean age of presentation was 4.02 (±214) months; range 1.75-11.0 months. Fifteen (62.5%) patients had surgery while 9 (37.5%) received medical treatment only. The mean age at death was 14.2 (±8.1) months; range 2.5-30 months. Conclusion: BA poses a daunting challenge in our practice. Outcome of treatment is still discouraging. We identified late presentation, lack of facilities to make early diagnosis, lack of adequately trained manpower to manage these children and lack of post-operative care and support for patients as the major challenges in the management of BA children in our region. PMID:24027409

  18. Vagrant western red-shouldered hawks: origins, natal dispersal patterns, and survival

    USGS Publications Warehouse

    Bloom, Peter H.; Scott, J. Michael; Papp, Joseph M.; Thomas, Scott E.; Kidd, Jeff W.

    2011-01-01

    We report the results of a 40-year study of the western Red-shouldered Hawk (Buteo lineatus elegans) involving the banding of 2742 nestlings in southern California from 1970 to 2009 (this study) plus 127 nestlings banded in other California studies (1956–2008) and the analyses of 119 records of subsequent recovery from the Bird Banding Laboratory (1957–2009). Of the Red-shouldered Hawks recovered, 109 (91.6%) moved 100 km (long-distance dispersers). Three (2.5%), all long-distance dispersers, were vagrants (recovered outside the species' range of residency), and were found 374 to 843 km northeast and south of their banding locations in the Mojave, Great Basin, and Vizcaino deserts. The distribution of directions of short-distance dispersal was bipolar, closely corresponding with the northwest—southeast orientation of the species' range in southern California, while that of long-distance dispersers was mainly to the north. One of 10 long-distance dispersers, a nonvagrant, survived well into the age of breeding (103.0 months), whereas eight of the other nine perished before 14.5 months. The implications of vagrancy for conservation of this resident subspecies are that a relatively small source area can contribute genetic material over a vastly larger receiving area but rarely does so because of high mortality rates. Nonetheless, the movements of vagrants we documented provide evidence for the species' potential to populate new landscapes in response to changing environmental conditions and to maintain genetic heterogeneity within existing populations.

  19. The anatomy of the corrugator supercilii muscle: part II. Supraorbital nerve branching patterns.

    PubMed

    Janis, Jeffrey E; Ghavami, Ashkan; Lemmon, Joshua A; Leedy, Jason E; Guyuron, Bahman

    2008-01-01

    This article focuses on delineation of supraorbital nerve branching patterns relative to the corrugator muscle fibers and identifies four branching patterns that help improve understanding of the local anatomy. Twenty-five fresh cadaver heads (50 corrugator supercilii muscles and 50 supraorbital nerves) were dissected and the corrugator supercilii muscles isolated. After corrugator supercilii muscle measurement points were recorded for part I of the study, the supraorbital nerve branches were then traced from their emergence points from the orbit and dissected out to the defined topographical boundaries of the muscle. Nerve branching patterns relative to the muscle fibers were analyzed, and a classification system for branching patterns relative to the muscle was created. Four types of supraorbital nerve branching patterns were found. In type I (40 percent), only the deep supraorbital nerve division sent branches that coursed directly along the undersurface of the muscle. In type II (34 percent), branches emerging directly from the superficial supraorbital nerve were found in addition to the branches from the deep division. Type III (4 percent) included discrete branches from the superficial division, but none from the deep division. In type IV (22 percent), significant branching began more cephalad relative to the muscle and, therefore, displayed no specific relation to the muscle fibers. Contrary to previous reports, both the deep and superficial divisions of the supraorbital nerve are intimately associated with corrugator supercilii muscle fibers. Four supraorbital nerve branching patterns from these divisions were found. Potential sites of supraorbital nerve compression were identified. This more detailed anatomical information may improve the safety and accuracy of performing complete corrugator supercilii muscle resection.

  20. Beclin-1 and LC3A expression in cutaneous malignant melanomas: a biphasic survival pattern for beclin-1.

    PubMed

    Sivridis, Efthimios; Koukourakis, Michael I; Mendrinos, Savvas E; Karpouzis, Antonios; Fiska, Aliki; Kouskoukis, Constantinos; Giatromanolaki, Alexandra

    2011-06-01

    Autophagy is an intracellular pathway for the degradation of long-lived proteins and damaged organelles. It is, in essence, a recycling process allowing cells to survive oxygen and nutrient depletion. The expression of two autophagy-related proteins, beclin 1 and light chain 3A (LC3A) was investigated in 79 nodular cutaneous melanomas. The results were correlated with histopathological factors, vascular density, and hypoxia-related proteins [hypoxia-inducible factors (HIF1α and HIF2α) and lactate dehydrogenase 5]. The reactivity of both autophagy-related proteins was uniformly cytoplasmically diffused. High beclin 1 and LC3A reactivity was related to tumor hypoxia, as this was inferred from the intense expression of HIF1α and lactate dehydrogenase 5, whereas low beclin 1 and LC3A expression was linked with an increased vascular density. In addition, beclin 1 was related to disease-specific survival which, however, exposed a biphasic pattern. A strong beclin 1 expression extending over a tumor area of more than 50% (high) was associated with an increased rate of early deaths, whereas a similarly strong, but less-extensive cytoplasmic reactivity (<10% tumor area; low) defined a sharp fall in the survival 5 years after surgery. Furthermore, the low beclin 1 expression was associated with high Breslow's depth, high Clark's level, and ulceration. Low LC3A expression was also related to ulceration, but not to other histopathological features nor prognosis. In multivariate analysis, beclin 1 was an independent prognostic variable. It is concluded that extensive autophagic activity is generated by tumor hypoxia and anaerobic glycolysis, whereas angiogenesis maintains low autophagic activity. Atg6/beclin 1 was proved to be capable of deciphering the prognosis in cutaneous malignant melanoma, but the matter requires further investigation.

  1. Survival by genotype: patterns at Mc1r are not black and white at the White Sands ecotone.

    PubMed

    Des Roches, S; Sollmann, R; Calhoun, K; Rothstein, A P; Rosenblum, E B

    2017-01-01

    Measuring links among genotype, phenotype and survival in the wild has long been a focus of studies of adaptation. We conducted a 4-year capture-recapture study to measure survival by genotype and phenotype in the Southwestern Fence Lizard (Sceloporus cowlesi) at the White Sands ecotone (transition area between white sands and dark soil habitats). We report several unanticipated findings. First, in contrast with previous work showing that cryptic blanched coloration in S. cowlesi from the heart of the dunes is associated with mutations in the melanocortin-1 receptor gene (Mc1r), ecotonal S. cowlesi showed minimal association between colour phenotype and Mc1r genotype. Second, the frequency of the derived Mc1r allele in ecotonal S. cowlesi appeared to decrease over time. Third, our capture-recapture data revealed a lower survival rate for S. cowlesi individuals with the derived Mc1r allele. Thus, our results suggest that selection at the ecotone may have favoured the wild-type allele in recent years. Even in a system where a genotype-phenotype association appeared to be black and white, our study suggests that additional factors - including phenotypic plasticity, epistasis, pleiotropy and gene flow - may play important roles at the White Sands ecotone. Our study highlights the importance of linking molecular, genomic and organismal approaches for understanding adaptation in the wild. Furthermore, our findings indicate that dynamics of natural selection can be particularly complex in transitional habitats like ecotones and emphasize the need for future research that examines the patterns of ongoing selection in other ecological 'grey' zones.

  2. Applying Data Mining Techniques to Extract Hidden Patterns about Breast Cancer Survival in an Iranian Cohort Study.

    PubMed

    Khalkhali, Hamid Reza; Lotfnezhad Afshar, Hadi; Esnaashari, Omid; Jabbari, Nasrollah

    2016-01-01

    Breast cancer survival has been analyzed by many standard data mining algorithms. A group of these algorithms belonged to the decision tree category. Ability of the decision tree algorithms in terms of visualizing and formulating of hidden patterns among study variables were main reasons to apply an algorithm from the decision tree category in the current study that has not studied already. The classification and regression trees (CART) was applied to a breast cancer database contained information on 569 patients in 2007-2010. The measurement of Gini impurity used for categorical target variables was utilized. The classification error that is a function of tree size was measured by 10-fold cross-validation experiments. The performance of created model was evaluated by the criteria as accuracy, sensitivity and specificity. The CART model produced a decision tree with 17 nodes, 9 of which were associated with a set of rules. The rules were meaningful clinically. They showed in the if-then format that Stage was the most important variable for predicting breast cancer survival. The scores of accuracy, sensitivity and specificity were: 80.3%, 93.5% and 53%, respectively. The current study model as the first one created by the CART was able to extract useful hidden rules from a relatively small size dataset.

  3. Metabolic patterns associated with the seasonal rhythm of seed survival after dehydration in germinated seeds of Schismus arabicus.

    PubMed

    Bai, Bing; Toubiana, David; Gendler, Tanya; Degu, Asfaw; Gutterman, Yitzchak; Fait, Aaron

    2015-02-05

    Seed of Shismus arabicus, a desert annual, display a seasonal tolerance to dehydration. The occurrence of a metabolic seasonal rhythm and its relation with the fluctuations in seed dehydration tolerance was investigated. Dry seeds metabolism was the least affected by the season, while the metabolism of germinated and dehydrated seeds exhibit distinct seasonal patterns. Negative associations exist between amino acids, sugars and TCA cycle intermediates and seed survival, while positive relations exist with seed germination. In contrast, associations between the level of secondary metabolites identified in the dehydrated seeds and survival percentage were evenly distributed in positive and negative values, suggesting a functional role of these metabolites in the establishment of seed dehydration tolerance. Our results indicate the occurrence of metabolic biorhythms in germinating and dehydrating seeds associated with seasonal changes in germination and, more pronouncedly, in seed dehydration tolerance. Increased biosynthesis of protective compounds (polyphenols) in dehydrating seeds during the winter season at the expenses of central metabolites likely contributes to the respective enhanced dehydration tolerance monitored.

  4. Cellular automata with inertia: species competition, spatial patterns, and survival in ecotones

    NASA Astrophysics Data System (ADS)

    Kramer, K.; Koehler, M.; da Luz, M. G. E.

    2010-09-01

    We consider a two-dimensional CA model with three possible states for the system individual cells, 0 and ±. As for the dynamical rules, only ± can exert pressure to change the cells actual states. In this way, the 0 state is neutral and in some sense competitively weaker than the other two states. We further assume an inner property, the inertia, which is an intrinsic resistance to changes in the system. We evolve an ensemble of initial configurations for the CA until reaching steady states. By calculating averages over some relevant quantities for the final stationary configurations, we discuss how certain features of the problem, namely, initial states population and degree of aggregation as well as the values of inertia, can determine the different characteristics of the spatio-temporal pattern created by the CA evolution. We finally discuss how our findings may be relevant in the understanding of structures formation due to species competition in biology, specially in the transition regions between different biomes, the so called ecotones.

  5. Intracellular Production of Brucella L Forms II. Induction and Survival of Brucella abortus L Forms in Tissue Culture1

    PubMed Central

    Hatten, Betty A.; Sulkin, S. Edward

    1966-01-01

    Hatten, Betty A. (The University of Texas Southwestern Medical School, Dallas), and S. Edward Sulkin. Intracellular production of Brucella L forms. II. Induction and survival of Brucella abortus L forms in tissue culture. J. Bacteriol. 91:14–20. 1966.—Intracellular survival of altered brucellae, possibly L forms, was not greatly affected by penicillin or streptomycin in concentrations ranging from 5.0 to 40 μg/ml, but a combination of these two antibiotics (2.5 to 20 μg/ml each) reduced the number of positive L-form cultures. Tetracycline (2.0 μg/ml) decreased the number of positive L-form cultures at about the same rate as combinations of the higher concentrations of penicillin and streptomycin. Various concentrations of tetracycline (0.1 to 2.0 μg/ml) with 5.0 μg/ml of penicillin or streptomycin significantly reduced the number of positive L-form cultures. L forms were recovered for several days after elimination of bacteria from the cultures by all of the antibiotics tested. L-form production was not dependent upon the presence of antibiotics in the culture medium, but they were recovered in greater numbers when bacteria were still present in the hamster kidney cells. Addition of thallium acetate to infected cells (at varying intervals of time after infection) to control bacterial growth and conversion to the L phase during cellular disintegration decreased the number of positive L-form cultures obtained over a 10-day period. Comparison of the antibiotic sensitivity of bacteria recovered from infected tissue culture cells with the stock strain of Brucella abortus indicated that some resistance to penicillin and tetracycline had developed. A marked resistance to streptomycin was observed in those bacteria recovered from cells maintained in the presence of this antibiotic. PMID:4955246

  6. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

    PubMed

    Dienstmann, R; Mason, M J; Sinicrope, F A; Phipps, A I; Tejpar, S; Nesbakken, A; Danielsen, S A; Sveen, A; Buchanan, D D; Clendenning, M; Rosty, C; Bot, B; Alberts, S R; Milburn Jessup, J; Lothe, R A; Delorenzi, M; Newcomb, P A; Sargent, D; Guinney, J

    2017-05-01

    TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include

  7. Treatment patterns and survival in metastatic breast cancer patients by tumor characteristics.

    PubMed

    Hao, Yanni; Meyer, Nicole; Song, Xue; Shi, Nianwen; Johnson, William; Juneau, Paul; Yardley, Denise A; Willemann Rogerio, Jaqueline

    2015-02-01

    Study objectives were to compare the treatment patterns and clinical outcomes among metastatic breast cancer (mBC) patients by receipt of HER2-targeted agents and among subgroups of HER2-targeted agent users. Adult women newly diagnosed with mBC (index date) during 2008-2012 were selected from the Truven MarketScan databases and followed until end of enrollment or inpatient death. Patients with <12 months of data, pre-index primary cancers other than breast cancer, pregnancy, or HIV/AIDS were excluded. Study cohorts were users and nonusers of HER2-targeted agents and women with no treatment; and HER2-targeted agent subgroups by receipt of hormonal therapy (HT), de novo vs. recurrent status, and age group. Pre- and post-index breast cancer treatments were compared across cohorts. Relative risk of progression and death were evaluated among the subset of patients with mortality data. Of 18,059 eligible women selected, 14.6% were users of HER2-targeted agents, 71.1% were nonusers, and 14.3% untreated. HER2-targeted agent users received more aggressive cancer treatments compared to nonusers. HER2-targeted agent users were 33% more likely to progress and had a similar risk of death compared to nonusers. Among HER2-targeted agent subgroups, the risk of progression was 30% lower among HT+ patients vs. HT-, 32% lower for de novo vs. recurrent, and similar across age groups. The risk of death was 52% lower for HT+ vs. HT-, 35% lower for de novo vs. recurrent, and increased with age. Identification of distant metastasis, tumor receptor expression and disease progression were based on claims data rather than on clinical assessment. Receipt of HER2-targeted agents (vs. non-HER2-targeted agents) was significantly associated with receipt of pre- and post-index breast cancer treatments. HER2-targeted agent users were more likely to progress but had a similar risk of death during follow-up. Among HER2-targeted agent subgroups, HT+ and de novo status were associated with a reduced

  8. Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse.

    PubMed

    Hale, L J; Welsh, G I; Perks, C M; Hurcombe, J A; Moore, S; Hers, I; Saleem, M A; Mathieson, P W; Murphy, A J; Jeansson, M; Holly, J M; Hardouin, S N; Coward, R J

    2013-05-01

    Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species.

  9. Human RNA polymerase II subunit hsRPB7 functions in yeast and influences stress survival and cell morphology.

    PubMed

    Khazak, V; Sadhale, P P; Woychik, N A; Brent, R; Golemis, E A

    1995-07-01

    Using a screen to identify human genes that promote pseudohyphal conversion in Saccharomyces cerevisiae, we obtained a cDNA encoding hsRPB7, a human homologue of the seventh largest subunit of yeast RNA polymerase II (RPB7). Overexpression of yeast RPB7 in a comparable strain background caused more pronounced cell elongation than overexpression of hsRPB7. hsRPB7 sequence and function are strongly conserved with its yeast counterpart because its expression can rescue deletion of the essential RPB7 gene at moderate temperatures. Further, immuno-precipitation of RNA polymerase II from yeast cells containing hsRPB7 revealed that the hsRPB7 assembles the complete set of 11 other yeast subunits. However, at temperature extremes and during maintenance at stationary phase, hsRPB7-containing yeast cells lose viability rapidly, stress-sensitive phenotypes reminiscent of those associated with deletion of the RPB4 subunit with which RPB7 normally complexes. Two-hybrid analysis revealed that although hsRPB7 and RPB4 interact, the association is of lower affinity than the RPB4-RPB7 interaction, providing a probable mechanism for the failure of hsRPB7 to fully function in yeast cells at high and low temperatures. Finally, surprisingly, hsRPB7 RNA in human cells is expressed in a tissue-specific pattern that differs from that of the RNA polymerase II largest subunit, implying a potential regulatory role for hsRPB7. Taken together, these results suggest that some RPB7 functions may be analogous to those possessed by the stress-specific prokaryotic sigma factor rpoS.

  10. Human RNA polymerase II subunit hsRPB7 functions in yeast and influences stress survival and cell morphology.

    PubMed Central

    Khazak, V; Sadhale, P P; Woychik, N A; Brent, R; Golemis, E A

    1995-01-01

    Using a screen to identify human genes that promote pseudohyphal conversion in Saccharomyces cerevisiae, we obtained a cDNA encoding hsRPB7, a human homologue of the seventh largest subunit of yeast RNA polymerase II (RPB7). Overexpression of yeast RPB7 in a comparable strain background caused more pronounced cell elongation than overexpression of hsRPB7. hsRPB7 sequence and function are strongly conserved with its yeast counterpart because its expression can rescue deletion of the essential RPB7 gene at moderate temperatures. Further, immuno-precipitation of RNA polymerase II from yeast cells containing hsRPB7 revealed that the hsRPB7 assembles the complete set of 11 other yeast subunits. However, at temperature extremes and during maintenance at stationary phase, hsRPB7-containing yeast cells lose viability rapidly, stress-sensitive phenotypes reminiscent of those associated with deletion of the RPB4 subunit with which RPB7 normally complexes. Two-hybrid analysis revealed that although hsRPB7 and RPB4 interact, the association is of lower affinity than the RPB4-RPB7 interaction, providing a probable mechanism for the failure of hsRPB7 to fully function in yeast cells at high and low temperatures. Finally, surprisingly, hsRPB7 RNA in human cells is expressed in a tissue-specific pattern that differs from that of the RNA polymerase II largest subunit, implying a potential regulatory role for hsRPB7. Taken together, these results suggest that some RPB7 functions may be analogous to those possessed by the stress-specific prokaryotic sigma factor rpoS. Images PMID:7579693

  11. Determination of Class II and Class III skeletal patterns: receiver operating characteristic (ROC) analysis on various cephalometric measurements.

    PubMed

    Han, U K; Kim, Y H

    1998-05-01

    Receiver operating characteristic analysis is an excellent method for evaluating and comparing the performance of diagnostic tests. The purpose of this study was to use the receiver operating characteristic analysis to evaluate the diagnostic ability of several cephalometric measurements in determining the presence of Class II and Class III skeletal patterns. Receiver operating characteristic analysis was performed on 976 cases. Fifteen cephalometric measurements were evaluated. A computer software program ROC ANALYZER was used to tabulate the areas under the curves and to perform the statistical comparison between the curves. The results of this study indicated that the Anteroposterior Dysplasia Indicator had the best diagnostic ability in identifying cases with Class II and Class III skeletal patterns. WITS Appraisal and Overjet were highly effective in diagnosing cases with Class II skeletal pattern. WITS Appraisal, Convexity, AB Plane Angle and Overjet also performed well in diagnosing cases with Class III skeletal pattern.

  12. Protein kinase A-mediated CREB phosphorylation is an oxidant-induced survival pathway in alveolar type II cells

    PubMed Central

    Barlow, Christy A.; Kitiphongspattana, Kajorn; Siddiqui, Nazli; Roe, Michael W.; Mossman, Brooke T.

    2008-01-01

    Oxidant stress plays a role in the pathogenesis of pulmonary diseases, including fibrotic lung disease and cancer. We previously found that hydrogen peroxide (H2O2) initiates an increase in Ca2+/cAMP-response element binding protein (CREB) phosphorylation in C10 alveolar type II cells that requires activation of extracellular regulated kinases 1/2 (ERK1/2). Here, we investigated the role of crosstalk between protein kinase A (PKA) and epidermal growth factor receptor (EGFR) in oxidant-induced signaling to ERK1/2 and CREB in C10 cells. Application of H2O2 increased nuclear accumulation of PKA, and inhibition of PKA with H89 reduced oxidant-mediated phosphorylation of both CREB and ERK1/2. Single cell measurements of cAMP and redox status, using a FRET-based biosensor and a redox-sensitive GFP, respectively, indicated that H2O2 increases production of cAMP that correlates with redox state. Inhibition of EGFR activity decreased both H2O2-induced CREB phosphorylation and translocation of PKA to the nucleus, suggesting that crosstalk between PKA and EGFR underlies the oxidant-induced CREB response. Furthermore, knockdown of CREB expression using siRNA led to a decrease in bcl-2 and an increase in oxidant-induced apoptosis. Together these data reveal a novel role for crosstalk between PKA, ERK1/2 and CREB that mediates cell survival during oxidant stress. PMID:18392938

  13. High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

    PubMed Central

    Jørgensen, Stine; Fog, Jacob Ulrik; Søkilde, Rolf; Christensen, Ib Jarle; Hansen, Ulla; Brünner, Nils; Baker, Adam; Møller, Søren; Nielsen, Hans Jørgen

    2010-01-01

    Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust in situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The miR-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06–1.55) in the stage II colon cancer patient group, whereas no significant correlation with disease-free survival was observed in the stage II rectal cancer group. In multivariate analysis both TB and TBR estimates were independent of other clinical parameters (age, gender, total leukocyte count, K-RAS mutational status and MSI). We conclude that miR-21 is primarily a stromal microRNA, which when measured by image analysis identifies a subgroup of stage II colon cancer patients with short disease-free survival. Electronic supplementary material The online version of this article (doi:10.1007/s10585-010-9355-7) contains supplementary material, which is available to authorized users. PMID:21069438

  14. Evaluation of mandibular length in subjects with Class I and Class II skeletal patterns using the cervical vertebrae maturation.

    PubMed

    Generoso, Rodrigo; Sadoco, Elaine Cristina; Armond, Mônica Costa; Gameiro, Gustavo Hauber

    2010-01-01

    The aim of this study was to compare the mandibular size in boys and girls with Class I and Class II skeletal patterns, taking into consideration the bone maturation stage, as defined by the cervical vertebrae maturation. One hundred and sixty cephalometric radiographs were obtained from subjects (aged between 7 and 12 years) with Class I or Class II skeletal patterns, according to the ANB angle and WITS appraisal. The Class I sample consisted of 80 subjects (40 boys, 40 girls). The Class II sample also consisted of 80 subjects (40 boys, 40 girls). On a cross-sectional basis, mandibular length (Co-Gn) was compared between groups and genders. The between-stages changes were also evaluated, with the cervical vertebrae analysis used for establishing the bone maturation stages at CS2, CS3, CS4 and CS5. The results were statistically analyzed by the Kruskal-Wallis test. The mandibular length differed between skeletal patterns only at the earlier stages of development. In the Class I pattern, the mandibular lengths of boys were greater than those of girls at stages CS2, CS4 and CS5, whereas in the Class II pattern, the mandibular lengths of boys were greater than those of girls at stages CS2, CS3 and CS4. The present results indicate a sexual dimorphism in the mandibular length at almost all stages of bone maturation, in exception of the CS5 stage in Class II.

  15. Computational Analysis of Intra-Ventricular Flow Pattern Under Partial and Full Support of BJUT-II VAD

    PubMed Central

    Zhang, Qi; Gao, Bin; Chang, Yu

    2017-01-01

    Background Partial support, as a novel support mode, has been widely applied in clinical practice and widely studied. However, the precise mechanism of partial support of LVAD in the intra-ventricular flow pattern is unclear. Material/Methods In this study, a patient-specific left ventricular geometric model was reconstructed based on CT data. The intra-ventricular flow pattern under 3 simulated conditions – “heart failure”, “partial support”, and “full support” – were simulated by using fluid-structure interaction (FSI). The blood flow pattern, wall shear stress (WSS), time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated to evaluate the hemodynamic effects. Results The results demonstrate that the intra-ventricular flow pattern is significantly changed by the support level of BJUT-II VAD. The intra-ventricular vortex was enhanced under partial support and was eliminated under full support, and the high OSI and RRT regions changed from the septum wall to the cardiac apex. Conclusions In brief, the support level of the BJUT-II VAD has significant effects on the intra-ventricular flow pattern. The partial support mode of BJUT-II VAD can enhance the intra-ventricular vortex, while the distribution of high OSI and RRT moved from the septum wall to the cardiac apex. Hence, the partial support mode of BJUT-II VAD can provide more benefit for intra-ventricular flow pattern. PMID:28239142

  16. Computational Analysis of Intra-Ventricular Flow Pattern Under Partial and Full Support of BJUT-II VAD.

    PubMed

    Zhang, Qi; Gao, Bin; Chang, Yu

    2017-02-27

    BACKGROUND Partial support, as a novel support mode, has been widely applied in clinical practice and widely studied. However, the precise mechanism of partial support of LVAD in the intra-ventricular flow pattern is unclear. MATERIAL AND METHODS In this study, a patient-specific left ventricular geometric model was reconstructed based on CT data. The intra-ventricular flow pattern under 3 simulated conditions - "heart failure", "partial support", and "full support" - were simulated by using fluid-structure interaction (FSI). The blood flow pattern, wall shear stress (WSS), time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated to evaluate the hemodynamic effects. RESULTS The results demonstrate that the intra-ventricular flow pattern is significantly changed by the support level of BJUT-II VAD. The intra-ventricular vortex was enhanced under partial support and was eliminated under full support, and the high OSI and RRT regions changed from the septum wall to the cardiac apex. CONCLUSIONS In brief, the support level of the BJUT-II VAD has significant effects on the intra-ventricular flow pattern. The partial support mode of BJUT-II VAD can enhance the intra-ventricular vortex, while the distribution of high OSI and RRT moved from the septum wall to the cardiac apex. Hence, the partial support mode of BJUT-II VAD can provide more benefit for intra-ventricular flow pattern.

  17. Gene expression patterns during somatic embryo development and germination in maize Hi II callus cultures.

    PubMed

    Che, Ping; Love, Tanzy M; Frame, Bronwyn R; Wang, Kan; Carriquiry, Alicia L; Howell, Stephen H

    2006-09-01

    Gene expression patterns were profiled during somatic embryogenesis in a regeneration-proficient maize hybrid line, Hi II, in an effort to identify genes that might be used as developmental markers or targets to optimize regeneration steps for recovering maize plants from tissue culture. Gene expression profiles were generated from embryogenic calli induced to undergo embryo maturation and germination. Over 1,000 genes in the 12,060 element arrays showed significant time variation during somatic embryo development. A substantial number of genes were downregulated during embryo maturation, largely histone and ribosomal protein genes, which may result from a slowdown in cell proliferation and growth during embryo maturation. The expression of these genes dramatically recovered at germination. Other genes up-regulated during embryo maturation included genes encoding hydrolytic enzymes (nucleases, glucosidases and proteases) and a few storage genes (an alpha-zein and caleosin), which are good candidates for developmental marker genes. Germination is accompanied by the up-regulation of a number of stress response and membrane transporter genes, and, as expected, greening is associated with the up-regulation of many genes encoding photosynthetic and chloroplast components. Thus, some, but not all genes typically associated with zygotic embryogenesis are significantly up or down-regulated during somatic embryogenesis in Hi II maize line regeneration. Although many genes varied in expression throughout somatic embryo development in this study, no statistically significant gene expression changes were detected between total embryogenic callus and callus enriched for transition stage somatic embryos.

  18. A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery.

    PubMed

    Peng, Jian-Hong; Fang, Yu-Jing; Li, Cai-Xia; Ou, Qing-Jian; Jiang, Wu; Lu, Shi-Xun; Lu, Zhen-Hai; Li, Pei-Xing; Yun, Jing-Ping; Zhang, Rong-Xin; Pan, Zhi-Zhong; Wan, De Sen

    2016-04-19

    Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

  19. Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study

    PubMed Central

    Mason, M. J.; Sinicrope, F. A.; Phipps, A. I.; Tejpar, S.; Nesbakken, A.; Danielsen, S. A.; Sveen, A.; Buchanan, D. D.; Clendenning, M.; Rosty, C.; Bot, B.; Alberts, S. R.; Milburn Jessup, J.; Lothe, R. A.; Delorenzi, M.; Newcomb, P. A.; Sargent, D.; Guinney, J.

    2017-01-01

    Background TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)—N0147 (NCT00079274) and PETACC3 (NCT00026273)—was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). Results TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61–0.68 in the TNM alone model to 0.63–0.71 in models with added molecular markers, 0.65–0.73 with clinicopathological features and 0.66–0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Conclusions Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases

  20. A Retrospective Study of the 3-Year Survival Rate of Resin-Modified Glass-Ionomer Cement Class II Restorations in Primary Molars.

    PubMed

    Webman, Mark; Mulki, Ezat; Roldan, Rosie; Arevalo, Oscar; Roberts, John F; Garcia-Godoy, Franklin

    2016-01-01

    To determine the three-year survival rate of Class II resin-modified glass-ionomer cement (RMGIC), Vitremer, restorations in primary molars and to compare these results with measurements of survival of Class II restorations of standard restorative materials. Data on Class II restorations placed in primary molars during a six-year period were collected through a chart review and radiographic evaluation in the office of a board-certified pediatric dentist. A radiograph showing that the restoration was intact was required at least 3 years after placement to qualify as successful. If no radiograph existed, the restoration was excluded. If the restoration was not found to be intact radiographically or was charted as having been replaced before three years it was recorded as a failure. The results of this study were then compared to other standard restorative materials using normalized annual failure rates. Of the 1,231 Class II resinmodified glass-ionomer cement restorations placed over six years 427 met the inclusion criteria. There was a 97.42% survival rate for a 3-year period equivalent to an annual failure rate of 0.86%. A novel approach comparing materials showed that in this study Vitremer compared very favorably to previously published success rates of other standard restorative materials (amalgam, composite, stainless steel crown, compomer) and other RMGIC studies.

  1. APACHE II scoring system on a general intensive care unit: audit of daily APACHE II scores and 6-month survival of 691 patients admitted to a general intensive care unit between May 1990 and December 1991.

    PubMed Central

    Campbell, N N; Tooley, M A; Willatts, S M

    1994-01-01

    In this paper we present a detailed analysis of the use of the APACHE II (acute physiological and chronic health evaluation) scoring system on all of the patients admitted to the general intensive care unit at the Bristol Royal Infirmary over a 20-month period. The 6-month survival of 691 adult medical and surgical patients following intensive care was recorded and this data was analysed with admission and daily APACHE II scores using a relational database. Our data confirms the relationship between admission APACHE II scores and outcome, with mean scores decreasing as duration of survival increases. We also demonstrate that the best day one scores are approximately 50% less than the admission score, irrespective of outcome, indicating the benefit of intensive care. By contrast, however, the scores on day one have either not improved or have worsened since admission, reflecting the importance of the pre-morbid health status of the patient in determining outcome from intensive care. PMID:8196033

  2. Prognostic interaction patterns in diabetes mellitus II: A random-matrix-theory relation

    NASA Astrophysics Data System (ADS)

    Rai, Aparna; Pawar, Amit Kumar; Jalan, Sarika

    2015-08-01

    We analyze protein-protein interactions in diabetes mellitus II and its normal counterpart under the combined framework of random matrix theory and network biology. This disease is the fifth-leading cause of death in high-income countries and an epidemic in developing countries, affecting around 8 % of the total adult population in the world. Treatment at the advanced stage is difficult and challenging, making early detection a high priority in the cure of the disease. Our investigation reveals specific structural patterns important for the occurrence of the disease. In addition to the structural parameters, the spectral properties reveal the top contributing nodes from localized eigenvectors, which turn out to be significant for the occurrence of the disease. Our analysis is time-efficient and cost-effective, bringing a new horizon in the field of medicine by highlighting major pathways involved in the disease. The analysis provides a direction for the development of novel drugs and therapies in curing the disease by targeting specific interaction patterns instead of a single protein.

  3. Prognostic interaction patterns in diabetes mellitus II: A random-matrix-theory relation.

    PubMed

    Rai, Aparna; Pawar, Amit Kumar; Jalan, Sarika

    2015-08-01

    We analyze protein-protein interactions in diabetes mellitus II and its normal counterpart under the combined framework of random matrix theory and network biology. This disease is the fifth-leading cause of death in high-income countries and an epidemic in developing countries, affecting around 8% of the total adult population in the world. Treatment at the advanced stage is difficult and challenging, making early detection a high priority in the cure of the disease. Our investigation reveals specific structural patterns important for the occurrence of the disease. In addition to the structural parameters, the spectral properties reveal the top contributing nodes from localized eigenvectors, which turn out to be significant for the occurrence of the disease. Our analysis is time-efficient and cost-effective, bringing a new horizon in the field of medicine by highlighting major pathways involved in the disease. The analysis provides a direction for the development of novel drugs and therapies in curing the disease by targeting specific interaction patterns instead of a single protein.

  4. Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival.

    PubMed

    Kuba, Sayaka; Ohtani, Hiroshi; Yamaguchi, Junzo; Hayashi, Hiroko; Uga, Tatsuya; Kanematsu, Takashi; Shimokawa, Isao

    2011-02-01

    Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.

  5. Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study

    PubMed Central

    Pugh, Siân A; Bowers, Megan; Ball, Alexandre; Falk, Stephen; Finch-Jones, Meg; Valle, Juan W; O'Reilly, Derek A; Siriwardena, Ajith K; Hornbuckle, Joanne; Rees, Myrddin; Rees, Charlotte; Iveson, Tim; Hickish, Tamas; Maishman, Tom; Stanton, Louise; Dixon, Elizabeth; Corkhill, Andrea; Radford, Mike; Garden, O James; Cunningham, David; Maughan, Tim S; Bridgewater, John A; Primrose, John N

    2016-01-01

    Background: The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome. Methods: A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012. Results: The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent. Conclusions: Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery. PMID:27434036

  6. Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study.

    PubMed

    Pugh, Siân A; Bowers, Megan; Ball, Alexandre; Falk, Stephen; Finch-Jones, Meg; Valle, Juan W; O'Reilly, Derek A; Siriwardena, Ajith K; Hornbuckle, Joanne; Rees, Myrddin; Rees, Charlotte; Iveson, Tim; Hickish, Tamas; Maishman, Tom; Stanton, Louise; Dixon, Elizabeth; Corkhill, Andrea; Radford, Mike; Garden, O James; Cunningham, David; Maughan, Tim S; Bridgewater, John A; Primrose, John N

    2016-08-09

    The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome. A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012. The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent. Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.

  7. Effect of changing patterns of care and duration of survival on the cost of treating the acquired immunodeficiency syndrome (AIDS).

    PubMed Central

    Seage, G R; Landers, S; Lamb, G A; Epstein, A M

    1990-01-01

    We performed a two-year cost of illness study of 240 AIDS patients (55 percent of all Massachusetts cases) diagnosed and treated at five hospitals from March 1984 through February 1986. Sociodemographic and clinical data as well as information on medical utilization were obtained from review of inpatient and outpatient hospital records. The yearly inpatient cost per patient decreased by 28 percent from $38,369 in year one to $27,714 in year two. These changes were related to shorter lengths of stay (from 20.6 days to 16.8 days per hospitalization, mean difference of 3.8 days, 95% CI of the difference -.2, 7.8), and less costly hospitalizations (from $12,463 to $9,957, mean difference of $2,506, 95% CI of the difference $135, $4,877). The probability of hospitalization, however, was similar in both years. These patterns of care were still evident after controlling for transmission category, race, site, mortality, insurance, age, gender, number and type of opportunistic diseases and time since diagnosis. Although the cost per patient per year decreased between years one and two, median survival increased by 70 percent (from 10 to 17 months). Hence overall estimated lifetime costs increased by 24 percent. PMID:2356908

  8. Segal crystallinity index revisited by the simulation of X-ray diffraction patterns of cotton cellulose Iβ and cellulose II.

    PubMed

    Nam, Sunghyun; French, Alfred D; Condon, Brian D; Concha, Monica

    2016-01-01

    The Segal method estimates the amorphous fraction of cellulose Iβ materials simply based on intensity at 18° 2θ in an X-ray diffraction pattern and was extended to cellulose II using 16° 2θ intensity. To address the dependency of Segal amorphous intensity on crystal size, cellulose polymorph, and the degree of polymorphic conversion, we simulated the diffraction patterns of cotton celluloses (Iβ and II) and compared the simulated amorphous fractions with the Segal values. The diffraction patterns of control and mercerized cottons, respectively, were simulated with perfect crystals of cellulose Iβ (1.54° FWHM) and cellulose II (2.30° FWHM) as well as 10% and 35% amorphous celluloses. Their Segal amorphous fractions were 15% and 31%, respectively. The higher Segal amorphous fraction for control cotton was attributed to the peak overlap. Although the amorphous fraction was set in the simulation, the peak overlap induced by the increase of FWHM further enhanced the Segal amorphous intensity of cellulose Iβ. For cellulose II, the effect of peak overlap was smaller; however the lower reflection of the amorphous cellulose scattering in its Segal amorphous location resulted in smaller Segal amorphous fractions. Despite this underestimation, the relatively good agreement of the Segal method with the simulation for mercerized cotton was attributed to the incomplete conversion to cellulose II. The (1-10) and (110) peaks of cellulose Iβ remained near the Segal amorphous location of cellulose II for blends of control and mercerized cotton fibers.

  9. Lysosomal acid phosphatase 2 is an unfavorable prognostic factor but is associated with better survival in stage II colorectal cancer patients receiving chemotherapy.

    PubMed

    Lee, Yu-Chieh; Su, Chia-Yu; Lin, Yuan-Feng; Lin, Chun-Mao; Fang, Chih-Yeu; Lin, Yen-Kuang; Hsiao, Michael; Chen, Chi-Long

    2017-02-14

    Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression (p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors.Among patients who received chemotherapy, those with an high expression of ACP2 showed better survival in both stage II and III CRC than those with low ACP2 expression. In stage II CRC patients, univariate analysis showed ACP2 expression and T stage to be cofactors significantly associated with overall survival (ACP2: p = 0.006; T stage: p = 0.034). Multivariate Cox proportion hazard model analysis also revealed ACP2 to be an independent prognostic factor for overall survival (ACP2: p = 0.006; T stage: p = 0.041). Furthermore, ACP2-knockdown CRC cells showed an increase in chemoresistance to 5-FU treatment and increased proliferation marker in the ACP2 knockdown clone.Taken together, our results suggested that ACP2 is an unfavorable prognostic factor for stage II CRC and may serve as a potential chemotherapy-sensitive marker to help identify a subset of stage II and III CRC patients for whom chemotherapy would improve survival.Highlights1. To the best of our knowledge, the study is the first report to show ACP2 overexpression in human colorectal cancer (CRC) and its association with poor outcome in stage II CRC.2. Patients with stage II and III CRCs with high expression of ACP2 were more sensitive to chemotherapy than those with a low expression.3. ACP2 expression may serve as a marker for CRC patients receiving chemotherapy and help identify the subset of CRC patients who would

  10. Changes in the patterns of care of central nervous system tumours among 16-24 year olds and the effect on survival in Yorkshire between 1990 and 2009.

