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  1. Rich Medium Composition Affects Escherichia coli Survival, Glycation, and Mutation Frequency during Long-Term Batch Culture

    PubMed Central

    Kram, Karin E.

    2015-01-01

    Bacteria such as Escherichia coli are frequently grown to high density to produce biomolecules for study in the laboratory. To achieve this, cells can be incubated in extremely rich media that increase overall cell yield. In these various media, bacteria may have different metabolic profiles, leading to changes in the amounts of toxic metabolites produced. We have previously shown that stresses experienced during short-term growth can affect the survival of cells during the long-term stationary phase (LTSP). Here, we incubated cells in LB, 2× yeast extract-tryptone (YT), Terrific Broth, or Super Broth medium and monitored survival during the LTSP, as well as other reporters of genetic and physiological change. We observe differential cell yield and survival in all media studied. We propose that differences in long-term survival are the result of changes in the metabolism of components of the media that may lead to increased levels of protein and/or DNA damage. We also show that culture pH and levels of protein glycation, a covalent modification that causes protein damage, affect long-term survival. Further, we measured mutation frequency after overnight incubation and observed a correlation between high mutation frequencies at the end of the log phase and loss of viability after 4 days of LTSP incubation, indicating that mutation frequency is potentially predictive of long-term survival. Since glycation and mutation can be caused by oxidative stress, we measured expression of the oxyR oxidative stress regulator during log-phase growth and found that higher levels of oxyR expression during the log phase are consistent with high mutation frequency and lower cell density during the LTSP. Since these complex rich media are often used when producing large quantities of biomolecules in the laboratory, the observed increase in damage resulting in glycation or mutation may lead to production of a heterogeneous population of plasmids or proteins, which could affect the

  2. Long-term haemodialysis survival

    PubMed Central

    Nielsen, Arne Høj; Hansen, Henrik Post

    2012-01-01

    Haemodialysis (HD) treatment for end-stage renal disease bears a poor prognosis. We present a case of a patient who, apart from two transplant periods lasting 8 months in all, was treated with conventional in-centre HD three times a week and who survived for 41 years. Patients should be aware that there is no theoretical upper limit for patient survival on HD. PMID:22833810

  3. [Long-term survival after severe trauma].

    PubMed

    Mutschler, W; Mutschler, M; Graw, M; Lefering, R

    2016-07-01

    Long-term survival after severe trauma is rarely addressed in German trauma journals although knowledge of life expectancy and identification of factors contributing to increased mortality are important for lifetime care management, development of service models, and targeting health promotion and prevention interventions. As reliable data in Germany are lacking, we compiled data mainly from the USA and Australia to describe life expectancy, risk factors, and predictors of outcome in patients experiencing traumatic spinal cord injury, traumatic brain injury, and polytrauma. Two years after trauma, life expectancy in all three categories was significantly lower than that of the general population. It depends strongly on severity of disability, age, and gender and is quantifiable. Whereas improvements in medical care have led to a marked decline in short-term mortality, surprisingly long-term survival in severe trauma has not changed over the past 30 years. Therefore, there is need to intensify long-term trauma patient care and to find new strategies to limit primary damage. PMID:27342106

  4. The Cumulative Cisplatin Dose Affects the Long-Term Survival Outcomes of Patients with Nasopharyngeal Carcinoma Receiving Concurrent Chemoradiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Li, Wen-Fei; Guo, Rui; Mao, Yan-Ping; Zhang, Yuan; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of the cumulative cisplatin dose (CCD) remains controversial for patients with nasopharyngeal carcinoma (NPC) receiving only concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 549 consecutive patients with non-metastatic, histologically-proven NPC treated using intensity-modulated radiotherapy (IMRT) at Sun Yat-sen university cancer center. Patient survival between different CCD groups were compared. The cut-off value of pre-treatment plasma EBV DNA (pre-DNA) and CCD based on disease-free survival (DFS) were 1460 copies/ml (AUC, 0.691; sensitivity, 0.717; specificity, 0.635) and 240 mg/m2 (AUC, 0.506; sensitivity, 0.526; specificity, 0.538), respectively. Of the entire cohort, 92/549 (16.8%) patients received a CCD ≥ 240 mg/m2 and 457 (83.2%) patients, <240 mg/m2. For CCD ≥ 240 mg/m2 vs. < 240 mg/m2, the estimated 4-year DFS, overall survival (OS), locoregional-free survival (LRFFS) and distant metastasis-free survival (DMFS) rates were 89.1% vs. 81.3% (P = 0.097), 92.4% vs. 90.0% (P = 0.369), 95.6% vs. 91.2% (P = 0.156), and 91.3% vs. 88.4% (P = 0.375), respectively. For the whole cohort, multivariate analysis identified the CCD was an independent prognostic factor for DFS (HR, 0.515; 95% CI, 0.267–0.995; P = 0.048). However, CCD (≥240 mg/m2) had no prognostic value in subgroup analysis with stratification by the cut-off value of pre-DNA (P > 0.05 for all rates). PMID:27071833

  5. Skin self-examination and long-term melanoma survival.

    PubMed

    Paddock, Lisa E; Lu, Shou En; Bandera, Elisa V; Rhoads, George G; Fine, Judith; Paine, Susan; Barnhill, Raymond; Berwick, Marianne

    2016-08-01

    To evaluate the effect of skin self-examination (SSE) on melanoma mortality, we estimated the survival for individuals performing SSE compared with those who did not. Participants were from a previously carried out case-control study, who were newly diagnosed melanoma cases in 1987-1989. A 20-year survival analysis was carried out using death (event) and other causes of death (competing). Cumulative incidence functions were evaluated using Gray's test and proportional subdistribution hazards regression models were fitted to study the effect of SSE and other covariates on melanoma survival. Forty-five percent of patients died, with 48.4% melanoma deaths. Individuals who did not perform SSE experienced a continuous increase in the risk of melanoma death trending toward significance for nearly 20 years after diagnosis, whereas melanoma deaths in skin self-examiners plateaued before 10 years after diagnosis (P=0.32). Univariate analyses suggested a 25% lower risk of melanoma death for those who performed SSE [hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.43-1.32, P=0.32]. After adjusting for competing risks, the multivariate risk estimate was above one (HR=1.12, 95% CI=0.61-2.06, P=0.71). Skin awareness (HR=0.46, 95% CI=0.28-0.75, P≤0.01) was associated independently with a decreased risk of melanoma death. Although we did not find a significant association between melanoma mortality and SSE when adjusting for competing mortality and other covariates, we extended previous findings that increased skin awareness and tumor thickness are strongly inversely related to survival. Research is needed to continue developing best practices for melanoma screening and to further explore the components of SSE and long-term melanoma survival. PMID:26990272

  6. Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia.

    PubMed

    Girmenia, Corrado; Micozzi, Alessandra; Piciocchi, Alfonso; Gentile, Giuseppe; Di Caprio, Luigi; Nasso, Daniela; Minotti, Clara; Capria, Saveria; Cartoni, Claudio; Alimena, Giuliana; Meloni, Giovanna; Amadori, Sergio; Foà, Robin; Venditti, Adriano

    2014-04-01

    We retrospectively evaluated, in a logistic-regression-model, the role of proven/probable invasive fungal diseases (PP-IFD), occurring during first induction chemotherapy, on the achievement of complete remission (CR) and overall survival (OS) in 198 acute myeloid leukemia (AML) patients. A PP-IFD was documented in 34 (17.2%) patients. Younger age, good performance status at AML diagnosis and no development of a PP-IFD (OR 4.09, 95% CI 1.71-9.81, p<0.0001) were independent factors associated to CR achievement. Younger age, good performance status, favorable genetic risk and no development of PP-IFD (HR 1.86, 95% CI 1.20-2.88, p=0.005) were independent factors associated to OS at 3 years.

  7. Risk Factors of Anastomotic Leakage and Long-Term Survival After Colorectal Surgery

    PubMed Central

    Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

    2016-01-01

    Abstract Anastomotic leakage (AL) is one of the most serious complications of colorectal surgery. It can affect long-term oncologic outcomes, but the impact on long-term survival remains uncertain. The aim of this study is to evaluate the operative characteristics of leakage and no leakage groups and to analyze long-term oncologic outcomes. We prospectively enrolled 10,477 patients from 2000 to 2011 and retrospectively reviewed the data. Male sex (odds ratio [OR], 3.90; P < 0.001), intraoperative transfusion (OR, 2.31; P = 0.042), and operative time (OR, 1.73; P = 0.032) were independent risk factors of AL in the colon. In the rectum, male sex (OR, 2.37; P < 0.001), neoadjuvant chemoradiotherapy (OR, 2.26; P < 0.001), and regional lymph node metastasis (OR, 1.43; P = 0.012) were independent risk factors of AL, and diverting stoma (OR, 0.24; P < 0.001) was associated with a deceased risk of AL. AL in the rectum without a diverting stoma was associated with disease-free survival (DFS, OR, 1.47; P = 0.037). Colonic leakage was not associated with 5-year DFS (leakage group vs nonleakage group, 72.4% vs 80.9%, P = 0.084); however, in patients undergoing rectal resection, there was a significant difference in 5-year DFS (67.0% vs 76.6%, P = 0.005, respectively). AL in the rectum is associated with worse long-term DFS and overall survival. A diverting stoma was shown to protect against this effect and was associated with long-term survival in rectal surgery. Therefore, creating a diverting stoma should be considered in high-risk patients undergoing rectal surgery. PMID:26937928

  8. Risk Factors of Anastomotic Leakage and Long-Term Survival After Colorectal Surgery.

    PubMed

    Park, Jong Seob; Huh, Jung Wook; Park, Yoon Ah; Cho, Yong Beom; Yun, Seong Hyeon; Kim, Hee Cheol; Lee, Woo Yong

    2016-02-01

    Anastomotic leakage (AL) is one of the most serious complications of colorectal surgery. It can affect long-term oncologic outcomes, but the impact on long-term survival remains uncertain. The aim of this study is to evaluate the operative characteristics of leakage and no leakage groups and to analyze long-term oncologic outcomes.We prospectively enrolled 10,477 patients from 2000 to 2011 and retrospectively reviewed the data.Male sex (odds ratio [OR], 3.90; P < 0.001), intraoperative transfusion (OR, 2.31; P = 0.042), and operative time (OR, 1.73; P = 0.032) were independent risk factors of AL in the colon. In the rectum, male sex (OR, 2.37; P < 0.001), neoadjuvant chemoradiotherapy (OR, 2.26; P < 0.001), and regional lymph node metastasis (OR, 1.43; P = 0.012) were independent risk factors of AL, and diverting stoma (OR, 0.24; P < 0.001) was associated with a deceased risk of AL. AL in the rectum without a diverting stoma was associated with disease-free survival (DFS, OR, 1.47; P = 0.037). Colonic leakage was not associated with 5-year DFS (leakage group vs nonleakage group, 72.4% vs 80.9%, P = 0.084); however, in patients undergoing rectal resection, there was a significant difference in 5-year DFS (67.0% vs 76.6%, P = 0.005, respectively).AL in the rectum is associated with worse long-term DFS and overall survival. A diverting stoma was shown to protect against this effect and was associated with long-term survival in rectal surgery. Therefore, creating a diverting stoma should be considered in high-risk patients undergoing rectal surgery. PMID:26937928

  9. Long-term survival of individuals with myelomeningocele.

    PubMed

    Davis, Beth Ellen; Daley, Colleen M; Shurtleff, David B; Duguay, Sharon; Seidel, Kristy; Loeser, John D; Ellenbogan, Richard G

    2005-01-01

    The objectives of this study were to extend survival analysis into adulthood for patients with myelomeningocele (MM) and to compare survival curves for patients born with varying defect severity before and after 1975. We have reviewed existing data for 904 patients with MM seen in a large multidisciplinary children's clinic over 43 years. Before 1975, a major contributor to decreased survival is death during infancy. The presence of cerebral spinal fluid shunting is a major contributor to increased survival. After 1975, survival to adolescence is similar regardless of shunt status (p = 0.17). For all patients alive at age 16, a significant decrease in survival probability after age 34 years was found for individuals with shunted hydrocephalus compared to those without a shunt (p = 0.03). Although childhood survival for individuals born after 1975 is not related to shunt status, adults with MM and shunted hydrocephalus may be at risk for decreased longevity.

  10. Long-term and preventative treatment for seasonal affective disorder.

    PubMed

    Westrin, Asa; Lam, Raymond W

    2007-01-01

    Recurrent major depressive disorder with regular seasonal patterns, commonly known as seasonal affective disorder (SAD), has evoked substantial research in the last two decades. It is now recognised that SAD is a common condition with prevalence rates between 0.4% and 2.9% of the general population, and that patients with SAD experience significant morbidity and impairment in psychosocial function. There is good evidence that bright light therapy and antidepressant medications are effective for the short-term treatment of SAD; however, given that SAD is characterised by recurrent major depressive episodes, long-term and maintenance treatment must be considered. Unfortunately, there are few studies of longer term (>8 weeks) and maintenance (preventative) treatments for SAD. The weight of evidence suggests that light therapy usually needs to be continued daily throughout the winter season because of rapid relapse when light is stopped too early in the treatment period. However, some studies support the use of antidepressants to continue the response from a brief (1-2 weeks) course of light therapy early in the depressive episode, as soon as the first symptoms emerge in autumn. Only small studies have examined preventative treatment (before onset of symptoms) with light therapy, all of which have methodological limitations. The best evidence for preventative treatment in SAD comes from antidepressant studies. Three large, randomised, placebo-controlled studies have shown that preventative treatment with bupropion XL reduces the recurrence rate of depressive episodes in patients with SAD. Given the limitations in the evidence base and the inconsistent recurrence rate of winter depressive episodes, clinical recommendations for long-term and preventative treatment must individualise treatment choices and weigh potential benefits against possible adverse effects. PMID:17927295

  11. Factors Affecting Long-Term Abstinence from Substances Use

    ERIC Educational Resources Information Center

    Elsheikh, Salah Elgaily

    2008-01-01

    Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

  12. Impact of Combination Epidural and General Anesthesia on the Long-Term Survival of Gastric Cancer Patients: A Retrospective Study

    PubMed Central

    Wang, Jiangling; Guo, Wenjing; Wu, Qicheng; Zhang, Runze; Fang, Jun

    2016-01-01

    Background Whether regional anesthesia is associated with tumor-free and long-term survival is controversial. Here, we focused on whether epidural anesthesia affects the long-term survival of gastric cancer patients after surgery. Material/Methods We obtained the records of 273 patients undergoing gastric cancer surgery between August 2006 and December 2010. All patients received elective surgery, and the end-point was death. The general anesthesia group comprised 116 patients and the epidural-supplemented group comprised 157 patients. The results were analyzed using a multivariable model to determine the relationship between epidural use and long-term survival. Results No obvious association was detected between epidural use and long-term survival according to the Cox model (P=0.522); the adjusted estimated hazard ratio was 0.919 (95% CI 0.71–1.19). However, according to Kaplan-Meier analysis, epidural anesthesia was associated with long-term survival among younger patients (age up to 64) (p=0.042, log-rank) (but not among older patients (p=0.203, log-rank). A lower American Society of Anesthesiologists (ASA) class and less chemoradiotherapy exposure were also associated with a longer survival. However, advanced tumor stage still has a significant negative impact on survival. Conclusions No obvious difference was detected between the 2 anesthesia groups, but younger patients may benefit from epidural anesthesia. PMID:27386842

  13. Long-term survival of bacterial spores in space.

    PubMed

    Horneck, G; Bucker, H; Reitz, G

    1994-10-01

    On board of the NASA Long Duration Exposure Facility (LDEF), spores of Bacillus subtilis in monolayers (10(6)/sample) or multilayers (10(8)/sample) were exposed to the space environment for nearly six years and their survival was analyzed after retrieval. The response to space parameters, such as vacuum (10(-6) Pa), solar electromagnetic radiation up to the highly energetic vacuum-ultraviolet range (10(9) J/m2) and/or cosmic radiation (4.8 Gy), was studied and compared to the results of a simultaneously running ground control experiment. If shielded against solar ultraviolet (UV)-radiation, up to 80 % of spores in multilayers survive in space. Solar UV-radiation, being the most deleterious parameter of space, reduces survival by 4 orders of magnitude or more. However, up to 10(4) viable spores were still recovered, even in completely unprotected samples. Substances, such as glucose or buffer salts serve as chemical protectants. With this 6 year study in space, experimental data are provided to the discussion on the likelihood of "Panspermia".

  14. Cerebral metastases from Merkel cell carcinoma: long-term survival

    PubMed Central

    Honeybul, S.

    2016-01-01

    Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumour that is locally aggressive. In most cases the primary treatment is local surgical excision; however, there is a high incidence recurrence both local and distant. Cerebral metastases from Merkel cell carcinoma are extremely uncommon with only 12 cases published in the literature. This case is particularly unusual in that, not only was no established primary lesion identified, but also the patient has survived for 10 years following initial diagnosis and for 9 years following excision of a single brain metastasis. PMID:27765804

  15. [Russell's syndrome: a case of long-term survival and review of the literature].

    PubMed

    Amoroso, L; Cacchione, A; Valentini, D; Foco, M; Gonfiantini, M; Cappelli, C; Ceccarelli, G

    2004-06-01

    We report the case of a two years old, normally eating child, affected by organic macies and severe dystrophy. After the negative response of blood and laboratory examinations let us exclude a malabsorption syndrome, only the performance of neuro-radiologic exams showed evidence of a subthalamic tumor as the cause of a "Diencephalic syndrome". Diencephalic syndrome or Russell's syndrome is a diencephalic tumor induced disease, which sets in the first time of life. The disease clinical markers are a severe emaciation with appetite preservation and absence or very scarce evidence of any telltale neurological sign. The tumoral histo-pathology most frequently shows a low grade of malignancy astrocytoma, whose eradication is very often difficult because of particular anatomic site. Treatment of choice includes an excisional biopsy with chemotherapy and radiotherapy. We report a clinical case of long-term survival and review of the literature.