    PubMed

    Nicholson, B D; Picton, S V; Chumas, P; Dixit, S; van Laar, M; Loughrey, C; O'Reilly, G; Stark, D P; Feltbower, R G

    2013-03-01

    There is a paucity of work documenting the influence of patterns of care on survival for teenagers and young adults with primary central nervous system tumours. Therefore, the aim of this study was to undertake a detailed assessment examining any changes in the patterns of care over time and how these related to survival outcomes for 16-24 year olds diagnosed with a primary central nervous system tumour between 1990 and 2009. We used high-quality data from one population-based cancer registry in Yorkshire, UK to describe primary central nervous system tumours in teenagers and young adults (16-24 years) diagnosed between 1990 and 2009. The Birch classification scheme was used to identify differences by tumour subgroup. Incidence, patterns of care and survival trends were described using Poisson and Cox regression. There were 163 cases comprising 98 astrocytomas, 17 'other gliomas', 14 ependymomas, 11 medulloblastomas and 23 'other intracranial and intraspinal neoplasms' yielding an overall incidence of 18.1 million person-years. Care varied significantly over time and by principal treatment centre (Leeds 77%, Hull 23%), co-ordinating specialty (neurosurgery 53%, clinical oncology 22%, paediatrics 17%, other adult services 8%) and treatment received. Cox regression showed no significant difference in survival by age, gender, treatment centre, level of deprivation, year of diagnosis or co-ordinating specialty, but a significant difference by tumour grade and diagnostic group. Survival improved for all diagnostic groups except astrocytoma, although only the medulloblastoma group showed a significant change over time. The lack of any significant improvement in survival over time in most diagnostic groups warrants further investigation and provides justification for a more collaborative regional approach to the care of central nervous system tumours, perhaps through the development of regional guidelines for this unique population. More detailed analysis of relapse

  11. UVB-induced DNA and photosystem II damage in two intertidal green macroalgae: distinct survival strategies in UV-screening and non-screening Chlorophyta.

    PubMed

    Pescheck, Frauke; Lohbeck, Kai T; Roleda, Michael Y; Bilger, Wolfgang

    2014-03-05

    Ultraviolet-B-induced (UVB, 280-315 nm) accumulation of cyclobutane pyrimidine dimers (CPDs) and deactivation of photosystem II (PS II) was quantified in two intertidal green macroalgae, Ulva clathrata and Rhizoclonium riparium. The species were chosen due to their shared habitats but contrasting UVB screening potentials. In the non-screening U. clathrata CPDs accumulated and PS II activity declined as a linear function of applied UVB irradiance. In R. riparium UVB-induced damage was significantly lower than in U. clathrata, demonstrating an efficient UVB protection of DNA and PS II by screening. Based on the UVB irradiance reaching the chloroplasts, both species showed an identical intrinsic sensitivity of PS II towards UVB, but DNA lesions accumulated slower in U. clathrata. While repair of CPDs was similar in both species, U. clathrata was capable of restoring its PS II function decidedly faster than R. riparium. In R. riparium efficient screening may represent an adaptation to its high light habitat, whereas in U. clathrata high repair rates of PS II appear to be important to survive natural UVB exposure. The role of shading of the nucleus by the large chloroplasts in U. clathrata is discussed.

  12. Diabetic Ketoacidosis in an Adult Patient With Spinal Muscular Atrophy Type II: Further Evidence of Extraneural Pathology Due to Survival Motor Neuron 1 Mutation?

    PubMed

    Lamarca, Nicole Holuba; Golden, Lauren; John, Rita Marie; Naini, Ali; Vivo, Darryl C De; Sproule, Douglas M

    2013-11-01

    Spinal muscular atrophy is an autosomal recessive neurodegenerative disease caused by homozygous mutation to the survival motor neuron 1 (SMN1) gene. Historically, spinal muscular atrophy has been considered to almost exclusively affect the function and survival of alpha motor neurons of the spinal cord and brainstem. With the development of animal models of spinal muscular atrophy, the presence of widespread systemic abnormalities affecting the brain, heart, and pancreas has been repeatedly noted among animals with diminished survival motor neuron protein expression. While these observations suggest similar possible effects in humans, reports of primary systemic disease manifestations among humans affected by spinal muscular atrophy are strikingly lacking. Here we report a case of a 29-year-old man with genetically confirmed spinal muscular atrophy type II who presented with new onset diabetes mellitus and diabetic ketoacidosis.

  13. Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4+ CD25+ regulatory T cells population

    PubMed Central

    Zheng, Quan-you; Liang, Shen-ju; Li, Gui-qing; Lv, Yan-bo; Li, You; Tang, Ming; Zhang, Kun; Xu, Gui-lian; Zhang, Ke-qin

    2016-01-01

    Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3−/−) as skin graft donors or recipients. Compared with C3+/+ B6 allografts, C3−/− B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2bm12 B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3+/+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3−/− allografts. Moreover, C3−/− allografts caused attenuated Th1/Th17 responses, but increased CD4+CD25+Foxp3+ regulatory T (Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4+ CD25+ Treg cell population expansion and attenuated Th1/Th17 response. PMID:27641978

  14. Survival in Resected Stage II Colorectal Cancer Is Dependent on Tumor Depth, Vascular Invasion, Postoperative CEA Level, and The Number of Examined Lymph Nodes.

    PubMed

    Tsai, Hsiang-Lin; Huang, Ching-Wen; Chen, Chao-Wen; Yeh, Yung-Sung; Ma, Cheng-Jen; Wang, Jaw-Yuan

    2016-04-01

    The aim of the present study was to determine which aspects of tumor histology influence postoperative early relapse and overall survival rates after radical resection of stage II colorectal cancer (CRC). Data were collected for 425 patients with stage II CRC who began treatment at a single institution between January 2006 and October 2013. All the enrolled patients were followed up on until death or until December 2014. Clinically significant factors affecting postoperative early relapse and overall survival rates were analyzed. Using a multivariate analysis, tumor invasion depth (P = 0.008), vascular invasion (P = 0.029), postoperative carcinoembryonic antigen (CEA) level (P = 0.001), and retrieval of less than 12 lymph nodes (P = 0.002) were found to be independent predictors for postoperative early relapse. A combination of tumor invasion depth, vascular invasion, postoperative CEA level, and number of lymph nodes retrieved showed that the greater the number of predictors involved, the higher the likelihood of postoperative early relapse and the poorer the overall survival. This study revealed that T4 invasion, vascular invasion, postoperative CEA level, and the number of examined lymph nodes may significantly affect the prognosis of stage II CRC patients after radical resection. The risks of postoperative early relapse and worse clinical outcome increase in proportion to the values of these four parameters.

  15. Patterns of Hospitalization Risk for Women Surviving Into Very Old Age: Findings From the Australian Longitudinal Study on Women's Health.

    PubMed

    Dolja-Gore, Xenia; Harris, Melissa L; Kendig, Hal; Byles, Julie E

    2017-04-01

    By 2050, adults aged 80 years and over will represent around 20% of the global population. Little is known about how adults surviving into very old age use hospital services over time. The objective of the study was to examine patterns of hospital usage over a 10-year period for women who were aged 84 to 89 in 2010 and examine factors associated with increased use. Survey data from 1936 women from the 1921 to 1926 cohort of the Australian Longitudinal Study on Women's Health were matched with the state-based Admitted Patients Data Collection. Hospital use profiles were determined using repeated measures latent class analysis. Four latent class trajectories were identified. One-quarter of the sample were at low risk of hospitalization, while 20.6% demonstrated increased risk of hospitalization and a further 38.1% had moderate hospitalization risk over time. Only 16.8% of the sample was classified as having high hospitalization risk. Correlates of hospital use for very old women differed according to hospital use class and were contingent on the timing of exposure (ie, short-term or long-term). Despite the perception that older adults place a significant burden on health care systems, the majority of women demonstrated relatively low hospital use over an extended period, even in the presence of chronic health conditions. High hospitalization risk was found to be concentrated among a small minority of these long-term survivors. The findings suggest the importance of service planning and treatment regimes that take account of the diverse trajectories of hospital use into and through advanced old age.

  16. Segal crystallinity index revisited by the simulation of x-ray diffraction patterns of cotton cellulose IB and cellulose II

    USDA-ARS?s Scientific Manuscript database

    The Segal method estimates the amorphous fraction of cellulose IB materials simply based on intensity at 18o 20 in an X-ray diffraction pattern and was extended to cellulose II using 16o 2O intensity. To address the dependency of Segal amorphous intensity on crystal size, cellulose polymorph, and th...

  17. Sleep and Alertness Management II: Effects on Sleep Pattern and Sleep Quality in Marmosets (slaap- en alertheidsmanagement II: effecten op slaapritme en slaapkwaliteit in marmosetapen)

    DTIC Science & Technology

    2006-10-01

    II: Effects on F +31 15 284 39 91 sleep pattern and sleep quality in marmosets Info-DenV@tno.nf Date October 2006 Author(s) Dr I.l1.C.H.M. Philippens...5126 Summary In this study, the marmoset monkey model was validated using nocturnal electroencephalogram measurements for evaluating effects on sleep...the effects of the short acting hypnotic drugs temazepam, zolpidem and zaleplon on sleep were determined in the marmoset monkey. The results showed

  18. Tracking simulations for the HLS- II with a passive harmonic cavity in the symmetric and asymmetric fill patterns

    NASA Astrophysics Data System (ADS)

    Fan, Hao; Wu, Cong-Feng; Wang, Lin

    2012-11-01

    A simulation code that executes the tracking of longitudinal oscillations of the bunches for the double rf system of the Hefei Light Source II Project (HLS- II) is presented to estimate the mean beam lifetime and the Robinson instabilities. The tracking results show that the mean beam lifetime is in agreement with the analytical results and the system is stable when we tune the harmonic cavity in the optimum lengthening conditions. Moreover, the simulated results of the asymmetric fill pattern show that some bunches are compressed only with a 7% gap (3 gaps), which will lead to the reduction in the mean bunch lengthening and potential beam lifetime. It is demonstrated that HLS- II with a passive higher harmonic cavity is not suitable for operating in an asymmetric fill pattern.

  19. Comparison of survival patterns of northern and southern genotypes of the North American tick Ixodes scapularis (Acari: Ixodidae) under northern and southern conditions.

    PubMed

    Ginsberg, Howard S; Rulison, Eric L; Azevedo, Alexandra; Pang, Genevieve C; Kuczaj, Isis M; Tsao, Jean I; LeBrun, Roger A

    2014-08-26

    Several investigators have reported genetic differences between northern and southern populations of Ixodes scapularis in North America, as well as differences in patterns of disease transmission. Ecological and behavioral correlates of these genetic differences, which might have implications for disease transmission, have not been reported. We compared survival of northern with that of southern genotypes under both northern and southern environmental conditions in laboratory trials. Subadult I. scapularis from laboratory colonies that originated from adults collected from deer from several sites in the northeastern, north central, and southern U.S. were exposed to controlled conditions in environmental chambers. Northern and southern genotypes were exposed to light:dark and temperature conditions of northern and southern sites with controlled relative humidities, and mortality through time was recorded. Ticks from different geographical locations differed in survival patterns, with larvae from Wisconsin surviving longer than larvae from Massachusetts, South Carolina or Georgia, when held under the same conditions. In another experiment, larvae from Florida survived longer than larvae from Michigan. Therefore, survival patterns of regional genotypes did not follow a simple north-south gradient. The most consistent result was that larvae from all locations generally survived longer under northern conditions than under southern conditions. Our results suggest that conditions in southern North America are less hospitable than in the north to populations of I. scapularis. Southern conditions might have resulted in ecological or behavioral adaptations that contribute to the relative rarity of I. scapularis borne diseases, such as Lyme borreliosis, in the southern compared to the northern United States.

  20. Comparison of survival patterns of northern and southern genotypes of the North American tick Ixodes scapularis (Acari: Ixodidae) under northern and southern conditions

    USGS Publications Warehouse

    Ginsberg, Howard S.; Rulison, Eric L.; Azevedo, Alexandra; Pang, Genevieve C.; Kuczaj, Isis M.; Tsao, Jean I.; LeBrun, Roger A.

    2014-01-01

    BackgroundSeveral investigators have reported genetic differences between northern and southern populations of Ixodes scapularis in North America, as well as differences in patterns of disease transmission. Ecological and behavioral correlates of these genetic differences, which might have implications for disease transmission, have not been reported. We compared survival of northern with that of southern genotypes under both northern and southern environmental conditions in laboratory trials.MethodsSubadult I. scapularis from laboratory colonies that originated from adults collected from deer from several sites in the northeastern, north central, and southern U.S. were exposed to controlled conditions in environmental chambers. Northern and southern genotypes were exposed to light:dark and temperature conditions of northern and southern sites with controlled relative humidities, and mortality through time was recorded.ResultsTicks from different geographical locations differed in survival patterns, with larvae from Wisconsin surviving longer than larvae from Massachusetts, South Carolina or Georgia, when held under the same conditions. In another experiment, larvae from Florida survived longer than larvae from Michigan. Therefore, survival patterns of regional genotypes did not follow a simple north–south gradient. The most consistent result was that larvae from all locations generally survived longer under northern conditions than under southern conditions.ConclusionsOur results suggest that conditions in southern North America are less hospitable than in the north to populations of I. scapularis. Southern conditions might have resulted in ecological or behavioral adaptations that contribute to the relative rarity of I. scapularis borne diseases, such as Lyme borreliosis, in the southern compared to the northern United States.

  1. Is there role of additional chemotherapy after definitive local treatment for stage I/II marginal zone lymphoma?: Consortium for Improving Survival of Lymphoma (CISL) study.

    PubMed

    Koh, Myeong Seok; Kim, Won Seog; Kim, Seok Jin; Oh, Sung Yong; Yoon, Dok Hyun; Lee, Soon Il; Hong, Junshik; Song, Moo Kon; Shin, Ho-Jin; Kwon, Jung Hye; Kim, Hyo Jung; Do, Yong Rok; Suh, Cheolwon; Kim, Hyo Jin

    2015-10-01

    Even though local stage (Ann Arbor stage I/II) marginal zone lymphoma (MZL) is well controlled with local treatment-based therapy, no data exist on the role of additional chemotherapy after local treatment for stage I/II MZL. Patients with biopsy-confirmed Ann Arbor stage I/II MZL (n = 210) were included for analysis in this study. Of these, 180 patients (85.7 %) were stage I and 30 (14.3 %) were stage II. Most patients (n = 182, 86.7 %) were treated with a local modality including radiation therapy or surgery and 28 (13.3 %) received additional systemic chemotherapy after local treatment. The overall response rate was 98.3 % (95 % CI 96-100 %), with 187 complete responses and 20 partial responses. In the local treatment group, the mean progression-free survival (PFS) was 147.4 months (95 % CI 126.7-168.1 months) and the overall survival (OS) was 188.2 months (95 % CI 178.8-197.7 months). In the additional chemotherapy group, the mean PFS was 103.4 months (95 % CI 84.9-121.9 months) and the OS was 137.3 months (95 % CI 127.9-146.7 months). There was no difference between the two groups in OS (p = 0.836) and PFS (p = 0.695). Local stage MZL has a good clinical course and is well controlled with a local treatment modality without additional chemotherapy.

  2. Patterning adhesion of mammalian cells with visible light, tris(bipyridyl)ruthenium(II) chloride, and a digital micromirror array.

    PubMed

    Luebke, Kevin J; Carter, Duane E; Garner, Harold R; Brown, Kathlynn C

    2004-03-15

    Patterns of cellular adhesion were created on a surface using novel photochemistry that is stimulated with visible light. A glass surface coated with polyethylene glycol is nonadhesive to a variety of adherent mammalian cell types. Treatment of that surface with a mixture of tris(bipyridyl)ruthenium(II) chloride, ammonium persulfate, and a tryptophan derivative or tryptophan-bearing peptide in conjunction with irradiation with visible light (447 nm) made the surface adhesive to several cell types including mouse fibroblasts, human myoblasts, and human lung tumor cells. Immunostaining data suggest that tryptophan-containing peptides are crosslinked intact to the surface by this chemistry, which enables patterning of peptides containing only naturally occurring amino acids. Microscopic patterns of cellular adhesion were created with this chemistry by projecting microscopic patterns of visible light with a digital micromirror array. Using this method, regions of cellular adhesion were patterned with single-cell resolution.

  3. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial.

    PubMed

    Iten, Fabienne; Müller, Beat; Schindler, Christian; Rochlitz, Christoph; Oertli, Daniel; Mäcke, Helmut R; Müller-Brand, Jan; Walter, Martin A

    2007-11-15

    We aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N-'''-tetraacetic acid ((90)Y-DOTA)-Tyr(3)-octreotide (TOC) therapy in advanced medullary thyroid cancer. In a phase II trial, we investigated the response, survival, and long-term safety profile of systemic [(90)Y-DOTA]-TOC treatment in metastasized medullary thyroid cancer. Adverse events were assessed according to the criteria of the National Cancer Institute. Survival analyses were done using multiple regression models. Thirty-one patients were enrolled. A median cumulative activity of 12.6 GBq (range, 1.7-29.6 GBq) of [(90)Y-DOTA]-TOC was administered. Response was found in nine patients (29.0%). Four patients (12.9%) developed hematologic toxicities and seven patients (22.6%) developed renal toxicities. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio, 0.20; 95% confidence interval, 0.05-0.81; P = 0.02) and from time of first [(90)Y-DOTA]-TOC therapy (hazard ratio, 0.16; 95% confidence interval, 0.04-0.63; P = 0.009). The visual grade of scintigraphic tumor uptake was not associated with treatment response or survival. Response to [(90)Y-DOTA]-TOC therapy in metastasized medullary thyroid cancer is associated with a long-term survival benefit. Treatment should be considered independently from the result of the pretherapeutic scintigraphy.

  4. A Survey of Optometry Graduates to Determine Practice Patterns: Part II: Licensure and Practice Establishment Experiences.

    ERIC Educational Resources Information Center

    Bleimann, Robert L.; Smith, Lee W.

    1985-01-01

    A summary of Part II of a two-volume study of optometry graduates conducted by the Association of Schools and Colleges of Optometry is presented. Part II includes the analysis of the graduates' licensure and practice establishment experiences. (MLW)

  5. Survival outcomes improved in contemporary cohort of patients with pelvic or abdominal recurrence after treatment for Stage I/II endometrial carcinoma

    PubMed Central

    Xu, Melody J.; Chu, Christina; Rubin, Stephen; Lin, Lilie L.

    2015-01-01

    Objectives Pelvic and abdominal recurrences in Stage I/II endometrial carcinoma are associated with poor outcomes, yet prognostic factors for survival after recurrence are not well-described. Herein we identify patients with pelvic or abdominal recurrence after surgery for Stage I/II endometrial carcinoma and describe symptoms at presentation, prognostic factors, and salvage treatment toxicity. Methods This is a retrospective cohort of 20 consecutively treated patients with recurrence after treatment for Stage I/II endometrial carcinoma followed by our Institution’s Radiation Oncology Department from 1998-2015. Results The median time to pelvic or abdominal recurrence was 18.1 months (range, 4.2-59.6 months), with 50% of recurrences at extra-nodal locations. Two year progression-free survival (PFS) was 44% and 2 year overall survival (OS) was 82%. Salvage treatments varied widely, including chemotherapy and radiation therapy (RT) (7), surgery and RT (3), and surgery, chemotherapy, and RT (3). On univariate analysis of PFS, symptoms at recurrence (p=0.04) and extra-nodal recurrences (p<0.01) were found to be statistically significant negative prognosticators for PFS. On univariate analysis of OS, increasing age at recurrence and presence of symptoms were found to have a trend toward statistically significant association with negative OS outcomes (p=0.08 and p=0.10, respectively). Conclusions Our study demonstrates long-term survival for pelvic or abdominal recurrences is possible with curative salvage therapy. The presence of symptoms is a negative prognostic factor in treatment outcome and imaging may be effective for diagnosis in symptomatic and asymptomatic patients. Larger studies need to be performed to confirm these findings. PMID:26237194

  6. Survival, Growth and Reproduction of Non-Native Nile Tilapia II: Fundamental Niche Projections and Invasion Potential in the Northern Gulf of Mexico

    PubMed Central

    Lowe, Michael R.; Wu, Wei; Peterson, Mark S.; Brown-Peterson, Nancy J.; Slack, William T.; Schofield, Pamela J.

    2012-01-01

    Understanding the fundamental niche of invasive species facilitates our ability to predict both dispersal patterns and invasion success and therefore provides the basis for better-informed conservation and management policies. Here we focus on Nile tilapia (Oreochromis niloticus Linnaeus, 1758), one of the most widely cultured fish worldwide and a species that has escaped local aquaculture facilities to become established in a coastal-draining river in Mississippi (northern Gulf of Mexico). Using empirical physiological data, logistic regression models were developed to predict the probabilities of Nile tilapia survival, growth, and reproduction at different combinations of temperature (14 and 30°C) and salinity (0–60, by increments of 10). These predictive models were combined with kriged seasonal salinity data derived from multiple long-term data sets to project the species' fundamental niche in Mississippi coastal waters during normal salinity years (averaged across all years) and salinity patterns in extremely wet and dry years (which might emerge more frequently under scenarios of climate change). The derived fundamental niche projections showed that during the summer, Nile tilapia is capable of surviving throughout Mississippi's coastal waters but growth and reproduction were limited to river mouths (or upriver). Overwinter survival was also limited to river mouths. The areas where Nile tilapia could survive, grow, and reproduce increased during extremely wet years (2–368%) and decreased during extremely dry years (86–92%) in the summer with a similar pattern holding for overwinter survival. These results indicate that Nile tilapia is capable of 1) using saline waters to gain access to other watersheds throughout the region and 2) establishing populations in nearshore, low-salinity waters, particularly in the western portion of coastal Mississippi. PMID:22848533

  7. Survival, growth and reproduction of non-native Nile tilapia II: fundamental niche projections and invasion potential in the northern Gulf of Mexico.

    PubMed

    Lowe, Michael R; Wu, Wei; Peterson, Mark S; Brown-Peterson, Nancy J; Slack, William T; Schofield, Pamela J

    2012-01-01

    Understanding the fundamental niche of invasive species facilitates our ability to predict both dispersal patterns and invasion success and therefore provides the basis for better-informed conservation and management policies. Here we focus on Nile tilapia (Oreochromis niloticus Linnaeus, 1758), one of the most widely cultured fish worldwide and a species that has escaped local aquaculture facilities to become established in a coastal-draining river in Mississippi (northern Gulf of Mexico). Using empirical physiological data, logistic regression models were developed to predict the probabilities of Nile tilapia survival, growth, and reproduction at different combinations of temperature (14 and 30°C) and salinity (0-60, by increments of 10). These predictive models were combined with kriged seasonal salinity data derived from multiple long-term data sets to project the species' fundamental niche in Mississippi coastal waters during normal salinity years (averaged across all years) and salinity patterns in extremely wet and dry years (which might emerge more frequently under scenarios of climate change). The derived fundamental niche projections showed that during the summer, Nile tilapia is capable of surviving throughout Mississippi's coastal waters but growth and reproduction were limited to river mouths (or upriver). Overwinter survival was also limited to river mouths. The areas where Nile tilapia could survive, grow, and reproduce increased during extremely wet years (2-368%) and decreased during extremely dry years (86-92%) in the summer with a similar pattern holding for overwinter survival. These results indicate that Nile tilapia is capable of 1) using saline waters to gain access to other watersheds throughout the region and 2) establishing populations in nearshore, low-salinity waters, particularly in the western portion of coastal Mississippi.

  8. Survival, growth and reproduction of non-native Nile tilapia II: fundamental niche projections and invasion potential in the northern Gulf of Mexico

    USGS Publications Warehouse

    Lowe, Michael R.; Wu, Wei; Peterson, Mark S.; Brown-Peterson, Nancy J.; Slack, William T.; Schofield, Pamela J.

    2012-01-01

    Understanding the fundamental niche of invasive species facilitates our ability to predict both dispersal patterns and invasion success and therefore provides the basis for better-informed conservation and management policies. Here we focus on Nile tilapia (Oreochromis niloticus Linnaeus, 1758), one of the most widely cultured fish worldwide and a species that has escaped local aquaculture facilities to become established in a coastal-draining river in Mississippi (northern Gulf of Mexico). Using empirical physiological data, logistic regression models were developed to predict the probabilities of Nile tilapia survival, growth, and reproduction at different combinations of temperature (14 and 30°C) and salinity (0–60, by increments of 10). These predictive models were combined with kriged seasonal salinity data derived from multiple long-term data sets to project the species' fundamental niche in Mississippi coastal waters during normal salinity years (averaged across all years) and salinity patterns in extremely wet and dry years (which might emerge more frequently under scenarios of climate change). The derived fundamental niche projections showed that during the summer, Nile tilapia is capable of surviving throughout Mississippi's coastal waters but growth and reproduction were limited to river mouths (or upriver). Overwinter survival was also limited to river mouths. The areas where Nile tilapia could survive, grow, and reproduce increased during extremely wet years (2–368%) and decreased during extremely dry years (86–92%) in the summer with a similar pattern holding for overwinter survival. These results indicate that Nile tilapia is capable of 1) using saline waters to gain access to other watersheds throughout the region and 2) establishing populations in nearshore, low-salinity waters, particularly in the western portion of coastal Mississippi.

  9. In a mature trauma system, there is no difference in outcome (survival) between Level I and Level II trauma centers.

    PubMed

    Rogers, Frederick B; Osler, Turner; Lee, John C; Sakorafas, Lois; Wu, Daniel; Evans, Tracy; Edavettal, Mathew; Horst, Michael

    2011-06-01

    The state of Pennsylvania (PA) has one of the oldest, most well-established trauma systems in the country. The requirements for verification for Level I versus Level II trauma centers within PA differ minimally (only in the requirement for patient volume, residency, and research). We hypothesized that there would be no difference in outcome at Level I versus Level II trauma centers. Odds of mortality for 16 Level I and 11 Level II hospitals in PA over a 5-year period (2004-2008) was computed using a random effects logistic regression model. Overall adjusted mortality rates at Level I versus Level II hospitals were compared using the nonparametric Wilcoxon's rank sum test. The crude mortality rates for 140,691 patients over the 5-year period were similar (5.07% Level II vs. 5.48% Level I), but statistically significant (odds ratio mortality at Level I = 1.084, p = 0.002 Fisher's exact test). Although Level I centers had on average crude mortality rates that were higher than those of Level II centers, median adjusted mortality rates were not different for the two types of centers (Wilcoxon's rank sum test). Performance of Level I versus Level II shows considerable variability among centers (basic random effects model, age, blunt/penetrating, and Injury Severity Score [ISS]). However, Level II centers seem no different from Level I. As trauma systems mature, the distinction between Level I and Level II trauma centers blurs. The hierarchal descriptors "Level I" or "Level II" in a mature trauma system is pejorative and implies in those hospitals labeled "Level II" as inferior, and as such should be replaced with nonhierarchal descriptors.

  10. Predicting Pattern Tooling and Casting Dimensions for Investment Casting, Phase II

    SciTech Connect

    Nick Cannell; Adrian S. Sabau

    2005-09-30

    The investment casting process allows the production of complex-shape parts and close dimensional tolerances. One of the most important phases in the investment casting process is the design of the pattern die. Pattern dies are used to create wax patterns by injecting wax into dies. The first part of the project involved preparation of reports on the state of the art at that time for all the areas under consideration (die-wax, wax-shell, and shell-alloy). The primary R&D focus during Phase I was on the wax material since the least was known about it. The main R&D accomplishments during this phase were determination of procedures for obtaining the thermal conductivity and viscoelastic properties of an unfilled wax and validating those procedures. Phase II focused on die-wax and shell-alloy systems. A wax material model was developed based on results obtained during the previous R&D phase, and a die-wax model was successfully incorporated into and used in commercial computer programs. Current computer simulation programs have complementary features. A viscoelastic module was available in ABAQUS but unavailable in ProCAST, while the mold-filling module was available in ProCAST but unavailable in ABAQUS. Thus, the numerical simulation results were only in good qualitative agreement with experimental results, the predicted shrinkage factors being approximately 2.5 times larger than those measured. Significant progress was made, and results showed that the testing and modeling of wax material had great potential for industrial applications. Additional R&D focus was placed on one shell-alloy system. The fused-silica shell mold and A356 aluminum alloy were considered. The experimental part of the program was conducted at ORNL and commercial foundries, where wax patterns were injected, molds were invested, and alloys were poured. It was very important to obtain accurate temperature data from actual castings, and significant effort was made to obtain temperature profiles in

  11. Investigation of long-term survival outcomes and failure patterns of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a retrospective analysis

    PubMed Central

    Zhao, Wei; Lei, Hao; Zhu, Xiaodong; Li, Ling; Qu, Song; Liang, Xia

    2016-01-01

    Intensity-modulated radiotherapy (IMRT) has replaced the conventional radiotherapy (2D-RT) and improved clinical efficacy in Nasopharyngeal Carcinoma (NPC) patients. In the present study, we retrospectively analyzed the clinical characteristics of patients with NPC treated with IMRT to assess the long-term survival outcomes and failure patterns. Of the 527 patients, One hundred and twenty-one patients experienced treatment failure, 86 patients developed distant metastases, and 12 patients developed a second primary tumor. The local and regional recurrence rates were 31.4% and 14.0%, respectively. The 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastatic relapse-free survival (DMFS) rates were 80.9%, 75.6%, 91.7%, 96.2%, and 83.0%, respectively. The 5-year LRFS rates of Stage T1-4 patients were 100.0%, 93.1%, 92.0%, and 85.8%, respectively. The 5-year DMFS rates of Stage N0-3 patients were 95.0%, 86.1%, 79.5%, and 67.2%, respectively. Multivariate analysis showed age and T-stage were independent predictors of OS, T-stage was an independent predictor of LRFS, and age and N-stage were independent predictors of PFS and DMFS. In summary, the improved treatment results with IMRT are primarily due to the achievement of a higher local tumor control rate and OS in NPC patients. However, distant metastasis was the most commonly observed failure pattern after treatment. These results provide deep insights about the value of IMRT in the treatment and prognosis of NPC patients. PMID:27894100

  12. Diurnal Cortisol Patterns, Future Diabetes, and Impaired Glucose Metabolism in the Whitehall II Cohort Study.

    PubMed

    Hackett, Ruth A; Kivimäki, Mika; Kumari, Meena; Steptoe, Andrew

    2016-02-01

    The hypothalamic pituitary-adrenal axis is thought to play a role in type 2 diabetes (T2D). However, evidence for an association between cortisol and future glucose disturbance is sparse. The aim was to examine the association of diurnal cortisol secretion with future T2D and impaired glucose metabolism in a community-dwelling population. This is a prospective cohort study of salivary cortisol measured at the 2002-2004 clinical examination of the Whitehall II study, United Kingdom. We measured cortisol (nmol/l) from six saliva samples obtained over the course of a day: at waking, +30 minutes, +2.5 hours, +8 hours, +12 hours, and bedtime. Participants who were normoglycemic in 2002-2004 (phase 7) were reexamined in 2012-2013 (phase 11). The occupational cohort was originally recruited in 1985-1988. A total of 3270 men and women with an average age of 60.85 years at phase 7 (2002-2004). Incident T2D and impaired fasting glucose in 2012-2013 were measured. Raised evening cortisol at phase 7 was predictive of new-onset T2D at phase 11 (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37) with a trend for a flatter slope in participants with incident T2D (odds ratio, 1.15; 95% CI, 0.99-1.33). When expanding this analysis to a broader category of glucose disturbance we found that a flattened diurnal cortisol slope at phase 7 was predictive of future impaired fasting glucose or T2D at phase 11 (OR, 1.12; 95% CI, 1.02-1.22), as was high bedtime cortisol (OR, 1.10; 95% CI, 1.01-1.20). In this nonclinical population, alterations in diurnal cortisol patterns were predictive of future glucose disturbance.

  13. Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture.

    PubMed

    Arold, Stephen P; Bartolák-Suki, Erzsébet; Suki, Béla

    2009-04-01

    Secretion of pulmonary surfactant that maintains low surface tension within the lung is primarily mediated by mechanical stretching of alveolar epithelial type II (AEII) cells. We have shown that guinea pigs ventilated with random variations in frequency and tidal volume had significantly larger pools of surfactant in the lung than animals ventilated in a monotonous manner. Here, we test the hypothesis that variable stretch patterns imparted on the AEII cells results in enhanced surfactant secretion. AEII cells isolated from rat lungs were exposed to equibiaxial strains of 12.5, 25, or 50% change in surface area (DeltaSA) at 3 cycles/min for 15, 30, or 60 min. (3)H-labeled phosphatidylcholine release and cell viability were measured 60 min following the onset of stretch. Whereas secretion increased following 15-min stretch at 50% DeltaSA and 30-min stretch at 12.5% DeltaSA, 60 min of cyclic stretch diminished surfactant secretion regardless of strain. When cells were stretched using a variable strain profile in which the amplitude of each stretch was randomly pulled from a uniform distribution, surfactant secretion was enhanced both at 25 and 50% mean DeltaSA with no additional cell injury. Furthermore, at 50% mean DeltaSA, there was an optimum level of variability that maximized secretion implying that mechanotransduction in these cells exhibits a phenomenon similar to stochastic resonance. These results suggest that application of variable stretch may enhance surfactant secretion, possibly reducing the risk of ventilator-induced lung injury. Variable stretch-induced mechanotransduction may also have implications for other areas of mechanobiology.

  14. Individual quality, survival variation and patterns of phenotypic selection on body condition and timing of nesting in birds

    USGS Publications Warehouse

    Blums, P.; Nichols, J.D.; Hines, J.E.; Lindberg, M.; Mednis, A.

    2005-01-01

    Questions about individual variation in 'quality' and fitness are of great interest to evolutionary and population ecologists. Such variation can be investigated using either a random effects approach or an approach that relies on identifying observable traits that are themselves correlated with fitness components. We used the latter approach with data from 1,925 individual females of three species of ducks (tufted duck, Aythya fuligula; common pochard, Aythya ferina; northern shoveler, Anas clypeata) sampled on their breeding grounds at Engure Marsh, Latvia, for over 15 years. Based on associations with reproductive output, we selected two traits, one morphological (relative body condition) and one behavioral (relative time of nesting), that can be used to characterize individual females over their lifetimes. We then asked whether these traits were related to annual survival probabilities of nesting females. We hypothesized quadratic, rather than monotonic, relationships based loosely on ideas about the likely action of stabilizing selection on these two traits. Parameters of these relationships were estimated directly using ultrastructural models embedded within capture-recapture-band-recovery models. Results provided evidence that both traits were related to survival in the hypothesized manner. For all three species, females that tended to nest earlier than the norm exhibited the highest survival rates, but very early nesters experienced reduced survival and late nesters showed even lower survival. For shovelers, females in average body condition showed the highest survival, with lower survival rates exhibited by both heavy and light birds. For common pochard and tufted duck, the highest survival rates were associated with birds of slightly above-average condition, with somewhat lower survival for very heavy birds and much lower survival for birds in relatively poor condition. Based on results from this study and previous work on reproduction, we conclude that

  15. CuII(atsm) improves the neurological phenotype and survival of SOD1G93A mice and selectively increases enzymatically active SOD1 in the spinal cord

    PubMed Central

    Hilton, James B.; Mercer, Stephen W.; Lim, Nastasia K. H.; Faux, Noel G.; Buncic, Gojko; Beckman, Joseph S.; Roberts, Blaine R.; Donnelly, Paul S.; White, Anthony R.; Crouch, Peter J.

    2017-01-01

    Ubiquitous expression of mutant Cu/Zn-superoxide dismutase (SOD1) selectively affects motor neurons in the central nervous system (CNS), causing the adult-onset degenerative disease amyotrophic lateral sclerosis (ALS). The CNS-specific impact of ubiquitous mutant SOD1 expression is recapitulated in transgenic mouse models of the disease. Here we present outcomes for the metallo-complex CuII(atsm) tested for therapeutic efficacy in mice expressing SOD1G93A on a mixed genetic background. Oral administration of CuII(atsm) delayed the onset of neurological symptoms, improved locomotive capacity and extended overall survival. Although the ALS-like phenotype of SOD1G93A mice is instigated by expression of the mutant SOD1, we show the improved phenotype of the CuII(atsm)-treated animals involves an increase in mature mutant SOD1 protein in the disease-affected spinal cord, where concomitant increases in copper and SOD1 activity are also evident. In contrast to these effects in the spinal cord, treating with CuII(atsm) had no effect in liver on either mutant SOD1 protein levels or its activity, indicating a CNS-selective SOD1 response to the drug. These data provide support for CuII(atsm) as a treatment option for ALS as well as insight to the CNS-selective effects of mutant SOD1. PMID:28205575

  16. Socioeconomic and Racial/Ethnic Disparities in Cancer Mortality, Incidence, and Survival in the United States, 1950–2014: Over Six Decades of Changing Patterns and Widening Inequalities

    PubMed Central

    Jemal, Ahmedin

    2017-01-01

    We analyzed socioeconomic and racial/ethnic disparities in US mortality, incidence, and survival rates from all-cancers combined and major cancers from 1950 to 2014. Census-based deprivation indices were linked to national mortality and cancer data for area-based socioeconomic patterns in mortality, incidence, and survival. The National Longitudinal Mortality Study was used to analyze individual-level socioeconomic and racial/ethnic patterns in mortality. Rates, risk-ratios, least squares, log-linear, and Cox regression were used to examine trends and differentials. Socioeconomic patterns in all-cancer, lung, and colorectal cancer mortality changed dramatically over time. Individuals in more deprived areas or lower education and income groups had higher mortality and incidence rates than their more affluent counterparts, with excess risk being particularly marked for lung, colorectal, cervical, stomach, and liver cancer. Education and income inequalities in mortality from all-cancers, lung, prostate, and cervical cancer increased during 1979–2011. Socioeconomic inequalities in cancer mortality widened as mortality in lower socioeconomic groups/areas declined more slowly. Mortality was higher among Blacks and lower among Asian/Pacific Islanders and Hispanics than Whites. Cancer patient survival was significantly lower in more deprived neighborhoods and among most ethnic-minority groups. Cancer mortality and incidence disparities may reflect inequalities in smoking, obesity, physical inactivity, diet, alcohol use, screening, and treatment. PMID:28408935

  17. Socioeconomic and Racial/Ethnic Disparities in Cancer Mortality, Incidence, and Survival in the United States, 1950-2014: Over Six Decades of Changing Patterns and Widening Inequalities.

    PubMed

    Singh, Gopal K; Jemal, Ahmedin

    2017-01-01

    We analyzed socioeconomic and racial/ethnic disparities in US mortality, incidence, and survival rates from all-cancers combined and major cancers from 1950 to 2014. Census-based deprivation indices were linked to national mortality and cancer data for area-based socioeconomic patterns in mortality, incidence, and survival. The National Longitudinal Mortality Study was used to analyze individual-level socioeconomic and racial/ethnic patterns in mortality. Rates, risk-ratios, least squares, log-linear, and Cox regression were used to examine trends and differentials. Socioeconomic patterns in all-cancer, lung, and colorectal cancer mortality changed dramatically over time. Individuals in more deprived areas or lower education and income groups had higher mortality and incidence rates than their more affluent counterparts, with excess risk being particularly marked for lung, colorectal, cervical, stomach, and liver cancer. Education and income inequalities in mortality from all-cancers, lung, prostate, and cervical cancer increased during 1979-2011. Socioeconomic inequalities in cancer mortality widened as mortality in lower socioeconomic groups/areas declined more slowly. Mortality was higher among Blacks and lower among Asian/Pacific Islanders and Hispanics than Whites. Cancer patient survival was significantly lower in more deprived neighborhoods and among most ethnic-minority groups. Cancer mortality and incidence disparities may reflect inequalities in smoking, obesity, physical inactivity, diet, alcohol use, screening, and treatment.