  16. Clinical review: Beyond immediate survival from resuscitation – long-term outcome considerations after cardiac arrest

    PubMed Central

    Arawwawala, Dilshan; Brett, Stephen J

    2007-01-01

    A substantial body of literature concerning resuscitation from cardiac arrest now exists. However, not surprisingly, the greater part concerns the cardiac arrest event itself and optimising survival and outcome at relatively proximal time points. The aim of this review is to present the evidence base for interventions and therapeutic strategies that might be offered to patients surviving the immediate aftermath of a cardiac arrest, excluding components of resuscitation itself that may lead to benefits in long-term survival. In addition, this paper reviews the data on long-term impact, physical and neuropsychological, on patients and their families, revealing a burden that is often underestimated and underappreciated. As greater numbers of patients survive cardiac arrest, outcome measures more sophisticated than simple survival are required. PMID:18177512

  17. Forced vital capacity predicts long-term survival for curative-resected NSCLC.

    PubMed

    Guo, Xi; Cao, Hongxin; Xu, Jun; Yu, Jianyu; Zheng, Chunlong; Meng, Long; Du, Jiajun

    2014-09-01

    We conducted a retrospective study in patients with non-small cell lung cancer (NSCLC) who underwent curative lung resection to seek for better lung function parameters associated with long-term survival after lung resection. From January 2006 to December 2008, 470 patients who underwent lung resection with a postoperative diagnosis of NSCLC were studied. Median survival time was 60 months. Patients with pulmonary function values <80 % of predicted were defined as lung function impairment. Patients with impaired vital capacity, maximal voluntary ventilation, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) or diffusion capacity for carbon monoxide (DLCO) had significant shorter overall survival time (P = 0.024; P = 0.026; P < 0.001; P = 0.027; P = 0.007). In univariate analysis, VC, FVC, FEV1 and DLCO were found to have significant effect on overall survival. In multivariate analysis, FVC (HR, 2.029; 95 % CI 1.126-3.659; P = 0.019) was found to be an independent prognostic predictor of long-term overall survival. For cancer-specific survival, FVC (HR 2.404; 95 % CI 1.300-4.445; P = 0.005) was also found to be an independent prognostic predictor in multivariable analysis. Preoperative FVC, rather than FEV1 or DLCO, is an independent prognostic predictor for long-term survival. FVC is not only an indicator of lung function but also of great value for surgeons to predict survival after lung resection.

  18. How Do Observer's Responses Affect Visual Long-Term Memory?

    ERIC Educational Resources Information Center

    Makovski, Tal; Jiang, Yuhong V.; Swallow, Khena M.

    2013-01-01

    How does responding to an object affect explicit memory for visual information? The close theoretical relationship between action and perception suggests that items that require a response should be better remembered than items that require no response. However, conclusive evidence for this claim is lacking, as semantic coherence, category size,…

  19. Estimating Long-Term Survival Temperatures at the Assemblage Level in the Marine Environment: Towards Macrophysiology

    PubMed Central

    Richard, Joëlle; Morley, Simon Anthony; Thorne, Michael A. S.; Peck, Lloyd Samuel

    2012-01-01

    Defining ecologically relevant upper temperature limits of species is important in the context of environmental change. The approach used in the present paper estimates the relationship between rates of temperature change and upper temperature limits for survival in order to evaluate the maximum long-term survival temperature (Ts). This new approach integrates both the exposure time and the exposure temperature in the evaluation of temperature limits. Using data previously published for different temperate and Antarctic marine environments, we calculated Ts in each environment, which allowed us to calculate a new index: the Warming Allowance (WA). This index is defined as the maximum environmental temperature increase which an ectotherm in a given environment can tolerate, possibly with a decrease in performance but without endangering survival over seasonal or lifetime time-scales. It is calculated as the difference between maximum long-term survival temperature (Ts) and mean maximum habitat temperature. It provides a measure of how close a species, assemblage or fauna are living to their temperature limits for long-term survival and hence their vulnerability to environmental warming. In contrast to data for terrestrial environments showing that warming tolerance increases with latitude, results here for marine environments show a less clear pattern as the smallest WA value was for the Peru upwelling system. The method applied here, relating upper temperature limits to rate of experimental warming, has potential for wide application in the identification of faunas with little capacity to survive environmental warming. PMID:22509340

  20. Short communication: Long-term survival of flag eartags on an Israeli dairy farm.

    PubMed

    Seroussi, E; Yakobson, E; Garazi, S; Oved, Z; Halachmi, I

    2011-11-01

    Two-plated self-piercing eartags were first developed in the 19th century, but information on their retention rates is scarce. A method is presented that facilitates estimation of eartag retention rate by using a random sample of cows that initially had 2 tags (1 on each ear) placed for identification and at least 1 of which survived. Striving to adopt the European Union standard for cattle ear tagging, the Israeli veterinary service conducted a field test to evaluate the performance of plastic eartags under the conditions of a typical Israeli dairy farm. The initial sample (n=900 cows) was tagged on a single farm. Retention rates were estimated based on the ratio between the observed numbers of cows with 1 or 2 eartags in the surviving group (n=97 cows). Based on this long-term (>3 yr) field test, the highest yearly retention of flag eartags (0.89±0.03) was lower than expected (0.98). Tag design and on-farm management were key factors affecting tag retention. A better design of the feedline yoke system in the feeding area, avoiding slits that can entangle the eartags, would help increase tag retention.

  1. Expected long-term survival of patients diagnosed with multiple myeloma in 2006-2010.

    PubMed

    Brenner, Hermann; Gondos, Adam; Pulte, Dianne

    2009-02-01

    New therapeutic options have led to substantial increases in survival expectations of younger patients with multiple myeloma in recent years. In the past, the impact of these innovations on long-term survival has been disclosed only with substantial delay. We aimed to derive up-to-date estimates of long-term survival expectations of concurrently diagnosed multiple myeloma patients. Using data from the 1973-2005 database of the Surveillance, Epidemiology, and End Results (SEER) Program, we employed a novel model-based projection method to project 5-and 10-year relative survival expectations of multiple myeloma patients in the United States diagnosed in 2006-2010. Preliminary empirical evaluation of the method using historical data indicated good performance. Projected 5-year relative survival for patients diagnosed in 2006-2010 below 45 years of age is 68.0%, which exceeds the most up-to-date estimates obtained from traditional cohort and period analysis by 15.5 and 7.0 percent units respectively. Ten-year relative survival projection for patients in this age group is 55.3%, exceeding the most up-to-date estimates from traditional cohort and period analysis by 19.7 and 7.4 percent units respectively. By contrast, survival projections remain much lower and hardly exceed estimates from traditional survival analysis for older patients. Patients diagnosed with multiple myeloma in 2006-2010, especially those diagnosed at younger ages, are expected to have much higher long-term survival perspectives than suggested by previously available survival statistics. PMID:19144659

  2. Desiccation as a Long-Term Survival Mechanism for the Archaeon Methanosarcina barkeri

    PubMed Central

    Anderson, Kimberly L.; Apolinario, Ethel E.

    2012-01-01

    Viable methanogens have been detected in dry, aerobic environments such as dry reservoir sediment, dry rice paddies and aerobic desert soils, which suggests that methanogens have mechanisms for long-term survival in a desiccated state. In this study, we quantified the survival rates of the methanogenic archaeon Methanosarcina barkeri after desiccation under conditions equivalent to the driest environments on Earth and subsequent exposure to different stress factors. There was no significant loss of viability after desiccation for 28 days for cells grown with either hydrogen or the methylotrophic substrates, but recovery was affected by growth phase, with cells desiccated during the stationary phase of growth having a higher rate of recovery after desiccation. Synthesis of methanosarcinal extracellular polysaccharide (EPS) significantly increased the viability of desiccated cells under both anaerobic and aerobic conditions compared with that of non-EPS-synthesizing cells. Desiccated M. barkeri exposed to air at room temperature did not lose significant viability after 28 days, and exposure of M. barkeri to air after desiccation appeared to improve the recovery of viable cells compared with that of desiccated cells that were never exposed to air. Desiccated M. barkeri was more resistant to higher temperatures, and although resistance to oxidative conditions such as ozone and ionizing radiation was not as robust as in other desiccation-resistant microorganisms, the protection mechanisms are likely adequate to maintain cell viability during periodic exposure events. The results of this study demonstrate that after desiccation M. barkeri has the innate capability to survive extended periods of exposure to air and lethal temperatures. PMID:22194299

  3. Long-term survival expectations of cancer patients in Europe in 2000-2002.

    PubMed

    Brenner, Hermann; Francisci, Silvia; de Angelis, Roberta; Marcos-Gragera, Rafael; Verdecchia, Arduino; Gatta, Gemma; Allemani, Claudia; Ciccolallo, Laura; Coleman, Michel; Sant, Milena

    2009-04-01

    Period analysis has been shown to provide more up-to-date estimates of long-term cancer survival rates than traditional cohort-based analysis. Here, we provide detailed period estimates of 5- and 10-year relative survival by cancer site, country, sex and age for calendar years 2000-2002. In addition, pan-European estimates of 1-, 5- and 10-year relative survival are provided. Overall, survival estimates were mostly higher than previously available cohort estimates. For most cancer sites, survival in countries from Northern Europe, Central Europe and Southern Europe was substantially higher than in the United Kingdom and Ireland and in countries from Eastern Europe. Furthermore, relative survival was also better in female than in male patients and decreased with age for most cancer sites.

  4. Disturbance frequency and vertical distribution of seeds affect long-term population dynamics: a mechanistic seed bank model.

    PubMed

    Eager, Eric Alan; Haridas, Chirakkal V; Pilson, Diana; Rebarber, Richard; Tenhumberg, Brigitte

    2013-08-01

    Seed banks are critically important for disturbance specialist plants because seeds of these species germinate only in disturbed soil. Disturbance and seed depth affect the survival and germination probability of seeds in the seed bank, which in turn affect population dynamics. We develop a density-dependent stochastic integral projection model to evaluate the effect of stochastic soil disturbances on plant population dynamics with an emphasis on mimicking how disturbances vertically redistribute seeds within the seed bank. We perform a simulation analysis of the effect of the frequency and mean depth of disturbances on the population's quasi-extinction probability, as well as the long-term mean and variance of the total density of seeds in the seed bank. We show that increasing the frequency of disturbances increases the long-term viability of the population, but the relationship between the mean depth of disturbance and the long-term viability of the population are not necessarily monotonic for all parameter combinations. Specifically, an increase in the probability of disturbance increases the long-term viability of the total seed bank population. However, if the probability of disturbance is too low, a shallower mean depth of disturbance can increase long-term viability, a relationship that switches as the probability of disturbance increases. However, a shallow disturbance depth is beneficial only in scenarios with low survival in the seed bank.