  18. The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent.

    PubMed

    Rajasooriyar, Chrishanthi; Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Mileshkin, Linda; Narayan, Kailash

    2014-10-01

    The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent. One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service's prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy. The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001). Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes.

  19. The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent

    PubMed Central

    Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Mileshkin, Linda; Narayan, Kailash

    2014-01-01

    Objective The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent. Methods One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service's prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy. Results The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001). Conclusion Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes. PMID:25142629

  20. Clinical Utility of Metrics Based on Tumor Measurements in Phase II Trials to Predict Overall Survival Outcomes in Phase III Trials by Using Resampling Methods

    PubMed Central

    An, Ming-Wen; Han, Yu; Meyers, Jeffrey P.; Bogaerts, Jan; Sargent, Daniel J.; Mandrekar, Sumithra J.

    2015-01-01

    Purpose Phase II clinical trials inform go/no-go decisions for proceeding to phase III trials, and appropriate end points in phase II trials are critical for facilitating this decision. Phase II solid tumor trials have traditionally used end points such as tumor response defined by Response Evaluation Criteria for Solid Tumors (RECIST). We previously reported that absolute and relative changes in tumor measurements demonstrated potential, but not convincing, improvement over RECIST to predict overall survival (OS). We have evaluated the metrics by using additional measures of clinical utility and data from phase III trials. Methods Resampling methods were used to assess the clinical utility of metrics to predict phase III outcomes from simulated phase II trials. In all, 2,000 phase II trials were simulated from four actual phase III trials (two positive for OS and two negative for OS). Cox models for three metrics landmarked at 12 weeks and adjusted for baseline tumor burden were fit for each phase II trial: absolute changes, relative changes, and RECIST. Clinical utility was assessed by positive predictive value and negative predictive value, that is, the probability of a positive or negative phase II trial predicting an effective or ineffective phase III conclusion, by prediction error, and by concordance index (c-index). Results Absolute and relative change metrics had higher positive predictive value and negative predictive value than RECIST in five of six treatment comparisons and lower prediction error curves in all six. However, differences were negligible. No statistically significant difference in c-index across metrics was found. Conclusion The absolute and relative change metrics are not meaningfully better than RECIST in predicting OS. PMID:26503199

  1. Survival disparities in Australia: an analysis of patterns of care and comorbidities among indigenous and non-indigenous cancer patients

    PubMed Central

    2014-01-01

    Background Indigenous Australians have lower overall cancer survival which has not yet been fully explained. To address this knowledge deficit, we investigated the associations between comorbidities, cancer treatment and survival in Indigenous and non-Indigenous people in Queensland, Australia. Methods A cohort study of 956 Indigenous and 869 non-Indigenous patients diagnosed with cancer during 1998–2004, frequency-matched on age, sex, remoteness of residence and cancer type, and treated in Queensland public hospitals. Survival after cancer diagnosis, and effect of stage, treatment, and comorbidities on survival were examined using Cox proportional hazard models. Results Overall Indigenous people had more advanced cancer stage (p = 0.03), more comorbidities (p < 0.001), and received less cancer treatment (77% vs. 86%, p = 0.001). Among patients without comorbidities and social disadvantage, there was a lower uptake of treatment among Indigenous patients compared to non-Indigenous patients. For those who received treatment, time to commencement, duration and dose of treatment were comparable. Unadjusted cancer survival (HR = 1.30, 95% CI 1.15-1.48) and non-cancer survival (HR = 2.39, 95% CI 1.57-3.63) were lower in the Indigenous relative to non-Indigenous patients over the follow-up period. When adjusted for clinical factors, there was no difference in cancer-specific survival between the groups (HR = 1.10, 95% CI 0.96-1.27). One-year survival was lower for Indigenous people for all-causes of death (adjusted HR = 1.33, 95% CI 1.12-1.83). Conclusion In this study, Indigenous Australians received less cancer treatment, had more comorbidities and had more advanced cancer stage at diagnosis, factors which contribute to poorer cancer survival. Moreover, for patients with a more favourable distribution of such prognostic factors, Indigenous patients received less treatment overall relative to non-Indigenous patients. Personalised cancer care

  2. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/− cetuximab in oesophageal cancer

    PubMed Central

    Crosby, T; Hurt, C N; Falk, S; Gollins, S; Staffurth, J; Ray, R; Bridgewater, J A; Geh, J I; Cunningham, D; Blazeby, J; Roy, R; Maughan, T; Griffiths, G; Mukherjee, S

    2017-01-01

    Background: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. Methods: SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m−2 (day 1) and capecitabine 625 mg m−2 bd (days 1–21) for four cycles +/− cetuximab 400 mg m−2 day 1 then by 250 mg m−2 weekly. Radiotherapy consisted of 50 Gy/25# given concurrently with cycles 3 and 4. Recruitment was between February 2008 and February 2012, when the IDMC recommended closure on the basis of futility. Results: About 258 patients (dCRT=129; dCRT+cetuximab (dCRT+C)=129) were recruited from 36 centres. About 72.9% (n=188) had squamous cell histology. The median follow-up (IQR) was 46.2 (35.9–48.3) months for surviving patients. The median overall survival (OS; months; 95% CI) was 34.5 (24.7–42.3) in dCRT and 24.7 (18.6–31.3) in dCRT+C (hazard ratio (HR)=1.25, 95% CIs: 0.93–1.69, P=0.137). Median progression-free survival (PFS; months; 95% CI) was 24.1 (15.3–29.9) and 15.9 (10.7–20.8) months, respectively (HR=1.28, 95% CIs: 0.94–1.75; P=0.114). On multivariable analysis only earlier stage, full-dose RT, and higher cisplatin dose intensity were associated with improved OS. Conclusions: The mature analysis demonstrates that the dCRT regimen used in the study provided useful survival outcomes despite its use in patients who were largely unfit for surgery or who had inoperable disease. Given the competing risk of systemic and local failure, future studies should continue to focus on enhancing local control as well as optimising systemic therapy. PMID:28196063

  3. Investigating patterns and processes of demographic variation: environmental correlates of pre-breeding survival in red-billed choughs Pyrrhocorax pyrrhocorax.

    PubMed

    Reid, J M; Bignal, E M; Bignal, S; McCracken, D I; Bogdanova, M I; Monaghan, P

    2008-07-01

    1. Quantifying the pattern of temporal and spatial variation in demography, and identifying the factors that cause this variation, are essential steps towards understanding the structure and dynamics of any population. 2. One critical but understudied demographic rate is pre-breeding survival. We used long-term colour-ringing data to quantify temporal (among-year) and spatial (among-nest site) variation in pre-breeding survival in red-billed choughs (Pyrrhocorax pyrrhocorax) inhabiting Islay, Scotland, and identified environmental correlates of this variation. 3. Random-effects capture-mark-recapture models demonstrated substantial temporal and spatial process variance in first-year survival; survival from fledging to age 1 year varied markedly among choughs fledged in different years and fledged from different nest sites. Spatial variance exceeded temporal variance across choughs fledged from well-studied nest sites. 4. The best-supported models of temporal variation suggested that first-year survival was higher in years following high tipulid larvae abundance and when weather conditions favoured increased invertebrate productivity and/or availability to foraging choughs. These variables explained up to 80% of estimated temporal process variance. 5. The best-supported models of spatial variation suggested that first-year survival was higher in choughs fledged from nest sites that were further from exposed coasts and closer to flocking areas, and surrounded by better habitat and higher chough density. These variables explained up to 40% of estimated spatial process variance. 6. Importantly, spatio-temporal models indicated interactive effects of weather, tipulid abundance, local habitat and local chough density on first-year survival, suggesting that detrimental effects of poor weather and low tipulid abundance may be reduced in choughs fledged from nest sites surrounded by better foraging habitat and lower chough density. 7. These analyses demonstrate substantial

  4. Mesothelioma in the United States: a Surveillance, Epidemiology, and End Results (SEER)–Medicare investigation of treatment patterns and overall survival

    PubMed Central

    Beebe-Dimmer, Jennifer L; Fryzek, Jon P; Yee, Cecilia L; Dalvi, Tapashi B; Garabrant, David H; Schwartz, Ann G; Gadgeel, Shirish

    2016-01-01

    Introduction Mesothelioma is a rare malignancy typically associated with exposure to asbestos and poor survival. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and overall survival (OS) utilizing the National Cancer Institute’s Surveillance, Epidemiology, and End Results–Medicare database. Materials and methods Patients in this study were diagnosed with malignant mesothelioma of the pleura or peritoneum between January 1, 2005 and December 31, 2009 with follow-up for survival through December 31, 2010. We examined both patient and tumor characteristics at time of diagnosis and subsequent treatment patterns (surgery, radiation, and chemotherapy). Among patients treated with chemotherapy, we determined chemotherapy regimen and OS by line of therapy. Results Of the 1,625 patients considered eligible for this investigation, the median age at diagnosis was 78 years. Nearly a third of patients (30%) had surgery as part of their treatment and 45% were given chemotherapy. The median OS was 8 months (range 1–69 months). Among chemotherapy patients, the most commonly (67%) prescribed regimen for first-line therapy was cisplatin or carboplatin (Ca/Ci) combined with pemetrexed (Pe). Among those prescribed Ca/Ci + Pe as first-line therapy, retreatment with Ca/Ci + Pe (28%) or treatment with gemcitabine (30%) were the most common second-line therapies. Median OS for those receiving first-line chemotherapy was 7 months, and among those receiving second-line therapy median OS was extended an additional 5 months. Conclusion Irrespective of surgical resection, mesothelioma patients receiving some form of chemotherapy survived longer than patients who did not, with an additional survival benefit among those patients receiving multimodal treatment. PMID:27822122

  5. Treatment Patterns and Differences in Survival of Non-Small Cell Lung Cancer Patients Between Academic and Non-Academic Hospitals in the Netherlands.

    PubMed

    van der Linden, Naomi; Bongers, Mathilda L; Coupé, Veerle M H; Smit, Egbert F; Groen, Harry J M; Welling, Alle; Schramel, Franz M N H; Uyl-de Groot, Carin A

    2017-09-01

    The aims of this study are to analyze differences in survival between academic and non-academic hospitals and to provide insight into treatment patterns for non-small cell lung cancer (NSCLC). Results show the state of NSCLC survival and care in the Netherlands. The Netherlands Cancer Registry provided data on NSCLC survival for all Dutch hospitals. We used the Kaplan-Meier estimate to calculate median survival time by hospital type and a Cox proportional hazards model to estimate the relative risk of mortality (expressed as hazard ratios) for patients diagnosed in academic versus non-academic hospitals, with adjustment for age, gender, and tumor histology, and stratifying for disease stage. Data on treatment patterns in Dutch hospitals was obtained from 4 hospitals (2 academic, 2 non-academic). A random sample of patients diagnosed with NSCLC from January 2009 until January 2011 was identified through hospital databases. Data was obtained on patient characteristics, tumor characteristics, and treatments. The Cox proportional hazards model shows a significantly decreased hazard ratio of mortality for patients diagnosed in academic hospitals, as opposed to patients diagnosed in non-academic hospitals. This is specifically true for primary radiotherapy patients and patients who receive systemic treatment for non-metastasized NSCLC. Patients diagnosed in academic hospitals have better median overall survival than patients diagnosed in non-academic hospitals, especially for patients treated with radiotherapy, systemic treatment, or combinations. This difference may be caused by residual confounding since the estimates were not adjusted for performance status. A wide variety of surgical, radiotherapeutic, and systemic treatments is prescribed. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Wildlife Inquiry through Zoo Education (WIZE) Module II: Survival Strategies. Dissemination Project Evaluation Report 1995-96.

    ERIC Educational Resources Information Center

    Mei, Dolores M.

    This report is a dissemination project evaluation of the Wildlife Inquiry through Zoo Education (WIZE) program, a well-known life science program for grades seven through ten that takes a non-traditional, multi-disciplinary approach to learning. The program content focuses on population ecology, wildlife conservation, and species survival. Chapter…

  7. Wildlife Inquiry through Zoo Education (WIZE) Module II: Survival Strategies. Dissemination Project Evaluation Report 1995-96.

    ERIC Educational Resources Information Center

    Mei, Dolores M.

    This report is a dissemination project evaluation of the Wildlife Inquiry through Zoo Education (WIZE) program, a well-known life science program for grades seven through ten that takes a non-traditional, multi-disciplinary approach to learning. The program content focuses on population ecology, wildlife conservation, and species survival. Chapter…

  8. Human T lymphotropic virus types I and II proviral sequences in Argentinian blood donors with indeterminate Western blot patterns.

    PubMed

    Mangano, A M; Remesar, M; del Pozo, A; Sen, Luisa

    2004-10-01

    Human T-cell lymphotropic virus (HTLV) seroindeterminate blood donors have been reported worldwide including Argentina. To investigate the significance of HTLV-I/II seroindeterminate Western blot (WB) patterns, we conducted an 8-year cross-sectional study. Of 86,238 Argentinian blood donors, 146 sera were reactive by screening tests. The WB results indicated that 20% were HTLV-I reactive, 8% HTLV-II reactive, 61% indeterminate, and 11% negative. The overall seroprevalence was 0.034% for HTLV-I, 0.014% for HTLV-II, and 0.103% for indeterminate. In 57 reactive specimens, HTLV-I/II provirus could be examined by type specific PCR for tax, pol, and env regions. When at least two gene fragments were amplified HTLV-I/II infection was considered confirmed. PCR results confirmed all WB seropositive samples for HTLV-I (n = 15), and HTLV-II (n = 7), and the only WB negative case was also PCR negative, showing a complete concordance between PCR and WB. However, of 34 WB seroindeterminate sera studied by PCR, in 5 was proviral DNA amplified. According to our criteria PCR confirmed one to be HTLV-I, and one HTLV-II, 3 remained indeterminate since only tax sequences were amplified. Among WB indeterminate samples tested by PCR, most of their serological profile showed reactivity to gag codified proteins but lacked env reactivities (70%). One sample with a WB gag pattern showed proviral tax sequences, but of the four samples with reactivity to env proteins GD21 (n = 3) or rgp46II (n = 1) PCR results indicated that one was HTLV-I, one was HTLV-II, and two were indeterminate (only tax sequences). In conclusion, the majority of HTLV-seroindeterminate WB donors exhibited a gag indeterminate profile lacking HTLV provirus, and were thus considered uninfected. However, seroreactivity to env proteins, in particular to GD21, may indicate infection and a follow-up study of each seroreactive blood donor should be considered.

  9. Rcan1-1L overexpression induces mitochondrial autophagy and improves cell survival in angiotensin II-exposed cardiomyocytes

    SciTech Connect

    Duan, Hongyan; Li, Yongqiang; Yan, Lijie; Yang, Haitao; Wu, Jintao; Qian, Peng; Li, Bing; Wang, Shanling

    2015-07-01

    Mitochondrial autophagy is an important adaptive stress response and can be modulated by various key molecules. A previous study found that the regulator of calcineurin 1-1L (Rcan1-1L) may regulate mitochondrial autophagy and cause mitochondria degradation in neurocytes. However, the effect of Rcan1-1L on cardiomyocytes has not been determined. In the present study, we aimed to investigate the role of Rcan1-1L in angiotensin II (Ang II)-exposed human cardiomyocytes. Above all, Human adult cardiac myocytes (HACMs) were exposed to 200 nmol/L Ang II for 4 days. Enhanced H{sub 2}O{sub 2} production, cytochrome C release and mitochondrial permeability were observed in these cells, which were blocked by valsartan. Consistently, Ang II exposure significantly reduced cardiomyocyte viability. However, transfection of Rcan1-1L vector promoted cell viability and ameliorated the apoptosis caused by Ang II. Rcan1-1L clearly promoted mitochondrial autophagy in HACMs, with elevated autophagy protein (ATG) 5 and light chain 3 (LC3) expression. Transient mitochondrial biogenesis and reduced cytochrome C release was also induced by Rcan1-1L. Additionally, Rcan1-1L significantly inhibited calcineurin/nuclear factor of activated T cells (NFAT) signaling. We thus conclude that Rcan1-1L may play a protective role in Ang II-treated cardiomyocytes through the induction of mitochondrial autophagy, and may be an alternative method of cardiac protection. - Highlights: • Transfection of Rcan1-1L into HACMs promoted cell viability and reduced apoptosis. • Transfection of Rcan1-1L promoted mitochondrial autophagy in HACMs. • Rcan1-1L inhibited the calcineurin/nuclear factor of activated T cells signaling.

  10. Comparative Study of LDR (Manchester System) and HDR Image-guided Conformal Brachytherapy of Cervical Cancer: Patterns of Failure, Late Complications, and Survival

    SciTech Connect

    Narayan, Kailash Dyk, Sylvia van; Bernshaw, David; Rajasooriyar, Chrishanthi; Kondalsamy-Chennakesavan, Srinivas

    2009-08-01

    Purpose: To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. Materials and Methods: A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. Results: Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. Conclusions: Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

  11. Patterns of practice and survival in a retrospective analysis of 1722 adult astrocytoma patients treated between 1985 and 2001 in 12 Italian radiation oncology centers

    SciTech Connect

    Magrini, Stefano Maria . E-mail: magrini@med.unibs.it; Ricardi, Umberto; Santoni, Riccardo; Krengli, Marco; Lupattelli, Marco; Cafaro, Ines; Scoccianti, Silvia; Menichelli, Claudia; Bertoni, Filippo; Enrici, Riccardo Maurizi; Tombolini, Vincenzo; Buglione, Michela; Pirtoli, Luigi

    2006-07-01

    Purpose: To analyze the patterns of practice and survival in a series of 1722 adult astrocytoma patients treated in 12 Italian radiotherapy centers. Methods and Materials: A total of 1722 patients were treated with postoperative radiotherapy (90% World Health Organization [WHO] Grade 3-4, 62% male, 44% aged >60 years, 25% with severe neurologic deficits, 44% after gross total resection, 52% with high-dose radiotherapy, and 16% with chemotherapy). Variations in the clinical-therapeutic features in three subsequent periods (1985 through 2001) were evaluated, along with overall survival for the different subgroups. Results: The proportion of women, of older patients, of those with worse neurologic performance status (NPS), with WHO Grade 4, and with smaller tumors increased with time, as did the proportion of those treated with radical surgery, hypofractionated radiotherapy, and more sophisticated radiotherapy techniques, after staging procedures progressively became more accurate. The main prognostic factors for overall survival were age, sex, neurologic performance status, WHO grade, extent of surgery, and radiation dose. Conclusions: Recently, broader selection criteria for radiotherapy were adopted, together with simpler techniques, smaller total doses, and larger fraction sizes for the worse prognostic categories. Younger, fit patients are treated more aggressively, more often in association with chemotherapy. Survival did not change over time. The accurate evaluation of neurologic status is therefore of utmost importance before the best treatment option for the individual patient is chosen.

  12. TRPM1 (melastatin) expression is an independent predictor of overall survival in clinical AJCC stage I and II melanoma patients.

    PubMed

    Brożyna, Anna A; Guo, Huazhang; Yang, Sun-Eun; Cornelius, Lynn; Linette, Gerald; Murphy, Michael; Sheehan, Christine; Ross, Jeffrey; Slominski, Andrzej; Carlson, J Andrew

    2017-04-01

    The expression of TRPM1 (melastatin) mRNA is an independent marker, as measured by radioactive in situ hybridization (RISH), of disease-free survival in primary cutaneous melanoma (PM). The aim of the study was to determine if chromogenic in situ hybridization (CISH) can reproduce results examining diagnostic and prognostic utility of TRPM1 mRNA expression in melanocytic proliferations as measured by RISH. The expression of TRPM1 mRNA was detected by CISH in melanocytic nevi (MN, n = 61), PM (n = 145) and metastatic melanomas (MMs, n = 15). A progressive loss of TRPM1 was found moving from MN to PM to MM. The histologic stepwise model of melanoma progression revealed that loss of TRPM1 occurred at the transition of RGP PM to VGP PM. As a diagnostic marker, TRPM1 gradient loss showed 93.8% sensitivity and 52.4% specificity for PM. Loss of TRPM1 mRNA correlated with melanoma aggressiveness markers and was independent predictor of disease-free and overall survival. The corresponding survival curves for degree of melanoma pigmentation matched those for degree of loss of TPRM1 mRNA. Loss of TRPM1 mRNA expression appears to be a crucial event in the progression of melanoma to a more malignant, metastatic phenotype. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. The pattern of excitation of human lower limb motoneurones by probable group II muscle afferents

    PubMed Central

    Simonetta-Moreau, M; Marque, P; Marchand-Pauvert, V; Pierrot-Deseilligny, E

    1999-01-01

    Heteronymous group II effects were investigated in the human lower limb. Changes in firing probability of single motor units in quadriceps (Q), biceps (Bi), semitendinosus (ST), gastrocnemius medialis (GM) and tibialis anterior (TA) were studied after electrical stimuli between 1 and 3 times motor threshold (MT) applied to common peroneal (CP), superficial (SP) and deep (DP) peroneal, Bi and GM nerves in those nerve-muscle combinations without recurrent inhibition. Stimulation of the CP and Bi nerves evoked in almost all of the explored Q motor units a biphasic excitation with a low-threshold early peak, attributable to non-monosynaptic group I excitation, and a higher threshold late peak. When the CP nerve was cooled (or the stimulation applied to a distal branch, DP), the increase in latency was greater for the late than for the early peak, indicating that the late excitation is due to stimulation of afferents with a slower conduction velocity than group I fibres, presumably in the group II range. In ST motor units the group II excitation elicited by stimulation of the GM and SP nerves was particularly large and frequent, and the non-monosynaptic group I excitation was often replaced by an inhibition. A late group II-induced excitation from CP to Q motoneurones and from GM and SP to ST motoneurones was also observed when using the H reflex as a test. The electrical threshold and conduction velocity of the largest diameter fibres evoking the group II excitation were estimated to be 2·1 and 0·65 times those of the fastest Ia afferents, respectively. In the combinations tested in the present investigation the group II input seemed to be primarily of muscle origin. The potent heteronymous group II excitation of motoneurones of both flexors and extensors of the knee contrasted with the absence of a group II effect from DP to GM and from GM to TA. In none of the combinations explored was there any evidence for group II inhibition of motoneurones. The possible

  14. Pattern formation at liquid interfaces II. The KI/chloral hydrate/starch system

    NASA Astrophysics Data System (ADS)

    Liu, Cliff Zeh-Wen; Knobler, Charles M.

    1992-02-01

    Measurements are reported of pattern formation at a liquid interface produced by a photochemical reaction involving the system KI/chloral hydrate/ starch. The dependence of the wavelength on the concentrations of the reactants, the viscosity, and the height of the sample has been examined. It is concluded that the pattern is produced by a hydrodynamic mechanism.

  15. Maternal effects and Symbiodinium community composition drive differential patterns in juvenile survival in the coral Acropora tenuis

    PubMed Central

    Willis, Bette L.; Bay, Line K.

    2016-01-01

    Coral endosymbionts in the dinoflagellate genus Symbiodinium are known to impact host physiology and have led to the evolution of reef-building, but less is known about how symbiotic communities in early life-history stages and their interactions with host parental identity shape the structure of coral communities on reefs. Differentiating the roles of environmental and biological factors driving variation in population demographic processes, particularly larval settlement, early juvenile survival and the onset of symbiosis is key to understanding how coral communities are structured and to predicting how they are likely to respond to climate change. We show that maternal effects (that here include genetic and/or effects related to the maternal environment) can explain nearly 24% of variation in larval settlement success and 5–17% of variation in juvenile survival in an experimental study of the reef-building scleractinian coral, Acropora tenuis. After 25 days on the reef, Symbiodinium communities associated with juvenile corals differed significantly between high mortality and low mortality families based on estimates of taxonomic richness, composition and relative abundance of taxa. Our results highlight that maternal and familial effects significantly explain variation in juvenile survival and symbiont communities in a broadcast-spawning coral, with Symbiodinium type A3 possibly a critical symbiotic partner during this early life stage. PMID:27853562

  16. Absence of effects from immunocontraception on seasonal birth patterns and foal survival among barrier island wild horses.

    PubMed

    Kirkpatrick, Jay F; Turner, Allison

    2003-01-01

    Despite a large body of safety data, concern exists that porcine zonae pellucidae (PZP) immunocontraception--used to manage wild horse populations--may cause out-of-season births with resulting foal mortality. Our study at Assateague, Maryland indicated the effects of immunocontraception on season of birth and foal survival between 1990 and 2002 on wild horses from Assateague Island. Among 91 mares never treated, 69 (75.8%) of foals were born in April, May, and June (in season). Among 77 treated mares, 50 (64.9%) were born in season. Of 29 mares foaling within 1 year after treatment (contraceptive failures), 20 (68.9%) were born in season. Of 48 mares treated for greater than 2 years then withdrawn from treatment, 30 (62.5%) of 48 foals were born in season. There were no significant differences (p <.05) between either treatment group or untreated mares. Survival did not differ significantly among foals born in or out of season or among foals born to treated or untreated mares. Data indicate a lack of effect of PZP contraception on season of birth or foal survival on barrier island habitats.

  17. Genes associated with metabolic syndrome predict disease-free survival in stage II colorectal cancer patients. A novel link between metabolic dysregulation and colorectal cancer.

    PubMed

    Vargas, Teodoro; Moreno-Rubio, Juan; Herranz, Jesús; Cejas, Paloma; Molina, Susana; González-Vallinas, Margarita; Ramos, Ricardo; Burgos, Emilio; Aguayo, Cristina; Custodio, Ana B; Reglero, Guillermo; Feliu, Jaime; Ramírez de Molina, Ana

    2014-12-01

    Studies have recently suggested that metabolic syndrome and its components increase the risk of colorectal cancer. Both diseases are increasing in most countries, and the genetic association between them has not been fully elucidated. The objective of this study was to assess the association between genetic risk factors of metabolic syndrome or related conditions (obesity, hyperlipidaemia, diabetes mellitus type 2) and clinical outcome in stage II colorectal cancer patients. Expression levels of several genes related to metabolic syndrome and associated alterations were analysed by real-time qPCR in two equivalent but independent sets of stage II colorectal cancer patients. Using logistic regression models and cross-validation analysis with all tumour samples, we developed a metabolic syndrome-related gene expression profile to predict clinical outcome in stage II colorectal cancer patients. The results showed that a gene expression profile constituted by genes previously related to metabolic syndrome was significantly associated with clinical outcome of stage II colorectal cancer patients. This metabolic profile was able to identify patients with a low risk and high risk of relapse. Its predictive value was validated using an independent set of stage II colorectal cancer patients. The identification of a set of genes related to metabolic syndrome that predict survival in intermediate-stage colorectal cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy and avoid the toxic and unnecessary chemotherapy in patients classified as low risk. Our results also confirm the linkage between metabolic disorder and colorectal cancer and suggest the potential for cancer prevention and/or treatment by targeting these genes. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  18. Contrasting patterns of selection acting on MHC class I and class II DRB genes in the Alpine marmot (Marmota marmota).

    PubMed

    Kuduk, K; Johanet, A; Allainé, D; Cohas, A; Radwan, J

    2012-08-01

    The major histocompatibility complex (MHC) genes code for proteins that play a critical role in the immune system response. The MHC genes are among the most polymorphic genes in vertebrates, presumably due to balancing selection. The two MHC classes appear to differ in the rate of evolution, but the reasons for this variation are not well understood. Here, we investigate the level of polymorphism and the evolution of sequences that code for the peptide-binding regions of MHC class I and class II DRB genes in the Alpine marmot (Marmota marmota). We found evidence for four expressed MHC class I loci and two expressed MHC class II loci. MHC genes in marmots were characterized by low polymorphism, as one to eight alleles per putative locus were detected in 38 individuals from three French Alps populations. The generally limited degree of polymorphism, which was more pronounced in class I genes, is likely due to bottleneck the populations undergone. Additionally, gene duplication within each class might have compensated for the loss of polymorphism at particular loci. The two gene classes showed different patterns of evolution. The most polymorphic of the putative loci, Mama-DRB1, showed clear evidence of historical positive selection for amino acid replacements. However, no signal of positive selection was evident in the MHC class I genes. These contrasting patterns of sequence evolution may reflect differences in selection pressures acting on class I and class II genes.

  19. Type III Secretion and Effectors Shape the Survival and Growth Pattern of Pseudomonas syringae on Leaf Surfaces1[W][OA

    PubMed Central

    Lee, Jiyoung; Teitzel, Gail M.; Munkvold, Kathy; del Pozo, Olga; Martin, Gregory B.; Michelmore, Richard W.; Greenberg, Jean T.

    2012-01-01

    The bacterium Pseudomonas syringae pv syringae B728a (PsyB728a) uses a type III secretion system (T3SS) to inject effector proteins into plant cells, a process that modulates the susceptibility of different plants to infection. Analysis of GREEN FLUORESCENT PROTEIN-expressing PsyB728a after spray inoculation without additives under moderate relative humidity conditions permitted (1) a detailed analysis of this strain’s survival and growth pattern on host (Nicotiana benthamiana) and nonhost (tomato [Solanum lycopersicum]) leaf surfaces, (2) an assessment of the role of plant defenses in affecting PsyB728a leaf surface (epiphytic) growth, and (3) the contribution of the T3SS and specific effectors to PsyB728a epiphytic survival and growth. On host leaf surfaces, PsyB728a cells initially persist without growing, and show an increased population only after 48 h, unless plants are pretreated with the defense-inducing chemical benzothiazole. During the persistence period, some PsyB728a cells induce a T3SS reporter, whereas a T3SS-deficient mutant shows reduced survival. By 72 h, rare invasion by PsyB728a to the mesophyll region of host leaves occurs, but endophytic and epiphytic bacterial growths are not correlated. The effectors HopZ3 and HopAA1 delay the onset of epiphytic growth of PsyB728a on N. benthamiana, whereas they promote epiphytic survival/growth on tomato. These effectors localize to distinct sites in plant cells and likely have different mechanisms of action. HopZ3 may enzymatically modify host targets, as it requires residues important for the catalytic activity of other proteins in its family of proteases. Thus, the T3SS, HopAA1, HopZ3, and plant defenses strongly influence epiphytic survival and/or growth of PsyB728a. PMID:22319072

  20. Adenocarcinoma of the esophagus and esophago-gastric junction: The effects of single and combined modalities on the survival and patterns of failure following treatment

    SciTech Connect

    Whittington, R.; Coia, L.R.; Haller, D.G.; Rubenstein, J.H.; Rosato, E.F. )

    1990-09-01

    One hundred sixty-five patients with localized adenocarcinomas of the esophagus or esophago-gastric (EG) junction were treated with surgery alone, radiation therapy alone, chemotherapy alone, surgery followed by post-operative radiation therapy, chemotherapy, or chemosensitized radiation therapy, and chemosensitized radiation therapy alone. Patients were retrospectively evaluated for survival, control of tumor within the mediastinum, post-operative swallowing function, patterns of failure, and treatment-related morbidity. Follow-up of survivors ranges from 9-88 months (median 23 months). Chemotherapy and radiation therapy as single modalities were associated with a recurrence rate of 100%. Combined modality therapy significantly reduced the risk of local recurrence in all patient groups. Chemosensitized radiation therapy alone reduced the local recurrence rate to 48%, and surgery followed by radiation therapy reduced the local failure rate to 24%. When chemotherapy or chemosensitization was added to surgery plus radiation, the risk was further reduced to 15%. The use of combined modality therapy was also found to extend the survival of patients without excessive toxicity. Median survival was shortest among the group treated with radiation alone (5 months) and intermediate among patients following chemosensitized radiation alone (10 months) or complete surgical resection alone (15 months). Patients treated with all three modalities had the longest median survival (21 months). Based on this experience, the optimum treatment of these patients appears to include aggressive attempts at surgical resection with chemosensitized radiation therapy. Excellent pallination can also be achieved in unresectable patients with chemosensitized radiation therapy with a smaller chance for long term survival.

  1. Survival of solo practitioners and small group practices in today's challenging marketplace: setting the ground work now--Part II.

    PubMed

    Cascardo, Debra

    2011-01-01

    In Part I of this article, in the January/February 2011 issue, we discussed how the delivery of healthcare of the future will be dramatically different from the past for physicians in private practice. As the debate continues to swirl around the Patient Protection and Affordable Care Act, physicians in private practice continue to face the biggest challenges of their careers: how to maintain profitability and survive in this recession that appears to have no end in sight. This article provides guidelines to empower physicians and their staff with proven practice management tools and techniques that have stood the test of time.

  2. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    SciTech Connect

    Olszewski, Adam J. Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  3. Migration of radio-marked whooping cranes from the Aransas-Wood Buffalo population: Patterns of habitat use, behavior, and survival

    USGS Publications Warehouse

    Howe, M.A.

    1989-01-01

    Use of migration stop-overs by radio-tracked whooping cranes (Grus americana) was studied in fall 1981-83 and spring 1983-84. Information on habitat use, time-activity budgets, and hazards encountered is presented for a sample of 27 individuals, including 9 radio-marked birds. Survival rate is calculated for radio-marked birds and compared with estimates for birds not radio-marked. Distribution patterns of birds for which complete stopover information is available are contrasted with distributions derived from opportunistic observations.

  4. NRPB3, the third largest subunit of RNA polymerase II, is essential for stomatal patterning and differentiation in Arabidopsis.

    PubMed

    Chen, Liang; Guan, Liping; Qian, Pingping; Xu, Fan; Wu, Zhongliang; Wu, Yujun; He, Kai; Gou, Xiaoping; Li, Jia; Hou, Suiwen

    2016-05-01

    Stomata are highly specialized epidermal structures that control transpiration and gas exchange between plants and the environment. Signal networks underlying stomatal development have been previously uncovered but much less is known about how signals involved in stomatal development are transmitted to RNA polymerase II (Pol II or RPB), which plays a central role in the transcription of mRNA coding genes. Here, we identify a partial loss-of-function mutation of the third largest subunit of nuclear DNA-dependent Pol II (NRPB3) that exhibits an increased number of stomatal lineage cells and paired stomata. Phenotypic and genetic analyses indicated that NRPB3 is not only required for correct stomatal patterning, but is also essential for stomatal differentiation. Protein-protein interaction assays showed that NRPB3 directly interacts with two basic helix-loop-helix (bHLH) transcription factors, FAMA and INDUCER OF CBF EXPRESSION1 (ICE1), indicating that NRPB3 serves as an acceptor for signals from transcription factors involved in stomatal development. Our findings highlight the surprisingly conserved activating mechanisms mediated by the third largest subunit of Pol II in eukaryotes. © 2016. Published by The Company of Biologists Ltd.

  5. The effect of farrowing crate heat lamp location on sow and pig patterns of lying and pig survival.

    PubMed

    Hrupka, B J; Leibbrandt, V D; Crenshaw, T D; Benevenga, N J

    1998-12-01

    Three experiments were conducted to study sow and pig behavior during the 1st 3 d after birth and pig survival during the 1st 2 wk after farrowing. In Exp. 1, 23 sows were housed in conventional farrowing crates that were divided into five sections: a .5- x 1.5-m front creep section and the remaining area divided into four sections, .75 x 1.05 m each. Air temperature was maintained at 19 degrees C, and a 250-W heat lamp was placed at the right side of the front creep in Treatment 1 (T1), or in the creep at the right side of the sow for Treatment 2 (T2). The percentage of pigs within 8 cm of the sow's trunk was not affected by treatment, but it decreased (P < .001) from 61.8 +/- 3.4% on d 1 to 28.1 +/- 3.5% on d 3. As the percentage of pigs near the sow decreased, the percentage of pigs within the section containing the heat lamp increased (T1, P < .05; T2, P < .10). Experiment 2 involved 15 sows and litters housed as in Exp. 1, except that heat lamps were not provided, and average air temperature was 27.3 +/- .2 degrees C during behavioral observations. Even though the portion of the litter near the sow decreased (P < .001) from d 1 to d 3 (d 1, 57.0 +/- 3.4%; d 2, 42.9 +/- 3.3%; d 3, 31.7 +/- 3.3%), pigs did not concentrate in any specific section as they moved away from the sow. The average number of pigs within the front creep section (Section 1) for the 3-d period was less than (P < .01) the number in any other crate section. Experiment 3 involved 147 sows and tested the effect of solid creep floor covering on pig survival for each of the heat lamp locations used in Exp. 1. Neither heat lamp location nor floor covering affected pig survival. During the 1st 3 d of life, pigs tend to lie near the sow regardless of heat lamp location or air temperature. Heat lamp position and floor covering under the lamp do not affect pig survival.

  6. Mandibular growth comparisons of Class I and Class II division 1 skeletofacial patterns.

    PubMed

    Jacob, Helder B; Buschang, Peter H

    2014-09-01

    To determine class and sex differences in mandibular growth and modeling. A mixed-longitudinal sample of 130 untreated French-Canadian adolescents, 77 (45 boys and 32 girls) with Class I (normal or abnormal) occlusion and 53 (26 boys and 27 girls) with Class II division 1 malocclusion, was used. Based on eight landmarks, eight traditional measurements were used to compare the anteroposterior position of the maxilla and mandible, relationship between the jaws, and mandibular size. Mandibular superimpositions were used to compare the horizontal and vertical changes of condylion, gonion, and menton. While there were no differences in maxillary position based on the SNA angle, Class IIs had more retrognathic mandibles than did Class Is. Total mandibular length was greater in Class Is than in Class IIs at 15 years of age. Superior and total growth and modeling changes at condylion and gonion, respectively, were greater for Class Is than Class IIs. Boys were more prognathic than girls; they had larger mandibles and exhibited greater size increases and growth changes than girls did. There are both class and sex differences in mandibular growth and modeling.

  7. Studies in Enrollment Trends and Patterns. Part II--Summer Quarter: 1940-1964.

    ERIC Educational Resources Information Center

    Schmid, Calvin F.; Watson, F. Jean

    This is the second part of a report on major facets of institutional change at the University of Washington. Part II is a detailed analysis of Summer Quarter students and covers: class differentials in enrollment trends; trends in undergraduate students by major field and college; trends in graduate and professional students by major field and…

  8. A Competency Pattern Approach To Curriculum Construction In Distributive Teacher Education. Final Report, Volume II.

    ERIC Educational Resources Information Center

    Crawford, Lucy C.

    This study involved all distributive education state supervisory and teacher education personnel in the United States, 48 distributive education teacher coordinators, and 400 distributive workers at the entry, supervisory, and management level. This document, Volume II, includes the critical tasks, competencies needed to perform the tasks, and a…

  9. Patterns of adjuvant chemotherapy for stage II and III colon cancer in France and Italy.

    PubMed

    Bouvier, Anne-Marie; Minicozzi, Pamela; Grosclaude, Pascale; Bouvier, Véronique; Faivre, Jean; Sant, Milena

    2013-08-01

    European guidelines recommend adjuvant chemotherapy for stage III colon cancer but not for stage II. To determine the extent to which adjuvant chemotherapy was used in Italy and France. A common retrospective database of 2186 colon cancers diagnosed between 2003 and 2005 was analysed according to age, stage and presenting features. 38.9% of patients with stage II and 64.6% with stage III received chemotherapy in Italy, 21.7% and 65.1% in France. For stage II, the association between country and chemotherapy was only significant in patients diagnosed out of emergency (ORItaly/France: 3.05 [2.12-4.37], p<0.001) whereas patients diagnosed in emergency were as likely to receive chemotherapy in both countries. For stage III, there was a trend to a higher administration of chemotherapy for elderly patients in France compared to Italy. French patients were more likely than Italian to receive chemotherapy (OR: 1.91[1.32-2.78], p=0.001). Chemotherapy for stage III colon cancer was as extensively used in Italy as in France for young patients. Its administration could be increased in patients over 75. Stage II patients with a lower risk of relapse received chemotherapy more often in Italy than in France. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  10. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  11. Consistent Aspirin Use Associated with Improved Arteriovenous Fistula Survival among Incident Hemodialysis Patients in the Dialysis Outcomes and Practice Patterns Study

    PubMed Central

    Hasegawa, Takeshi; Elder, Stacey J.; Bragg-Gresham, Jennifer L.; Pisoni, Ronald L; Yamazaki, Shin; Akizawa, Tadao; Jadoul, Michel; Hugh, Rayner C.; Port, Friedrich K; Fukuhara, Shunichi

    2008-01-01

    Background and objectives: The relationship between aspirin use and arteriovenous fistula (AVF) survival has been lacking. The aim of this study was to evaluate the association between AVF survival and aspirin use. Design, setting, participants, & measurements: Data on 2815 incident hemodialysis patients (on dialysis ≤ 30 d) using an AVF at enrollment into the Dialysis Outcomes and Practice Patterns Study between 1996 and 2004 were analyzed. Cox regression was used to examine the association between aspirin use and the risk of final AVF failure, first AVF failure, and a gastrointestinal bleeding event. Aspirin use was determined at baseline and one year later. Patients using aspirin at baseline and one year later were considered consistent aspirin users. All models accounted for facility clustering effects and were adjusted for age, race, gender, body mass index, prior permanent access failure, prior placement of a catheter, 10 comorbid conditions, laboratory data, and other medications, and stratified by regions. Results: Consistent aspirin use was significantly related to a lower risk of final AVF failure. Facility-level analysis, which may reduce confounding by indication, also showed a nearly significant trend of reduced risk of final AVF failure with greater prevalence of consistent aspirin use within dialysis facilities (P for trend = 0.07). The occurrence of a new gastrointestinal bleeding event during the study period was not associated with aspirin use. Conclusions: These results suggest that consistent aspirin use may be beneficial for AVF survival among incident hemodialysis patients. PMID:18596119

  12. Carcinoma of the cervical stump: comparison of radiation therapy factors, survival and patterns of failure with carcinoma of the intact uterus

    SciTech Connect

    Igboeli, P.; Kapp, D.S.; Lawrence, R.; Schwartz, P.E.

    1983-02-01

    Eighty-nine patients with previously untreated invasive carcinoma of the cervical stump were seen at Yale-New Haven Hospital from 1953 through 1977. This represented 9.4% of the carcinomas of the cervix seen during this time period. Eighty-five of the 89 patients (95.5%) had ''true'' cancers of the cervical stump diagnosed 2 years or more after subtotal hysterectomy, while 4 of the 89 patients (4.5%) had ''coincident'' cancers diagnosed within 2 years of the subtotal hysterectomy. All cervical cancers were staged by the F.I.G.O. classification. Patient characteristics, methods of management, failure sites and survival of patients with carcinoma of the cervical stump were compared to those patients with carcinoma in the intact uterus. Patients with cervical stump cancers were treated in a similar manner to those with carcinomas of the intact uterus, using a combination of external beam irradiation and intracavitary radium. The stump cancer patients had a similar stage distribution to the patients with cancers of the intact uterus but, on the average, they were older and received less irradiation. The patterns of failure were similar on a stage for stage basis, but the survival and disease-free survival for stump cancer patients were superior to those of the patients with carcinoma of the intact uterus.

  13. Population Genetics of Drosophila Amylase. II. Geographic Patterns in D. PSEUDOOBSCURA

    PubMed Central

    Powell, Jeffrey R.

    1979-01-01

    Morph frequencies of three related polymorphisms were determined in ten natural populations of Drosophila pseudoobscura. They are the well-known inversion polymorphism of the third chromosome and the polymorphism for α-amylase produced by the structural gene Amy (which resides on the third chromosome). The third polymorphism was for tissue-specific expression of Amy in adult midguts; a total of 13 different patterns of activity have been observed. The preceding paper (Powell and Lichtenfels 1979) reports evidence that the variation in Amy expression is under polygenic control. Here we show that the polymorphism for midgut activity patterns occurs in natural populations and is not an artifact of laboratory rearing.—From population to population, Amy allele freuencies and frequencies of inversions belonging to different phylads vary coordinately. The geographic variation in α-amylase midgut activity patterns is uncorrelated with that for the other two types of polymorphisms. Furthermore, no correlation was detected between activity pattern(s) and Amy genotype(s) when both were assayed in the same individual.—These results imply that whatever the evolutionary-ecological forces are that control frequencies of the structural gene variants, they are not the same factors that control the frequencies of polymorphic genetic factors responsible for the tissue-specific expression of the enzyme. PMID:488707

  14. Surviving the Messinian Salinity Crisis? Divergence patterns in the genus Dendropoma (Gastropoda: Vermetidae) in the Mediterranean Sea.

    PubMed

    Calvo, Marta; Alda, Fernando; Oliverio, Marco; Templado, José; Machordom, Annie

    2015-10-01

    Four genetically distinct clades were recently described under the name Dendropoma petraeum, a Mediterranean endemic vermetid gastropod. The aim of this work is to date the processes that drove to the diversification within this taxon and to relate them to the corresponding historical events occurred in the Mediterranean Sea. Sequences from mitochondrial and nuclear markers were obtained from specimens collected in 29 localities spanning over 4000km across the entire distribution range of D. petraeum species complex. The phylogenetic and coalescent-based analyses confirmed the four well-supported and largely differentiated lineages of D. petraeum, clearly delimited geographically along a west-east axis within the Mediterranean Sea: Western, Tyrrhenian-Sicilian, Ionian-Aegean and Levantine lineages. Divergence time estimates, obtained using a range of known substitution rates for other marine gastropods, indicated two main stages of diversification. In the first period (between 9.5 and 4.5mya), the ancestral D. petraeum diverged into the current four lineages. The most recent period occurred between 3.72 and 0.66mya in the late Pliocene-early Pleistocene, and included the main within-lineage diversification events. Therefore, if the divergence time between the major lineages of Dendropoma in the Mediterranean actually predated or coincided with the Messinian Salinity Crisis, then they should have survived to this dramatic period within the Mediterranean, as supported by Bayes Factors model comparison. Conversely, if the divergence started after the crisis, congruent with the idea that no true marine organism survived the Messinian Salinity Crisis, then our results indicate substitution rates of Dendropoma much higher than usual (5.16% per million years for COI, 3.04% for 16S). More recent climate changes seem to have conditioned the demographic history of each lineage differently. While Western and Tyrrhenian-Sicilian lineages both underwent an increase in their

  15. [Establishment of full-sib families of Branchiostoma japonicum and the relationship between early development patterns and larvae survival rates].

    PubMed

    Li, Wei-Ye; Wang, Yi-Quan

    2013-10-01

    One general requirement of individual laboratory animals is that they have known genetic backgrounds. However, ensuring such genetic similarity is difficult, and can be facilitated by breeding a full strain for experimentation. To this end, the authors bred 34 full-sib families of amphioxus larvae/embryos. Due to the high mortality of the embryos and larvae, only seven full-sib families of juvenile amphioxus Branchiostoma japonicum were obtained. Among them, the highest and lowest survival ratios were 32.4% and 1.67%, respectively, whereas the shortest metamorphosis and longest larva duration were 24 d and 42 d, respectively. These results demonstrate the feasibility of establishing full-sib families of amphioxus, and provide fundamental data needed for the future breeding of amphioxus strains.

  16. Ultra-High Pressure Driver and Nozzle Survivability in the RDHWT/MARIAH II Hypersonic Wind Tunnel

    SciTech Connect

    Costantino, M.; Brown, G.; Raman, K.; Miles, R.; Felderman, J.

    2000-06-02

    An ultra-high pressure device provides a high enthalpy (> 2500 kJ/kg), low entropy (< 5 kJ/kg-K) air source for the RDHWT/MARIAH II Program Medium Scale Hypersonic Wind Tunnel. The design uses stagnation conditions of 2300 MPa (330,000 Psi) and 750 K (900 F) in a radial configuration of intensifiers around an axial manifold to deliver pure air at 100 kg/s mass flow rates for run times suitable for aerodynamic, combustion, and test and evaluation applications. Helium injection upstream of the nozzle throat reduces the throat wall recovery temperature to about 1200 K and reduces the oxygen concentration at the nozzle wall.

  17. Patterns of Intellectual Ability in Jewish and Arab Children in Israel: II. Urban Matched Samples

    ERIC Educational Resources Information Center

    Lieblich, Amia; And Others

    1975-01-01

    Arab and Jewish children living in a city in northern Israel were matched as closely as possible for school grade, age and SES, and tested on the Wechsler Preschool Primary Scale of Intelligence. Results indicated little if any difference between Jewish and Arab children in level or pattern of the intellectual abilities as elicited by the WPPSI…

  18. Patterns of Citizen Participation in Educational Decisionmaking. Volume II. Grassroots Perspectives: Diverse Forms of Participation.

    ERIC Educational Resources Information Center

    Davies, Don; And Others

    This second volume of a status report on citizen participation in educational decision-making considers in more detail a variety of channels for participation. In chapter 1, three examples of community councils illumine the importance of race, class, and economic factors in patterns of participation. Chapter 2 focuses on mandated school councils…

  19. Impact of Angiotensin I-converting Enzyme Inhibitors and Angiotensin II Type-1 Receptor Blockers on Survival of Patients with NSCLC

    PubMed Central

    Miao, Lili; Chen, Wei; Zhou, Ling; Wan, Huanying; Gao, Beili; Feng, Yun

    2016-01-01

    It has been shown that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can decrease tumor growth and tumor-associated angiogenesis and inhibit metastasis. Epidermal growth factor receptor (EGFR) mutations are found in approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) in East Asia and in 10–15% of such patients in Western countries. We retrospectively identified 228 patients with histologically confirmed advanced NSCLC and 73 patients with early stage disease; 103 of these patients took antihypertensive drugs, and 112 received treatment with EGFR tyrosine kinase inhibitors (TKIs). There was a significant difference in progression-free survival after first-line therapy (PFS1) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients treated with TKIs, there was a significant difference in PFS but not in overall survival (OS) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients with advanced NSCLC, there was a significant difference in PFS1 between the ACEI/ARB group and the non-ACEI/ARB group. ACEI/ARB in combination with standard chemotherapy or TKIs had a positive effect on PFS1 or OS, regardless of whether the lung cancer was in the early or advanced stage. PMID:26883083

  20. Overall Survival Analysis From a Randomized Phase II Study of Axitinib With or Without Dose Titration in First-Line Metastatic Renal Cell Carcinoma.

    PubMed

    Rini, Brian I; Tomita, Yoshihiko; Melichar, Bohuslav; Ueda, Takeshi; Grünwald, Viktor; Fishman, Mayer N; Uemura, Hirotsugu; Oya, Mototsugu; Bair, Angel H; Andrews, Glen I; Rosbrook, Brad; Jonasch, Eric

    2016-12-01

    In a randomized phase II trial in metastatic renal cell carcinoma (mRCC), objective response rate was significantly higher with axitinib versus placebo titration (54% vs. 34%; 1-sided P = .019). Treatment-naive patients with mRCC (n = 213) received axitinib 5 mg twice per day (b.i.d.) for 4 weeks. Patients meeting dose titration criteria were randomized to receive axitinib 5 mg b.i.d. with axitinib or placebo titration (n = 56 each); 91 patients ineligible for randomization continued axitinib 5 mg b.i.d.; 10 discontinued before randomization. Median overall survival (95% confidence interval [CI]) was 42.7 months (24.7-not estimable) with axitinib titration versus 30.4 months (23.7-45.0) with placebo titration (stratified hazard ratio, 0.785; 95% CI, 0.485-1.272; 1-sided P = .162), and 41.6 months (95% CI, 33.0-not estimable) in nonrandomized patients. Safety data were consistent with previous reports. Median overall survival was numerically longer in patients with first-line mRCC who received axitinib versus placebo titration. No new safety signal was observed after long-term axitinib treatment in first-line mRCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial.

    PubMed

    Oh, Sung Yong; Kim, Won Seog; Kim, Jin Seok; Chae, Yee Soo; Lee, Gyeong-Won; Eom, Hyeon Seok; Ryoo, Hun Mo; Lee, Suee; Kim, Seok Jin; Yoon, Dok Hyun; Won, Jong Ho; Hong, Junshik; Park, Jinny; Lee, Sang-Min; Hong, Jung Yong; Park, Eunkyung; Kim, Hyo Jung; Yang, Deok-Hwan; Kim, Hyo-Jin; Suh, Cheolwon

    2016-01-01

    Overall, more than 50% of marginal zone lymphoma (MZL) patients experience a relapse within 10 years. This phase II trial was conducted to assess the efficacy and safety of oxaliplatin-prednisone (Ox-P) chemotherapy for patients with relapsed or refractory MZL. Patients received oxaliplatin 130 mg/m(2) on day 1 and prednisone 100 mg/day on days 1-5 of each cycle. A total of 38 patients were enrolled. The median age of the 34 (16 males, 18 females) evaluated patients was 53 (range = 27-74) years. There were seven complete responses (20.6%) and 15 partial responses (44.1%) (Overall response rate = 64.7%). No treatment-related deaths occurred. The median progression-free survival was 14.2 months (95% CI = 2.1-26.3 months); 3-year overall survival rate was 77.7%. Thus, salvage Ox-P chemotherapy for patients with relapsed or refractory MZL at the stated dosage and schedule showed moderate clinical activity and was considerable in very few selected patients (NCT01068392).

  2. Predicting Pattern Tooling and Casting Dimensions for Investment Casting - Phase II

    SciTech Connect

    Sabau, Adrian S

    2005-09-01

    The investment casting process allows the production of complex-shape parts and close dimensional tolerances. One of the most important phases in the investment casting process is the design of the pattern die. Pattern dies are used to create wax patterns by injecting wax into dies. The wax patterns are used to create a ceramic shell by the application of a series of ceramic coatings, and the alloy is cast into the dewaxed shell mold (Fig. 1.1). However, the complexity of shape and the close dimensional tolerances required in the final casting make it difficult to determine tooling dimensions. The final linear dimension of the casting depends on the cumulative effects of the linear expansions or contractions in each step of the investment casting process (Fig. 1.2). In most cases, the mold geometry or cores restrict the shrinkage of the pattern or the cast part, and the final casting dimensions may be affected by time-dependent processes such as viscoelastic deformation of the wax, and viscoplastic creep and plastic deformations of the shell and alloy. The pattern die is often reworked several times to produce castings whose dimensions are within acceptable tolerances. To date, investment casting technology has been based on hands-on training and experience. Technical literature is limited to experimental, phenomenological studies aimed at obtaining empirical correlations for quick and easy application in industry. The goal of this project was to predict casting dimensions for investment castings in order to meet blueprint nominal during the first casting run. Several interactions have to be considered in a coupled manner to determine the shrinkage factors: these are the die-wax, wax-shell, and shell-alloy interactions (as illustrated in Fig. 1.3). In this work, the deformations of the die-wax and shell-alloy systems were considered in a coupled manner, while the coupled deformation of the wax-shell system was not considered. Future work is needed in order to

  3. CHANGES IN ORO-PHARYNGEAL AIRWAY DIMENSIONS AFTER TREATMENT WITH FUNCTIONAL APPLIANCE IN CLASS II SKELETAL PATTERN.

    PubMed

    Ali, Batool; Shaikh, Attiya; Fida, Mubassar

    2015-01-01

    Functional appliances have been used since many decades for the correction of mandibular retrognathism. Similar oral appliances are a treatment modality for patients with Obstructive sleep apnoea. Hence, interception at the right age with these growth modification appliances might benefit a child from developing long-term respiratory insufficiency. Therefore, the purpose of our study was to assess the short-term effects of Twin block appliance (CTB) on pharyngeal airway size in subjects with skeletal Class-II pattern in a sample of Pakistani population. A retrospective study was conducted from orthodontic records of 62 children (31 males, 31 females) with retrognathic mandibles using lateral cephalograms obtained at initial visit and after CTB treatment. Paired t-test was used to compare the pre-functional and post-functional treatment airway size. Independent sample t-test was used for comparison between the genders and statistical significance was kept at ≤ 00.5. The upper airway width (p < 0.001), nasopharyngeal depth (p = 0.03) and upper airway thickness (p = 0.008) was substantially improved after CTB treatment. Males showed a greater increase in upper airway width (p = 0.03) and nasopharyngeal depth (p = 0.01) in comparison to the females. Functional appliance therapy can improve the narrow pharyngeal airway of growing children presenting with deficient mandibles having Class-II skeletal pattern.

  4. Uncontrolled non-heartbeating donors (types i-ii) with normothermic recirculation vs. heartbeating donors: evaluation of functional results and survival.

    PubMed

    Miranda-Utrera, N; Medina-Polo, J; Pamplona-Casamayor, M; Passas-Martínez, J B; Rodríguez-Antolín, A; de la Rosa Kehrmann, F; Duarte-Ojeda, J M; Tejido-Sánchez, A; Villacampa Aubá, F; Andrés Belmonte, A

    2015-09-01

    Non-heartbeating donors (NHBD) are an alternative to heartbeating donors (HBD). Our objective was to compare functional results and kidney survival from NHBDs and HBDs. A retrospective study comparing the results of 236 normothermically preserved kidneys from type i and ii type NHBDs with the results of 250 from HBDs that were transplanted in our center between 2005 and 2012. Homogeneity between groups was tested and we evaluated the presence of delayed graft function (DGF) associated with pretransplant variables of the donor and recipient. Both groups show homogeneity in pretransplant characteristics in terms of: age, HLA incompatibilities, and recipient hemodialysis time. Average follow-up time was 33 months (range 0-87) for NHBDs and 38 months (range 0-90) for HBDs. 5.5% of NHBDs showed primary non-function (PNF) vs. 4% of HBDs (P=.42) and 80.9% of DGF vs. 46.8% of HBDs (P<.001). At the end of the follow-up, there were no statistically significant differences in the survival of grafts (92.8% for NHBD vs. 93.6% for HBD, P=.71) and recipients (99.1% NHBD vs. 98.6% HBD, P=.28). Although the DGF percentage was greater for NHBDs, final creatinine as well as graft and recipient survival were similar for both groups. Therefore, in our experience, kidneys from NHBDs have similar results to those from HBDs and are an excellent source of organs for transplantation. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Spawning areas of eastern Baltic cod revisited: Using hydrodynamic modelling to reveal spawning habitat suitability, egg survival probability, and connectivity patterns

    NASA Astrophysics Data System (ADS)

    Hinrichsen, H.-H.; Lehmann, A.; Petereit, C.; Nissling, A.; Ustups, D.; Bergström, U.; Hüssy, K.

    2016-04-01

    In the highly variable environment of the Baltic Sea two genetically distinct cod stocks exist, one west of the island of Bornholm, which is referred to as the western stock, and one to the east of Bornholm, the eastern stock. A hydrodynamic model combined with a Lagrangian particle tracking technique was utilised to provide spatially and temporally resolved long-term information on environmentally-related (i) spawning habitat size, (ii) egg/yolk-sac larval survival, (iii) separation of causes of mortality, and (iv) connectivity between spawning areas of eastern Baltic cod. Simulations were performed to quantify processes generating heterogeneity in spatial distribution of cod eggs and yolk sac larvae up to the first-feeding stage. The spatial extent of cod eggs represented as virtual drifters is primarily determined by oxygen and salinity conditions at spawning, which define the habitat requirement to which cod's physiology is suited for egg development. The highest habitat suitability occurred in the Bornholm Basin, followed by the Gdansk Deep, while relatively low habitat suitability was obtained for the Arkona and the Gotland Basin. During drift egg and yolk sac larval survival is to a large extent affected by sedimentation. Eggs initially released in the western spawning grounds (Arkona and Bornholm Basin) were more affected by sedimentation than those released in the eastern spawning grounds (Gdansk Deep and Gotland Basin). Highest relative survival of eastern Baltic cod eggs occurred in the Bornholm Basin, with a pronounced decrease towards the Gdansk Deep and the Gotland Basin. Relatively low survival rates in the Gdansk Deep and in the Gotland Basin were attributable to oxygen-dependent mortality. Low oxygen content had almost no impact on survival in the Arkona Basin. For all spawning areas temperature dependent mortality was only evident after severe winters. Egg buoyancy in relation to topographic features like bottom sills and strong bottom slopes

  6. Patterns of evolution of MHC class II genes of crows (Corvus) suggest trans-species polymorphism.

    PubMed

    Eimes, John A; Townsend, Andrea K; Sepil, Irem; Nishiumi, Isao; Satta, Yoko

    2015-01-01

    A distinguishing characteristic of genes that code for the major histocompatibility complex (MHC) is that alleles often share more similarity between, rather than within species. There are two likely mechanisms that can explain this pattern: convergent evolution and trans-species polymorphism (TSP), in which ancient allelic lineages are maintained by balancing selection and retained by descendant species. Distinguishing between these two mechanisms has major implications in how we view adaptation of immune genes. In this study we analyzed exon 2 of the MHC class IIB in three passerine bird species in the genus Corvus: jungle crows (Corvus macrorhynchos japonensis) American crows (C. brachyrhynchos) and carrion crows (C. corone orientalis). Carrion crows and American crows are recently diverged, but allopatric, sister species, whereas carrion crows and jungle crows are more distantly related but sympatric species, and possibly share pathogens linked to MHC IIB polymorphisms. These patterns of evolutionary divergence and current geographic ranges enabled us to test for trans-species polymorphism and convergent evolution of the MHC IIB in crows. Phylogenetic reconstructions of MHC IIB sequences revealed several well supported interspecific clusters containing all three species, and there was no biased clustering of variants among the sympatric carrion crows and jungle crows. The topologies of phylogenetic trees constructed from putatively selected sites were remarkably different than those constructed from putatively neutral sites. In addition, trees constructed using non-synonymous substitutions from a continuous fragment of exon 2 had more, and generally more inclusive, supported interspecific MHC IIB variant clusters than those constructed from the same fragment using synonymous substitutions. These phylogenetic patterns suggest that recombination, especially gene conversion, has partially erased the signal of allelic ancestry in these species. While clustering of

  7. Patterns of evolution of MHC class II genes of crows (Corvus) suggest trans-species polymorphism

    PubMed Central

    Townsend, Andrea K.; Sepil, Irem; Nishiumi, Isao; Satta, Yoko

    2015-01-01

    A distinguishing characteristic of genes that code for the major histocompatibility complex (MHC) is that alleles often share more similarity between, rather than within species. There are two likely mechanisms that can explain this pattern: convergent evolution and trans-species polymorphism (TSP), in which ancient allelic lineages are maintained by balancing selection and retained by descendant species. Distinguishing between these two mechanisms has major implications in how we view adaptation of immune genes. In this study we analyzed exon 2 of the MHC class IIB in three passerine bird species in the genus Corvus: jungle crows (Corvus macrorhynchos japonensis) American crows (C. brachyrhynchos) and carrion crows (C. corone orientalis). Carrion crows and American crows are recently diverged, but allopatric, sister species, whereas carrion crows and jungle crows are more distantly related but sympatric species, and possibly share pathogens linked to MHC IIB polymorphisms. These patterns of evolutionary divergence and current geographic ranges enabled us to test for trans-species polymorphism and convergent evolution of the MHC IIB in crows. Phylogenetic reconstructions of MHC IIB sequences revealed several well supported interspecific clusters containing all three species, and there was no biased clustering of variants among the sympatric carrion crows and jungle crows. The topologies of phylogenetic trees constructed from putatively selected sites were remarkably different than those constructed from putatively neutral sites. In addition, trees constructed using non-synonymous substitutions from a continuous fragment of exon 2 had more, and generally more inclusive, supported interspecific MHC IIB variant clusters than those constructed from the same fragment using synonymous substitutions. These phylogenetic patterns suggest that recombination, especially gene conversion, has partially erased the signal of allelic ancestry in these species. While clustering of

  8. Proof-Carrying Survivability

    DTIC Science & Technology

    2013-01-15

    relationships among the survivability properties required for a system • Fuzzy pattern matching and constrained reasoning in proof construction and...framework facilitates constrained reasoning, i.e., possibilistic uncertainty and survivability requirement constraints are effectively linked to...logical reasoning. The framework makes it possible to express fuzzy pattern matching and arbitrary user-defined constraints in formal proofs. The above

  9. Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients

    PubMed Central

    van den Broek, Evert; Krijgsman, Oscar; Sie, Daoud; Tijssen, Marianne; Mongera, Sandra; van de Wiel, Mark A.; Th. Belt, Eric J.; den Uil, Sjoerd H.; Bril, Herman; Stockmann, Hein B.A.C.; Ylstra, Bauke; Carvalho, Beatriz; Meijer, Gerrit A.; Fijneman, Remond J.A.

    2016-01-01

    Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs). For 60 of these samples mutation status of APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS was determined using targeted massive parallel sequencing. Loss of chromosome 18q12.1-18q12.2 occurred more frequently in tumors that relapsed than in relapse-free tumors (p < 0.001; FDR = 0.13). In total, 267 genes were recurrently affected by SVs (FDR < 0.1). CNAs and SVs were not associated with disease-free survival (DFS). Mutations in APC and TP53 were associated with increased CNAs. APC mutations were associated with poor prognosis in (5-fluorouracil treated) stage III colon cancers (p = 0.005; HR = 4.1), an effect that was further enhanced by mutations in MAPK pathway (KRAS, NRAS, BRAF) genes. We conclude that among multiple genomic alterations in CRC, strongest associations with clinical outcome were observed for common mutations in APC. PMID:27729614

  10. Formation of the regular satellites of giant planets in an extended gaseous nebula II: satellite migration and survival

    NASA Astrophysics Data System (ADS)

    Mosqueira, Ignacio; Estrada, Paul R.

    2003-05-01

    For a satellite to survive in the disk the time scale of satellite migration must be longer than the time scale for gas dissipation. For large satellites (˜1000 km) migration is dominated by the gas tidal torque. We consider the possibility that the redistribution of gas in the disk due to the tidal torque of a satellite with mass larger than the inviscid critical mass causes the satellite to stall and open a gap (W.R. Ward, 1997, Icarus 26, 261-281). We adapt the inviscid critical mass criterion to include gas drag, and m-dependent nonlocal deposition of angular momentum. We find that such a model holds promise of explaining the survival of satellites in the subnebula, the mass versus distance relationship apparent in the saturnian and uranian satellite systems, the concentration of mass in Titan, and the observation that the satellites of Jupiter get rockier closer to the planet whereas those of Saturn become increasingly icy. It is also possible that either weak turbulence (close to the planet) or gap-opening satellite tidal torque removes gas on a similar time scale (10 4-10 5 years) as the orbital decay time of midsized (200-700 km) regular satellites forming in the inner disk (inside the centrifugal radius (I. Mosqueira and P.R. Estrada, 2003, Icarus, this issue)). We argue that Saturn's satellite system bridges the gap between those of Jupiter and Uranus by combining the formation of a Galilean-sized satellite in a gas optically thick subnebula with a strong temperature gradient, and the formation of smaller satellites, closer to the planet, in a disk with gas optical depth ≲1, and a weak temperature gradient. Using an optically thick inner disk (given gaseous opacity), and an extended, quiescent, optically thin outer disk, we show that there are regions of the disk of small net tidal torque (even zero) where satellites (Iapetus-sized or larger) may stall far from the planet. For our model these outer regions of small net tidal torque correspond roughly

  11. Longitudinal analysis of deciduous tooth emergence: II. Parametric survival analysis in Bangladeshi, Guatemalan, Japanese, and Javanese children.

    PubMed

    Holman, D J; Jones, R E

    1998-02-01

    We present a form of parametric survival analysis that incorporates exact, interval-censored, and right-censored times to deciduous tooth emergence. The method is an extension of common cross-sectional procedures such as logit and probit analysis, so that data arising from mixed longitudinal and cross-sectional studies can be properly combined. We extended the method to incorporate and estimate a proportion of agenic teeth. While we concentrate on deciduous tooth emergence, the method is relevant to studies of permanent tooth emergence and other developmental events. Deciduous tooth emergence data were analyzed from four longitudinal studies. The samples are 1,271 rural Guatemalan children examined every three months up to age two and every six months thereafter as part of the INCAP study; 397 rural Bangladeshi children examined monthly to age one and quarterly thereafter as part of the Meheran Growth and Development Study; 468 rural Indonesian children examined monthly as part of the Ngaglik study; and 114 urban Japanese children examined monthly in studies from 1910 and 1920. Although all four studies were longitudinal, many observations from the Guatemala and Bangladesh studies were effectively cross-sectionally observed. Three different parametric forms were used to model the eruption process: a normal distribution, a lognormal distribution, and a lognormal distribution with age shifted to shortly after conception. All three distributions produced reliable estimates of central tendencies, but the shifted lognormal distribution produced the best overall estimates of shape (variance) parameters. Estimates of emergence were compared to other studies that used similar methods. Japanese children showed relatively fast emergence times for all teeth. Bangladeshi and Javanese children showed emergence times that were slower than are found in most previous studies. Estimates of agenesis were not significantly different from zero for most teeth. One or two central

  12. Hierarchical crack pattern as formed by successive domain divisions. II. From disordered to deterministic behavior

    NASA Astrophysics Data System (ADS)

    Bohn, S.; Platkiewicz, J.; Andreotti, B.; Adda-Bedia, M.; Couder, Y.

    2005-04-01

    Hierarchical crack patterns, such as those formed in the glaze of ceramics or in desiccated layers of mud or gel, can be understood as a successive division of two-dimensional domains. We present an experimental study of the division of a single rectangular domain in drying starch and show that the dividing fracture essentially depends on the domain size, rescaled by the thickness of the cracking layer e . Utilizing basic assumptions regarding the conditions of crack nucleation, we show that the experimental results can be directly inferred from the equations of linear elasticity. Finally, we discuss the impact of these results on hierarchical crack patterns, and in particular the existence of a transition from disordered cracks at large scales—the first ones—to a deterministic behavior at small scales—the last cracks.

  13. Models of central pattern generators for quadruped locomotion. II. Secondary gaits.

    PubMed

    Buono, P L

    2001-04-01

    We continue the analysis of the network of symmetrically coupled cells modeling central pattern generators (CPG) for quadruped locomotion proposed by Golubitsky, Stewart, Buono and Collins by studying secondary gaits. Secondary gaits are modeled by output signals from the CPG where each cell emits one of two different output signals along with exact phase shifts. Examples of secondary gaits are transverse gallop, rotary gallop, and canter. We classify secondary gaits that bifurcate when the Poincaré map of a primary gait has a real eigenvalue crossing the unit circle. In particular, we show that periodic solutions modeling transverse gallop and rotary gallop bifurcate from primary gaits. Moreover, we find gaits from period-doubling bifurcations and analyze plausible footfall patterns. Numerical simulations are performed using the Morris-Lecar equations as cell dynamics.

  14. Development, Reproduction, Survival, and Demographic Patterns of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) on Different Commercial Tomato Cultivars.

    PubMed

    Krechemer, F S; Foerster, L A

    2017-03-25

    The increase in the production of tomato, Solanum lycopersicon Mill. (Solanaceae), has favored the proliferation of pests, especially Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). In this study, the development, reproduction, survival, and demographic parameters of T. absoluta reared on six commercial tomato cultivars (Cherry, Cordilheira, Giuliana, Nemoneta, Paron, and Santa Clara) were evaluated. Tuta absoluta completed its development in all tomato cultivars. Development from newly hatched caterpillar to newly emerged adult varied between 24.8 and 28.2 days. Female fecundity ranged from 126.3 to 166.9 eggs, with fertility from 54.2 to 84.1%. Mortality during egg-adult development varied between 21.4 and 46.4% for insects reared on cultivars Cherry and Giuliana, respectively. The cultivars Cordilheira, Giuliana, and Santa Clara are promising options to tomato producers in order to decrease the attack and proliferation of T. absoluta. However, the development and population growth of T. absoluta is faster on the tomato cultivar Cherry.

  15. Survival of Hoxa13 Homozygous Mutants Reveals a Novel Role in Digit Patterning and Appendicular Skeletal Development

    PubMed Central

    Perez, Wilma D.; Weller, Crystal R.; Shou, Siming; Stadler, H. Scott

    2010-01-01

    The loss of HOXA13 function severely disrupts embryonic limb development. However, because embryos lacking HOXA13 die by mid-gestation, the defects present in the mutant limb could arise as a secondary consequence of failing embryonic health. In our analysis of the mutant Hoxa13GFP allele, we identified a surviving cohort of homozygous mutants exhibiting severe limb defects including: missing phalanx elements, fusions of the carpal/tarsal elements, and significant reductions in metacarpal/metatarsal length. Characterization of prochondrogenic genes in the affected carpal/tarsal regions revealed significant reduction in Gdf5 expression, whereas Bmp2 expression was significantly elevated. Analysis of Gdf5 mRNA localization also revealed diffuse expression in the carpal/tarsal anlagen, suggesting a role for HOXA13 in the organization of the cells necessary to delineate individual carpal/tarsal elements. Together these results identify Gdf5 as a potential target gene of HOXA13 target gene and confirm a specific role for HOXA13 during appendicular skeletal development. PMID:20034107

  16. Mathematical modeling of cement paste microstructure by mosaic pattern. Part II. Application

    SciTech Connect

    Tennis, P.D.; Xi, Y.; Jennings, H.M.

    1997-07-01

    A model based on mosaic pattern analysis is shown to have the potential to describe the complex shapes and spatial distribution of phases in the microstructures of multiphase materials. Several characteristics of both micrographs of portland cement pastes and images generated using the few parameters of the model are determined and, for the most part, agreement is good. The advantage is that spatial features of the microstructures can be captured by a few parameters. {copyright} {ital 1997 Materials Research Society.}

  17. Calretinin and calbindin distribution patterns specify subpopulations of type I and type II spiral ganglion neurons in postnatal murine cochlea

    PubMed Central

    Liu, Wenke; Davis, Robin L.

    2014-01-01

    As the first neural element in the auditory pathway, neurons in the spiral ganglion shape the initial coding of sound stimuli for subsequent processing. Within the ganglion, type I and type II neurons form divergent and convergent innervation patterns, respectively, with their hair cell sensory receptors, indicating that very different information is gathered and conveyed. Layered onto these basic innervation patterns are structural and electrophysiological features that provide additional levels of processing multifaceted sound stimuli. To understand the nature of this additional complexity of signal coding, we characterized the distribution of calretinin and calbindin, two regulators of intracellular calcium that serve as markers for neuronal subpopulations. We showed in acute preparations and in vitro that calretinin and calbindin staining levels were heterogeneous. Immunocytochemical analysis of co-localization further showed that high levels of staining for the two molecules rarely overlapped. Although varied amounts of calbindin and calretinin were found within each tonotopic location and neuronal type, some distinct sub-distributions were noted. For example, calretinin levels were highest in neurons innervating the mid-cochlea region, whereas calbindin levels were similar across the entire ganglion. Furthermore, we noted that apical type II neurons, identified by anti-peripherin labeling had significantly lower levels of calretinin and higher levels of calbindin. We also established that the endogenous firing feature of onset tau of the sub-threshold response showed a pattern related to quantified calretinin and calbindin staining levels. Taken together, our results are suggestive of an additional dimension of complexity within the spiral ganglion beyond that currently categorized. PMID:24414968

  18. Restrictive pattern in spirometry as a predictor of poor survival in chronic heart failure patients on betaceptor-antagonist, with possible indications for heart transplantation.

    PubMed

    Lizak, Maria K; Zakliczyński, Michał; Jarosz, Anna; Zembala, Marian; Kalarus, Zbigniew

    2011-01-01

    Restrictive spirometry pattern is commonly associated with chronic heart failure (CHF), but its prognostic value is poorly documented. Utility of Lower Limit of Normal (LLN)-based spirometry interpretation has not yet been evaluated in CHF patients. Impact of restrictive pattern defined according to classic or LLN criteria on prognosis in CHF patients was therefore addressed. 171 CHF patients on long-term beta-antagonist treatment with PeakVO2 >12 ml/kg/min (147 men, 49±9 years, LVEF 26±8%, 51% ischemic) were divided into groups based on their spirometry: Group 1A (N=129) - classic criteria: no restriction, Group 2A (N=12) - classic criteria: restrictive pattern, Group 1B (N=90) - LLN criteria: no restriction, Group 2B (N=26) - LLN criteria: restrictive pattern. PeakVO2 in the study groups equaled 12.1-19.9 ml/kg/min. Control group (N=30) - PeakVO2 >20 ml/kg/min, absence of restriction or obstruction (FEV1%FVC ≥70) defined by classic criteria. Classic criteria: VCin% <70 and FEV1%FVC ≥70. LLN criteria: VCin% survival was observed in groups 2A and 2B when compared to the control group. One-year and 2-year mortality were significantly higher in group 2B (19.2 and 40.9%; control group: 0% and 0%, respectively) and 2-year mortality was higher in group 2A (40.0%). Restrictive spirometry pattern is associated with worse survival in CHF patients with PeakVO2 above the cutoff point for OHT listing. Use of LLN criteria may be useful to predict poor 1-year prognosis.

  19. Disequilibrium patterns of the peptide transporter loci within the HLA class II region

    SciTech Connect

    Klitz, W.; Stephens, C.J.; Carrington, M.

    1994-09-01

    Disequilibrium between genetic markers is expected to decline monotonically with recombinational map distance. We present evidence from the HLA class II region which seems to violate this principle. Pairwise disequilibrium values from a sample of northern Europeans were calculated for six loci ranging in physical separation from 7 kb to 550 kb. The histocompatibility loci DRB1, DQA1 and DQB1 located on the distal end of the class II region behave as a single evolutionary unit within which extremely high linkage disequilibrium exists. Lower but significant levels of disequilibrium are present between these loci and DPB1 located at the proximal edge of the HLA complex. The peptide transporter loci TAP1 and TAP2, located in the intervening region, reveal no disequilibrium with each other and low or negligible disequilibrium with the flanking loci. This evidence suggests either a high rate of gene conversion in the TAP loci which mixes TAP alleles among haplotypes while maintaining the flanking markers, or recombinational hot spots near and between the TAP loci operating in combination with selection to preserve particular combinations of alleles at the flanking histocompatibility loci. Whatever explanation proves correct, this work demonstrates that the lack of association of TAP alleles with a DR-DQ associated disease cannot be used as evidence for a centromeric boundary of influence on that disease.