  5. Long-term survival from gastrocolic fistula secondary to adenocarcinoma of the transverse colon

    PubMed Central

    Forshaw, Matthew J; Dastur, Jamasp K; Murali, Kothandaraman; Parker, Michael C

    2005-01-01

    Background Gastrocolic fistula is a rare presentation of both benign and malignant diseases of the gastrointestinal tract. Malignant gastrocolic fistula is most commonly associated with adenocarcinoma of the transverse colon in the Western World. Despite radical approaches to treatment, long-term survival is rarely documented. Case presentation We report a case of a 24-year-old woman who presented with the classic triad of symptoms associated with gastrocolic fistula. Radical en-bloc surgery and adjuvant chemotherapy were performed. She is still alive ten years after treatment. Conclusions Gastrocolic fistula is an uncommon presentation of adenocarcinoma of the transverse colon. Radical en-bloc surgery with adjuvant chemotherapy may occasionally produce long-term survival. PMID:15705194

  6. Comparison of Long-term Survival of Implants and Endodontically Treated Teeth

    PubMed Central

    Setzer, F.C.; Kim, S.

    2014-01-01

    The outcomes of both dental implants and endodontically treated teeth have been extensively studied. However, there is still a great controversy over when to keep a natural tooth and when to extract it for a dental implant. This article reviews the benefits and disadvantages of both treatment options and discusses success vs. survival outcomes, as well as the impact of technical advances for modern endodontics and endodontic microsurgery on the long-term prognosis of tooth retention. PMID:24065635

  7. Long-Term Survival of Pathogenic and Sanitation Indicator Bacteria in Experimental Biowaste Composts

    PubMed Central

    Lemunier, Mélanie; Francou, Cédric; Rousseaux, Sandrine; Houot, Sabine; Dantigny, Philippe; Piveteau, Pascal; Guzzo, Jean

    2005-01-01

    For economic, agricultural, and environmental reasons, composting is frequently used for organic waste recycling. One approach to limiting the potential risk from bacterial food-borne illnesses is to ensure that soil amendments and organic fertilizers are disinfected. However, more knowledge concerning the microbiological safety of composted substrates other than sludge and manure is necessary. Experimental in-vessel biowaste composts were used to study the survival of seeded Listeria monocytogenes, Salmonella enterica subsp. enterica serotype Enteritidis, and Escherichia coli. Four organic waste mixtures, containing various proportions of paper and cardboard, fruits and vegetables, and green waste, were composted in laboratory reactors with forced aeration. The physicochemical and microbiological parameters were monitored for 12 weeks during composting. The survival of bacteria over a 3-month period at 25°C was assessed with samples collected after different experimental composting times. Strain survival was also monitored in mature sterilized composts. Nonsterile composts did not support pathogen growth, but survival of seeded pathogens was observed. Salmonella serovar Enteritidis survived in all composts, and longer survival (3 months) was observed in mature composts (8 and 12 weeks of composting). Mature biowaste composts may support long-term survival of Salmonella serovar Enteritidis during storage at room temperature. E. coli and L. monocytogenes survival was observed only in 4-week-old composts and never in older composts. Proper composting may prevent long-term survival of E. coli and L. monocytogenes. These results suggest that like composted sewage sludge or manure, domestic waste composts may support pathogen survival. Survival was not related to the physicochemical characteristics of the composts. PMID:16204488

  8. Characterization of Ancient DNA Supports Long-Term Survival of Haloarchaea

    PubMed Central

    Lowenstein, Tim K.; Timofeeff, Michael N.; Schubert, Brian A.; Lum, J. Koji

    2014-01-01

    Abstract Bacteria and archaea isolated from crystals of halite 104 to 108 years old suggest long-term survival of halophilic microorganisms, but the results are controversial. Independent verification of the authenticity of reputed living prokaryotes in ancient salt is required because of the high potential for environmental and laboratory contamination. Low success rates of prokaryote cultivation from ancient halite, however, hamper direct replication experiments. In such cases, culture-independent approaches that use the polymerase chain reaction (PCR) and sequencing of 16S ribosomal DNA are a robust alternative. Here, we use amplification, cloning, and sequencing of 16S ribosomal DNA to investigate the authenticity of halophilic archaea cultured from subsurface halite, Death Valley, California, 22,000 to 34,000 years old. We recovered 16S ribosomal DNA sequences that are identical, or nearly so (>99%), to two strains, Natronomonas DV462A and Halorubrum DV427, which were previously isolated from the same halite interval. These results provide the best independent support to date for the long-term survival of halophilic archaea in ancient halite. PCR-based approaches are sensitive to small amounts of DNA and could allow investigation of even older halites, 106 to 108 years old, from which microbial cultures have been reported. Such studies of microbial life in ancient salt are particularly important as we search for microbial signatures in similar deposits on Mars and elsewhere in the Solar System. Key Words: Ancient DNA—Halite—Haloarchaea—Long-term survival. Astrobiology 14, 553–560. PMID:24977469

  9. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    PubMed Central

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  10. Postcastration eventration in 18 horses: the prognostic indicators for long-term survival (1985-1995).

    PubMed Central

    Thomas, H L; Zaruby, J F; Smith, C L; Livesey, M A

    1998-01-01

    Castration of horses is considered a common and routine surgical procedure, but the potential for complications is high. By far the most serious of these is eventration. The objectives of this study were to determine the long-term survival of horses undergoing surgical treatment of indirect (1) inguinal eventration of the small intestine following castration, and to identify prognostic indicators for survival. The case records of 18 horses undergoing surgical treatment of postcastration eventration (PCE) between 1985 and 1995 were reviewed. Follow-up information was obtained by telephone interviews 2 to 13 y postoperatively. A Cox proportional hazard regression model was fitted to determine which clinical features were of significant influence to survival. Clinical features with a significant negative influence on survival were an inguinal surgical approach for correction, an increased length of prolapsed bowel, and performance of bowel resection and anastomosis. Significant postoperative complications developed in 89% of cases; 44% of cases in the "inguinal" surgical approach group developed peritonitis, compared with 10% in the "midline" approach group. Of all horses in this study, 72% were discharged from the hospital; however, only 40% of horses in the inguinal approach group were discharged. The long term survival rate (> 1 y) for all horses in this study was 44%, with a median survival time of 3-1/2 mo. PMID:9861501

  11. Listeria monocytogenes adapts to long-term stationary phase survival without compromising bacterial virulence.

    PubMed

    Bruno, Joseph C; Freitag, Nancy E

    2011-10-01

    Bacteria withstand starvation during long-term stationary phase through the acquisition of mutations that increase bacterial fitness. The evolution of the growth advantage in stationary phase (GASP) phenotype results in the ability of bacteria from an aged culture to outcompete bacteria from a younger culture when the two are mixed together. The GASP phenotype was first described for Escherichia coli, but has not been examined for an environmental bacterial pathogen, which must balance long-term survival strategies that promote fitness in the outside environment with those that promote fitness within the host. Listeria monocytogenes is an environmental bacterium that lives as a saprophyte in soil, but is capable of replicating within the cytosol of mammalian cells. Herein, we demonstrate the ability of L. monocytogenes to express GASP via the acquisition of mutations during long-term stationary growth. Listeria monocytogenes GASP occurred through mechanisms that were both dependent and independent of the stress-responsive alternative sigma factor SigB. Constitutive activation of the central virulence transcriptional regulator PrfA interfered with the development of GASP; however, L. monocytogenes GASP cultures retained full virulence in mice. These results indicate that L. monocytogenes can accrue mutations that optimize fitness during long-term stationary growth without negatively impacting virulence. PMID:22092717

  12. Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival

    PubMed Central

    Gordon, Stephen B.; Chaponda, Mas; Walsh, Amanda L.; Whitty, Christopher J.M.; Gordon, Melita A.; Machili, C. Edward; Gilks, Charles F.; Boeree, Martin J.; Kampondeni, Sam; Read, Robert C.; Molyneux, Malcolm E.