  20. Niche separation in Varecia variegata rubra and Eulemur fulvus albifrons: II. Intraspecific patterns.

    PubMed

    Vasey, Natalie

    2002-06-01

    Based on a year-long field study in northeastern Madagascar, I summarize annual patterns of niche use (food patch size, diet, forest height, and forest site) in two sympatric lemurs, Varecia variegata rubra and Eulemur fulvus albifrons. Furthermore, I examine intraspecific patterns of niche use according to sex, season, and reproductive stage in these two lemurs that differ in terms of energetic investment in reproduction. Lemurs as a group provide a special opportunity to test hypotheses concerning sex differences in niche use. Due to their body size monomorphism and seasonal, synchronous pattern of breeding, it is possible to directly evaluate whether sex differences in diet reflect high energetic investment in reproduction by females. Results confirm the hypothesis that intraspecific variation in niche use (e.g., sex differences, seasonal differences) would be more pronounced in V. v. rubra than in E. f. albifrons, due in large measure to the former's relatively high energetic investment in reproduction: 1a) Dietary sex differences in V. v. rubra are most pronounced during costly reproductive stages and involve acquisition of low-fiber, high-protein plant foods. Females of both species consume more seasonally available low-fiber protein (young leaves, flowers) relative to conspecific males during the hot dry season, but only in V. v. rubra females is this pattern also evident during gestation and lactation. 1b) The diets of female V. v. rubra and female E. f. albifrons are more similar to each other than are the diets of conspecific males and females in the case of V. v. rubra. This is not uniformly the case for female E. f. albifrons. This finding confirms a hypothesis put forward in Vasey ([2000] Am J Phys Anthropol 112:411-431) that energetic requirements of reproductive females drive niche separation more than do the energetic requirements of males. 1c) Both species synchronize most or all of lactation with seasonal food abundance and diversity. E. f

  1. The evolutionary history of vertebrate cranial placodes II. Evolution of ectodermal patterning.

    PubMed

    Schlosser, Gerhard; Patthey, Cedric; Shimeld, Sebastian M

    2014-05-01

    Cranial placodes are evolutionary innovations of vertebrates. However, they most likely evolved by redeployment, rewiring and diversification of preexisting cell types and patterning mechanisms. In the second part of this review we compare vertebrates with other animal groups to elucidate the evolutionary history of ectodermal patterning. We show that several transcription factors have ancient bilaterian roles in dorsoventral and anteroposterior regionalisation of the ectoderm. Evidence from amphioxus suggests that ancestral chordates then concentrated neurosecretory cells in the anteriormost non-neural ectoderm. This anterior proto-placodal domain subsequently gave rise to the oral siphon primordia in tunicates (with neurosecretory cells being lost) and anterior (adenohypophyseal, olfactory, and lens) placodes of vertebrates. Likewise, tunicate atrial siphon primordia and posterior (otic, lateral line, and epibranchial) placodes of vertebrates probably evolved from a posterior proto-placodal region in the tunicate-vertebrate ancestor. Since both siphon primordia in tunicates give rise to sparse populations of sensory cells, both proto-placodal domains probably also gave rise to some sensory receptors in the tunicate-vertebrate ancestor. However, proper cranial placodes, which give rise to high density arrays of specialised sensory receptors and neurons, evolved from these domains only in the vertebrate lineage. We propose that this may have involved rewiring of the regulatory network upstream and downstream of Six1/2 and Six4/5 transcription factors and their Eya family cofactors. These proteins, which play ancient roles in neuronal differentiation were first recruited to the dorsal non-neural ectoderm in the tunicate-vertebrate ancestor but subsequently probably acquired new target genes in the vertebrate lineage, allowing them to adopt new functions in regulating proliferation and patterning of neuronal progenitors. Copyright © 2014 Elsevier Inc. All rights

  2. Alveolar septal patterning during compensatory lung growth: Part II the effect of parenchymal pressure gradients.

    PubMed

    Haber, Shimon; Weisbord, Michal; Mentzer, Steven J; Tsuda, Akira

    2017-05-21

    In most mammals, compensatory lung growth occurs after the removal of one lung (pneumonectomy). Although the mechanism of alveolar growth is unknown, the patterning of complex alveolar geometry over organ-sized length scales is a central question in regenerative lung biology. Because shear forces appear capable of signaling the differentiation of important cells involved in neoalveolarization (fibroblasts and myofibroblasts), interstitial fluid mechanics provide a potential mechanism for the patterning of alveolar growth. The movement of interstitial fluid is created by two basic mechanisms: 1) the non-uniform motion of the boundary walls, and 2) parenchymal pressure gradients external to the interstitial fluid. In a previous study (Haber et al., Journal of Theoretical Biology 400: 118-128, 2016), we investigated the effects of non-uniform stretching of the primary septum (associated with its heterogeneous mechanical properties) during breathing on generating non-uniform Stokes flow in the interstitial space. In the present study, we analyzed the effect of parenchymal pressure gradients on interstitial flow. Dependent upon lung microarchitecture and physiologic conditions, parenchymal pressure gradients had a significant effect on the shear stress distribution in the interstitial space of primary septa. A dimensionless parameter δ described the ratio between the effects of a pressure gradient and the influence of non-uniform primary septal wall motion. Assuming that secondary septa are formed where shear stresses were the largest, it is shown that the geometry of the newly generated secondary septa was governed by the value of δ. For δ smaller than 0.26, the alveolus size was halved while for higher values its original size was unaltered. We conclude that the movement of interstitial fluid, governed by parenchymal pressure gradients and non-uniform primary septa wall motion, provides a plausible mechanism for the patterning of alveolar growth. Copyright © 2017

  3. VHL-dependent patterns of RNA polymerase II hydroxylation in human renal clear cell carcinomas

    PubMed Central

    Yi, Ying; Mikhaylova, Olga; Mamedova, Aygun; Bastola, Prabhat; Biesiada, Jacek; Alshaikh, Enas; Levin, Linda; Sheridan, Rachel M.; Meller, Jarek; Czyzyk-Krzeska, Maria F.

    2010-01-01

    Purpose We have previously shown that VHL regulates ubiquitylation and Proline P1465 hydroxylation of the large subunit of RNA polymerase II, Rpb1, in human RCC cell lines. Here, our goal was to determine the impact of this VHL function and the status of P1465 hydroxylation in human RCC tumors. Experimental Design Primary human tumors and matched normal kidney samples were probed for expression levels of the large subunit of RNA polymerase II (Rpb1), Rpb1 hydroxylated on P1465 (Rpb1(OH)), Rpb1 phosphorylated on Ser5 (Rpb1(S5P)), and proline hydroxylases PHD1, PHD2, and PHD3. Results from RCC tumors were categorized according to the status of VHL gene. Mechanistic analysis was performed in orthotopic xenograft model using 786-O RCC cells with wild-type VHL and knockdown of PHD2, characterized by high levels of Rpb1(OH) and PHD1. Results Levels of Rpb1(OH), PHD1, and PHD2 were significantly higher in RCC tumors as compared with normal kidneys. RCC tumors with wild-type VHL had higher levels of Rpb1(OH) and PHD1 and lower levels of PHD2 than tumors with VHL gene alterations. Levels of Rpb1(OH) significantly correlated with levels of PHD1 in tumors and in normal kidneys. Knockdown of PHD2 in 786-O VHL(+) cells resulted in a more malignant phenotype in orthotopic xenografts and higher expression of specific cell cycle regulators (CDC25A, CDK2, CCNA2), as compared with VHL(−) RCC cells. Conclusions Elevated PHD1 concomitant with decreased PHD2 are causatively related to Rpb1 hydroxylation and oncogenesis in human RCC tumors with wild-type VHL gene. Thus, P1465-hydroxylated Rpb1 and PHD1 represent attractive drug targets for new RCC treatments. PMID:20978146

  4. PsbI affects the stability, function, and phosphorylation patterns of photosystem II assemblies in tobacco.

    PubMed

    Schwenkert, Serena; Umate, Pavan; Dal Bosco, Cristina; Volz, Stefanie; Mlçochová, Lada; Zoryan, Mikael; Eichacker, Lutz A; Ohad, Itzhak; Herrmann, Reinhold G; Meurer, Jörg

    2006-11-10

    Photosystem II (PSII) core complexes consist of CP47, CP43, D1, D2 proteins and of several low molecular weight integral membrane polypeptides, such as the chloroplast-encoded PsbE, PsbF, and PsbI proteins. To elucidate the function of PsbI in the photosynthetic process as well as in the biogenesis of PSII in higher plants, we generated homoplastomic knock-out plants by replacing most of the tobacco psbI gene with a spectinomycin resistance cartridge. Mutant plants are photoautotrophically viable under green house conditions but sensitive to high light irradiation. Antenna proteins of PSII accumulate to normal amounts, but levels of the PSII core complex are reduced by 50%. Bioenergetic and fluorescence studies uncovered that PsbI is required for the stability but not for the assembly of dimeric PSII and supercomplexes consisting of PSII and the outer antenna (PSII-LHCII). Thermoluminescence emission bands indicate that the presence of PsbI is required for assembly of a fully functional Q(A) binding site. We show that phosphorylation of the reaction center proteins D1 and D2 is light and redox-regulated in the wild type, but phosphorylation is abolished in the mutant, presumably due to structural alterations of PSII when PsbI is deficient. Unlike wild type, phosphorylation of LHCII is strongly increased in the dark due to accumulation of reduced plastoquinone, whereas even upon state II light phosphorylation is decreased in delta psbI. These data attest that phosphorylation of D1/D2, CP43, and LHCII is regulated differently.

  5. Laser Patterning of Diamond. Part II. Surface Nondiamond Carbon Formation and its Removal

    SciTech Connect

    Smedley, J.; Jaye, C; Bohon, J; Rao, T; Fischer, D

    2009-01-01

    As diamond becomes more prevalent for electronic and research applications, methods of patterning diamond will be required. One such method, laser ablation, has been investigated in a related work. We report on the formation of surface nondiamond carbon during laser ablation of both polycrystalline and single-crystal synthetic diamonds. Near edge x-ray absorption fine structure spectroscopy was used to confirm that the nondiamond carbon layer formed during the ablation was amorphous, and Fourier transform infrared absorption spectroscopy (FTIR) was used to estimate the thickness of this layer to be {approx} 60 nm. Ozone cleaning was used to remove the nondiamond carbon layer.

  6. An investigation of climate patterns on Earth-like planets using the NASA GISS global climate model II

    NASA Astrophysics Data System (ADS)

    Elowitz, Robert Mark

    To determine the capability of NASA's GISS GCM-II global climate model, the user-friendly EdGCM interface to the 3-D climate model code was evaluated by simulating global climate patterns that Earth-like planets may experience. The simulation scenarios involved different greenhouse gas emissions trends, planetary orbital parameters, and solar irradiance variations. It is found that the EdGCM interface to the GCM-II 3-D climate model is capable of studying climate patterns on hypothetical Earth-like planets, with some limitations involved. Studying extreme climate patterns on Earth-like planets as a function of planetary obliquity, orbital eccentricity, atmospheric composition, solar irradiance variations, and location with the host star's habitable zone is needed to determine whether such planets are habitable for life as we know it. Studying the behavior of climate on hypothetical Earth-like planet also provides insight into the future climate of our own planet. A database of climate models based on hypothetical Earth-like worlds will provide a valuable resource to the astrobiology community in support of future detections of exoplanets with masses, sizes, and composition similar to Earth. At present, most studies involved the use of 1-D, or 2-D climate models to explore planetary climate on Earth-like planets. This is due to the difficulty of using very complex 3-D climate model codes that typically have poor user interfaces or interfaces that are very difficult to use. EdGCM provides scientists with a user-friendly interface to a full 3-D climate model capable of simulating the climate on Earth-like planets. However, EdGCM is extremely limited in studying global climate on exo-Earth planets outside our solar system. The user is able to change the simulation initial conditions, including different greenhouse gas concentrations and their associated trends, solar irradiance and its trend over time, planetary obliquity and orbit eccentricity, and heliocentric

  7. Resilience potential of an Indian Ocean reef: an assessment through coral recruitment pattern and survivability of juvenile corals to recurrent stress events.

    PubMed

    Manikandan, Balakrishnan; Ravindran, Jeyaraman; Vidya, Pottekkatt Jayabalan; Shrinivasu, Selvaraju; Manimurali, Rajagopal; Paramasivam, Kaliyaperumal

    2017-05-01

    Coral reefs are degraded by the synergistic action of climate and anthropogenic stressors. Coral cover in the Palk Bay reef at the northern Indian Ocean largely declined in the past decade due to frequent bleaching events, tsunami and increased fishing activities. In this study, we carried out a comparative assessment to assess the differences in the recovery and resilience of three spatially distant reefs viz. Vedhalai, Mandapam and Pamban along Palk Bay affected by moderate, severe and low fishing pressure respectively. The assessment was based on the juvenile coral recruitment pattern and its survivability combined with availability of hard substratum, live coral cover and herbivore reef fish stock. The Vedhalai reef has the highest coral cover (14.6 ± 6.3%), and ≥90% of the live corals in Vedhalai and Mandapam were affected by turf algal overgrowth. The density of herbivore reef fish was low in Vedhalai and Mandapam reefs compared to the Pamban reef with relatively few grazing species. The juvenile coral diversity and density were high in the Pamban reef and low in Vedhalai and Mandapam reefs despite high hard substratum cover. In total, 22 species of juvenile corals of 10 genera were recorded in Palk Bay. Comparison of the species diversity of juvenile corals with adult ones suggested that the Pamban reef is connected with other distant reefs whereas Vedhalai and Mandapam reefs were self-seeded. There was no statistically significant difference in the survivability of juvenile corals between the study sites, and in total, ≥90% of the juvenile corals survived the high sedimentation stress triggered by the northeast monsoon and bleaching stress that occurred recurrently. Our results indicated that the human activities indirectly affected the juvenile coral recruitment by degrading the live coral cover and contributed to the spatial variation in the recovery and resilience of the Palk Bay reef. Low species diversity of the juvenile corals will increase the

  8. The pace of modern life II: from rates of contemporary microevolution to pattern and process.

    PubMed

    Kinnison, M T; Hendry, A P

    2001-01-01

    We compiled a database of microevolution on contemporary time scales in nature (47 source articles; 30 animal species), comprising 2649 evolutionary rates in darwins (proportional change per million years) and 2151 evolutionary rates in haldanes (standard deviations per generation). Here we demonstrate how quantitative rate measures can provide general insights into patterns and processes of evolution. The frequency distribution of evolutionary rates was approximately log-normal, with many slow rates and few fast rates. Net selection intensities estimated from haldanes were on average lower than selection intensities commonly measured directly in natural populations. This difference suggests that natural selection could easily accomplish observed microevolution but that the intensities of selection typically measured in nature are rarely maintained for long (otherwise observed evolutionary rates would be higher). Traits closely associated with fitness (life history traits) appear to evolve at least as fast as traits less closely tied to fitness (morphology). The magnitude of evolutionary difference increased with the length of the time interval, particularly when maximum rates from a given study were considered. This pattern suggests a general underlying tendency toward increasing evolutionary diversification with time. However, evolutionary rates also tended to decrease with time, perhaps because longer time intervals average increasingly disparate rates over time, or because evolution slows when populations approach new optima or as genetic variation is depleted. In combination, our results suggest that macroevolutionary transitions may ultimately arise through microevolution occasionally 'writ large' but are perhaps temporally characterized by microevolution 'writ in fits and starts'.

  9. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    SciTech Connect

    Varlotto, John M.; Yao, Aaron N.; DeCamp, Malcolm M.; Ramakrishna, Satvik; Recht, Abe; Flickinger, John; Andrei, Adin; Reed, Michael F.; Toth, Jennifer W.; Fizgerald, Thomas J.; Higgins, Kristin; Zheng, Xiao; Shelkey, Julie; and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  10. A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change.

    PubMed

    Daly, Bobby; Olopade, Olufunmilayo I

    2015-01-01

    It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed. © 2015 American Cancer Society.

  11. Soft tissue sarcomas of the extremities: survival and patterns of failure with conservative surgery and postoperative irradiation compared to surgery alone

    SciTech Connect

    Leibel, S.A.; Tranbaugh, R.F.; Wara, W.M.; Beckstead, J.H.; Bovill, E.G.; Phillips, T.L.

    1982-09-15

    Between 1960 and 1978, 81 patients received their primary treatment for localized soft tissue sarcomas of the extremities, buttock and shoulder at the University of California, San Francisco. Initial treatment consisted of surgery alone in 47 patients, planned conservative surgery followed by radiation therapy in 29 patients, and irradiation alone in five patients. The two- and five-year determinate survival for all cases was 86% and 73%, respectively. The local control rate achieved with surgery alone was related to the extent of surgery. Eighty-seven percent (14/16) of the patients undergoing amputation were locally controlled. Seventy-two percent (8/11) were treated with wide en bloc resection and had local tumor control while only 30% (6/20) having simple excision were controlled. The local control rate with surgery and postoperative irradiation was 90% (26/29). No patients treated with irradiation therapy alone were controlled. This review suggests that local tumor control achieved with limb preserving conservative surgery and postoperative irradiation is superior to limited surgery alone. The survival and patterns of failure of patients undergoing radical surgery is comparable to combined treatment with the risk-benefit ratio favoring the latter. (JMT)

  12. Greater sage-grouse (Centrocercus urophasianus) nesting and brood-rearing microhabitat in Nevada and California—Spatial variation in selection and survival patterns

    USGS Publications Warehouse

    Coates, Peter S.; Brussee, Brianne E.; Ricca, Mark A.; Dudko, Jonathan E.; Prochazka, Brian G.; Espinosa, Shawn P.; Casazza, Michael L.; Delehanty, David J.

    2017-08-10

    Greater sage-grouse (Centrocercus urophasianus; hereinafter, "sage-grouse") are highly dependent on sagebrush (Artemisia spp.) dominated vegetation communities for food and cover from predators. Although this species requires the presence of sagebrush shrubs in the overstory, it also inhabits a broad geographic distribution with significant gradients in precipitation and temperature that drive variation in sagebrush ecosystem structure and concomitant shrub understory conditions. Variability in understory conditions across the species’ range may be responsible for the sometimes contradictory findings in the scientific literature describing sage-grouse habitat use and selection during important life history stages, such as nesting. To help understand the importance of this variability and to help guide management actions, we evaluated the nesting and brood-rearing microhabitat factors that influence selection and survival patterns in the Great Basin using a large dataset of microhabitat characteristics from study areas spanning northern Nevada and a portion of northeastern California from 2009 to 2016. The spatial and temporal coverage of the dataset provided a powerful opportunity to evaluate microhabitat factors important to sage-grouse reproduction, while also considering habitat variation associated with different climatic conditions and areas affected by wildfire. The summary statistics for numerous microhabitat factors, and the strength of their association with sage-grouse habitat selection and survival, are provided in this report to support decisions by land managers, policy-makers, and others with the best-available science in a timely manner.

  13. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

    SciTech Connect

    Kuban, Deborah A.; Levy, Lawrence B.; Cheung, M. Rex; Lee, Andrew K.; Choi, Seungtaek; Frank, Steven; Pollack, Alan

    2011-04-01

    Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

  14. The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival.

    PubMed

    Vasconcelos, Ines; Hussainzada, Afsana; Berger, Stefan; Fietze, Ellen; Linke, Jörg; Siedentopf, Friederike; Schoenegg, Winfried

    2016-10-01

    To evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival. Subtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables. A total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001). The St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Irregular Liesegang-type patterns in gas phase revisited. II. Statistical correlation analysis

    NASA Astrophysics Data System (ADS)

    Torres-Guzmán, José C.; Martínez-Mekler, Gustavo; Müller, Markus F.

    2016-05-01

    We present a statistical analysis of Liesegang-type patterns formed in a gaseous HCl-NH3 system by ammonium chloride precipitation along glass tubes, as described in Paper I [J. C. Torres-Guzmán et al., J. Chem. Phys. 144, 174701 (2016)] of this work. We focus on the detection and characterization of short and long-range correlations within the non-stationary sequence of apparently irregular precipitation bands. To this end we applied several techniques to estimate spatial correlations stemming from different fields, namely, linear auto-correlation via the power spectral density, detrended fluctuation analysis (DFA), and methods developed in the context of random matrix theory (RMT). In particular RMT methods disclose well pronounced long-range correlations over at least 40 bands in terms of both, band positions and intensity values. By using a variant of the DFA we furnish proof of the nonlinear nature of the detected long-range correlations.

  16. Human walking along a curved path. II. Gait features and EMG patterns.

    PubMed

    Courtine, Grégoire; Schieppati, Marco

    2003-07-01

    We recorded basic gait features and associated patterns of leg muscle activity, occurring during continuous body progression when humans walked along a curved trajectory, in order to gain insight into the nervous mechanisms underlying the control of the asymmetric movements of the two legs. The same rhythm was propagated to both legs, in spite of inner and outer strides diverging in length (P < 0.001). There was a phase lag in limb displacement between the inner and outer leg of 7% of the total cycle duration (P = 0.0001). Swing velocity was greater for outer than inner foot (P < 0.001). The duration of the stance phase diminished and increased in the outer and inner leg (P < 0.01), respectively, and was associated with trunk leaning toward the inside of the path. Muscle activity was not dramatically altered during curved walking. The amplitude of soleus burst during stance increased in the outer (P < 0.05) and decreased in the inner leg (P < 0.05), without changes in timing. Tibialis anterior activity increased in both legs during the swing phase (P < 0.05); it was advanced on the outer and delayed on the inner side (P < 0.01; 2% of the cycle). The peroneus longus burst decreased in both legs, but more in the inner than the outer leg, and lasted longer in the inner leg at the onset of swing. Closing the eyes did not affect the gait pattern and muscle activity during turning. The command to walk along a curved path may exploit the basic mechanisms of the spinal locomotor generator, thereby limiting the computational cost of turning.

  17. Identification of Type II Interferon Receptors in Geese: Gene Structure, Phylogenetic Analysis, and Expression Patterns.

    PubMed

    Zhou, Hao; Chen, Shun; Qi, Yulin; Zhou, Qin; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Chen, Xiaoyue; Cheng, Anchun

    2015-01-01

    Interferon γ receptor 1 (IFNGR1) and IFNGR2 are two cell membrane molecules belonging to class II cytokines, which play important roles in the IFN-mediated antiviral signaling pathway. Here, goose IFNGR1 and IFNGR2 were cloned and identified for the first time. Tissue distribution analysis revealed that relatively high levels of goose IFNγ mRNA transcripts were detected in immune tissues, including the harderian gland, cecal tonsil, cecum, and thymus. Relatively high expression levels of both IFNGR1 and IFNGR2 were detected in the cecal tonsil, which implicated an important role of IFNγ in the secondary immune system of geese. No specific correlation between IFNγ, IFNGR1, and IFNGR2 expression levels was observed in the same tissues of healthy geese. IFNγ and its cognate receptors showed different expression profiles, although they appeared to maintain a relatively balanced state. Furthermore, the agonist R848 led to the upregulation of goose IFNγ but did not affect the expression of goose IFNGR1 or IFNGR2. In summary, trends in expression of goose IFNγ and its cognate receptors showed tissue specificity, as well as an age-related dependency. These findings may help us to better understand the age-related susceptibility to pathogens in birds.

  18. Identification of Type II Interferon Receptors in Geese: Gene Structure, Phylogenetic Analysis, and Expression Patterns

    PubMed Central

    Zhou, Hao; Chen, Shun; Qi, Yulin; Zhou, Qin; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Liu, Fei; Chen, Xiaoyue; Cheng, Anchun

    2015-01-01

    Interferon γ receptor 1 (IFNGR1) and IFNGR2 are two cell membrane molecules belonging to class II cytokines, which play important roles in the IFN-mediated antiviral signaling pathway. Here, goose IFNGR1 and IFNGR2 were cloned and identified for the first time. Tissue distribution analysis revealed that relatively high levels of goose IFNγ mRNA transcripts were detected in immune tissues, including the harderian gland, cecal tonsil, cecum, and thymus. Relatively high expression levels of both IFNGR1 and IFNGR2 were detected in the cecal tonsil, which implicated an important role of IFNγ in the secondary immune system of geese. No specific correlation between IFNγ, IFNGR1, and IFNGR2 expression levels was observed in the same tissues of healthy geese. IFNγ and its cognate receptors showed different expression profiles, although they appeared to maintain a relatively balanced state. Furthermore, the agonist R848 led to the upregulation of goose IFNγ but did not affect the expression of goose IFNGR1 or IFNGR2. In summary, trends in expression of goose IFNγ and its cognate receptors showed tissue specificity, as well as an age-related dependency. These findings may help us to better understand the age-related susceptibility to pathogens in birds. PMID:26345454

  19. Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial

    PubMed Central

    Anota, Amélie; Mouillet, Guillaume; Trouilloud, Isabelle; Dupont-Gossart, Anne-Claire; Artru, Pascal; Lecomte, Thierry; Zaanan, Aziz; Gauthier, Mélanie; Fein, Francine; Dubreuil, Olivier; Paget-Bailly, Sophie; Taieb, Julien; Bonnetain, Franck

    2015-01-01

    Background A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study. Methods HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS. Results 98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1. Conclusion Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics. Trial registration information Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM). PMID:26010884

  20. Frequency of Class I and II HLA alleles in patients with lung cancer according to chemotherapy response and 5-year survival.

    PubMed

    Araz, Omer; Ucar, Elif Yilmazel; Meral, Mehmet; Yalcin, Aslıhan; Acemoglu, Hamit; Dogan, Hasan; Karaman, Adem; Aydin, Yener; Gorguner, Metin; Akgun, Metin

    2015-07-01

    Lung cancer is the most common cause of cancer death in the world, and the most common type is non-small-cell lung cancer (NSCLC). At present, surgical resection, chemotherapy, and radiation therapy are the main treatments for patients with NSCLC, but unfortunately outcome remains unsatisfactory. This study aimed to determine whether Class I and II histocompatibility leukocyte antigen (HLA) alleles are related with response to chemotherapy and survival of lung cancer. A total of 65 NSCLC patients (56 men and 9 women, mean age 58.4 ± 11 years) were included in the study. Patient groups were compared with a control group of 88 unrelated healthy kidney or bone marrow donors in order to clearly identify susceptible and protective HLA alleles in lung cancer. Target lesions and tumor response were assessed using the Response Evaluation Criteria for Solid Tumors (RECIST) guidelines. Results were classified into two groups: complete-partial response and stable-progressive disease. We found that expression of HLA-A32, HLA-B41, HLA-B57, HLA-DRB1*13, and HLA-DQ5 were more frequent in the complete and partial response groups to chemotherapy than in the control group. The frequency of HLA-A11, HLA-A29, HLA-BW6, HLA-CW3, HLA-DR1*1, and HLA-DRB1*3 were determined to be higher in the stable and progressive disease groups taking chemotherapy than in the control group. Additionally, expressions of HLA-A2 and HLA-B49 were statistically related with 5-year survival. Our results suggested that expressions of HLA-BW6 and HLA-DRB1*13 alleles may be predictable markers for response to chemotherapy in lung cancer patients. © 2014 John Wiley & Sons Ltd.

  1. Discordant patterns of linkage disequilibrium of the peptide-transporter loci within the HLA class II region

    SciTech Connect

    Klitz, W.; Grote, M.; Stephens, J.C.

    1995-12-01

    Disequilibrium between genetic markers is expected to decline monotonically with recombinational map distance. We present evidence from the HLA class II region that seems to violate this principle. Pairwise disequilibrium values were calculated for six loci ranging in physical separation from 15 kb to 550 kb. The histocompatibility loci DRB1, DQA1, and DQBI, located on the distal end of the class II region, behave as a single evolutionary unit within which extremely high linkage disequilibrium exists. Lower but still significant levels of disequilibrium are present between these loci and DPB1, located at the proximal edge of the HLA complex. The peptide-transporter loci TAP1 and TAP2, located in the intervening region, reveal no disequilibrium with each other and low or negligible disequilibrium with the flanking loci. The action of two genetic processes is required to account for this phenomenon: a recombinational hotspot operating between TAP1 and TAP2, to eliminate disequilibrium between these loci, and at the same time selection operating on particular combinations of alleles across the DR-DP region, to create disequilibrium in the favored haplotypes. The forces producing the patterns of disequilibrium observed here have implications for the mapping of trait loci and disease genes: markers of TAP1, for example, would give a false impression as to the influence of DPB1 on a trait known to be associated with DQB1. 44 refs., 2 figs., 3 tabs.

  2. MHC class II genes in the European badger (Meles meles): characterization, patterns of variation, and transcription analysis.

    PubMed

    Sin, Yung Wa; Dugdale, Hannah L; Newman, Chris; Macdonald, David W; Burke, Terry

    2012-04-01

    The major histocompatibility complex (MHC) comprises many genes, some of which are polymorphic with numerous alleles. Sequence variation among alleles is most pronounced in exon 2 of the class II genes, which encodes the α1 and β1 domains that form the antigen-binding site (ABS) for the presentation of peptides. The MHC thus plays an important role in pathogen defense. European badgers (Meles meles) are a good species in which to study the MHC, as they harbor a variety of pathogens. We present the first characterization of MHC class II genes, isolated from genomic DNA (gDNA) and complementary DNA (cDNA), in the European badger. Examination of seven individuals revealed four DRB, two DQB, two DQA, and two DRA putatively functional gDNA sequences. All of these sequences, except DRA, exhibited high variability in exon 2; DRB had the highest variability. The ABS codons demonstrated high variability, due potentially to balancing selection, while non-ABS codons had lower variability. Positively selected sites were detected in DRB and DQA. Phylogenetic analysis demonstrated trans-species polymorphism of class II genes. Comparison with cDNA from whole blood revealed that only DRB had a transcription pattern reflecting the alleles that were present in the gDNA, while the other three genes had disparities between gDNA and cDNA. Only one sequence was transcribed, even though two gDNA sequences were present, from each of both DQB and DRA. Our characterization of badger MHC sequences forms a basis for further studies of MHC variability, mate choice, and pathogen resistance in this, and other, species.

  3. Survival in Extreme Conditions.

    ERIC Educational Resources Information Center

    Bloom, Martin; Halsema, James

    1983-01-01

    Explores the psychosocial and environmental configurations involved in the survival of 500 civilians in a Japanese internment camp in the Philippines during World War II. Although conditions were very harsh, the survival rate of this group was better than expected. Discusses available demographic, social organizational, and cultural information.…

  4. Survival in Extreme Conditions.

    ERIC Educational Resources Information Center

    Bloom, Martin; Halsema, James

    1983-01-01

    Explores the psychosocial and environmental configurations involved in the survival of 500 civilians in a Japanese internment camp in the Philippines during World War II. Although conditions were very harsh, the survival rate of this group was better than expected. Discusses available demographic, social organizational, and cultural information.…

  5. Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas.

    PubMed

    Roelcke, Ulrich; Wyss, Matthias T; Nowosielski, Martha; Rudà, Roberta; Roth, Patrick; Hofer, Silvia; Galldiks, Norbert; Crippa, Flavio; Weller, Michael; Soffietti, Riccardo

    2016-05-01

    Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas

    PubMed Central

    Roelcke, Ulrich; Wyss, Matthias T.; Nowosielski, Martha; Rudà, Roberta; Roth, Patrick; Hofer, Silvia; Galldiks, Norbert; Crippa, Flavio; Weller, Michael; Soffietti, Riccardo

    2016-01-01

    Background Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). Methods PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. Results One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). Conclusions Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome. PMID:26578622

  7. Emergence of patterns in random processes. II. Stochastic structure in random events

    NASA Astrophysics Data System (ADS)

    Newman, William I.

    2014-06-01

    Random events can present what appears to be a pattern in the length of peak-to-peak sequences in time series and other point processes. Previously, we showed that this was the case in both individual and independently distributed processes as well as for Brownian walks. In addition, we introduced the use of the discrete form of the Langevin equation of statistical mechanics as a device for connecting the two limiting sets of behaviors, which we then compared with a variety of observations from the physical and social sciences. Here, we establish a probabilistic framework via the Smoluchowski equation for exploring the Langevin equation and its expected peak-to-peak sequence lengths, and we introduce a concept we call "stochastic structure in random events," or SSRE. We extend the Brownian model to include antipersistent processes via autoregressive (AR) models. We relate the latter to describe the behavior of Old Faithful Geyser in Yellowstone National Park, and we devise a further test for the validity of the Langevin and AR models. Given our analytic results, we show how the Langevin equation can be adapted to describe population cycles of three to four years observed among many mammalian species in biology.

  8. Emergence of patterns in random processes. II. Stochastic structure in random events.

    PubMed

    Newman, William I

    2014-06-01

    Random events can present what appears to be a pattern in the length of peak-to-peak sequences in time series and other point processes. Previously, we showed that this was the case in both individual and independently distributed processes as well as for Brownian walks. In addition, we introduced the use of the discrete form of the Langevin equation of statistical mechanics as a device for connecting the two limiting sets of behaviors, which we then compared with a variety of observations from the physical and social sciences. Here, we establish a probabilistic framework via the Smoluchowski equation for exploring the Langevin equation and its expected peak-to-peak sequence lengths, and we introduce a concept we call "stochastic structure in random events," or SSRE. We extend the Brownian model to include antipersistent processes via autoregressive (AR) models. We relate the latter to describe the behavior of Old Faithful Geyser in Yellowstone National Park, and we devise a further test for the validity of the Langevin and AR models. Given our analytic results, we show how the Langevin equation can be adapted to describe population cycles of three to four years observed among many mammalian species in biology.

  9. Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle: II. Heterogeneity of metabolite labeling pattern.

    PubMed

    Yang, Lili; Kasumov, Takhar; Kombu, Rajan S; Zhu, Shu-Han; Cendrowski, Andrea V; David, France; Anderson, Vernon E; Kelleher, Joanne K; Brunengraber, Henri

    2008-08-08

    In this second of two companion articles, we compare the mass isotopomer distribution of metabolites of liver gluconeogenesis and citric acid cycle labeled from NaH(13)CO(3) or dimethyl [1,4-(13)C(2)]succinate. The mass isotopomer distribution of intermediates reveals the reversibility of the isocitrate dehydrogenase + aconitase reactions, even in the absence of a source of alpha-ketoglutarate. In addition, in many cases, a number of labeling incompatibilities were found as follows: (i) glucose versus triose phosphates and phosphoenolpyruvate; (ii) differences in the labeling ratios C-4/C-3 of glucose versus (glyceraldehyde 3-phosphate)/(dihydroxyacetone phosphate); and (iii) labeling of citric acid cycle intermediates in tissue versus effluent perfusate. Overall, our data show that gluconeogenic and citric acid cycle intermediates cannot be considered as sets of homogeneously labeled pools. This probably results from the zonation of hepatic metabolism and, in some cases, from differences in the labeling pattern of mitochondrial versus extramitochondrial metabolites. Our data have implications for the use of labeling patterns for the calculation of metabolic rates or fractional syntheses in liver, as well as for modeling liver intermediary metabolism.

  10. Antibiotic Prescribing Patterns in Outpatient Emergency Clinics at Queen Rania Al Abdullah II Children's Hospital, Jordan, 2013

    PubMed Central

    Al-Niemat, Sahar I.; Aljbouri, Tareq M.; Goussous, Lana S.; Efaishat, Rania A.; Salah, Rehab K.

    2014-01-01

    Objective To investigate antibiotics prescribing patterns in the outpatient pediatric emergency clinic at Queen Rania Al Abdullah II Children’s Hospital at Royal Medical Services in Amman, Jordan. Methods The data was collected from the emergency pharmacy over the period of a -five consecutive months. The methodology recommended by the World Health Organization for investigating drug use in a health facility was followed. The study measures the percentage of encounter with a prescribed antibiotic and the percentage share of each antibiotic category. The distribution of diagnostic categories that accounted for all antibiotics being prescribed and the distribution of each antibiotic being prescribed for upper respiratory tract infections (URTIs) were also measured. Results Antibiotic prescribing was frequent during pediatric visits to the outpatient pediatric emergency clinic resulting in a high percentage of encounters (85%) when compared to appropriate. Emergency physicians continue to frequently prescribe broad spectrum antibiotics which accounted for approximately (60%) of the total prescribed antibiotics and (83%) of prescribed antibiotics for upper respiratory tract infections and macrolides (primarily azithromycin) were the leading class among them. Conclusion Our results showed high consumption of antibiotics by emergency department pediatricians which highlight the importance for interventions to promote rational and judicious prescribing. An insight into factors influencing antibiotics prescribing patterns by military prescribers is required. PMID:25170404

  11. Dietary Patterns during Adulthood among Lesbian, Bisexual, and Heterosexual Women in the Nurses' Health Study II.

    PubMed

    VanKim, Nicole A; Austin, S Bryn; Jun, Hee-Jin; Hu, Frank B; Corliss, Heather L

    2017-03-01

    Lesbian and bisexual women are at greater risk of being obese than heterosexual women; however, there is little research on dietary intake among lesbian and bisexual women. This study estimated differences in dietary quality and intake during adulthood comparing heterosexual women to lesbian and bisexual women. Biennial mailed questionnaires were used to collect data from a cohort between 1991 and 2011. Heterosexual-identified women were the reference group. More than 100,000 female registered nurses in the United States, aged 24 to 44 years, were recruited in 1989 to participate in the Nurses' Health Study II. More than 90% of the original sample are currently active in the study. About 1.3% identified as lesbian or bisexual. Dietary measures were calculated from a 133-item food frequency questionnaire administered every 4 years. Measures included diet quality (Alternative Healthy Eating Index-2010 and Dietary Approaches to Stop Hypertension); calorie, fat, and fiber intake; and glycemic load and index. Multivariable adjusted repeated measures linear regression models were fit. On average, lesbian and bisexual women reported better diet quality (P<0.001) and diets lower in glycemic index (P<0.001) than heterosexual women. In the whole cohort, diet quality scores increased as participants aged, and were lower among women living in rural compared to urban regions. Comparisons in dietary intake across sexual orientation groups were generally similar across age and rurality status. However, differences between lesbian and heterosexual women in Alternative Healthy Eating Index-2010 were larger during younger compared to older ages, suggesting that diet quality estimates among sexual orientation groups converged as women aged. Lesbian and bisexual women reported higher diet quality than heterosexuals. More research examining how diet affects risk for chronic conditions, such as diabetes, among sexual minorities is needed. Physical activity, sedentary behavior

  12. Comparison of interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns using cone-beam computed tomography

    PubMed Central

    Khumsarn, Nattida; Patanaporn, Virush; Jotikasthira, Dhirawat

    2016-01-01

    Purpose This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Materials and Methods Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Results Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. Conclusion In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns. PMID:27358819

  13. Comparison of interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns using cone-beam computed tomography.

    PubMed

    Khumsarn, Nattida; Patanaporn, Virush; Janhom, Apirum; Jotikasthira, Dhirawat

    2016-06-01

    This study evaluated and compared interradicular distances and cortical bone thickness in Thai patients with Class I and Class II skeletal patterns, using cone-beam computed tomography (CBCT). Pretreatment CBCT images of 24 Thai orthodontic patients with Class I and Class II skeletal patterns were included in the study. Three measurements were chosen for investigation: the mesiodistal distance between the roots, the width of the buccolingual alveolar process, and buccal cortical bone thickness. All distances were recorded at five different levels from the cementoenamel junction (CEJ). Descriptive statistical analysis and t-tests were performed, with the significance level for all tests set at p<0.05. Patients with a Class II skeletal pattern showed significantly greater maxillary mesiodistal distances (between the first and second premolars) and widths of the buccolingual alveolar process (between the first and second molars) than Class I skeletal pattern patients at 10 mm above the CEJ. The maxillary buccal cortical bone thicknesses between the second premolar and first molar at 8 mm above the CEJ in Class II patients were likewise significantly greater than in Class I patients. Patients with a Class I skeletal pattern showed significantly wider mandibular buccolingual alveolar processes than did Class II patients (between the first and second molars) at 4, 6, and 8 mm below the CEJ. In both the maxilla and mandible, the mesiodistal distances, the width of the buccolingual alveolar process, and buccal cortical bone thickness tended to increase from the CEJ to the apex in both Class I and Class II skeletal patterns.

  14. Postembryonic lineages of the Drosophila brain: II. Identification of lineage projection patterns based on MARCM clones

    PubMed Central

    Wong, Darren C.; Lovick, Jennifer K.; Ngo, Kathy T.; Borisuthirattana, Wichanee; Omoto, Jaison J.; Hartenstein, Volker

    2014-01-01

    The Drosophila central brain is largely composed of lineages, units of sibling neurons derived from a single progenitor cell or neuroblast. During the early embryonic period neuroblast generate the primary neurons that constitute the larval brain. Neuroblasts reactivate in the larva, adding to their lineages a large number of secondary neurons which, according to previous studies in which selected lineages were labeled by stably expressed markers, differentiate during metamorphosis, sending terminal axonal and dendritic branches into defined volumes of the brain neuropil. We call the overall projection pattern of neurons forming a given lineage the “projection envelope” of that lineage. By inducing MARCM clones at the early larval stage, we labeled the secondary progeny of each neuroblast. For the supraesophageal ganglion excluding mushroom body (the part of the brain investigated in the present work) we obtained 81 different types of clones, Based on the trajectory of their secondary axon tracts (described in the accompanying paper), we assigned these clones to specific lineages defined in the larva. Since a labeled clone reveals all aspects (cell bodies, axon tracts, terminal arborization) of a lineage, we were able to describe projection envelopes for all secondary lineages of the supraesophageal ganglion. This work provides a framework by which the secondary neurons (forming the vast majority of adult brain neurons) can be assigned to genetically and developmentally defined groups. It also represents a step towards the goal to establish, for each lineage, the link between its mature anatomical and functional phenotype, and the genetic make-up of the neuroblast it descends from. PMID:23872236

  15. Drinking Patterns, Gender and Health II: Predictors of Preventive Service Use.

    PubMed

    Green, Carla A; Polen, Michael R; Leo, Michael C; Perrin, Nancy A; Anderson, Bradley M; Weisner, Constance M

    2010-07-01

    Chronic diseases and injuries are elevated among people with substance use problems/dependence, yet heavier drinkers use fewer routine and preventive health services than non-drinkers and moderate drinkers, while former drinkers and abstainers use more than moderate drinkers. Researchers hypothesize that drinking clusters with attitudes and practices that produce better health among moderate drinkers and that heavy drinkers avoid doctors until becoming ill, subsequently quitting and using more services. Gender differences in alcohol consumption, health-related attitudes, practices, and prevention-services use may affect these relationships. A stratified random sample of health-plan members (7884; 2995 males, 4889 females) completed a mail survey that was linked to 24 months of health-plan records. Data were used to examine relationships between alcohol use, gender, health-related attitudes/practices, health, and prevention-service use. Controlling for attitudes, practices, and health, female lifelong abstainers and former drinkers were less likely to have mammograms; individuals with alcohol use disorders and positive AUDIT scores were less likely to obtain influenza vaccinations. AUDIT-positive women were less likely to undergo colorectal screening than AUDIT-positive men. Consistent predictors of prevention-services use were: self-report of having a primary care provider (positive); disliking visiting the doctor (negative); smoking cigarettes (negative), and higher BMI (negative). When factors associated with drinking are controlled, patterns of alcohol consumption have limited effects on preventive service use. Individuals with stigmatized behaviors (e.g., hazardous/harmful drinking, smoking, or high BMIs) are less likely to receive care. Making care experiences positive and carefully addressing stigmatized health practices could increase preventive service use.

  16. Drinking Patterns, Gender and Health II: Predictors of Preventive Service Use

    PubMed Central

    Green, Carla A.; Polen, Michael R.; Leo, Michael C.; Perrin, Nancy A.; Anderson, Bradley M.; Weisner, Constance M.

    2012-01-01

    Background Chronic diseases and injuries are elevated among people with substance use problems/dependence, yet heavier drinkers use fewer routine and preventive health services than non-drinkers and moderate drinkers, while former drinkers and abstainers use more than moderate drinkers. Researchers hypothesize that drinking clusters with attitudes and practices that produce better health among moderate drinkers and that heavy drinkers avoid doctors until becoming ill, subsequently quitting and using more services. Gender differences in alcohol consumption, health-related attitudes, practices, and prevention-services use may affect these relationships. Methods A stratified random sample of health-plan members (7884; 2995 males, 4889 females) completed a mail survey that was linked to 24 months of health-plan records. Data were used to examine relationships between alcohol use, gender, health-related attitudes/practices, health, and prevention-service use. Results Controlling for attitudes, practices, and health, female lifelong abstainers and former drinkers were less likely to have mammograms; individuals with alcohol use disorders and positive AUDIT scores were less likely to obtain influenza vaccinations. AUDIT-positive women were less likely to undergo colorectal screening than AUDIT-positive men. Consistent predictors of prevention-services use were: self-report of having a primary care provider (positive); disliking visiting the doctor (negative); smoking cigarettes (negative), and higher BMI (negative). Conclusions When factors associated with drinking are controlled, patterns of alcohol consumption have limited effects on preventive service use. Individuals with stigmatized behaviors (e.g., hazardous/harmful drinking, smoking, or high BMIs) are less likely to receive care. Making care experiences positive and carefully addressing stigmatized health practices could increase preventive service use. PMID:23814545

  17. Lymph Node Involvement Pattern and Survival Differences of FIGO IIIC and FIGO IIIA1 Ovarian Cancer Patients After Primary Complete Tumor Debulking Surgery: A 10-Year Retrospective Analysis of the Tumor Bank Ovarian Cancer Network.

    PubMed

    Gasimli, Khayal; Braicu, Elena Ioana; Nassir, Mani; Richter, Rolf; Babayeva, Aygun; Chekerov, Radoslav; Darb-Esfahani, Silvia; Sehouli, Jalid; Muallem, Mustafa Zelal

    2016-04-01

    The main goal of the current study was to compare survival differences among subgroups of primary ovarian cancer patients in International Federation of Gynecology and Obstetrics (FIGO) stages IIIC and IIIA1 after complete tumor debulking surgery. A total of 218 patients with primary ovarian cancer who received complete cytoreductive surgery were included in the current retrospective analysis of the validated Tumor Bank Ovarian Cancer Network Database, which covers the periods January 2002 until December 2012. According to their tumor spread pattern, patients were divided into three groups: Group A (peritoneum only), Group B (peritoneum and lymph nodes), and Group C (lymph nodes only). Associations between groups and clinicopathological factors were analyzed using standard statistical procedures. The vast majority of patients were classified into Group B. Lymph node involvement was detected in 70.5 % of the cases where peritoneal implants presented ≥2 cm beyond the pelvis (Group A + B). The estimated 5-year overall survival (OS) rates were 47.4 % in Group A, 45.1 % in Group B, and 91.7 % in Group C (p < 0.01). In the subgroup analysis of Group B, both pelvic and para-aortic lymph node involvement was found in 57 % of patients. Patients in Group B who had para-aortic lymph node involvement only had better median progression-free survival (PFS) compared with patients with pelvic lymph node involvement only and pelvic and para-aortic lymph node involvement (28, 16, and 18 months, respectively; p = 0.02). The median OS differed significantly between patients with para-aortic lymph node involvement only versus patients with both pelvic and para-aortic involvement (68.5 vs. 46.7 months; p = 0.02). Three-year PFS was 90.0 % in FIGO IIIA1(i) and 62.6 % in FIGO IIIA1(ii) (hazard ratio 2.30, 95 % confidence interval 0.45-11.58). Patients with FIGO stage IIIC with lymph node involvement only had the best clinical outcome compared with patients in the

  18. Increased survival and reduced renal injury in MRL/lpr mice treated with a human Fcγ receptor II (CD32) peptide.

    PubMed

    Xi, Jun; Zhang, Gai P; Qiao, Song L; Guo, Jun Q; Wang, Xuan N; Yang, Yan Y; Zhang, Li N; Miao, Xian W; Zhao, Dong; Zhi, Yu B; Cai, Shu J; Luo, Jun; Deng, Rui G

    2012-05-01

    Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease affecting many organs. The deposition in kidney tissue of immune complexes and their interaction with macrophages is thought to trigger the inflammatory response leading to glomerulonephritis. It has been demonstrated that inhibition of this interaction in murine models can alleviate the disease. Six synthetic peptides were derived from the membrane-proximal extracellular domain (EC2) of human Fcγ receptor II (huFcγRII). Of these, one peptide, huRII6, was shown to be a potent competitive inhibitor of IgG binding to recombinant FcγRII in vitro. To examine the possible therapeutic impact of huRII6 in vivo, this peptide, or a control, was given by subcutaneous injection to female MRL/lpr mice from weeks 7 to 36, resulting in an enhanced survival rate compared with control-treated animals and a reduction of proteinuria. Histopathological examination of the kidneys showed a reduction in deposition of immune complexes and preservation of structure. Such a functional peptide should prove useful for examining the role of IgG-FcγR interactions in experimental models of disease and may provide for the development of FcR-targeting drugs to treat autoimmune disorders.

  19. Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

    SciTech Connect

    Pai Panandiker, Atmaram S.; Merchant, Thomas E.; Beltran, Chris; Wu, Shengjie; Sharma, Shelly; Boop, Frederick A.; Jenkins, Jesse J.; Helton, Kathleen J.; Wright, Karen D.; Broniscer, Alberto; Kun, Larry E.; Gajjar, Amar

    2012-04-01

    Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolled into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic

  20. Spatial and temporal expression patterns of diverse Pin-II proteinase inhibitor genes in Capsicum annuum Linn.

    PubMed

    Tamhane, Vaijayanti A; Giri, Ashok P; Kumar, Pavan; Gupta, Vidya S

    2009-08-01

    Pin-II type proteinase inhibitor (PI) genes were cloned from fruit and stem tissues of Capsicum annuum L. var Phule Jyoti using primers designed from reported CanPI gene sequence (AF039398). In total, 21 novel CanPIs, members of the Pin-II PI family, were identified in the study, with three isoforms of 1-inhibitory repeat domain (IRD), eight isoforms of 2-IRD, three isoforms of 3-IRD, five isoforms of 4-IRD and two partial CanPI sequences. Most of the sequences showed variation (2 to 20%) in the deduced AA sequences which were pronounced close to the reactive site loop. Expression patterns of CanPIs in the fruit and stem tissues of mature C. annuum plants were shown to vary qualitatively and quantitatively using semi-quantitative RT-PCR expression analysis. In the fruit tissue, CanPIs with different IRDs (from 1 to 4) were expressed simultaneously. In stem tissue, 1- and 2-IRD CanPIs were strongly expressed along moderate expression of 3- and 4-IRD genes. Analysis of CanPI protein activity showed a range of active forms across the tissues. CanPI expression was differentially up-regulated upon wounding and insect attack. Although infestation by aphids (Myzus persicae) and lepidopteran pests (Spodoptera litura) specifically induced 4-IRD CanPIs, virus-infected leaves did not affect CanPI expression. Analysis of CanPI protein activity indicated that the up-regulation in CanPI expression was not always correlated with increase in PI activity. Our results demonstrated that CanPI expression is regulated spatially, temporally as well as qualitatively and quantitatively.

  1. CO2 induced seawater acidification impacts sea urchin larval development II: gene expression patterns in pluteus larvae.

    PubMed

    Stumpp, M; Dupont, S; Thorndyke, M C; Melzner, F

    2011-11-01

    Extensive use of fossil fuels is leading to increasing CO(2) concentrations in the atmosphere and causes changes in the carbonate chemistry of the oceans which represents a major sink for anthropogenic CO(2). As a result, the oceans' surface pH is expected to decrease by ca. 0.4 units by the year 2100, a major change with potentially negative consequences for some marine species. Because of their carbonate skeleton, sea urchins and their larval stages are regarded as likely to be one of the more sensitive taxa. In order to investigate sensitivity of pre-feeding (2 days post-fertilization) and feeding (4 and 7 days post-fertilization) pluteus larvae, we raised Strongylocentrotus purpuratus embryos in control (pH 8.1 and pCO(2) 41 Pa e.g. 399 μatm) and CO(2) acidified seawater with pH of 7.7 (pCO(2) 134 Pa e.g. 1318 μatm) and investigated growth, calcification and survival. At three time points (day 2, day 4 and day 7 post-fertilization), we measured the expression of 26 representative genes important for metabolism, calcification and ion regulation using RT-qPCR. After one week of development, we observed a significant difference in growth. Maximum differences in size were detected at day 4 (ca. 10% reduction in body length). A comparison of gene expression patterns using PCA and ANOSIM clearly distinguished between the different age groups (two-way ANOSIM: Global R=1) while acidification effects were less pronounced (Global R=0.518). Significant differences in gene expression patterns (ANOSIM R=0.938, SIMPER: 4.3% difference) were also detected at day 4 leading to the hypothesis that differences between CO(2) treatments could reflect patterns of expression seen in control experiments of a younger larva and thus a developmental artifact rather than a direct CO(2) effect. We found an up regulation of metabolic genes (between 10%and 20% in ATP-synthase, citrate synthase, pyruvate kinase and thiolase at day 4) and down regulation of calcification related genes

  2. Study on cell survival, induction of apoptosis and micronucleus formation in SCL-II cells after exposure to the auger electron emitter (99m)Tc.

    PubMed

    Kriehuber, R; Kadenbach, K; Schultz, F; Weiss, D G

    2004-01-01

    To study the biological effectiveness of Auger electrons emitted by (99m)Tc on cell survival, induction of apoptosis and micronucleus (MN) formation in the human squamous cell carcinoma cell line SCL-II and compare the effects observed to those observed after exposure to external 60Co gamma radiation. Cells were either gamma(60Co)-irradiated (0.67 Gy/min) or exposed to (99m)Tc-pertechnetate (0.95-14.3 MBq/ml) for 24 h under cell culture conditions and assayed for cell survival (colony-forming assay), micronucleus formation (cytochalasin B assay) and the frequency of apoptotic cells (fluorescence microscopy). Monte Carlo based dosimetry has been applied to derive the absorbed dose corresponding to the accumulated decays of (99m)Tc under the given geometry. Absorbed doses up to 0.5 Gy could be achieved after 99mTc-exposure leading to no substantial cell killing in this dose range except at one dose point (0.1 Gy) resulting in an relative biological effectiveness (RBE)SF 0.9 of 0.64 when compared to the 60Co reference radiation. MN formation was described best by a linear dose response and was consistently lower after 99mTc exposure when compared to 60Co irradiated cells resulting in an RBE of 0.37. Apoptosis induction was significantly increased after 99mTc exposure at much lower doses (0.1 Gy) when compared to the reference radiation. The (99m)Tc uptake experiments revealed an activity concentration ratio cells vs. medium of 0.07 after 24 h of exposure. No overall increased biological effectiveness due to the emitted Auger electrons of (99m)Tc, applied as sodium-pertechnetate, could be observed in the investigated cell line when compared to acute external gamma radiation. The RBEs in the range of 0.37-0.64 might be well explained by dose rate effects. The significantly increased apoptotic response after (99m)Tc-exposure at very low doses has to be further investigated.

  3. Radiomics Signature: A Potential Biomarker for the Prediction of Disease-Free Survival in Early-Stage (I or II) Non-Small Cell Lung Cancer.

    PubMed

    Huang, Yanqi; Liu, Zaiyi; He, Lan; Chen, Xin; Pan, Dan; Ma, Zelan; Liang, Cuishan; Tian, Jie; Liang, Changhong

    2016-12-01

    Purpose To develop a radiomics signature to estimate disease-free survival (DFS) in patients with early-stage (stage I-II) non-small cell lung cancer (NSCLC) and assess its incremental value to the traditional staging system and clinical-pathologic risk factors for individual DFS estimation. Materials and Methods Ethical approval by the institutional review board was obtained for this retrospective analysis, and the need to obtain informed consent was waived. This study consisted of 282 consecutive patients with stage IA-IIB NSCLC. A radiomics signature was generated by using the least absolute shrinkage and selection operator, or LASSO, Cox regression model. Association between the radiomics signature and DFS was explored. Further validation of the radiomics signature as an independent biomarker was performed by using multivariate Cox regression. A radiomics nomogram with the radiomics signature incorporated was constructed to demonstrate the incremental value of the radiomics signature to the traditional staging system and other clinical-pathologic risk factors for individualized DFS estimation, which was then assessed with respect to calibration, discrimination, reclassification, and clinical usefulness. Results The radiomics signature was significantly associated with DFS, independent of clinical-pathologic risk factors. Incorporating the radiomics signature into the radiomics-based nomogram resulted in better performance (P < .0001) for the estimation of DFS (C-index: 0.72; 95% confidence interval [CI]: 0.71, 0.73) than with the clinical-pathologic nomogram (C-index: 0.691; 95% CI: 0.68, 0.70), as well as a better calibration and improved accuracy of the classification of survival outcomes (net reclassification improvement: 0.182; 95% CI: 0.02, 0.31; P = .02). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinical-pathologic nomogram. Conclusion The

  4. Contribution of Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase to neural activity-induced neurite outgrowth and survival of cerebellar granule cells.

    PubMed

    Borodinsky, Laura N; Coso, Omar A; Fiszman, Mónica L

    2002-03-01

    In this report we describe our studies on intracellular signals that mediate neurite outgrowth and long-term survival of cerebellar granule cells. The effect of voltage-gated calcium channel activation on neurite complexity was evaluated in cultured cerebellar granule cells grown for 48 h at low density; the parameter measured was the fractal dimension of the cell. We explored the contribution of two intracellular pathways, Ca2+ calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase (MEK1), to the effects of high [K+ ]e under serum-free conditions. We found that 25 mm KCl (25K) induced an increase in calcium influx through L subtype channels. In neurones grown for 24-48 h under low-density conditions, the activation of these channels induced neurite outgrowth through the activation of Ca2+ calmodulin-dependent protein kinase II. This also produced an increase in long-term neuronal survival with a partial contribution from the MEK1 pathway. We also found that the addition of 25K increased the levels of the phosphorylated forms of Ca2+ calmodulin-dependent protein kinase II and of the extracellular signal-regulated kinases 1 and 2. Neuronal survival under resting conditions is supported by the MEK1 pathway. We conclude that intracellular calcium oscillations can triggered different biological effects depending on the stage of maturation of the neuronal phenotype. Ca2+ calmodulin-dependent protein kinase II activation determines the growth of neurites and the development of neuronal complexity.

  5. Patterns of Müllerian Inhibiting Substance Type II and Candidate Type I Receptors in Epithelial Ovarian Cancer†

    PubMed Central

    Basal, E.; Ayeni, T.; Zhang, Q.; Langstraat, C.; Donahoe, P.K.; Pepin, D.; Yin, X.; Leof, E.; Cliby, W.

    2016-01-01

    The MIS pathway is a potential therapeutic target in epithelial ovarian cancer (EOC): signaling requires both type II (T2R) and type I receptors (T1R), and results in growth inhibition. MISR2 is expressed in EOC, but the prevalence and relative contributions of candidate T1R remain unknown. We sought to: a) determine expression of T1R in EOC; b) assess impact of T1R expression with clinical outcomes; c) verify MIS-dependent Smad signaling and growth inhibition in primary EOC cell cultures. Tissue microarrays (TMA) were developed for analysis of T1Rs (ALK2/3/6) and MISR2 expression. Primary cell cultures were initiated from ascites harvested at surgery which were used to characterize response to MIS. TMA’s from 311 primary cancers demonstrated the most common receptor combinations were: MISR2+/ALK2+3+6+ (36%); MISR2+/ALK2+3+6- (34%); MISR2-/ALK2+3+6- (18%); and MISR2-/ALK2+3+6+ (6.8%). No differences in overall survival (OS) were noted between combinations. The ALK6 receptor was least often expressed T1R and was associated with lower OS in early stage disease only (p =0.03). Most primary cell cultures expressed MISR2 (14/22 (63.6%)): 95% of these express ALK 2 and ALK3, whereas 54.5% expressed ALK6. MIS-dependent Smad phosphorylation was seen in the majority of cultures (75%). Treatment with MIS led to reduced cell viability at an average of 71% (range: 57–87%) in primary cultures. MIS signaling is dependent upon the presence of both MISR2 and specific T1R. In the majority of EOC, the T1R required for MIS-dependent signaling are present and such cells demonstrate appropriate response to MIS. PMID:26917267

  6. Immunofluorescence assay reactivity patterns of serum samples presenting indeterminate Western blot results for antibodies to HIV-1 and HTLV-I/II in Cordoba, Argentina.

    PubMed

    Gastaldello, R; Gallego, S; Isa, M B; Maturano, E; Sileoni, S; Nates, S; Medeot, S

    2001-01-01

    Serum samples (n: 110) from blood donors and high risk individuals from Cordoba, Argentina with indeterminate HIV-1 and HTLV-I/II Wb profiles were studied for specific antibodies to HTLV-I/II and HIV-1 by indirect immunofluorescence assay (IFA) and for the presence or absence of HIV-1 and HTLV-I/II specific bands by Wb. This study was carried out in order to characterize their putative reactions with HIV-1 and HTLV-I/II proteins and to resolve the retrovirus infection status of these individuals. Results indicated that blood donors sera displaying indeterminate HIV-1 or HTLV-I/II Wb patterns were not immunoreactive to HTLV-I/II and HIV-1 on IFA. However, a high rate of indeterminate HIV-1 and HTLV-I/II Wb samples from high risk individuals had positive HTLV-I/II and HIV-1 IFA results respectively. Our study supports the growing evidence that HTLV-HIV indeterminate seroreactivity in low risk population is due to a cross reaction against nonviral antigens, and in high risk populations the indeterminate samples show serological cross-recognition between HIV-1 proteins and HTLV-I/II proteins on Wb. These results point out the necessity to investigate the HTLV-I/II reactivity in indeterminate HIV-1 samples and vice versa in order to confirm the diagnosis. Finally, this study shows the potential usefulness of IFA in elucidating the status of HIV-1 and HTLV-I/II infection of individuals with indeterminate Wb profiles, thus enabling resolution of retrovirus infection status.

  7. Real-world treatment patterns and associated progression-free survival in relapsed/refractory multiple myeloma among US community oncology practices.

    PubMed

    Jagannath, Sundar; Roy, Anuja; Kish, Jonathan; Lunacsek, Orsolya; Globe, Denise; Eaddy, Michael; Kuriakose, Emil T; Willey, Joanne; Butler-Bird, Stephanie; Siegel, David

    2016-07-01

    Evidence supporting optimal treatment sequencing in relapsed/refractory multiple myeloma (RRMM) patients requiring multiple therapy lines is lacking. Using retrospective chart data, this study describes real-world RRMM treatment patterns and related progression-free survival (PFS) in US community oncology clinics. Bortezomib ± a non-immunomodulatory drug (IMiD), lenalidomide ± a non-proteasome inhibitor (PI), bortezomib + an IMiD were the most commonly used regimens in early lines of therapy. Median PFS was similar in 1(st) (11.1 months) and 2(nd) line (10.5) and decreased in lines 3 through 5 (3(rd): 7.9; 4(th): 7.2, 5(th): 5.4). Longest PFS (12.5 months) in first line was with bortezomib + ImiD; longest PFS in second line was with lenalidomide ± a non-PI was (13.2 months). Re-treatment with bortezomib was common; novel agents were reserved for later therapy lines. Overall, the observed PFS associated with real-world treatment sequences were shorter than those reported in clinical trials.

  8. Intracellular patterns of Her-2/neu, ras, and ploidy abnormalities in primary human breast cancers predict postoperative clinical disease-free survival.

    PubMed

    Shackney, Stanley E; Smith, Charles A; Pollice, Agnese; Brown, Kathryn; Day, Roger; Julian, Thomas; Silverman, Jan F

    2004-05-01

    In an earlier study, the presence of aneuploidy, Her-2/neu overexpression, and ras overexpression in the same cells (triple-positive cells) was of prognostic significance (P < 0.015) in 91 patients with localized breast cancer (median follow up, 32 months). Here, we present results involving a larger group of patients with longer follow-up. Fixed cell suspensions prepared from primary tumors of 189 patients with early breast cancer were studied prospectively by multiparameter flow cytometry. Correlated intracellular fluorescence-based measurements of cell DNA content and Her-2/neu and ras protein were obtained on each of >2000 cells in each tumor. Intracellular combinations of abnormalities in these measurements were correlated with subsequent patient disease-free survival (DFS). Median time on study was 54 months (range, 7-128 months). DFS of patients with > or = 5% triple-positive tumor cells was shorter than those who did not meet this criterion (P = 0.004). The difference remained statistically significant after accounting for nodal status, tumor size, and each of the component abnormalities (P = 0.006). Node-negative patients whose tumors had fewer than 2 abnormalities/cell had an especially favorable clinical course, with a 5-year DFS of 96% (lower confidence bound, 86%). Patterns of accumulated intracellular molecular abnormalities in cells of primary human breast cancers are predictive for subsequent DFS independently of the abnormalities themselves taken individually.

  9. C-propeptides of procollagens I alpha 1 and II that differentially accumulate in enchondromas versus chondrosarcomas regulate tumor cell survival and migration.

    PubMed

    Vincourt, Jean-Baptiste; Etienne, Stéphanie; Cottet, Justine; Delaunay, Camille; Malanda, Claudie Bantsimba; Malanda, Bantsimba; Lionneton, Frédéric; Sirveaux, François; Netter, Patrick; Plénat, François; Mainard, Didier; Vignaud, Jean-Michel; Magdalou, Jacques

    2010-06-01

    Chondrogenic tumors that exhibit benign or malignant behaviors synthesize variable amounts of cartilage-like extracellular matrix. To define the regulators of these phenotypes, we performed a proteomic comparison of multiple human chondrogenic tumors, which revealed differential accumulation of the C-propeptides of procollagens Ialpha1 and II (PC1CP and PC2CP) in malignant versus benign tumors, respectively. Expression patterns of PC1CP correlated with levels of tumor vascularization, whereas expression patterns of PC2CP suggested its susceptibility to immobilization within the extracellular matrix. Prompted by these observations, we investigated the functions of recombinant PC1CP and PC2CP in the extracellular matrix in soluble or immobilized states. Each induced beta1 integrin-mediated chondrocyte adhesion by distinct domains and efficacies, suggesting that they initiated distinct signaling pathways. Indeed, immobilized PC2CP, but not PC1CP, induced apoptosis of primary chondrocytes and EAhy926 endothelial cells. In contrast, soluble PC1CP, but not PC2CP, induced the migration of EAhy926 cells and increased vascular endothelial growth factor (VEGF) and CXCR4 expression in chondrocytes. Soluble PC2CP also increased VEGF expression, but along with a more pronounced effect on CXCR4 and matrix metalloproteinase 13 expression. Our findings suggest that PC1CP favors angiogenesis and tumor progression, but that PC2CP acts in a more complex manner, exerting antitumor and antiangiogenic properties through apoptosis induction when immobilized, but progression and metastasis when soluble. In summary, the relative levels of PC1CP and PC2CP and their interactions within the extracellular matrix contribute to tumor progression, angiogenesis, and metastasis in chondrogenic tumors.

  10. Phase II Trial of Cetuximab, Gemcitabine, and Oxaliplatin Followed by Chemoradiation With Cetuximab for Locally Advanced (T4) Pancreatic Adenocarcinoma: Correlation of Smad4(Dpc4) Immunostaining With Pattern of Disease Progression

    PubMed Central

    Crane, Christopher H.; Varadhachary, Gauri R.; Yordy, John S.; Staerkel, Gregg A.; Javle, Milind M.; Safran, Howard; Haque, Waqar; Hobbs, Bridgett D.; Krishnan, Sunil; Fleming, Jason B.; Das, Prajnan; Lee, Jeffrey E.; Abbruzzese, James L.; Wolff, Robert A.

    2011-01-01

    Purpose This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Patients and Methods Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m2) and oxaliplatin (100 mg/m2) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m2 twice daily on radiation treatment days). Cetuximab (500 mg/m2) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Results Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). Conclusion This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment

  11. Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression.

    PubMed

    Crane, Christopher H; Varadhachary, Gauri R; Yordy, John S; Staerkel, Gregg A; Javle, Milind M; Safran, Howard; Haque, Waqar; Hobbs, Bridgett D; Krishnan, Sunil; Fleming, Jason B; Das, Prajnan; Lee, Jeffrey E; Abbruzzese, James L; Wolff, Robert A

    2011-08-01

    This phase II trial was designed to assess the efficacy and safety of cetuximab, gemcitabine, and oxaliplatin followed by cetuximab, capecitabine, and radiation therapy in locally advanced pancreatic cancer (LAPC). Treatment-naive eligible patients (n = 69) received intravenous gemcitabine (1,000 mg/m(2)) and oxaliplatin (100 mg/m(2)) every 2 weeks for four doses, followed by radiation (50.4 Gy to the gross tumor only) with concurrent capecitabine (825 mg/m(2) twice daily on radiation treatment days). Cetuximab (500 mg/m(2)) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy. Diagnostic cytology specimens were immunostained for Smad4(Dpc4) expression. Median overall survival time was 19.2 months (95% CI, 14.2 to 24.2 months), and 1-year, 2-year, and 4-year actuarial overall survival rates were 66.0%, 25.02%, and 11.3%, respectively. Acneiform rash correlated with improved survival (P = .001), but initial CA19-9, borderline resectable initial stage, and surgical resection (n = 7) did not. The 1-year and 2-year radiographic local progression rates were 22.8% and 61.0%, respectively. The worst acute toxic effects were GI toxicity (32% and 10% for grades 2 and 3, respectively); fatigue (26% and 6% for grades 2 and 3, respectively); sensory neuropathy (9% and 1% for grades 2 and 3, respectively); and acneiform rash (54% and 3% for grades 2 and 3, respectively). Smad4(Dpc4) expression correlated with a local rather than a distant dominant pattern of disease progression (P = .016). This regimen appears effective and has acceptable toxicity. The primary end point (1-year overall survival rate > 45%) was met, with encouraging survival duration. Smad4(Dpc4) immunostaining correlated with the pattern of disease progression. Prospective validation of Smad4(Dpc4) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized

  12. Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival.

    PubMed

    Souwer, Yuri; Chamuleau, Martine E D; van de Loosdrecht, Arjan A; Tolosa, Eva; Jorritsma, Tineke; Muris, Jettie J F; Dinnissen-van Poppel, Marion J; Snel, Sander N; van de Corput, Lisette; Ossenkoppele, Gert J; Meijer, Chris J L M; Neefjes, Jacques J; Marieke van Ham, S

    2009-05-01

    In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL.

  13. Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival.

    PubMed Central

    Koukourakis, M. I.; Giatromanolaki, A.; Kakolyris, S.; O'Byrne, K. J.; Apostolikas, N.; Skarlatos, J.; Gatter, K. C.; Harris, A. L.

    1998-01-01

    Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequently results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltration in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early stage I-II NSCLC treated with surgery alone were analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP) reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP overexpression related to high vascular grade and to advanced T stage (P = 0.0004 and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high angiogenesis (P = 0.01), but was independent of cancer cell expression. Fibroblast TP overexpression was related to abundant stroma (P = 0.003), suggesting that TP may be a marker of active stroma. Moreover, intense macrophage infiltration was associated with fibroblast TP reactivity, regardless of the amount of stroma, suggesting that macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was related to poor prognosis (P = 0.005). Although stroma TP is related to angiogenesis, in the low vascular grade group it defined a group of patients with better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an indirect marker of tumour infiltration by functional macrophages, which have an antitumour effect. We conclude that stromal macrophage and fibroblast TP reactivity may have an important role in non-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprotein expression is essential for the elucidation of lung cancer pathogenesis. Images Figure 1 PMID:9635852

  14. Treatment of hydrocephalus determined by the European Orbis Sigma Valve II survey: a multicenter prospective 5-year shunt survival study in children and adults in whom a flow-regulating shunt was used.

    PubMed

    Hanlo, Patrick W; Cinalli, Giuseppe; Vandertop, W Peter; Faber, Joop A J; Bøgeskov, Lars; Børgesen, Svend E; Boschert, Jürgen; Chumas, Paul; Eder, Hans; Pople, Ian K; Serlo, Willy; Vitzthum, Eckehard

    2003-07-01

    The goal of this study was to evaluate the long-term results of a flow-regulating shunt (Orbis Sigma Valve [OSV] II Smart Valve System; Integra NeuroSciences, Sophia Antipolis, France) in the treatment of hydrocephalus, whether it was a first insertion procedure or surgical revision of another type of shunt, in everyday clinical practice in a multicenter prospective study. Patients of any age who had hydrocephalus underwent implantation of an OSV II system. The primary end point of the study was defined as any shunt-related surgery. The secondary end point was a mechanical complication (shunt obstruction, overdrainage, catheter misplacement, migration, or disconnection) or infection. The overall 5-year shunt survival rates and survival as it applied to different patient subgroups were assessed. Five hundred fifty-seven patients (48% of whom were adults and 52% of whom were children) were selected for OSV II shunt implantation; 196 patients reached the primary end point. Shunt obstruction occurred in 75 patients (13.5%), overdrainage in 10 patients (1.8%), and infection in 46 patients (8.2%). The probability of having experienced a shunt failure-free interval at 1 year was 71% and at 2 years it was 67%; thereafter the probability remained quite stable in following years (62% at the 5-year follow-up examination). No difference in shunt survival was observed between the overall pediatric (< or = 16 years of age) and adult populations. In the pediatric age group, however, there was a significantly lower rate of shunt survival in children younger than 6 months of age (55% at the 5-year follow-up examination). In this prospective study the authors demonstrate the effectiveness of flow regulation in the treatment of hydrocephalus both in children and in adults. Flow-regulating shunts limit the incidence of overdrainage and shunt-related complications. The overall 5-year shunt survival rate (62%) compares favorably with rates cited in other recently published series.

  15. RNA-binding Protein Insulin-like Growth Factor mRNA-binding Protein 3 (IMP-3) Promotes Cell Survival via Insulin-like Growth Factor II Signaling after Ionizing Radiation*

    PubMed Central

    Liao, Baisong; Hu, Yan; Brewer, Gary

    2011-01-01

    Ionizing radiation (IR) induces proapoptotic gene expression programs that inhibit cell survival. These programs often involve RNA-binding proteins that associate with their mRNA targets to elicit changes in mRNA stability and/or translation. The RNA-binding protein IMP-3 is an oncofetal protein overexpressed in many human malignancies. IMP-3 abundance correlates with tumor aggressiveness and poor prognosis. As such, IMP-3 is proving to be a highly significant biomarker in surgical pathology. Among its many mRNA targets, IMP-3 binds to and promotes translation of insulin-like growth factor II (IGFII) mRNA. Our earlier studies showed that reducing IMP-3 abundance with siRNAs reduced proliferation of human K562 chronic myeloid leukemia cells because of reduced IGF-II biosynthesis. However, the role of IMP-3 in apoptosis is unknown. Here, we have used IR-induced apoptosis of K562 cells as a model to explore a role for IMP-3 in cell survival. Knockdown of IMP-3 with siRNA increased susceptibility of cells to IR-induced apoptosis and led to reduced IGF-II production. Gene reporter assays revealed that IMP-3 acts through the 5′ UTR of IGFII mRNA during apoptosis to promote translation. Finally, culture of IR-treated cells with recombinant IGF-II partially reversed the effects of IMP-3 knockdown on IR-induced apoptosis. Together, these results indicate that IMP-3 acts in part through the IGF-II pathway to promote cell survival in response to IR. Thus, IMP-3 might serve as a new drug target to increase sensitivity of CML cells or other cancers to IR therapy. PMID:21757716

  16. RNA-binding protein insulin-like growth factor mRNA-binding protein 3 (IMP-3) promotes cell survival via insulin-like growth factor II signaling after ionizing radiation.

    PubMed

    Liao, Baisong; Hu, Yan; Brewer, Gary

    2011-09-09

    Ionizing radiation (IR) induces proapoptotic gene expression programs that inhibit cell survival. These programs often involve RNA-binding proteins that associate with their mRNA targets to elicit changes in mRNA stability and/or translation. The RNA-binding protein IMP-3 is an oncofetal protein overexpressed in many human malignancies. IMP-3 abundance correlates with tumor aggressiveness and poor prognosis. As such, IMP-3 is proving to be a highly significant biomarker in surgical pathology. Among its many mRNA targets, IMP-3 binds to and promotes translation of insulin-like growth factor II (IGFII) mRNA. Our earlier studies showed that reducing IMP-3 abundance with siRNAs reduced proliferation of human K562 chronic myeloid leukemia cells because of reduced IGF-II biosynthesis. However, the role of IMP-3 in apoptosis is unknown. Here, we have used IR-induced apoptosis of K562 cells as a model to explore a role for IMP-3 in cell survival. Knockdown of IMP-3 with siRNA increased susceptibility of cells to IR-induced apoptosis and led to reduced IGF-II production. Gene reporter assays revealed that IMP-3 acts through the 5' UTR of IGFII mRNA during apoptosis to promote translation. Finally, culture of IR-treated cells with recombinant IGF-II partially reversed the effects of IMP-3 knockdown on IR-induced apoptosis. Together, these results indicate that IMP-3 acts in part through the IGF-II pathway to promote cell survival in response to IR. Thus, IMP-3 might serve as a new drug target to increase sensitivity of CML cells or other cancers to IR therapy.

  17. Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the Heart from Ischemic Injury in Female Rats1

    PubMed Central

    Xue, Qin; Xiao, Daliao; Zhang, Lubo

    2015-01-01

    Previous studies have shown that female offspring are resistant to fetal stress-induced programming of ischemic-sensitive phenotype in the heart; however, the mechanisms responsible remain unclear. The present study tested the hypothesis that estrogen plays a role in protecting females in fetal programming of increased heart vulnerability. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from Day 15 to 21 of gestation) groups. Ovariectomy (OVX) and estrogen (E2) replacement were performed in 8-wk-old female offspring. Hearts of 4-mo-old females were subjected to ischemia and reperfusion injury in a Langendorff preparation. OVX significantly decreased postischemic recovery of left ventricular function and increased myocardial infarction, and no difference was observed between normoxic and hypoxic groups. The effect of OVX was rescued by E2 replacement. OVX decreased the binding of glucocorticoid receptor (GR) to glucocorticoid response elements at angiotensin II type 1 (Agtr1) and type 2 (Agtr2) receptor promoters, resulting in a decrease in Agtr1 and an increase in Agtr2 in the heart. Additionally, OVX decreased estrogen receptor (ER) expression in the heart and inhibited ER/GR interaction in binding to glucocorticoid response elements at the promoters. Consistent with the changes in Agtrs, OVX significantly decreased Prkce abundance in the heart. These OVX-induced changes were abrogated by E2 replacement. The results indicate that estrogen is not directly responsible for the sex dimorphism in fetal programming of heart ischemic vulnerability but suggest a novel mechanism of estrogen in regulating cardiac Agtr1/Agtr2 expression patterns and protecting female hearts against ischemia and reperfusion injury. PMID:25972014

  18. Concussion-Management Practice Patterns of National Collegiate Athletic Association Division II and III Athletic Trainers: How the Other Half Lives.