    2016-01-01

    Objective HIV-infected patients in Africa are vulnerable to severe recurrent infection with Streptococcus pneumoniae, but no effective preventive strategy has been developed. We set out to determine which factors influence in-hospital mortality and long-term survival of Malawians with invasive pneumococcal disease. Design, setting and patients Acute clinical features, inpatient mortality and long-term survival were described among consecutively admitted hospital patients with S. pneumoniae in the blood or cerebrospinal fluid. Factors associated with inpatient mortality were determined, and patients surviving to discharge were followed to determine their long-term outcome. Results A total of 217 patients with pneumococcal disease were studied over an 18-month period. Among these, 158 out of 167 consenting to testing (95%) were HIV positive. Inpatient mortality was 65% for pneumococcal meningitis (n = 64), 20% for pneumococcaemic pneumonia (n = 92), 26% for patients with pneumococcaemia without localizing signs (n = 43), and 76% in patients with probable meningitis (n = 17). Lowered consciousness level, hypotension, and age exceeding 55 years at presentation were associated with inpatient death, but not long-term outcome in survivors. Hospital survivors were followed for a median of 414 days; 39% died in the community during the study period. Outpatient death was associated with multilobar chest signs, oral candidiasis, and severe anaemia as an inpatient. Conclusion Most patients with pneumococcal disease in Malawi have HIV co-infection. They have severe disease with a high mortality rate. At discharge, all HIV-infected adults have a poor prognosis but patients with multilobar chest signs or anaemia are at particular risk. PMID:12131218

  13. Proliferation rate but not mismatch repair affects the long-term response of colon carcinoma cells to 5FU treatment.

    PubMed

    Choudhary, B; Hanski, M L; Zeitz, M; Hanski, C

    2012-07-01

    The role of mismatch repair (MMR) in the response of colon carcinoma cells to 5-fluorouracil (5FU) is not well understood. In most of the in vitro studies only short-term response was investigated. We focussed here on the influence of MMR status on the mechanism of the short- and long-term response to clinically relevant 5FU concentrations by using isogenic or semiisogenic cell line pairs expressing/nonexpressing the hMLH1 protein, an important component of the MMR system. We show that the lower survival of MMR-proficient than of MMR-deficient cells in the clonogenic survival assay is due to a more frequent early cell arrest and to subsequent senescence. By contrast, the long-term cell growth after treatment, which is also affected by long-term arrest and senescence, is independent from the MMR status. The overall effect on the long-term cell growth is a cumulative result of cell proliferation rate-dependent growth inhibition, apoptosis and necrotic cell death. The main long-term cytotoxic effect of 5FU is the inhibition of growth while apoptosis and the necrotic cell death are minor contributions.

  14. Clinical predictors of long-term survival in HER2-positive metastatic breast cancer.

    PubMed

    Murthy, Pooja; Kidwell, Kelley M; Schott, Anne F; Merajver, Sofia D; Griggs, Jennifer J; Smerage, Jeffrey D; Van Poznak, Catherine H; Wicha, Max S; Hayes, Daniel F; Henry, N Lynn

    2016-02-01

    Prior to availability of anti-HER2 therapies, HER2-positive metastatic breast cancer (MBC) was associated with a poor prognosis. Prospective randomized trials have demonstrated survival benefit from anti-HER2 treatments. Anecdotal observations have suggested that a small but meaningful fraction of patients with HER2-positive MBC may be "exceptional responders" with long survival. We hypothesized that demographic and/or clinicopathologic characteristics can be identified to distinguish short-term from long-term survivors. A retrospective, single-institution review of 168 patients with HER2-positive MBC who received treatment with anti-HER2 therapy in the metastatic setting was performed. Cox proportional hazards analysis was used to assess factors associated with long-term survival. Median overall survival from the time of breast cancer recurrence was 3.9 years (95 % CI 3.4-5.2). From the time of diagnosis of MBC, 56 (33 %) survived for 5 or more years and 12 (7 %) survived more than 10 years. Of the 66 patients diagnosed with central nervous system metastases, 9 (14 %) survived more than 5 years following that diagnosis. Younger age at diagnosis, lower stage, hormone receptor positive status, and only having one organ involved at diagnosis were associated with longer survival. Four patients discontinued anti-HER2 therapy and are without evidence of progression of disease after a median 7.4 years (0.2-12.0) since stopping therapy. In a cohort of patients with HER2-positive MBC treated primarily with trastuzumab and lapatinib, 7 % of patients were "exceptional responders." Combining these clinical factors with molecular determinants of prolonged survival may provide insights for individualizing treatment selection. PMID:26875184

  15. Physiological predictors of long-term survival in juvenile Steller sea lions (Eumetopias jubatus)

    PubMed Central

    Shuert, C.; Mellish, J.; Horning, M.

    2015-01-01

    This study builds on a continued effort to document potential long-term research impacts on the individual, as well as to identify potential markers of survival for use in a field framework. The Transient Juvenile Steller sea lion (TJ) project was developed as a novel framework to gain access to wild individuals. We used three analyses to evaluate and predict long-term survival in temporarily captive sea lions (n = 45) through Cormack–Jolly–Seber open population modelling techniques. The first analysis investigated survival in relation to the observed responses to handling stress through changes in six principal blood parameters over the duration of captivity. The second analysis evaluated survival compared with body condition and mass at entry and exit from captivity. Finally, the third analysis sought to evaluate the efficacy of single-point sampling to project similar survival trends for use in field sampling operations. Results from a priori models ranked through Akaike information criterion model selection methods indicated that mass gains (4.2 ± 12%) over captivity and increases in leucocytes (WBC, 1.01 ± 3.54 × 103/mm3) resulted in a higher average survival rate (>3 years). Minor support was identified for the single-point measures of exit mass and entry WBC. A higher exit mass predicted a higher survival rate, whereas a higher WBC predicted a lower survival rate. While changes in mass and WBC appear to be the best predictors of survival when measured as a change over time, single-point sampling may still be an effective way to improve estimates of population health. PMID:27293728

  16. Physiological predictors of long-term survival in juvenile Steller sea lions (Eumetopias jubatus).

    PubMed

    Shuert, C; Mellish, J; Horning, M

    2015-01-01

    This study builds on a continued effort to document potential long-term research impacts on the individual, as well as to identify potential markers of survival for use in a field framework. The Transient Juvenile Steller sea lion (TJ) project was developed as a novel framework to gain access to wild individuals. We used three analyses to evaluate and predict long-term survival in temporarily captive sea lions (n = 45) through Cormack-Jolly-Seber open population modelling techniques. The first analysis investigated survival in relation to the observed responses to handling stress through changes in six principal blood parameters over the duration of captivity. The second analysis evaluated survival compared with body condition and mass at entry and exit from captivity. Finally, the third analysis sought to evaluate the efficacy of single-point sampling to project similar survival trends for use in field sampling operations. Results from a priori models ranked through Akaike information criterion model selection methods indicated that mass gains (4.2 ± 12%) over captivity and increases in leucocytes (WBC, 1.01 ± 3.54 × 10(3)/mm(3)) resulted in a higher average survival rate (>3 years). Minor support was identified for the single-point measures of exit mass and entry WBC. A higher exit mass predicted a higher survival rate, whereas a higher WBC predicted a lower survival rate. While changes in mass and WBC appear to be the best predictors of survival when measured as a change over time, single-point sampling may still be an effective way to improve estimates of population health.

  17. Conditional long-term survival following minimally invasive robotic mitral valve repair: a health services perspective

    PubMed Central

    Griffin, William F.; Gudimella, Preeti; O’Neal, Wesley T.; Davies, Stephen W.; Crane, Patricia B.; Anderson, Ethan J.; Kindell, Linda C.; Landrine, Hope; O’Neal, Jason B.; Alwair, Hazaim; Kypson, Alan P.; Nifong, Wiley L.; Chitwood, W. Randolph

    2015-01-01

    Background Conditional survival is defined as the probability of surviving an additional number of years beyond that already survived. The aim of this study was to compute conditional survival in patients who received a robotically assisted, minimally invasive mitral valve repair procedure (RMVP). Methods Patients who received RMVP with annuloplasty band from May 2000 through April 2011 were included. A 5- and 10-year conditional survival model was computed using a multivariable product-limit method. Results Non-smoking men (≤65 years) who presented in sinus rhythm had a 96% probability of surviving at least 10 years if they survived their first year following surgery. In contrast, recent female smokers (>65 years) with preoperative atrial fibrillation only had an 11% probability of surviving beyond 10 years if alive after one year post-surgery. Conclusions In the context of an increasingly managed healthcare environment, conditional survival provides useful information for patients needing to make important treatment decisions, physicians seeking to select patients most likely to benefit long-term following RMVP, and hospital administrators needing to comparatively assess the life-course economic value of high-tech surgical procedures. PMID:26539348

  18. Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

    PubMed Central

    Chapman, M. A.; Buckley, D.; Henson, D. B.; Armitage, N. C.

    1998-01-01

    Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value. PMID:9823977

  19. Serotonin prolongs survival of encapsulated pond snail embryos exposed to long-term anoxia.

    PubMed

    Shartau, Ryan B; Tam, Rose; Patrick, Spencer; Goldberg, Jeffrey I

    2010-05-01

    Embryos of the pond snail, Helisoma trivolvis, develop bilateral serotonergic neurons that innervate ciliary bands and stimulate cilia-driven rotation. This behaviour is postulated to increase oxygen availability during hypoxia by mixing the capsular fluid. We hypothesised that the stimulation of ciliary-driven rotation by serotonin (5-HT) enhances the survival of embryos during prolonged hypoxia. Embryo rotation and survival were monitored in different levels of oxygen for 24-48 h while in the presence or absence of 5-HT (100 micromol l(-1)) or a 5-HT antagonist (50 micromol l(-1)). Long-term hypoxia caused delayed embryonic development that appeared morphologically normal. Hypoxia also induced a transient increase in rotation rate in embryos exposed to artificial pond water (APW) or 5-HT that lasted around 3 h. 5-HT-treated embryos had an elevated rotation rate over embryos in APW throughout the long-term exposure to hypoxia. Long-term anoxia also induced a transient increase in rotation rate in embryos exposed to APW or 5-HT. Rotation ceased in embryos exposed to APW by 13 h but persisted in 5-HT-treated embryos for up to 40 h. Fifty percent mortality was reached at 9 h of anoxia in embryos in APW and at 24 h in 5-HT-treated embryos. The 5-HT antagonist mianserin partially inhibited the 5-HT enhancement of rotation but not the prolongation of survival in anoxia. The ability of 5-HT to prolong survival in anoxia reveals a 5-HT-activated metabolic pathway that liberates an alternative energy source.