    PubMed

    Buckley, Thomas A; Burdette, Glenn; Kelly, Kassandra

    2015-08-01

    The National Collegiate Athletic Association (NCAA) has published concussion-management practice guidelines consistent with recent position and consensus statements. Whereas NCAA Division I athletic trainers appear highly compliant, little is known about the concussion-management practice patterns of athletic trainers at smaller institutions where staffing and resources may be limited. To descriptively define the concussion-management practice patterns of NCAA Division II and III athletic trainers. Cross-sectional study. Web-based questionnaire. A total of 755 respondents (response rate = 40.2%) from NCAA Division II and Division III institutions. The primary outcome measures were the rate of multifaceted concussion-assessment techniques, defined as 3 or more assessments; the specific practice patterns of each assessment battery; and tests used during a clinical examination. Most respondents indicated using a multifaceted assessment during acute assessment (Division II = 76.9%, n = 473; Division III = 76.0%, n = 467) and determination of recovery (Division II = 65.0%, n = 194; Division III = 63.1%, n = 288) but not at baseline (Division II = 43.1%, n = 122; Division III = 41.0%, n = 176). Typically, when a postconcussion assessment was initiated, testing occurred daily until baseline values were achieved, and most respondents (80.6% [244/278]) reported using a graded exercise protocol before return to participation. We found limited use of the multifaceted assessment battery at baseline but higher rates at both acute assessment and return-to-participation time points. A primary reason cited for not using test-battery components was a lack of staffing or funding for the assessments. We observed limited use of neuropsychologists to interpret neuropsychological testing. Otherwise, most respondents reported concussion-management protocols consistent with recommendations, including a high level of use of objective measures and incorporation of a progressive return

  19. Concussion-Management Practice Patterns of National Collegiate Athletic Association Division II and III Athletic Trainers: How the Other Half Lives

    PubMed Central

    Buckley, Thomas A.; Burdette, Glenn; Kelly, Kassandra

    2015-01-01

    Context The National Collegiate Athletic Association (NCAA) has published concussion-management practice guidelines consistent with recent position and consensus statements. Whereas NCAA Division I athletic trainers appear highly compliant, little is known about the concussion-management practice patterns of athletic trainers at smaller institutions where staffing and resources may be limited. Objective To descriptively define the concussion-management practice patterns of NCAA Division II and III athletic trainers. Design Cross-sectional study. Setting Web-based questionnaire. Patients or Other Participants A total of 755 respondents (response rate = 40.2%) from NCAA Division II and Division III institutions. Main Outcome Measure(s) The primary outcome measures were the rate of multifaceted concussion-assessment techniques, defined as 3 or more assessments; the specific practice patterns of each assessment battery; and tests used during a clinical examination. Results Most respondents indicated using a multifaceted assessment during acute assessment (Division II = 76.9%, n = 473; Division III = 76.0%, n = 467) and determination of recovery (Division II = 65.0%, n = 194; Division III = 63.1%, n = 288) but not at baseline (Division II = 43.1%, n = 122; Division III = 41.0%, n = 176). Typically, when a postconcussion assessment was initiated, testing occurred daily until baseline values were achieved, and most respondents (80.6% [244/278]) reported using a graded exercise protocol before return to participation. Conclusions We found limited use of the multifaceted assessment battery at baseline but higher rates at both acute assessment and return-to-participation time points. A primary reason cited for not using test-battery components was a lack of staffing or funding for the assessments. We observed limited use of neuropsychologists to interpret neuropsychological testing. Otherwise, most respondents reported concussion-management protocols consistent with

  20. Magnetic domain patterns on strong perpendicular magnetization of Co/Ni multilayers as spintronics materials: II. Numerical simulations.

    PubMed

    Kudo, Kazue; Suzuki, Masahiko; Kojima, Kazuki; Yasue, Tsuneo; Akutsu, Noriko; Diño, Wilson Agerico; Kasai, Hideaki; Bauer, Ernst; Koshikawa, Takanori

    2013-10-02

    Magnetic domains in ultrathin films form domain patterns, which strongly depend on the magnetic anisotropy. The magnetic anisotropy in Co/Ni multilayers changes with the number of layers. We provide a model to simulate the experimentally observed domain patterns. The model assumes a layer-dependent magnetic anisotropy. With the anisotropy parameter estimated from experimental data, we reproduce the magnetic domain patterns.

  1. Observations on the effects of formaldehyde on cockroaches and their flora: II. Prolonged survival of cockroaches drinking formaldehyde or glutaraldehyde solutions.

    PubMed Central

    McCarthy, K.; Bartzokas, C. A.; Baker, B. F.

    1978-01-01

    Adult cockroaches were found to survive up to 22 weeks when provided with 1% Formalin (0.4% formaldehyde) in lieu of drinking water. Given 4% Formalin or 2% glutaraldehyde they survived up to 41 days. During the experiments eggs were laid and hatched and the offspring continued to grow. Combined with surface disinfection, this may hold out a simple method of rendering adult cockroaches gnotobiotic or even axenic. PMID:413865

  2. Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab.

    PubMed

    Hong, Jidong; Peng, Yuping; Liao, Yuping; Jiang, Wuzhong; Wei, Rui; Huo, Lei; Han, Zaide; Duan, Chaojun; Zhong, Meizuo

    2012-07-01

    The present study aimed to determine whether nimotuzumab enhances the effect of radiochemotherapy in malignant gliomas. Patients (n=41) with malignant gliomas were divided into 20 cases (treatment group) in which nimotuzumab plus radiochemotherapy were offered and 21 cases (control group) in which placebo and radiochemotherapy were administered to the patients. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors, the Kaplan-Meier method was used to calculate the mean and median survival times and 1-year survival rate, and the log-rank test and the Chi-square test were used to analyze the difference in the survival and response rate between the treatment and control groups. The mean survival times of the treatment and control groups were 14.3 and 10.4 months and the median survival times of the treatment and control groups were 16.5 and 10.5 months, respectively. The 1-year survival rates of the treatment and control groups were 81.3 and 69.1%, respectively, with no significant difference (P>0.05). The objective response rates of the treatment and control groups were 70.0 and 52.4%, respectively, with no significant difference (P>0.05). In conclusion, there was a trend towards improved treatment efficacy of radiochemotherapy combined with nimotuzumab against malignant gliomas. This study demonstrated that the use of nimotuzumab combined with radiotherapy and concomitant temozolomide chemotherapy is effective for malignant gliomas.

  3. Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab

    PubMed Central

    HONG, JIDONG; PENG, YUPING; LIAO, YUPING; JIANG, WUZHONG; WEI, RUI; HUO, LEI; HAN, ZAIDE; DUAN, CHAOJUN; ZHONG, MEIZUO

    2012-01-01

    The present study aimed to determine whether nimotuzumab enhances the effect of radiochemotherapy in malignant gliomas. Patients (n=41) with malignant gliomas were divided into 20 cases (treatment group) in which nimotuzumab plus radiochemotherapy were offered and 21 cases (control group) in which placebo and radiochemotherapy were administered to the patients. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors, the Kaplan-Meier method was used to calculate the mean and median survival times and 1-year survival rate, and the log-rank test and the Chi-square test were used to analyze the difference in the survival and response rate between the treatment and control groups. The mean survival times of the treatment and control groups were 14.3 and 10.4 months and the median survival times of the treatment and control groups were 16.5 and 10.5 months, respectively. The 1-year survival rates of the treatment and control groups were 81.3 and 69.1%, respectively, with no significant difference (P>0.05). The objective response rates of the treatment and control groups were 70.0 and 52.4%, respectively, with no significant difference (P>0.05). In conclusion, there was a trend towards improved treatment efficacy of radiochemotherapy combined with nimotuzumab against malignant gliomas. This study demonstrated that the use of nimotuzumab combined with radiotherapy and concomitant temozolomide chemotherapy is effective for malignant gliomas. PMID:23060940

  4. Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide.

    PubMed

    Redjal, Navid; Reinshagen, Clemens; Le, Andrew; Walcott, Brian P; McDonnell, Erin; Dietrich, Jorg; Nahed, Brian V

    2016-05-01

    Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings.

  5. Understanding the Patterns and Causes of Variability in Distribution, Habitat Use, Abundance, Survival and Reproductive Rates of Three Species of Cetacean in the Alboran Sea, Western Mediterranean

    DTIC Science & Technology

    2012-01-01

    Distribution, Habitat Use, Abundance, Survival and Reproductive Rates of Three Species of Cetacean in the Alborán Sea, Western Mediterranean Ana...habitat use, abundance, survival and reproductive rates of three species of cetacean in the Alborán Sea (western Mediterranean) in relation to variation...Species of Cetacean in the Alborán Sea, Western Mediterranean 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  6. Alveolar and symphysis regions of patients with skeletal class II division 1 anomalies with different vertical growth patterns

    PubMed Central

    Esenlik, Elcin; Sabuncuoglu, Fidan Alakus

    2012-01-01

    Objectives: The aim of this study was to investigate the alveolar and symphysis region properties in hyper-, hypo-, and normodivergent Class II division 1 anomalies. Methods: Pretreatment lateral cephalograms of 111 young adult female patients with skeletal Class II division 1 anomalies were compared to those of 54 Class I normal subjects (control group). Class II cases were divided into hyperdivergent (n = 58), hypodivergent (n = 19), and normodivergent groups (n = 34). The heights and widths of the symphysis and alveolus and the depth of maxillary palate were measured on the lateral cephalograms. Results: Mean symphysis width was wider in the hypodivergent Class II group than in the other groups, while mean symphysis height was similar among all groups. Maxillary palatal depth, upper incisor angle, upper and lower molar alveolar heights, and Id–Id′ width were also similar among groups. Conclusion: Symphysis width is the main factor in the differential diagnosis of Class II division 1 anomaly rather than symphysis height and hypodivergent Class II Division 1 anomaly is more suitable for mandibular incisors movements. PMID:22509114

  7. Alveolar and symphysis regions of patients with skeletal class II division 1 anomalies with different vertical growth patterns.

    PubMed

    Esenlik, Elcin; Sabuncuoglu, Fidan Alakus

    2012-04-01

    The aim of this study was to investigate the alveolar and symphysis region properties in hyper-, hypo-, and normodivergent Class II division 1 anomalies. Pretreatment lateral cephalograms of 111 young adult female patients with skeletal Class II division 1 anomalies were compared to those of 54 Class I normal subjects (control group). Class II cases were divided into hyperdivergent (n = 58), hypodivergent (n = 19), and normodivergent groups (n = 34). The heights and widths of the symphysis and alveolus and the depth of maxillary palate were measured on the lateral cephalograms. Mean symphysis width was wider in the hypodivergent Class II group than in the other groups, while mean symphysis height was similar among all groups. Maxillary palatal depth, upper incisor angle, upper and lower molar alveolar heights, and Id-Id' width were also similar among groups. Symphysis width is the main factor in the differential diagnosis of Class II division 1 anomaly rather than symphysis height and hypodivergent Class II Division 1 anomaly is more suitable for mandibular incisors movements.

  8. Bone Metastases in Castration-Resistant Prostate Cancer: Associations between Morphologic CT Patterns, Glycolytic Activity, and Androgen Receptor Expression on PET and Overall Survival

    PubMed Central

    Wassberg, Cecilia; Fox, Josef J.; Wibmer, Andreas; Goldman, Debra A.; Kuk, Deborah; Gonen, Mithat; Larson, Steven M.; Morris, Michael J.; Scher, Howard I.; Hricak, Hedvig

    2014-01-01

    Purpose To compare the features of bone metastases at computed tomography (CT) to tracer uptake at fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and fluorine 18 16β-fluoro-5-dihydrotestosterone (FDHT) PET and to determine associations between these imaging features and overall survival in men with castration-resistant prostate cancer. Materials and Methods This is a retrospective study of 38 patients with castration-resistant prostate cancer. Two readers independently evaluated CT, FDG PET, and FDHT PET features of bone metastases. Associations between imaging findings and overall survival were determined by using univariate Cox proportional hazards regression. Results In 38 patients, reader 1 detected 881 lesions and reader 2 detected 867 lesions. Attenuation coefficients at CT correlated inversely with FDG (reader 1: r = −0.3007; P < .001; reader 2: r = −0.3147; P < .001) and FDHT (reader 1: r = −0.2680; P = .001; reader 2: r = −0.3656; P < .001) uptake. The number of lesions on CT scans was significantly associated with overall survival (reader 1: hazard ratio [HR], 1.025; P = .05; reader 2: HR, 1.021; P = .04). The numbers of lesions on FDG and FDHT PET scans were significantly associated with overall survival for reader 1 (HR, 1.051–1.109; P < .001) and reader 2 (HR, 1.026–1.082; P ≤ .009). Patients with higher FDHT uptake (lesion with the highest maximum standardized uptake value) had significantly shorter overall survival (reader 1: HR, 1.078; P = .02; reader 2: HR, 1.092; P = .02). FDG uptake intensity was not associated with overall survival (reader 1, P = .65; reader 2, P = .38). Conclusion In patients with castration-resistant prostate cancer, numbers of bone lesions on CT, FDG PET, and FDHT PET scans and the intensity of FDHT uptake are significantly associated with overall survival. © RSNA, 2013 PMID:24475817

  9. Randomized Phase III Trial of Vinorelbine Plus Cisplatin Compared With Observation in Completely Resected Stage IB and II Non–Small-Cell Lung Cancer: Updated Survival Analysis of JBR-10

    PubMed Central

    Butts, Charles A.; Ding, Keyue; Seymour, Lesley; Twumasi-Ankrah, Philip; Graham, Barbara; Gandara, David; Johnson, David H.; Kesler, Kenneth A.; Green, Mark; Vincent, Mark; Cormier, Yvon; Goss, Glenwood; Findlay, Brian; Johnston, Michael; Tsao, Ming-Sound; Shepherd, Frances A.

    2010-01-01

    Purpose Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non–small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data. Patients and Methods Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis. Results Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms. Conclusion Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm. PMID:19933915

  10. Concurrent cognitive processes in rat serial pattern learning: II. Discrimination learning, rule learning, chunk length, and multiple-item memories.

    PubMed

    Muller, Melissa D; Fountain, Stephen B

    2016-01-01

    The current experiment examined the factors that determine acquisition for elements of highly structured serial patterns. Three groups of rats were trained on three patterns with parallel rule-based hierarchical structure, but with 3-, 4-, or 5-element chunks, each with a final violation element. Once rats mastered their patterns, probe patterns were introduced to answer several questions. To assess the extent to which the learned response pattern depended on intrachamber location cues for anticipating different element types, Spatial Shift Probes shifted the starting lever of patterns to locations that positioned chunk boundaries where they had never been experienced during training. To assess the extent to which a phrasing cue is necessary for rats to perform a chunk-boundary response, a Cue Removal Probe tested whether rats would produce a chunk-boundary response in the correct serial position if the phrasing cue was omitted. To assess the extent to which cues from multiple trials leading up to the violation element are required to anticipate the violation element, Multiple-Item Memory Probes required rats to make an unexpected response on one of the elements in the last two chunks of the pattern prior to the violation element. The results indicated that rats used multiple concurrent learning and memory processes to master serial patterns, including discrimination learning, rule learning, encoding of chunk length, and multiple-item memories.

  11. Evaluation of Nasal Proportions in Adults with Class I and Class II Skeletal Patterns: A Cephalometric Study.

    PubMed

    Umale, Vinay V; Singh, Kamlesh; Azam, Aftab; Bhardwaj, Madhvi; Kulshrestha, Rohit

    2017-01-01

    The aim of this study was to evaluate sexual dimorphism in nasal proportions of Class I and Class II skeletal malocclusions in adults. The sample comprised 120 patients (females 18 years and above and males 21 years and above), with no history of previous orthodontic treatment or functional jaw orthopedic treatment. They were divided into different groups based on point A-Nasion-point B (ANB) angle and gender. Groups I and II included 30 males and 30 females with skeletal class I malocclusion (ANB 0-4 degrees). Groups III and IV included 30 males and 30 females with skeletal class II malocclusion, respectively (ANB above 4 degrees). In regards to the comparison between males and females (Class I + Class II), nasal length (P < 0.001), nasal depth 1 (P < 0.001), nasal depth 2 (P < 0.001), nasobasal angle (P < 0.001), soft tissue convexity angle (P < 0.001), and nasal bone length (P < 0.008) were found to be statistically significant. Nasobasal angle was found to be significantly higher in females than in males (Class I) (P < 0.001). Nasolabial angle was prominent in class I males than in class I females (P < 0.001). Soft tissue convexity angle of Class I participants was significantly lower than that of Class II participants (P < 0.001), whereas nasobasal angle and nasomental angle of Class I participants were found to be significantly higher than that of Class II participants (P < 0.001). Sexual dimorphism was found in various nasal parameters. Significant amount of differences was found in the nasal proportions of Class I and Class II (male and female) participants.

  12. Hyperbolic reaction-diffusion equations and irreversible thermodynamics: II. Two-dimensional patterns and dissipation of energy and matter

    NASA Astrophysics Data System (ADS)

    Al-Ghoul, Mazen; Eu, Byung Chan

    In this work we continue the study of pattern formations and dissipation of energy and matter initiated in the previous papers by using hyperbolic reaction-diffusion equations for reacting systems. In this paper, two-dimensional hyperbolic reaction-diffusion equations are numerically solved for the Selkov model. It is shown that the evolution equations used can give rise to various kinds of patterns such as hexagonal structures, stripes, spirals, maze structures, chaotic structures, etc., depending on the values of the reaction-diffusion number Nrd and the initial and boundary conditions. Random initial conditions are shown to give rise to patterns which evolve to break symmetry and form a new series of patterns. Solitary waves are also observed. The entropy production (equivalently, the calortropy production for the approximations made) is studied for various patterns formed and its characteristic features are observed to be related to the patterns. As is the case of one-dimensional hyperbolic reaction-diffusion equations reported earlier, the values of the entropy production computed indicate that the system maintains the particular organized local structures at the expense of energy and matter on the part of other modes, and the global energy and matter dissipation is the same for all patterns formed. However, when the system produces a chaotic pattern, the entropy production is lower than the locally organized structures. The amplitude equations are derived and compared for the hyperbolic and parabolic reaction-diffusion equations. Except for the coefficients in the equations the basic structures are the same regardless of their precursor equations. Hyperbolic reaction-diffusion equations appear to be better suited for description of transient structures and richer in variety of patterns than the corresponding parabolic differential equations to which the former reduce in the limit of high reaction-diffusion number.

  13. Natural demodulation of two-dimensional fringe patterns. II. Stationary phase analysis of the spiral phase quadrature transform.

    PubMed

    Larkin, K G

    2001-08-01

    Utilizing the asymptotic method of stationary phase, I derive expressions for the Fourier transform of a two-dimensional fringe pattern. The method assumes that both the amplitude and the phase of the fringe pattern are well-behaved differentiable functions. Applying the limits in two distinct ways, I show, first, that the spiral phase (or vortex) transform approaches the ideal quadrature transform asymptotically and, second, that the approximation errors increase with the relative curvature of the fringes. The results confirm the validity of the recently proposed spiral phase transform method for the direct demodulation of closed fringe patterns.

  14. Membrane fluidity, membrane lipid pattern, and cytosolic Ca2+ content in platelets from a group of type II diabetic patients with macrovascular complications.

    PubMed

    Caimi, G; Lo Presti, R; Montana, M; Canino, B; Ventimiglia, G; Romano, A; Catania, A; Sarno, A

    1995-01-01

    To evaluate platelet membrane fluidity and some platelet metabolic parameters in type II diabetic patients with macrovascular complications. In a group of 21 type II diabetic patients with macrovascular complications, we evaluated platelet membrane fluidity [marking intact resting platelets with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH)], platelet membrane lipid pattern (cholesterol:phospholipid [C:PL] ratio and individual phospholipids), and platelet cytosolic Ca2+ content (marking intact resting platelets with the fluorescent probe Fura 2AM). Platelet membrane fluidity is decreased in type II diabetic patients with macrovascular complications compared with normal subjects (P < 0.001). Platelet membrane C:PL ratio and cytosolic Ca2+ content do not discriminate normal subjects from diabetic patients, and for individual phospholipids, only phosphatidylethanolamine is decreased in diabetic patients compared with control subjects (P = 0.051). In normal subjects, the polarization degree of TMA-DPH is related to phosphatidylserine (P < 0.05) and phosphatidylcholine (P < 0.05), and in diabetic patients the polarization degree of TMA-DPH is related to C:PL ratio (P < 0.05) and sphyngomyelin (P < 0.05). In type II diabetic patients with macrovascular complications, we observed an abnormality of platelet membrane fluidity, which may contribute to platelet functional alteration present in this clinical condition.

  15. Coastal coho salmon research in the West Fork Smith River: Patterns of coho salmon size and survival within a complex watershed

    EPA Science Inventory

    Effective habitat restoration planning requires the ability to anticipate fish population responses to altered habitats. The EPA has conducted network-scale research to document habitat-specific growth and survival of juvenile salmonids in a complex watershed. These findings ha...

  16. Coastal coho salmon research in the West Fork Smith River: Patterns of coho salmon size and survival within a complex watershed

    EPA Science Inventory

    Effective habitat restoration planning requires the ability to anticipate fish population responses to altered habitats. The EPA has conducted network-scale research to document habitat-specific growth and survival of juvenile salmonids in a complex watershed. These findings ha...

  17. Coronal Magnetic Field Strength from Decameter Zebra-Pattern Observations: Complementarity with Band-Splitting Measurements of an Associated Type II Burst

    NASA Astrophysics Data System (ADS)

    Stanislavsky, A. A.; Konovalenko, A. A.; Koval, A. A.; Dorovskyy, V. V.; Zarka, P.; Rucker, H. O.

    2015-01-01

    A zebra pattern and a type II burst with band splitting were analyzed to study the coronal magnetic field in the height range of 1.9 - 2 solar radii. To this aim we used an extremely sensitive telescope (the Ukrainian decameter radio telescope, UTR-2) with a low-noise, high-dynamic-range spectrometer for the observations below 32 MHz. Based on the analysis of the spectral structures, the field strength obtained is 0.43 G. The value was found by fitting two different field indicators together under the assumptions that the shock wave front was perpendicular to the radial direction, and the radio emission of the type II burst was in the fundamental frequency. The result is compared to and agrees with coronal magnetic-field models.

  18. Counselor's Handbook: I, Counselor's Interviewing Guides in Individual Appraisal; II, Counselee Appraisal Patterns Related to Fields of Work.

    ERIC Educational Resources Information Center

    Bureau of Employment Security (DOL), Washington, DC.

    Part I includes guides for appraising individual characteristics such as interests, temperament, educational development, and aptitudes, to help the counselee learn about himself. Part II includes guidelines for appraising individual characteristics as they relate to the 18 fields of work (occupational clusters) which help the counselee learn…

  19. [Correlation analysis of the nasolabial angle of Angle's Class II division 1 malocclusion patients with vertical growth pattern after tooth extraction orthodontic treatment].

    PubMed

    Peng, Minghui; Kang, Jing; Zhou, Jianming; Du, Bing

    2015-08-01

    This study aims to evaluate the nasolabial angle change and the correlation analysis ot Angle'Is Class II division 1 malocclusion patients with vertical growth pattern after tooth extraction orthodontic treatment and provide experimental results to help in making orthodontic treatment plan and treatments. A total of 38 Angle's Class II division 1 malocclusion patients with vertical growth pattern and tooth extraction orthodontic treatment were included in this study. Pre- and post-treatment cephalometric X-rays were performed, and 18 measurement items were measured. The change values of pre- and post-treatment, youngsters, and adults were compared to analyze the correlation of the nasolabial angle change. The nasolabial angle between youngsters and adults was enlarged after treatment, but the nasolabial angle of the adult group changed more significantly. Ul to FH, Ul to NA, U1-NA, Spr-Ptm were reduced after treatment, and the adult group decreased more significantly. The upper lip sulcus and flange thickness, A'-Ptm, upper lip length, and nose prominence were enlarged after the adolescent treatment, but the adult had a certain degree of decrease. The difference had statistical significance. In the correlation of the nasolabial angle change analysis of the two groups, namely, Ul to FH, Ul-NA and U1 to NA had significant negative correlation, significant positive correlation to the upper lip inclination angle, and more significant correlation in the adult group. Upper lip flange thickness and nasolabial angle were negatively correlated, and the upper lip sulcus thickness was positively correlated. However, no significant correlation was observed between these two in the adult group. The nasolabial angle change of adolescents with vertical growth pattern in class II division 1 malocclusion after extraction treatment is related to the upper anterior teeth hard tissue and upper lip soft tissue, whereas only adults and upper anterior teeth hard tissue are related.

  20. Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks

    PubMed Central

    Bi, Zedong; Zhou, Changsong

    2016-01-01

    Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations) influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP) and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded), by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF) neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy). PMID:27555816

  1. MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.

    PubMed

    Cecchin, E; Perrone, G; Nobili, S; Polesel, J; De Mattia, E; Zanusso, C; Petreni, P; Lonardi, S; Pella, N; D'Andrea, M; Errante, D; Rizzolio, F; Mazzei, T; Landini, I; Mini, E; Toffoli, G

    2015-06-01

    Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2-12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.

  2. Non-selective cation channel-mediated Ca2+-entry and activation of Ca2+/calmodulin-dependent kinase II contribute to G2/M cell cycle arrest and survival of irradiated leukemia cells.

    PubMed

    Heise, Nicole; Palme, Daniela; Misovic, Milan; Koka, Saisudha; Rudner, Justine; Lang, Florian; Salih, Helmut R; Huber, Stephan M; Henke, Guido

    2010-01-01

    Genotoxic stress induces cell cycle arrest and DNA repair which may enable tumor cells to survive radiation therapy. Here, we defined the role of Ca(2+) signaling in the cell cycle control and survival of chronic myeloid leukemia (CML) cells subjected to ionizing radiation (IR). To this end, K562 erythroid leukemia cells were irradiated (0-10 Gy). Tumor survival was analyzed by clonogenic survival assay and cell cycle progression via flow cytometry. Plasma membrane cation conductance was assessed by patch-clamp whole-cell recording and the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) was measured by fura-2 Ca(2+) imaging. Nuclear activity of Ca(2+)/calmodulin-dependent kinase II (CaMKII) was defined by Western blotting. In addition, the effect of IR (5 Gy) on the cation conductance of primary CML cells was determined. The results indicated that IR (10 Gy) induced a G(2)/M cell cycle arrest of K562 cells within 24 h post-irradiation (p.i.) and decreased the clonogenic survival to 0.5 % of that of the control cells. In K562 cells, G(2)/M cell cycle arrest was preceded by activation of TRPV5/6-like nonselective cation channels in the plasma membrane 1-5 h p.i., resulting in an elevated Ca(2+) entry as evident from fura-2 Ca(2+) imaging. Similarly, IR stimulated a Ca(2+)-permeable nonselective cation conductance in primary CML cells within 2-4 h p.i.. Ca(2+) entry, into K562 cells was paralleled by an IR-induced activation of nuclear CaMKII. The IR-stimulated accumulation in G(2) phase was delayed upon buffering [Ca(2+)](i) with the Ca(2+) chelator BAPTA-AM or inhibiting CaMKII with KN93 (1 nM). In addition, KN93 decreased the clonogenic survival of irradiated cells but not of control cells. In conclusion, the data suggest that IR-stimulated cation channel activation, Ca(2+) entry and CaMKII activity participate in control of cell cycle progression and survival of irradiated CML cells.

  3. Instability and Pattern Formation in Three-Species Food Chain Model via Holling Type II Functional Response on a Circular Domain

    NASA Astrophysics Data System (ADS)

    Abid, Walid; Yafia, R.; Aziz Alaoui, M. A.; Bouhafa, H.; Abichou, A.

    2015-06-01

    This paper is devoted to the study of food chain predator-prey model. This model is given by a reaction-diffusion system defined on a circular spatial domain, which includes three-state variables namely, prey and intermediate predator and top predator and incorporates the Holling type II and a modified Leslie-Gower functional response. The aim of this paper is to investigate theoretically and numerically the asymptotic behavior of the interior equilibrium of the model. The local and global stabilities of the positive steady-state solution and the conditions that enable the occurrence of Hopf bifurcation and Turing instability in the circular spatial domain are proved. In the end, we carry out numerical simulations to illustrate how biological processes can affect spatiotemporal pattern formation in a disc spatial domain and different types of spatial patterns with respect to different time steps and diffusion coefficients are obtained.

  4. 3-D Reconstruction of Macular Type II Cell Innervation Patterns in Space-Flight and Control Rats

    NASA Technical Reports Server (NTRS)

    Ross, Muriel Dorothy; Montgomery, K.; Linton, S.; Cheng, R.; Tomko, David L. (Technical Monitor)

    1995-01-01

    A semiautomated method for reconstructing objects from serial thin sections has been developed in the Biocomputation Center. The method is being used to completely, for the first time, type II hair cells and their innervations. The purposes are to learn more about the fundamental circuitry of the macula on Earth and to determine whether changes in connectivities occur under space flight conditions. Data captured directly from a transmission electron microscope via a video camera are sent to a graphics workstation. There, the digitized micrographs are mosaicked into sections and contours are traced, registered and displayed by semiautomated methods. Current reconstructions are of type II cells from the medial part of rat maculas collected in-flight on the Space Life Sciences-2 mission, 4.5 hrs post-flight, and from a ground control. Results show that typical type II cells receive processes from tip to six nearby calyces or afferents. Nearly all processes are elongated and have bouton-like enlargements; some have numerous vesicles. Multiple (2 to 4) processes from a single calyx to a type II cell are common, and approximately 1/3 of the processes innervale 2 or 3 type II cells or a neighboring cluster. From 2% to 6% of the cells resemble type I cells morphologically but have demi-calyces. Thus far, increments in synaptic number in type II cells of flight rats are prominent along processes that supply two hair cells. It is clear that reconstruction methods provide insights into details of macular circuitry not obtainable by other techniques. The results demonstrate a morphological basis for interactions between adjacent receptive fields through feed back-feed forward connections, and for dynamic alterations in receptive field range and activity during preprocessing of linear acceleratory information by the maculas. The reconstruction method we have developed will find further applications in the study of the details of neuronal architecture of more complex systems, to

  5. 3-D Reconstruction of Macular Type II Cell Innervation Patterns in Space-Flight and Control Rats

    NASA Technical Reports Server (NTRS)

    Ross, Muriel Dorothy; Montgomery, K.; Linton, S.; Cheng, R.; Tomko, David L. (Technical Monitor)

    1995-01-01

    A semiautomated method for reconstructing objects from serial thin sections has been developed in the Biocomputation Center. The method is being used to completely, for the first time, type II hair cells and their innervations. The purposes are to learn more about the fundamental circuitry of the macula on Earth and to determine whether changes in connectivities occur under space flight conditions. Data captured directly from a transmission electron microscope via a video camera are sent to a graphics workstation. There, the digitized micrographs are mosaicked into sections and contours are traced, registered and displayed by semiautomated methods. Current reconstructions are of type II cells from the medial part of rat maculas collected in-flight on the Space Life Sciences-2 mission, 4.5 hrs post-flight, and from a ground control. Results show that typical type II cells receive processes from tip to six nearby calyces or afferents. Nearly all processes are elongated and have bouton-like enlargements; some have numerous vesicles. Multiple (2 to 4) processes from a single calyx to a type II cell are common, and approximately 1/3 of the processes innervale 2 or 3 type II cells or a neighboring cluster. From 2% to 6% of the cells resemble type I cells morphologically but have demi-calyces. Thus far, increments in synaptic number in type II cells of flight rats are prominent along processes that supply two hair cells. It is clear that reconstruction methods provide insights into details of macular circuitry not obtainable by other techniques. The results demonstrate a morphological basis for interactions between adjacent receptive fields through feed back-feed forward connections, and for dynamic alterations in receptive field range and activity during preprocessing of linear acceleratory information by the maculas. The reconstruction method we have developed will find further applications in the study of the details of neuronal architecture of more complex systems, to

  6. Distribution of cell surface saccharides on pancreatic cells. II. Lectin-labeling patterns on mature guinea pig and rat pancreatic cells

    PubMed Central

    1979-01-01

    The surface saccharide composition of collagenase-dispersed pancreatic cells from adult guinea pig and rat glands was examined by using eight lectins and their ferritin conjugates: Concanavalin A (ConA); Lens culinaris (LCL); Lotus tetragonolobus (LTL); Ricinus communis agglutinins I and II (RCA I, RCA II); Soybean agglutinin (SBA); Ulex europeus lectin (UEL); and wheat germ agglutinin (WGA). Binding studies of iodinated lectins and lectin-ferritin conjugates both revealed one population of saturable, high-affinity receptor sites on the total cell population (approximately 95% acinar cells). Electron microscopy, however, revealed differences in lectin-ferritin binding to the plasmalemma of acinar, centroacinar, and endocrine cells. Whereas acinar cells bound heavily all lectin conjugates, endocrine and centroacinar cells were densely labeled only by ConA, LCL, WGA, and RCA I, and possessed few receptors for LTL, UEL, and SBA. Endocrine and centroacinar cells could be differentiated from each other by using RCA II, which binds to centroacinar cells but not to endocrine cells. Some RCA II receptors appeared to be glycolipids because they were extracted by ethanol and chloroform-methanol in contrast to WGA receptors which resisted solvent treatment but were partly removed by papain digestion. RCA I receptors were affected by neither treatment. The apparent absence of receptors for SBA on endocrine and centroacinar cells, and for RCA II on endocrine cells, was reversed by neuraminidase digestion, which suggested masking of lectin receptors by sialic acid. The absence of LTL and UEL receptors on endocrine and centroacinar cells was not reversed by neuraminidase. We suggest that the differential lectin- binding patterns observed on acinar, centroacinar, and endocrine cells from the adult pancreas surface-carbohydrate-developmental programs expressed during morphogenesis and cytodifferentiation of the gland. PMID:422654

  7. Distribution of cell surface saccharides on pancreatic cells. II. Lectin-labeling patterns on mature guinea pig and rat pancreatic cells.

    PubMed

    Maylié-Pfenninger, M F; Jamieson, J D

    1979-01-01

    The surface saccharide composition of collagenase-dispersed pancreatic cells from adult guinea pig and rat glands was examined by using eight lectins and their ferritin conjugates: Concanavalin A (ConA); Lens culinaris (LCL); Lotus tetragonolobus (LTL); Ricinus communis agglutinins I and II (RCA I, RCA II); Soybean agglutinin (SBA); Ulex europeus lectin (UEL); and wheat germ agglutinin (WGA). Binding studies of iodinated lectins and lectin-ferritin conjugates both revealed one population of saturable, high-affinity receptor sites on the total cell population (approximately 95% acinar cells). Electron microscopy, however, revealed differences in lectin-ferritin binding to the plasmalemma of acinar, centroacinar, and endocrine cells. Whereas acinar cells bound heavily all lectin conjugates, endocrine and centroacinar cells were densely labeled only by ConA, LCL, WGA, and RCA I, and possessed few receptors for LTL, UEL, and SBA. Endocrine and centroacinar cells could be differentiated from each other by using RCA II, which binds to centroacinar cells but not to endocrine cells. Some RCA II receptors appeared to be glycolipids because they were extracted by ethanol and chloroform-methanol in contrast to WGA receptors which resisted solvent treatment but were partly removed by papain digestion. RCA I receptors were affected by neither treatment. The apparent absence of receptors for SBA on endocrine and centroacinar cells, and for RCA II on endocrine cells, was reversed by neuraminidase digestion, which suggested masking of lectin receptors by sialic acid. The absence of LTL and UEL receptors on endocrine and centroacinar cells was not reversed by neuraminidase. We suggest that the differential lectin-binding patterns observed on acinar, centroacinar, and endocrine cells from the adult pancreas surface-carbohydrate-developmental programs expressed during morphogenesis and cytodifferentiation of the gland.

  8. Phase II open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (Pantar study).

    PubMed

    Aranda, E; Manzano, J L; Rivera, F; Galán, M; Valladares-Ayerbes, M; Pericay, C; Safont, M J; Mendez, M J; Irigoyen, A; Arrivi, A; Sastre, J; Díaz-Rubio, E

    2012-07-01

    Skin rash is an adverse event which might be associated with longer survival in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors. The aim of this nonrandomised phase II clinical trial is to prospectively evaluate the relationship between skin rash and overall survival (OS) in advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine. Patients were given gemcitabine (1000 mg/m2/week, 3 weeks every 4 weeks) plus erlotinib (100 mg/day orally continuously) until disease progression/unacceptable toxicity. The primary end point was OS. A total of 153 eligible patients were enrolled (grade≥2 rash, 25%; grade<2 rash, 75%). OS was longer in patients with grade≥2 rash versus grade<2 (11 versus 5 months; P<0.001). Progression-free survival was longer in patients with grade≥2 rash versus grade<2 (6 versus 3 months; P<0.001) and shorter in those without rash versus grade 1 (2 versus 4 months; P=0.005) or grade≥2 (2 versus 6 months; P<0.001). Patients with grade≥2 rash showed higher rates of overall response (21% versus 7%; P<0.05) and disease control (84% versus 43%; P<0.05) versus grade<2. This study prospectively confirms the relationship between rash and longer OS in unresectable locally advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.

  9. Hair biology and its comprehensive sequence in female pattern baldness: clinical connotation diagnosis and differential diagnosis--Part II.

    PubMed

    Sehgal, Virendra N; Srivastava, Govind; Aggarwal, Ashok K; Midha, Rashmi

    2013-01-01

    Hair can become a source of concern when there is a change in its texture, number, and thinning. Although female pattern baldness is common, it has received little attention compared with male pattern baldness. Thinning that affects the vertex is insidious and progressive. Hair loss in women has accordingly been interpreted and classified differently than that in men. The Ludwig scale is the most accepted classification. The gross anatomy and the general microanatomy of the hair follicle, including that of the anagen, catagen, and telogen phase, are presented. The hair growth cycle, encompassing anagen, catagen, telogen, exogen, and kenogen, is also discussed to address pattern hair loss in women and provide therapeutic options that are currently available.

  10. Self-organized pattern formation in the oxidation of supported iron thin films. II. A simulation study

    NASA Astrophysics Data System (ADS)

    Ogale, Abhijit S.

    2001-07-01

    The process of oxidation of supported iron thin films is modeled by casting it into the form of an activator-inhibitor system, with precursor oxidation state as the activator, and stress produced by the large density difference between the metal and its oxide as a fast-diffusing inhibitor. An activator-substrate mechanism also coexists due to the finite availability of iron. The redistribution of iron by diffusion via vacancies also indirectly contributes to the activation process. A slow process of ripening, which minimizes surface energy, is suggested to convert the early leaflike pattern to a spiral assembly of hillocks. This model simulation yields patterns, which closely resemble the patterns observed in experiments reported by Shinde et al. [Phys. Rev. B 64, 035408 (2001)], in the accompanying Paper I.

  11. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension.

    PubMed

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E; Arons, Elena; Zaman, Paula; Polach, Kevin J; Matar, Majed; Yung, Lai-Ming; Yu, Paul B; Bowman, Frederick P; Opotowsky, Alexander R; Waxman, Aaron B; Loscalzo, Joseph; Leopold, Jane A; Maron, Bradley A

    2016-07-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth

  12. Part I: In-situ fluorometric quantification of microalgal neutral lipids. Part II: Thermal degradation behavior of investment casting polymer patterns

    NASA Astrophysics Data System (ADS)

    Zhao, Hongfang

    Research described in this dissertation covers two topics. Part-I is focused on in-situ determination of neutral lipid content of microalgae using a lipophilic fluorescent dye. The traditional Nile red stain-based method for detecting microalgal intracellular lipids is limited due to varying composition and thickness of rigid cell walls. In this study, the addition of dilute acid and heating of solution, were found to greatly enhance staining efficiency of Nile red for microalgal species evaluated. Oil-in-water (O/W) microemulsion stabilized by a non-ionic surfactant was employed as a pseudo-standard that mimics lipid-bearing microalgal cells suspended in water. The average neutral lipid contents determined were very close to the results obtained by traditional gravimetric method and solid phase extraction. Part II of the dissertation explores thermo-physico-chemical properties of polymeric pattern materials, including expanded polystyrene (EPS) foam, polyurethane foam, and epoxy stereolithography (SLA) patterns, that are used in investment casting. Density, elastic modulus, expansion coefficient, thermal degradation behavior, etc. were experimentally investigated for their effects on metal casting quality. The reduction in toxic hydrogen cyanide (HCN) generated during thermal decomposition of polyurethane pattern was achieved by increasing either oxidant level or residence time in heated zone. Thermal degradation kinetics of the pattern materials were examined with a thermogravimetric analysis and activation energies were determined by Kissinger and Flynn-Wall-Ozawa methods.

  13. Treatment Patterns and Overall Survival Associated with First-Line Systemic Therapy for Patients with Advanced Non-Small Cell Lung Cancer.

    PubMed

    Spence, Michele M; Hui, Rita L; Chang, Jennifer T; Schottinger, Joanne E; Millares, Mirta; Rashid, Nazia

    2017-02-01

    A variety of regimens are used as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC), which may include combination regimens and single agents, depending on histology, molecular profile, and performance status. To describe the types of first-line therapies and compare overall survival between therapies used for patients with advanced NSCLC in an integrated health care system. This retrospective cohort study included patients aged 18 years or older from Kaiser Permanente California with a diagnosis of stage IIIB/IV NSCLC. First systemic treatment date occurred from January 1, 2008, through September 30, 2013. Overall survival was measured as the number of months from initial treatment until death, end of enrollment, or September 30, 2014. Treatment regimens were categorized into 6 mutually exclusive groups: platinum doublets; pemetrexed-based, bevacizumab-based, and pemetrexed + bevacizumab-based combinations; singlets; and tyrosine-kinase inhibitors (TKIs). Survival was compared using Kaplan-Meier curves and adjusted Cox proportional hazard models. Subgroup analyses were performed by age group and by nonsquamous histology. Of 2,081 patients, approximately half (52.3%) received platinum doublets, followed by TKIs (19.0%), pemetrexed-based regimens (13.4%), bevacizumab-regimens (8.0%), singlets (5.5%), and pemetrexed + bevacizumab-based combinations (1.8%). Median survival was longest for pemetrexed + bevacizumab-based combinations (18.5 months), followed by bevacizumab-based regimens (14.5), TKIs (12.7), pemetrexed-based regimens (10.4), doublets (9.2), and singlets (5.3). There was a significantly reduced risk of mortality for pemetrexed + bevacizumab-based combinations (HR = 0.64; 95% CI = 0.42-0.94) and TKIs (HR = 0.83; 95% CI = 0.73-0.94) compared with doublets. Singlets were associated with an increased risk of mortality (HR = 1.50; 95% CI = 1.22-1.84). Subgroup analysis among patients aged 65 years and over found no significant

  14. Counting forbidden patterns in irregularly sampled time series. II. Reliability in the presence of highly irregular sampling

    NASA Astrophysics Data System (ADS)

    Sakellariou, Konstantinos; McCullough, Michael; Stemler, Thomas; Small, Michael

    2016-12-01

    We are motivated by real-world data that exhibit severe sampling irregularities such as geological or paleoclimate measurements. Counting forbidden patterns has been shown to be a powerful tool towards the detection of determinism in noisy time series. They constitute a set of ordinal symbolic patterns that cannot be realised in time series generated by deterministic systems. The reliability of the estimator of the relative count of forbidden patterns from irregularly sampled data has been explored in two recent studies. In this paper, we explore highly irregular sampling frequency schemes. Using numerically generated data, we examine the reliability of the estimator when the sampling period has been drawn from exponential, Pareto and Gamma distributions of varying skewness. Our investigations demonstrate that some statistical properties of the sampling distribution are useful heuristics for assessing the estimator's reliability. We find that sampling in the presence of large chronological gaps can still yield relatively accurate estimates as long as the time series contains sufficiently many densely sampled areas. Furthermore, we show that the reliability of the estimator of forbidden patterns is poor when there is a high number of sampling intervals, which are larger than a typical correlation time of the underlying system.

  15. Natural selection coupled with intragenic recombination shapes diversity patterns in the major histocompatibility complex class II genes of the giant panda.

    PubMed

    Chen, Yi-Yan; Zhang, Ying-Ying; Zhang, He-Min; Ge, Yun-Fa; Wan, Qiu-Hong; Fang, Sheng-Guo

    2010-05-15

    Ample variations of the major histocompatibility complex (MHC) genes are essential for vertebrates to adapt to various environmental conditions. In this study, we investigated the genetic variations and evolutionary patterns of seven functional MHC class II genes (one DRA, two DRB, two DQA, and two DQB) of the giant panda. The results showed the presence of two monomorphic loci (DRA and DQB2) and five polymorphic loci with different numbers of alleles (seven at DRB1, six at DRB3, seven at DQA1, four at DQA2, six at DQB1). The presence of balancing selection in the giant panda was supported by the following pieces of evidence: (1) The observed heterozygosity was higher than expected. (2) Amino acid heterozygosity was significantly higher at antigen-binding sites (ABS) compared with non-ABS sequences. (3) The selection parameter omega (d(N)/d(S)) was significantly higher at ABS compared with non-ABS sequences. (4) Approximately 95.45% of the positively selected codons (P>0.95) were located at or adjacent to an ABS. Furthermore, this study showed that (1) The Qinling subspecies exhibited high omega values across each locus (all >1), supporting its extensive positive selection. (2) The Sichuan subspecies displayed small omega at DRB1 (omega<0.72) and DQA2 (omega<0.48), suggesting that these sites underwent strong purifying selection. (3) Intragenic recombination was detected in DRB1, DQA1, and DQB1. The molecular diversity in classic Aime-MHC class II genes implies that the giant panda had evolved relatively abundant variations in its adaptive immunity along the history of host-pathogen co-evolution. Collectively, these findings indicate that natural selection accompanied by recombination drives the contrasting diversity patterns of the MHC class II genes between the two studied subspecies of giant panda.

  16. The Design and Analysis of Salmonid Tagging Studies in the Columbia Basin : Volume II: Experiment Salmonid Survival with Combined PIT-CWT Tagging.

    SciTech Connect

    Newman, Ken

    1997-06-01

    Experiment designs to estimate the effect of transportation on survival and return rates of Columbia River system salmonids are discussed along with statistical modeling techniques. Besides transportation, river flow and dam spill are necessary components in the design and analysis otherwise questions as to the effects of reservoir drawdowns and increased dam spill may never be satisfactorily answered. Four criteria for comparing different experiment designs are: (1) feasibility, (2) clarity of results, (3) scope of inference, and (4) time to learn. In this report, alternative designs for conducting experimental manipulations of smolt tagging studies to study effects of river operations such as flow levels, spill fractions, and transporting outmigrating salmonids around dams in the Columbia River system are presented. The principles of study design discussed in this report have broad implications for the many studies proposed to investigate both smolt and adult survival relationships. The concepts are illustrated for the case of the design and analysis of smolt transportation experiments. The merits of proposed transportation studies should be measured relative to these principles of proper statistical design and analysis.

  17. Latent Fingermark Aging Patterns (Part II): Color Contrast Between Ridges and Furrows as One Indicator of Degradation.

    PubMed

    De Alcaraz-Fossoul, Josep; Barrot Feixat, Carme; Tasker, Jack; McGarr, Luke; Stow, Karen; Carreras-Marin, Clara; Turbany Oset, Jaume; Gené Badia, Manel

    2016-07-01

    Currently, no established methodology exists to determine degradation patterns of latent fingermarks by visual means. This article is the second in a series of reports exploring quantifiable degradation-related parameters, which focuses on color contrast changes between fingermark ridges and furrows over time. Experiment variables included type of secretion (eccrine and sebaceous), substrate (glass and plastic), and exposure to natural light (dark, shade, and direct light). Fingermarks were sequentially visualized with titanium dioxide powder and photographed. Image histogram profiles were evaluated and combined with statistical analysis of color data values. Results indicate that sebaceous depositions on glass were generally less degraded by the effect of environmental conditions compared with those on plastic. In addition, aging in darkness was not always the best condition for preservation, and direct exposure to light seemed to inhibit visual degradation under certain conditions. Overall, the technique provided sufficient sensitivity to discern degradation patterns of fingermarks.

  18. In silico analysis of interaction pattern switching in ligandreceptor binding in Golgi α-mannosidase II induced by the protonated states of inhibitors.

    PubMed

    Sladek, V; Kóňa, J; Tokiwa, H

    2017-05-21

    Golgi α-mannosidase II (GM) is a pharmaceutical target for the design of inhibitors with anticancer activity. The known potent GM inhibitors undergo complex interactions with Zn(2+) ions and the active-site amino acids, many of which contain ionisable functional groups. Herein, the physical insight into the ligandreceptor interactions has been provided based on energy decomposition techniques: SAPT (symmetry adapted perturbation theory) and FMO-PIEDA (fragment molecular orbital-pair interaction energy decomposition analysis) for a large GM active-site cluster. Protonation-dependent molecular recognition in Golgi α-mannosidase was demonstrated for five inhibitors, mannose, and its transition state. Zn(2+) ion and Asp472 induce the key interactions with the deprotonated inhibitors (bearing an amino group in the neutral state), followed by Asp92 and Asp341. This interaction pattern is consistent for all the studied inhibitors and is similar to the interaction pattern of the enzyme native substrate - mannose. The interactions with Zn(2+) ion become repulsive for the protonated states of the inhibitors (bearing an amino group with +1 charge) and the mannosyl transition state. The importance of Asp92 and Asp204 considerably increases, while the interactions with Asp472 and Asp341 are slightly modified. The interaction pattern for the protonated ligands seems to have an oxocarbenium transition state-like character, rather than a Michaelis complex of GM. The electrostatic interactions with amino acids coordinating zinc ion are of key importance for both the neutral and protonated states of the inhibitors. The ligand's diol group has a dual role as an electron donor, coordinating zinc ion, and as an electron acceptor, interacting with Asp92 and Asp472 via strong hydrogen bonds. This interaction pattern is an essential structural feature of the potent GM inhibitors, which is consistent with the experimental findings. Based on the calculations, either the protonated or

  19. Care Groups II: A Summary of the Child Survival Outcomes Achieved Using Volunteer Community Health Workers in Resource-Constrained Settings

    PubMed Central

    Morrow, Melanie; Davis, Thomas; Borger, Sarah; Weiss, Jennifer; DeCoster, Mary; Ricca, Jim; Ernst, Pieter

    2015-01-01

    The Care Group approach, described in detail in a companion paper in this journal, uses volunteers to convey health promotion messages to their neighbors. This article summarizes the available evidence on the effectiveness of the Care Group approach, drawing on articles published in the peer-reviewed literature as well as data from unpublished but publicly available project evaluations and summary analyses of these evaluations. When implemented by strong international NGOs with adequate funding, Care Groups have been remarkably effective in increasing population coverage of key child survival interventions. There is strong evidence that Care Groups can reduce childhood undernutrition and reduce the prevalence of diarrhea. Finally, evidence from multiple sources, comprising independent assessments of mortality impact, vital events collected by Care Group Volunteers themselves, and analyses using the Lives Saved Tool (LiST), that Care Groups are effective in reducing under-5 mortality. For example, the average decline in under-5 mortality, estimated using LiST, among 8 Care Group projects was 32%. In comparison, among 12 non-Care Group child survival projects, the under-5 mortality declined, on average, by an estimated 11%. Care Group projects cost in the range of US$3–$8 per beneficiary per year. The cost per life saved is in the range of $441–$3,773, and the cost per disability-adjusted life year (DALY) averted is in the range of $15–$126. The Care Group approach, when implemented as described, appears to be highly cost-effective based on internationally accepted criteria. Care Groups represent an important and promising innovative, low-cost approach to increasing the coverage of key child survival interventions in high-mortality, resource-constrained settings. Next steps include further specifying the adjustments needed in government health systems to successfully incorporate the Care Group approach, testing the feasibility of these adjustments and of the

  20. Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib.

    PubMed

    Italiano, Antoine; Cioffi, Angela; Coco, Paola; Maki, Robert G; Schöffski, Patrick; Rutkowski, Piotr; Le Cesne, Axel; Duffaud, Florence; Adenis, Antoine; Isambert, Nicolas; Bompas, Emmanuelle; Blay, Jean-Yves; Casali, Paolo; Keohan, Mary Louise; Toulmonde, Maud; Antonescu, Cristina R; Debiec-Rychter, Maria; Coindre, Jean-Michel; Bui, Binh

    2012-05-01

    Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited. Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed. The three most frequent drugs used in the 3rd-line setting were: nilotinib n = 67 (29.5%), sorafenib n = 55 (24.5%), and imatinib n = 40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd-line treatment were 3.6 months [95% confidence interval (95% CI), 3.1-4.1] and 9.2 months (95% CI, 7.5-10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC. In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib.

  1. Genetic diversity patterns in the SR-BI/II locus can be explained by a recent selective sweep.

    PubMed

    Le Jossec, Mireille; Wambach, Tina; Labuda, Damian; Sinnett, Daniel; Levy, Emile

    2004-04-01

    The human scavenger receptor class B type I (SR-BI and splice variant SR-BII) plays a central role in HDL cholesterol metabolism and represents a candidate gene for a number of related diseases. We examined the genetic diversity of its coding and flanking regions in a sample of 178 chromosomes from individuals of European, African, East Asian (including Southeast Asian), Middle-Eastern as well as Amerindian descent. Nine of the 14 polymorphisms observed are new. Four of the five variants causing amino acid replacements, G2S, S229G, R484W, and G499R, are likely to affect protein structure and function. SR-BI/BII diversity is partitioned among 19 haplotypes; all but one interconnected by single mutation or a recombination event. Such tight haplotype network and the unusual geographic partitioning of this diversity, high not only in Africa but in East Asia as well, suggests its recent origin and possible effect of selection. Coalescent analysis infers a relatively short time to the most recent common ancestor and points to population expansion in Africa and East Asia. These two continents differ significantly in pairwise F(ST) values, differing as well from a single cluster formed by Europe, Middle East and America. In the context of findings for similarly analyzed other loci, we propose that a selective sweep at the origin of modern human populations could explain the low level of ancestral SR-BI/II diversity. The unusually deep split between Africa and Asia, well beyond the Upper Paleolithic when inferred under neutrality, is consistent with subsequent geographical and demographic expansion favoring the accumulation of new variants, especially in groups characterized by large effective population sizes, such as Asians and Africans. The relevance of such partitioning of SR-BI/II diversity remains to be investigated in genetic epidemiological studies which can be guided by the present findings.

  2. Selection, diversity and evolutionary patterns of the MHC class II DAB in free-ranging Neotropical marsupials

    PubMed Central

    Meyer-Lucht, Yvonne; Otten, Celine; Püttker, Thomas; Sommer, Simone

    2008-01-01

    Background Research on the genetic architecture and diversity of the MHC has focused mainly on eutherian mammals, birds and fish. So far, studies on model marsupials used in laboratory investigations indicated very little or even no variation in MHC class II genes. However, natural levels of diversity and selection are unknown in marsupials as studies on wild populations are virtually absent. We used two endemic South American mouse opossums, Gracilinanus microtarsus and Marmosops incanus, to investigate characteristic features of MHC selection. This study is the first investigation of MHC selection in free-ranging Neotropical marsupials. In addition, the evolutionary history of MHC lineages within the group of marsupials was examined. Results G. microtarsus showed extensive levels of MHC diversity within and among individuals as 47 MHC-DAB alleles and high levels of sequence divergence were detected at a minimum of four loci. Positively selected codon sites were identified, of which most were congruent with human antigen binding sites. The diversity in M. incanus was rather low with only eight observed alleles at presumably two loci. However, these alleles also revealed high sequence divergence. Again, positive selection was identified on specific codon sites, all congruent with human ABS and with positively selected sites observed in G. microtarsus. In a phylogenetic comparison alleles of M. incanus interspersed widely within alleles of G. microtarsus with four alleles being present in both species. Conclusion Our investigations revealed extensive MHC class II polymorphism in a natural marsupial population, contrary to previous assumptions. Furthermore, our study confirms for the first time in marsupials the presence of three characteristic features common at MHC loci of eutherian mammals, birds and fish: large allelic sequence divergence, positive selection on specific sites and trans-specific polymorphism. PMID:18534008

  3. Staircase pattern in a superfluid He-II torsional-oscillator analog of the radio-frequency SQUID

    SciTech Connect

    Bonaldi, M. ); Cerdonio, M.; Dolesi, R.; Vitale, S. Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Trento, Sezione di Padova, I-38050, Povo, Trento )

    1994-01-01

    We are developing a superfluid [sup 4]He analog of the rf SQUID. A thin partition with a micrometric orifice is placed inside a toroidal container filled with liquid helium; ac and dc superflows through the orifice are induced by rotating the whole torus, which is the inertial member of a torsional oscillator. The torus oscillation amplitude vs drive curve shows a small but reproducible staircase pattern, which is detectable between 1.4 and 2.05 K, but is not modulated by a superimposed steady rotation. We discuss this behavior in terms of the occurrence of multiple phase slips.

  4. [Psychopharmacologic studies on the combined effect of alcohol and oxazepam on reactivity pattern. II. Subjective feeling and reaction behavior].

    PubMed

    Staak, M; Gottwald, K; Mallach, H J; Schubring, G

    1977-05-01

    Psychopharmacological investigations of the subjective state of being and the reactivity pattern of a group of 14 probands show a good agreement with the alterations of performance reported in the first part of this publication and with the data on polarity profiles. In addition to a sedative effect the interaction of alcohol and oxazepam in the oxazepam trial results in dysphoric changes of mood and related significant alterations of polarity profiles. A correlation of the changes of performance and the alterations of the polarity profiles with the respective blood levels of alcohol and oxazepam could be demonstrated.

  5. FROGG high-risk prostate cancer workshop: patterns of practice and literature review. Part II post-radical prostatectomy.

    PubMed

    Lehman, Margot; Sidhom, Mark; Kneebone, Andrew B; Hayden, Amy J; Martin, Jarad M; Christie, David; Skala, Marketa; Tai, Keen-Hun

    2014-01-01

    Australian and New Zealand radiation oncologists with an interest in uro-oncology were invited to undertake a pattern of practice survey dealing with issues encountered in the management of high-risk prostate cancer in the post-prostatectomy setting. Responses from practitioners revealed a lack of consensus regarding the optimal timing of radiation therapy, the use of whole pelvic radiation therapy and the use of androgen deprivation therapy. A review of the literature outlining the current body of knowledge and the clinical studies that will inform future practice is presented.

  6. Effects of brain-derived neurotrophic factor on cell survival, differentiation and patterning of neuronal connections and Müller glia cells in the developing retina.

    PubMed

    Pinzón-Duarte, Germán; Arango-González, Blanca; Guenther, Elke; Kohler, Konrad

    2004-03-01

    The aim of the present study was to determine the influence of brain-derived neurotrophic factor (BDNF) on survival, phenotype differentiation and network formation of retinal neurons and glia cells. To achieve a defined concentration and constant level of BDNF over several days, experiments were performed in an organotypic culture of the developing rat retina. After 6 days in vitro, apoptosis in the different cell layers was determined by TUNEL staining and cell-type-specific antibodies were used to identify distinct neuronal cell types and Müller cells. Cultured retinas treated with BDNF (100 ng BDNF/mL medium) were compared with untreated as well as with age-matched in vivo retinas. Quantitative morphometry was carried out using confocal microscopy. BDNF promoted the in vitro development and differentiation of the retina in general, i.e. the number of cells in the nuclear layers and the thickness of the plexiform layers were increased. For all neurons, the number of cells and the complexity of arborizations in the synaptic layers were clearly up-regulated by BDNF. In control cultures, the synaptic stratification of cone bipolar cells within the On- and Off-layer of the inner plexiform layer was disturbed and a strong reactivity of Müller cell glia was observed. These effects were not present in BDNF-treated cultures. Our data show that BDNF promotes the survival of retinal interneurons and plays an important role in establishing the phenotypes and the synaptic connections of a large number of neuronal types in the developing retina. Moreover, we show an effect of BDNF on Müller glia cells.

  7. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas.

    PubMed

    Olar, Adriana; Wani, Khalida M; Alfaro-Munoz, Kristin D; Heathcock, Lindsey E; van Thuijl, Hinke F; Gilbert, Mark R; Armstrong, Terri S; Sulman, Erik P; Cahill, Daniel P; Vera-Bolanos, Elizabeth; Yuan, Ying; Reijneveld, Jaap C; Ylstra, Bauke; Wesseling, Pieter; Aldape, Kenneth D

    2015-04-01

    Diffuse gliomas are up till now graded based upon morphology. Recent findings indicate that isocitrate dehydrogenase (IDH) mutation status defines biologically distinct groups of tumors. The role of tumor grade and mitotic index in patient outcome has not been evaluated following stratification by IDH mutation status. To address this, we interrogated 558 WHO grade II-III diffuse gliomas for IDH1/2 mutations and investigated the prognostic impact of WHO grade within IDH-mutant and IDH-wild type tumor subsets independently. The prognostic impact of grade was modest in IDH-mutant [hazard ratio (HR) = 1.21, 95 % confidence interval (CI) = 0.91-1.61] compared to IDH-wild type tumors (HR = 1.74, 95 % CI = 0.95-3.16). Using a dichotomized mitotic index cut-off of 4/1000 tumor cells, we found that while mitotic index was significantly associated with outcome in IDH-wild type tumors (log-rank p < 0.0001, HR = 4.41, 95 % CI = 2.55-7.63), it was not associated with outcome in IDH-mutant tumors (log-rank p = 0.5157, HR = 1.10, 95 % CI = 0.80-1.51), and could demonstrate a statistical interaction (p < 0.0001) between IDH mutation and mitotic index (i.e., suggesting that the effect of mitotic index on patient outcome is dependent on IDH mutation status). Patient age, an established prognostic factor in diffuse glioma, was significantly associated with outcome only in the IDH-wild type subset, and consistent with prior data, 1p/19q co-deletion conferred improved outcome in the IDH-mutant cohort. These findings suggest that stratification of grade II-III gliomas into subsets defined by the presence or absence of IDH mutation leads to subgroups with distinct prognostic characteristics. Further evaluation of grading criteria and prognostic markers is warranted within IDH-mutant versus IDH-wild type diffuse grade II-III gliomas as independent entities.

  8. Oblique shock breakout in supernovae and gamma-ray bursts. II. Numerical solutions for non-relativistic pattern speeds

    SciTech Connect

    Salbi, Pegah; Matzner, Christopher D.; Ro, Stephen; Levin, Yuri

    2014-07-20

    Non-spherical explosions develop non-radial flows as the pattern of shock emergence progresses across the stellar surface. In supernovae, these flows can limit ejecta speeds, stifle shock breakout emission, and cause collisions outside the star. Similar phenomena occur in stellar and planetary collisions, tidal disruption events, accretion-induced collapses, and propagating detonations. We present two-dimensional, nested-grid Athena simulations of non-radial shock emergence in a frame comoving with the breakout pattern, focusing on the adiabatic, non-relativistic limit in a plane stratified envelope. We set boundary conditions using a known self-similar solution and explore the role of box size and resolution on the result. The shock front curves toward the stellar surface, and exhibits a kink from which weak discontinuities originate. Flow around the point of shock emergence is neither perfectly steady nor self-similar. Waves and vortices, which are not predominantly due to grid effects, emanate from this region. The post-shock flow is deflected along the stellar surface and its pressure disturbs the stellar atmosphere upstream of the emerging shock. We use the numerical results and their analytical limits to predict the effects of radiation transfer and gravity, which are not included in our simulations.

  9. Elm leaves 'warned' by insect egg deposition reduce survival of hatching larvae by a shift in their quantitative leaf metabolite pattern.

    PubMed

    Austel, Nadine; Eilers, Elisabeth J; Meiners, Torsten; Hilker, Monika

    2016-02-01

    Plants may take insect eggs on their leaves as a warning of future herbivory and intensify their defence against feeding larvae. Responsible agents are, however, largely unknown, and little knowledge is available on this phenomenon in perennial plants. We investigated how egg deposition affects the anti-herbivore defence of elm against the multivoltine elm leaf beetle. Prior egg deposition caused changes in the quality of feeding-damaged leaves that resulted in increased larval mortality and reduced reproductive capacity of the herbivore by harming especially female larvae. Chemical analyses of primary and secondary leaf metabolites in feeding-damaged, egg-free (F) and feeding-damaged, egg-deposited (EF)-leaves revealed only small differences in concentrations when comparing metabolites singly. However, a pattern-focused analysis showed clearly separable patterns of (F) and (EF)-leaves because of concentration differences in especially nitrogen and phenolics, of which robinin was consumed in greater amounts by larvae on (EF) than on (F)-leaves. Our study shows that insect egg deposition mediates a shift in the quantitative nutritional pattern of feeding-damaged leaves, and thus might limit the herbivore's population growth by reducing the number of especially female herbivores. This may be a strategy that pays off in a long run particularly in perennial plants against multivoltine herbivores. © 2015 John Wiley & Sons Ltd.

  10. Eradication of minimal residual disease improves overall and progression-free survival in patients with chronic lymphocytic leukaemia, evidence from NCRN CLL207: a phase II trial assessing alemtuzumab consolidation.

    PubMed

    Varghese, Abraham M; Howard, Dena R; Pocock, Christopher; Rawstron, Andy C; Follows, George; McCarthy, Helen; Dearden, Claire; Fegan, Christopher; Milligan, Donald; Smith, Alexandra F; Gregory, Walter; Hillmen, Peter

    2017-02-01

    With immunochemotherapy, remission duration and survival in patients with chronic lymphocytic leukaemia is dependent on the level of minimal residual disease (MRD) after treatment. This phase II trial assessed alemtuzumab consolidation post-chemotherapy in patients who responded with persistent low levels of detectable disease. Blood was screened for MRD using multi-parameter flow cytometry, 6-24 months post-chemotherapy. MRD-positive participants received alemtuzumab 30 mg subcutaneously 3 times weekly for 6 weeks. Following a marrow assessment, MRD-negative participants or non-responders stopped therapy and MRD-positive participants with 1 + log reduction had 6 more weeks of alemtuzumab. Alemtuzumab consolidation was received by 47 participants. One death and 19 of 22 serious adverse events reported from 17 (36%) participants were alemtuzumab-related. MRD eradication from blood and bone marrow was achieved in 39 (83%) participants at the end of consolidation, with 18 (38%) remaining MRD-negative in the blood 6 months later. Of the 18 participants who were MRD-negative at 6 months, the median time to MRD relapse was 46 months, which was similar to patients who were MRD-negative at baseline and were followed up. The 5-year progression-free survival (PFS) and overall survival (OS) of participants who were MRD-negative at 6 months was significantly better than MRD-positive participants [PFS: 78% vs. 39% (P = 0·010), OS: 89% vs. 64% (P = 0·029)]. © 2016 John Wiley & Sons Ltd.

  11. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases.

    PubMed

    Nilsson, Sten; Franzén, Lars; Parker, Christopher; Tyrrell, Christopher; Blom, René; Tennvall, Jan; Lennernäs, Bo; Petersson, Ulf; Johannessen, Dag C; Sokal, Michael; Pigott, Katharine; O'Bryan-Tear, Charles Gillies; Thuresson, Marcus; Bolstad, Bjørg; Bruland, Øyvind S

    2013-03-01

    This phase II randomized, placebo-controlled study was conducted to evaluate efficacy and safety of radium-223 in patients with castration-resistant prostate cancer (CRPC) and painful bone metastases. Twelve- and 18-month survival results were reported previously. Here we report 24-month overall survival (OS) and safety data from the period 12 to 24 months after the first injection of study medication. Patients with CRPC and bone pain were randomized 1:1 to receive 4 injections of radium-223 (50 kBq/kg [n = 33]) or placebo (n = 31) after external-beam radiotherapy; each injection was given every 4 weeks. Endpoints for this report were 24-month OS, long-term safety, and treatment-related adverse events (AEs) occurring in the 12- to 24-month period. After 24 months, 10 (30%) patients were alive in the radium-223 group compared with 4 patients (13%) in the placebo group. Patients who received at least 1 dose of study medication had a median OS of 65 weeks in the radium-223 group vs. 46 weeks in the placebo group (log-rank P = .056). The hazard ratio (HR) for OS, adjusted for baseline covariates, was 0.476 (95% confidence interval [CI], 0.258-0.877; Cox regression P = .017). The most frequent cause of death for both arms was disease progression. There were no reports of treatment-related AEs or long-term hematologic toxicity during the 12- to 24-month follow-up. Radium-223 had a highly favorable safety profile, with no evidence of second malignancies at 24-month follow-up. The significant improvement in OS observed in patients receiving radium-223 vs. placebo suggests that treatment of bone disease with radium-223 has survival benefits. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Organ specific analysis of the anaerobic primary metabolism in rice and wheat seedlings II: light exposure reduces needs for fermentation and extends survival during anaerobiosis.

    PubMed

    Mustroph, Angelika; Boamfa, Elena I; Laarhoven, Lucas J J; Harren, Frans J M; Pörs, Yvonne; Grimm, Bernhard

    2006-12-01

    Low oxygen stress in plants can occur during flooding and compromise the availability and utilization of carbohydrates in root and shoot tissues. Low-oxygen-tolerant rice and -sensitive wheat plants were analyzed under anaerobiosis in light to evaluate main factors of the primary metabolism that affect sensitivity against oxygen deprivation: activity of glycolysis and the rate of photosynthesis. Relatively stable ATP contents (93 and 58% of aerated control levels after 24 h anaerobiosis) in illuminated shoot tissues account for enhanced tolerance of rice and wheat seedlings to anaerobiosis upon light exposure in comparison to anoxia in darkness. Although the photosynthetic process was inhibited during low oxygen stress, which was partly due to CO(2) deficiency, more light-exposed than dark-incubated seedlings survived. Illuminated plants could tolerate a 70% lower anaerobic ethanol production in shoots in comparison to darkness, although still an 18-times higher ethanol production rate was determined in rice than in wheat leaves. In conclusion, light-exposed plants grown under anaerobiosis may recycle low amounts of generated oxygen between photosynthesis and dissimilation and generate additional energy not only from substrate phosphorylation during glycolysis but also from other sources like cyclic electron transport.

  13. Element pattern of an axial dipole in a cylindrical phased array. I - Theory. II - Element design and experiments

    NASA Astrophysics Data System (ADS)

    Herper, J. C.; Hessel, A.; Tomasic, B.

    1985-03-01

    It is pointed out that circular cylindrical antenna arrays are of interest for radar and communication applications because of the uniformity of their circumferential radiation characteristics. In surveys of state-of-the-art arrays, most of the cited bibliographies deal with aperture arrays. On the other hand, a dipole element is an attractive choice for an array radiator due to its simplicity of manufacture, reasonably wide bandwidth and polarization purity. For this reason, a two-phase study has been conducted, taking into account a theoretical and experimental investigation. In the first phase, cylindrical stacked ring antenna arrays of uniformly spaced axial dipoles were investigated to establish the mutually coupled element pattern characteristics. The first part of the present paper is concerned with details of this investigation. The second part of the paper will provide an account of the second phase of the study, which consisted of experiments supporting the theoretical phase.

  14. Elastic strain relaxation in interfacial dislocation patterns: II. From long- and short-range interactions to local reactions

    NASA Astrophysics Data System (ADS)

    Vattré, A.

    2017-08-01

    The long- and short-range interactions as well as planar reactions between two infinitely periodic sets of crossing dislocations are investigated using anisotropic elasticity theory in face- (fcc) and body- (bcc) centered cubic materials. Two preliminary cases are proposed to examine the substantial changes in the elastic stress states and the corresponding strain energies due to a slight rearrangement in the internal dislocation geometries and characters. In general, significant differences and discrepancies resulting from the considered cubic crystal structure and the approximation of isotropic elasticity are exhibited. In a third scenario, special attention is paid to connecting specific internal dislocation structures from the previous cases with non-equilibrium configurations predicted by the quantized Frank-Bilby equation for the (111) fcc and (110) bcc twist grain boundaries. The present solutions lead to the formation of energetically favorable dislocation junctions with non-randomly strain-relaxed configurations of lower energy. In particular, the local dislocation interactions and reactions form equilibrium hexagonal-shaped patterns with planar three-fold dislocation nodes without producing spurious far-field stresses.Numerical application results are presented from a selection of cubic metals including aluminum, copper, tantalum, and niobium. In contrast to the fcc materials, asymmetric dislocation nodes occur in the anisotropic bcc cases, within which the minimum-energy paths for predicting the fully strain-relaxed dislocation patterns depend on the Zener anisotropic factor with respect to unity. The associated changes in the dislocation structures as well as the removal of the elastic strain energy upon relaxations are quantified and also discussed.

  15. Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

    SciTech Connect

    Chance, William W.; Rice, David C.; Allen, Pamela K.; Tsao, Anne S.; Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W.; Mehran, Reza J.; Gomez, Daniel R.

    2015-01-01

    Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

  16. Effect of oestradiol and pathogen-associated molecular patterns on class II-mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract

    PubMed Central

    Ochiel, Daniel O; Rossoll, Richard M; Schaefer, Todd M; Wira, Charles R

    2012-01-01

    Cells of the female reproductive tract (FRT) can present antigen to naive and memory T cells. However, the effects of oestrogen, known to modulate immune responses, on antigen presentation in the FRT remain undefined. In the present study, DO11.10 T-cell antigen receptor transgenic mice specific for the class II MHC-restricted ovalbumin (OVA) 323–339 peptide were used to study the effects of oestradiol and pathogen-associated molecular patterns on antigen presentation in the FRT. We report here that oestradiol inhibited antigen presentation of OVA by uterine epithelial cells, uterine stromal cells and vaginal cells to OVA-specific memory T cells. When ovariectomized animals were treated with oestradiol for 1 or 3 days, antigen presentation was decreased by 20–80%. In contrast, incubation with PAMP increased antigen presentation by epithelial cells (Pam3Cys), stromal cells (peptidoglycan, Pam3Cys) and vaginal cells (Pam3Cys). In contrast, CpG inhibited both stromal and vaginal cell antigen presentation. Analysis of mRNA expression by reverse transcription PCR indicated that oestradiol inhibited CD40, CD80 and class II in the uterus and CD40, CD86 and class II in the vagina. Expression in isolated uterine and vaginal cells paralleled that seen in whole tissues. In contrast, oestradiol increased polymeric immunoglobulin receptor mRNA expression in the uterus and decreased it in the vagina. These results indicate that antigen-presenting cells in the uterus and vagina are responsive to oestradiol, which inhibits antigen presentation and co-stimulatory molecule expression. Further, these findings suggest that antigen-presenting cells in the uterus and vagina respond to selected Toll-like receptor agonists with altered antigen presentation. PMID:22043860

  17. The Type II Collagen N-propeptide, PIIBNP, inhibits cell survival and bone resorption of osteoclasts via integrin-mediated signaling

    PubMed Central

    Hayashi, Shinya; Wang, Zhepeng; Bryan, Jennifer; Kobayashi, Chikashi; Faccio, Roberta; Sandell, Linda J.

    2011-01-01

    Objective Type IIB procollagen is characteristic of cartilage, comprising 50% of the extracellular matrix. The NH2-propeptide of type IIB collagen, PIIBNP, can kill tumor cells via binding to integrins αVβ3 and αVβ5. As osteoclasts rely on αVβ3 integrins for function in bone erosion, we sought to determine whether PIIBNP could inhibit osteoclast function. Methods We undertook in vitro and in vivo experiments to evaluate both osteoblast and osteoclast function in the presence of recombinant PIIBNP. Adhesion of osteoclasts to PIIBNP was analyzed by staining of attached cells with crystal violet. PIIBNP-induced cell death was evaluated by cell counting Trypan Blue stained cells. The mechanism of cell death was evaluated by DNA fragmentation, TUNEL staining and western blotting to detect cleaved caspases. To determine the role of αVβ3 integrin, osteoclasts were pretreated with αV or β3 integrin specific siRNA before the treatment with PIIBNP. To explore PIIBNP function in vivo, a lipopolysaccharide-induced mouse calvaria lysis model was employed. Results Osteoclasts adhered to PIIBNP via an RGD-mediated mechanism. When osteoclasts were plated on extracellular matrix proteins, PIIBNP induced apoptosis of osteoclasts via caspase 3/8 activation. Osteoblasts and macrophages were not killed. Reduction of αV or β3 integrin levels on osteoclasts by siRNA reduced cell death in a dose-dependent manner. In vivo, PIIBNP could inhibit bone resorption. Conclusion We conclude that PIIBNP can inhibit osteoclast survival and bone resorption via signal transduction through the αVβ3 integrins. Because of this property and the cell specificity, we propose that PIIBNP may play a role in vivo in protecting cartilage from osteoclast invasion and also could be a new therapeutic strategy for decreasing bone loss. PMID:21708300

  18. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension

    PubMed Central

    Aghamohammadzadeh, Reza; Zhang, Ying-Yi; Stephens, Thomas E.; Arons, Elena; Zaman, Paula; Polach, Kevin J.; Matar, Majed; Yung, Lai-Ming; Yu, Paul B.; Bowman, Frederick P.; Opotowsky, Alexander R.; Waxman, Aaron B.; Loscalzo, Joseph; Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10−9 to 10−7 M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor–small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro. Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo. Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.—Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery

  19. Cancer mortality patterns among female and male workers employed in a cable manufacturing plant during World War II.

    PubMed

    Ward, E M; Ruder, A M; Suruda, A; Smith, A B; Halperin, W; Fessler, C A; Zahm, S H

    1994-08-01

    A cohort mortality study was conducted among 9028 (3042 women, 5986 men) workers potentially exposed to chlorinated naphthalenes (chloracnegens structurally similar to dioxins) and asbestos in the manufacture of Navy cable during World War II. Based on mortality through December 31, 1985, standardized mortality ratios (SMRs) for all cancers was 1.03 in women (95% confidence interval [CI] = 0.9 to 1.17) and 1.18 in men (95% CI = 1.10 to 1.26). There were no significant elevations in causes of death hypothesized a prior to be associated with chlorinated naphthalene exposure (malignant neoplasms [MN] of connective tissue, liver, and lymphatic and hematopoietic organs). An excess of MN of the connective tissue was suggested for workers with over 1 year of exposure and 25 years of latency (SMR = 3.54; 95% CI = 0.97 to 9.07). Among cancer sites not hypothesized to be related a priori, three showed concordant excesses among both genders (MN of stomach; rectum; and trachea, bronchus, and lung). No significant elevations occurred in hormonally related cancers among women. Cancer mortality among 460 individuals with chloracne (431 men, 29 women) was similar to that of the entire cohort, although the chloracne subcohort showed significant excesses in two rare causes of death (MN of esophagus, SMR = 3.26; "benign and unspecified neoplasms," SMR = 4.93). Use of county referent rates decreased SMRs for stomach, rectal, and buccal cavity cancer, suggesting a role for nonoccupational risk factors. It is difficult to draw conclusions about carcinogenicity of chlorinated naphthalenes because of study limitations, most importantly, concomitant asbestos exposure and the relatively short duration of exposure to chlorinated naphthalenes among most of the cohort.

  20. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    PubMed Central

    Sanoff, Hanna K.; Stitzenberg, Karyn B.; Baron, John A.; Lund, Jennifer L.; Sandler, Robert S.

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n = 6, 862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50–69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50–69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years. PMID:28239395

  1. Patterns of hospital resource utilization of children with leukemia and CNS tumors: a comparison of children who survive and those who die within 3 years of diagnosis.

    PubMed

    Hendrickson, Karrie Cummings; Rimar, Joan

    2009-01-01

    Hospital admissions for children with cancer tend to be longer than admissions for adults with cancer and longer, more frequent, and more costly than other pediatric admissions. The two childhood cancers most commonly requiring hospitalization are leukemia and tumors of the central nervous system (CNS tumors). Determining the best use of limited financial resources and preparing children and their parents for what to expect requires a better understanding of the patterns and cost of hospital resource utilization by children with cancer. Both hospital administrators and third-party payers can use this understanding to better allocate resources and plan the care of children with cancer in the future. Because many parents of children with cancer struggle financially due to the high cost of treatments, time off of work, and other non-medical expenses, more education in this area may help parents to prepare, thus alleviating some of the uncertainty and unexpected financial costs associated with childhood cancer.