  20. Long-term survival after renal transplantation: the influence of pretransplant bilateral nephrectomy.

    PubMed

    Douglas, James F; Craig, W J Colin

    2010-01-01

    The long-term survival of first successful renal transplants, along with overall patient survival, was studied retrospectively in 309 recipients at Belfast City Hospital between 1968 and 1986, of whom 155 had undergone prior bilateral nephrectomy (BN) and 154 had not (non-BN). The groups were comparable as regards mean age, gender, primary diagnoses, clinical status, pre-existing hypertension and pre-transplant dialysis and transfusion. There were 34 organs (BN 14, non-BN 20) from living related donors. Donor ages were comparable, as were histocompatibility findings. Recipients more than 60, with diabetic nephropathy, or with other co-morbidity were excluded. All recipients took azathioprine and low-dose steroid as maintenance antirejection, fewer than 3% switching to cyclosporine or other drugs during first graft survival. Mean BN graft survival was 15.9 years (95% CI 14.1-17.7) compared to 12.9 for non-BN (95% CI 11.3-14.5; p < 0.01). Mean BN patient survival was 19.4 years (95% CI 17.6-21.2) and non-BN was 14.9 years (95% CI 13.2-16.6; p < 0.01). Cumulative BN graft survival was 76.8% at 5 years, 61.6% at 10 years, and 37.4% at 20 years, compared to 67.1%, 53.5% and 27.0% for non-BN (p < 0.01). Overall BN patient survival was 84.5% at 5 years, 74.2% at 10 years and 51.6% at 20 years, with non-BN equivalents of 72.3%, 49.0% and 24.5%, respectively (p < 0.01). Long-term BN survivors also had less hypertension than non-BN (22.8% v 54.8% at 20 years; p < 0.05) which may be relevant to their better survival. Overall (BN plus non-BN) median graft (14.4 years) and patient (17.6 years) survival are testimony to the continuing long-term success of the low-dose steroid regime followed in Belfast from 1968 to 1986.

  1. Prognostic factors for long term survival in patients with advanced non-small cell lung cancer

    PubMed Central

    Moumtzi, Despoina; Lampaki, Sofia; Porpodis, Konstantinos; Lagoudi, Kalliopi; Hohenforst-Schmidt, Wolfgang; Pataka, Athanasia; Tsiouda, Theodora; Zissimopoulos, Athanasios; Lazaridis, George; Karavasilis, Vasilis; Timotheadou, Helen; Barbetakis, Nikolaos; Pavlidis, Pavlos; Kontakiotis, Theodoros; Zarogoulidis, Konstantinos

    2016-01-01

    Background Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. Methods We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. Results The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally

  2. Stromal galectin-1 expression is associated with long-term survival in resectable pancreatic ductal adenocarcinoma

    PubMed Central

    Chen, Ru; Pan, Sheng; Ottenhof, NIki A.; de Wilde, Roeland F.; Wolfgang, Christopher L.; Lane, Zhaoli; Post, Jane; Bronner, Mary P.; Willmann, Jürgen K.; Maitra, Anirban; Brentnall, Teresa A.

    2012-01-01

    The overall 5 year survival rate for pancreatic ductal adenocarcinoma (i.e., PDAC) is a dismal 5%, although patients that have undergone surgical resection have a somewhat better survival rate of up to 20%. Very long-term survivors of PDAC (defined as patients with ≥ 10 year survival following apparently curative resection), on the other hand, are considerably less frequent. The molecular characteristics of very long-term survivors (VLTS) are poorly understood, but might provide novel insights into prognostication for this disease. In this study, a panel of five VLTS and stage-matched short-term survivors (STS, defined as disease-specific mortality within 14 months of resection) were identified, and quantitative proteomics was applied to comparatively profile tumor tissues from both cohorts. Differentially expressed proteins were identified in cancers from VLTS vs. STS patients. Specifically, the expression of galectin-1 was 2-fold lower in VLTS compared with STS tumors. Validation studies were performed by immunohistochemistry (IHC) in two additional cohorts of resected PDAC, including: 1) an independent cohort of VLTS and 2) a panel of sporadic PDAC with a considerable range of overall survival following surgery. Immunolabeling analysis confirmed that significantly lower expression of stromal galectin-1 was associated with VLTS (p = 0.02) and also correlated with longer survival in sporadic, surgically-treated PDAC cases (hazard ratio = 4.9, p = 0.002). The results from this study provide new insights to better understand the role of galectin-1 in PDAC survival, and might be useful for rendering prognostic information, and developing more effective therapeutic strategies aimed at improving survival. PMID:22785208

  3. Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival

    PubMed Central

    Shan, Jinlan; Zhang, Shizhen; Wang, Zhen; Fu, Yanbiao; Li, Ling; Wang, Xiaochen

    2016-01-01

    Abstract Background: Malignant phyllodes tumor (PT) is a rare fibro epithelial neoplasm of the breast, which is poor prognosis due to high risk of recurrence and distant metastasis. Methods: We report a case of malignant PT. It had recurred locally five times, and the sixth relapse was occurred 54 months after first diagnosis, presenting a huge pelvic mass (14 cm × 11 cm) by CT scan. Histopathological examination has demonstrated a metastatic phyllodes tumor. After postoperative chemotherapy treatment, a longer survival has been achieved, which is more than 72 months. Results: Our case report describes a breast PT with several local recurrences and a rare metastasis (pelvic cavity), but long-term overall survival was achieved after surgery and chemotherapy. Conclusion: We conclude that trustworthy prognosticators that identify patients with excessive potential of aggressive clinical course should be explored. Moreover, proper treatment could prolong overall survival of metastatic PT patients. PMID:27661051

  4. Human Engineered Heart Muscles Engraft and Survive Long-Term in a Rodent Myocardial Infarction Model

    PubMed Central

    Riegler, Johannes; Tiburcy, Malte; Ebert, Antje; Tzatzalos, Evangeline; Raaz, Uwe; Abilez, Oscar J.; Shen, Qi; Kooreman, Nigel G.; Neofytou, Evgenios; Chen, Vincent C.; Wang, Mouer; Meyer, Tim; Tsao, Philip S.; Connolly, Andrew J.; Couture, Larry A.; Gold, Joseph D.; Zimmermann, Wolfram H.; Wu, Joseph C.

    2015-01-01

    Rational Tissue engineering approaches may improve survival and functional benefits from human embryonic stem cell-derived cardiomyocte (ESC-CM) transplantation, thereby potentially preventing dilative remodelling and progression to heart failure. Objective Assessment of transport stability, long term survival, structural organisation, functional benefits, and teratoma risk of engineered heart muscle (EHM) in a chronic myocardial infarction (MI) model. Methods and Results We constructed EHMs from ESC-CMs and released them for transatlantic shipping following predefined quality control criteria. Two days of shipment did not lead to adverse effects on cell viability or contractile performance of EHMs (n=3, P=0.83, P=0.87). After ischemia/reperfusion (I/R) injury, EHMs were implanted onto immunocompromised rat hearts at 1 month to simulate chronic ischemia. Bioluminescence imaging (BLI) showed stable engraftment with no significant cell loss between week 2 and 12 (n=6, P=0.67), preserving up to 25% of the transplanted cells. Despite high engraftment rates and attenuated disease progression (change in ejection fraction for EHMs −6.7±1.4% vs control −10.9±1.5%, n>12, P=0.05), we observed no difference between EHMs containing viable or non-viable human cardiomyocytes in this chronic xenotransplantation model (n>12, P=0.41). Grafted cardiomyocytes showed enhanced sarcomere alignment and increased connexin 43 expression at 220 days after transplantation. No teratomas or tumors were found in any of the animals (n=14) used for long-term monitoring. Conclusions EHM transplantation led to high engraftment rates, long term survival, and progressive maturation of human cardiomyocytes. However, cell engraftment was not correlated with functional improvements in this chronic MI model. Most importantly, the safety of this approach was demonstrated by the lack of tumor or teratoma formation. PMID:26291556

  5. Long-term survival following intensive care: subgroup analysis and comparison with the general population.

    PubMed

    Wright, J C; Plenderleith, L; Ridley, S A

    2003-07-01

    This study aimed to compare the very long-term survival of critically ill patients with that of the general population, and examine the association among age, sex, admission diagnosis, APACHE II score and mortality. In a retrospective observational cohort study of prospectively gathered data, 2104 adult patients admitted to the intensive care unit (ICU) of a teaching hospital in Glasgow from 1985 to 1992, were followed until 1997. Vital status at five years was compared with that of an age- and sex-matched Scottish population. Five-year mortality for the ICU patients was 47.1%, 3.4 times higher than that of the general population. For those surviving intensive care the five-year mortality was 33.4%. Mortality was greater than that of the general population for four years following intensive care unit admission (95% confidence interval included 1.0 at four years). Multivariate analysis showed that risk factors for mortality in those admitted to ICU were age, APACHE II score on admission and diagnostic category. Mortality was higher for those admitted with haematological (87.5%) and neurological diseases (61.7%) and septic shock (62.9%). A risk score was produced: Risk Score = 10 (age hazard ratio + APACHE II hazard ratio + diagnosis hazard ratio). None of the patients with a risk score > 100 survived more than five years and for those who survived to five years the mean risk score was 57. Long-term survival following intensive care is not only related to age and severity of illness but also diagnostic category. The risk of mortality in survivors of critical illness matches that of the normal population after four years. Age, severity of illness and diagnosis can be combined to provide an estimate of five-year survival.

  6. Long-term tracking of microbial survivability and growth in a controlled environment

    NASA Astrophysics Data System (ADS)

    Sutandar, Andiyanto; Abdiel Foo, Jong Yong; Lim, Chu Sing; Hsu, Li-Yang

    2008-04-01

    The ecological and histological study of a microbial population in a given environment provides important information leading to its survivability and growth. Current standard laboratory practices adopt culture on a medium housed in an incubated environment. However, large numbers of cultures are usually required to investigate the effects of variations in parametric conditions on the microbes. This can result in a high use of resources such as consumables and man-hours. Automated systems that are able to replenish fresh nutrients and extract metabolic waste for long-term monitoring are also limited. In this study, a system capable of real-time monitoring of microbe survival and providing a suitable environment for their growth is presented. Housed within its structure is a customized chamber with temperature control, pH regulation, nutrient providence and metabolic waste removal functions. To assess the reliability of the system, five sets of Staphylococcus aureus ATCC 29213 strains are cultured and monitored continuously for 96 consecutive hours. The survival and growth of the pathogens are verified by standard laboratory techniques such as viable plate count after each successive 24 h of monitoring. The findings herein suggest that the system is able to monitor the microbial population with minimal human intervention and can be a valuable long-term tracking tool.

  7. Long-term Survival, Organ Function, and Malignancy after Hematopoietic Stem Cell Transplantation for Fanconi Anemia.

    PubMed

    Bonfim, Carmem; Ribeiro, Lisandro; Nichele, Samantha; Bitencourt, Marco; Loth, Gisele; Koliski, Adriana; Funke, Vaneuza A M; Pilonetto, Daniela V; Pereira, Noemi F; Flowers, Mary E D; Velleuer, Eunike; Dietrich, Ralf; Fasth, Anders; Torres-Pereira, Cassius C; Pedruzzi, Paola; Eapen, Mary; Pasquini, Ricardo

    2016-07-01

    We report on long-term survival in 157 patients with Fanconi anemia (FA) who survived 2 years or longer after their first transplantation with a median follow-up of 9 years. Marrow failure (80%) was the most common indication for transplantation. There were 20 deaths beyond 2 years after transplantation, with 12 of the deaths occurring beyond 5 years after transplantation. Donor chimerism was available for 149 patients: 112 (76%) reported > 95% chimerism, 27 (18%) reported 90% to 95% chimerism, and 8 (5%) reported 20% to 89% donor chimerism. Two patients have < 20% donor chimerism. The 10- and 15-year probabilities of survival were 90% and 79%, respectively. Results of multivariate analysis showed higher mortality risks for transplantations before 2003 (hazard ratio [HR], 7.87; P = .001), chronic graft-versus-host disease (GVHD) (HR, 3.80; P = .004) and squamous cell carcinoma after transplantation (HR, 38.17; P < .0001). The predominant cause of late mortality was squamous cell carcinoma, with an incidence of 8% and 14% at 10 and 15 years after transplantation, respectively, and was more likely to occur in those with chronic GVHD. Other causes of late mortality included chronic GVHD, infection, graft failure, other cancers, and hemorrhage. Although most patients are disease free and functional long term, our data support aggressive surveillance for long periods to identify those at risk for late mortality.

  8. Cardiopulmonary resuscitation of apparently stillborn infants: survival and long-term outcome.

    PubMed

    Jain, L; Ferre, C; Vidyasagar, D; Nath, S; Sheftel, D

    1991-05-01

    To determine the outcome of apparently stillborn infants who received cardiopulmonary resuscitation, we studied the short- and long-term outcome of 93 infants who had an Apgar score of 0 at 1 minute of age and were resuscitated at birth. Sixty-two (66.6%) responded and left the delivery room alive; 26 (42%) of the 62 infants died in the neonatal period and 36 infants were discharged home; of the 36 infants, three subsequently died during infancy. Of the 33 survivors, ten were lost to follow-up after discharge. Developmental assessment of 23 of 33 long-term survivors revealed normal outcome in 14 (61.7%), abnormal results in 6 (26%), and suspect status in 3 (13%). Fifty-eight infants had an Apgar score of 0 at greater than or equal to 10 minutes of age and all except one died; the surviving infant has an abnormal developmental outcome. We conclude that 39% of apparently stillborn infants who were resuscitated survived beyond the neonatal period and that 61% of the 23 survivors who were available for developmental follow-up had normal development at the time of last examination. Survival was unlikely if there was no response after 10 minutes of resuscitation.

  9. Extremely halophilic archaea from ancient salt sediments and their long term survival.

    NASA Astrophysics Data System (ADS)

    Stan-Lotter, Helga; Fendrihan, Sergiu; Dornmayr-Pfaffenhuemer, Marion

    Halophilic archaebacteria (haloarchaea) thrive in environments with salt concentrations approaching saturation, such as natural brines, marine solar salterns and alkaline salt lakes; they have also been isolated from rock salt of great geological age (195-250 million years) and some of those strains were described as novel species (1). The cells survived perhaps while being enclosed within small fluid inclusions in the halite. When simulating the embedding process of haloarchaea in laboratory-grown salt crystals, cells accumulated preferentially in fluid inclusions, as could be demonstrated by pre-staining with fluorescent dyes. The issue of extreme long term microbial survival in rock salt has considerable implications for the search for extraterrestrial life. Halite has been found in Martian meteorites, salts are present on the Martian surface and there is good evidence for a salty ocean on the Jovian moon Europa. Therefore the search for halophilic prokaryotic life in such environments appears plausible. The development of detection methods for subsurface haloarchaea, which might also be applicable to samples from future missions to space, is important and some examples such as fluorescence microscopy methods with novel dyes will be described. (1) Fendrihan, S., Legat, A., Gruber, C., Pfaffenhuemer, M., Weidler, G., Gerbl, F., Stan- Lotter, H. (2006) Extremely halophilic archaea and the issue of long term microbial survival. Reviews in Environmental Science and Bio/technology 5, 1569-1605.

  10. Molecular Predictors of Long-Term Survival in Glioblastoma Multiforme Patients

    PubMed Central

    Cowperthwaite, Matthew C.; Burnett, Mark G.; Shpak, Max

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive adult primary brain cancer, with <10% of patients surviving for more than 3 years. Demographic and clinical factors (e.g. age) and individual molecular biomarkers have been associated with prolonged survival in GBM patients. However, comprehensive systems-level analyses of molecular profiles associated with long-term survival (LTS) in GBM patients are still lacking. We present an integrative study of molecular data and clinical variables in these long-term survivors (LTSs, patients surviving >3 years) to identify biomarkers associated with prolonged survival, and to assess the possible similarity of molecular characteristics between LGG and LTS GBM. We analyzed the relationship between multivariable molecular data and LTS in GBM patients from the Cancer Genome Atlas (TCGA), including germline and somatic point mutation, gene expression, DNA methylation, copy number variation (CNV) and microRNA (miRNA) expression using logistic regression models. The molecular relationship between GBM LTS and LGG tumors was examined through cluster analysis. We identified 13, 94, 43, 29, and 1 significant predictors of LTS using Lasso logistic regression from the somatic point mutation, gene expression, DNA methylation, CNV, and miRNA expression data sets, respectively. Individually, DNA methylation provided the best prediction performance (AUC = 0.84). Combining multiple classes of molecular data into joint regression models did not improve prediction accuracy, but did identify additional genes that were not significantly predictive in individual models. PCA and clustering analyses showed that GBM LTS typically had gene expression profiles similar to non-LTS GBM. Furthermore, cluster analysis did not identify a close affinity between LTS GBM and LGG, nor did we find a significant association between LTS and secondary GBM. The absence of unique LTS profiles and the lack of similarity between LTS GBM and LGG, indicates

  11. Characterization of ancient DNA supports long-term survival of Haloarchaea.

    PubMed

    Sankaranarayanan, Krithivasan; Lowenstein, Tim K; Timofeeff, Michael N; Schubert, Brian A; Lum, J Koji

    2014-07-01

    Bacteria and archaea isolated from crystals of halite 10(4) to 10(8) years old suggest long-term survival of halophilic microorganisms, but the results are controversial. Independent verification of the authenticity of reputed living prokaryotes in ancient salt is required because of the high potential for environmental and laboratory contamination. Low success rates of prokaryote cultivation from ancient halite, however, hamper direct replication experiments. In such cases, culture-independent approaches that use the polymerase chain reaction (PCR) and sequencing of 16S ribosomal DNA are a robust alternative. Here, we use amplification, cloning, and sequencing of 16S ribosomal DNA to investigate the authenticity of halophilic archaea cultured from subsurface halite, Death Valley, California, 22,000 to 34,000 years old. We recovered 16S ribosomal DNA sequences that are identical, or nearly so (>99%), to two strains, Natronomonas DV462A and Halorubrum DV427, which were previously isolated from the same halite interval. These results provide the best independent support to date for the long-term survival of halophilic archaea in ancient halite. PCR-based approaches are sensitive to small amounts of DNA and could allow investigation of even older halites, 10(6) to 10(8) years old, from which microbial cultures have been reported. Such studies of microbial life in ancient salt are particularly important as we search for microbial signatures in similar deposits on Mars and elsewhere in the Solar System.

  12. Long-term survival of an urban fruit bat seropositive for Ebola and Lagos bat viruses.

    PubMed

    Hayman, David T S; Emmerich, Petra; Yu, Meng; Wang, Lin-Fa; Suu-Ire, Richard; Fooks, Anthony R; Cunningham, Andrew A; Wood, James L N

    2010-01-01

    Ebolaviruses (EBOV) (family Filoviridae) cause viral hemorrhagic fevers in humans and non-human primates when they spill over from their wildlife reservoir hosts with case fatality rates of up to 90%. Fruit bats may act as reservoirs of the Filoviridae. The migratory fruit bat, Eidolon helvum, is common across sub-Saharan Africa and lives in large colonies, often situated in cities. We screened sera from 262 E. helvum using indirect fluorescent tests for antibodies against EBOV subtype Zaire. We detected a seropositive bat from Accra, Ghana, and confirmed this using western blot analysis. The bat was also seropositive for Lagos bat virus, a Lyssavirus, by virus neutralization test. The bat was fitted with a radio transmitter and was last detected in Accra 13 months after release post-sampling, demonstrating long-term survival. Antibodies to filoviruses have not been previously demonstrated in E. helvum. Radio-telemetry data demonstrates long-term survival of an individual bat following exposure to viruses of families that can be highly pathogenic to other mammal species. Because E. helvum typically lives in large urban colonies and is a source of bushmeat in some regions, further studies should determine if this species forms a reservoir for EBOV from which spillover infections into the human population may occur. PMID:20694141

  13. Biologically-equivalent dose and long-term survival time in radiation treatments

    NASA Astrophysics Data System (ADS)

    Zaider, Marco; Hanin, Leonid

    2007-10-01

    Within the linear-quadratic model the biologically-effective dose (BED)—taken to represent treatments with an equal tumor control probability (TCP)—is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, Teff. By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between Teff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than Teff) may result in a miscalculation (underestimation) of the initial number of clonogens.

  14. Mesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival.

    PubMed

    Baumann, Francine; Flores, Erin; Napolitano, Andrea; Kanodia, Shreya; Taioli, Emanuela; Pass, Harvey; Yang, Haining; Carbone, Michele

    2015-01-01

    BRCA1-associated protein-1 (BAP1) mutations cause a new cancer syndrome, with a high rate of malignant mesothelioma (MM). Here, we tested the hypothesis that MM associated with germline BAP1 mutations has a better prognosis compared with sporadic MM. We compared survival among germline BAP1 mutation MM patients with that of all MM (N = 10 556) recorded in the United States Surveillance, Epidemiology, and End Results (SEER) data from 1973 to 2010. We identified 23 MM patients--11 alive--with germline BAP1 mutations and available data on survival. Ten patients had peritoneal MM, ten pleural MM and three MM in both locations. Thirteen patients had one or more malignancies in addition to MM. Actuarial median survival for the MM patients with germline BAP1 mutations was 5 years, as compared with <1 year for the median survival in the United States SEER MM group. Five-year survival was 47%, 95% confidence interval (24-67%), as compared with 6.7% (6.2-7.3%) in the control SEER group. Analysis of the pooled cohort of germline BAP1 mutation MM showed that patients with peritoneal MM (median survival of 10 years, P = 0.0571), or with a second malignancy in addition to MM (median survival of 10 years, P = 0.0716), survived for a longer time compared with patients who only had pleural MM, or MM patients without a second malignancy, respectively. In conclusion, we found that MM patients with germline BAP1 mutations have an overall 7-fold increased long-term survival, independently of sex and age. Appropriate genetic counseling and clinical management should be considered for MM patients who are also BAP1 mutation carriers.

  15. Glycated Albumin Predicts Long-term Survival in Patients Undergoing Hemodialysis

    PubMed Central

    Lu, Chien-Lin; Ma, Wen-Ya; Lin, Yuh-Feng; Shyu, Jia-Fwu; Wang, Yuan-Hung; Liu, Yueh-Min; Wu, Chia-Chao; Lu, Kuo-Cheng

    2016-01-01

    Background: In patients with advanced renal dysfunction undergoing maintenance hemodialysis, glycated albumin (GA) levels may be more representative of blood glucose levels than hemoglobin A1C levels. The aim of this study was to determine the predictive power of GA levels on long-term survival in hemodialysis patients. Methods: A total of 176 patients with a mean age of 68.2 years were enrolled. The median duration of follow-up was 51.0 months. Receiver-operating characteristic curve analysis was utilized to determine the optimal cutoff value. We examined the cumulative survival rate by Kaplan-Meier estimates and the influence of known survival factors with the multivariate Cox proportional-hazard regression model. Results: In the whole patient group, cumulative survival in the low GA group was better than in the high GA group (p=0.030), with more prominence in those aged <70 years (p=0.029). In subgroup analysis, both diabetic (DM) and non-DM patients with low GA had a better cumulative survival compared with those with high GA. The risk of mortality increased by 3.0% for each 1% increase in serum GA level in all patients undergoing hemodialysis. Conclusions: In addition to serving as a glycemic control marker, GA levels may be useful for evaluating the risk of death in both DM and non-DM patients on hemodialysis. PMID:27226780

  16. Long-Term Survival in Patients with Metastatic Melanoma Treated with DTIC or Temozolomide

    PubMed Central

    Kim, Christina; Lee, Christopher W.; Kovacic, Laurel; Shah, Amil; Klasa, Richard

    2010-01-01

    Background. Patients with metastatic melanoma typically have a poor outcome; however, a small proportion of patients achieve long-term survival (LTS). It is unclear how often LTS is related to sensitivity to chemotherapy. Methods. All patients with metastatic melanoma treated with either dacarbazine (DTIC) or temozolomide (TMZ) at the British Columbia Cancer Agency (BCCA) from January 1, 1988 to February 1, 2006 were identified through the BCCA pharmacy electronic database, which was then linked to the surveillance and outcomes unit to identify patients with LTS, defined as survival ≥18 months following chemotherapy. Results. In total, 397 patients were treated with either DTIC (n = 349) or TMZ (n = 48) and 43 patients (10.8%) were identified with LTS. Two additional patients with LTS were added prior to 1988 for a total of 45 patients. The 5-year overall and progression-free survival rates for patients with LTS were 33% and 16%, respectively. In total, 16% had a complete response (CR) to chemotherapy, which was the only factor identified that correlated with survival in the multivariate analysis. However, most patients with LTS had an incomplete response to chemotherapy. Conclusions. LTS occurs in select patients who achieve a CR to chemotherapy. However, this occurs in only a minority of patients and, in most cases, the longer survival is likely the result of indolent disease biology or host factors. PMID:20538743

  17. Long-term survival after chest-wall reconstruction with musculocutaneous flaps

    SciTech Connect

    Kroll, S.S.; Schusterman, M.A.; Larson, D.L.; Fender, A. )

    1990-10-01

    Reconstruction of chest-wall defects with musculocutaneous flaps permits resection of advanced chest-wall tumors and of tissues severely damaged by radiotherapy in patients who in a previous era were not surgically treatable. To determine the long-term outcome from this surgery, the records of 96 patients who had undergone chest-wall resection with musculocutaneous flap reconstruction were reviewed. Median survival for the entire group was 20.5 months, but a more accurate prediction of outcome could be obtained by dividing the patients into three groups. In group I, patients free of known malignancy and undergoing resection of radionecrotic tissues, median survival was 60.0 months. In group II, patients with resectable disease and free of tumor following surgery, median survival was 31.1 months. In group III, patients incompletely resected or known to have metastatic disease following surgery, median survival was only 12.5 months. Even in group III, however, some individuals achieved prolonged survival and lasting benefits from the surgery, so these data should not be used to exclude patients from undergoing necessary palliative procedures.

  18. Impact of Intraoperative Blood Loss on Long-Term Survival after Lung Cancer Resection

    PubMed Central

    Saji, Hisashi; Kurimoto, Noriaki; Shinmyo, Takuo; Tagaya, Rie

    2014-01-01

    Purpose: The purpose of this study was to clarify relationships between intraoperative blood loss (IBL) and long-term postsurgical survival in lung cancer patients. Methods: We retrospectively analyzed 1336 patients undergoing surgery: lobectomy in 1016, sublobar resection in 174, pneumonectomy in 106, and combined resection with adjacent organs in 40. The lobectomy group was stratified further by pathologic stages; overall survival difference was examined according to amount of IBL. Results: Volume of IBL differed significantly according to surgical procedure when all patients were included. Within the lobectomy group, IBL differed significantly between gender, pathologic stage, histologic type (adenocarcinoma vs. non-adenocarcinoma), and year of operation (1983 to 2002 vs. 2003 to 2012). After stratification by pathologic stage, survival differed with IBL for stages IB to IIIB. Multivariate analysis identified gender, patients age (<69 vs. ≥69), pathologic stage (IA to IIB vs. IIIA to IV), year of operation, histologic type, and IBL as significant predictors of survival. Conclusion: Since degree of IBL is an independent predictor of overall survival after lung cancer resection, IBL should be minimized carefully during surgery. PMID:24583702

  19. Contrasting long-term survival of two outplanted Mojave Desert perennials for post-fire revegetation

    USGS Publications Warehouse

    Scoles-Sciulla, Sara J.; Defalco, Lesley A.; Esque, Todd C.

    2015-01-01

    Post-fire recovery of arid shrublands is typically slow, and planting greenhouse-raised seedlings may be a means of jump-starting this process. Recovery can be further accelerated by understanding the factors controlling post-planting survival. In fall 2007 and 2009, we outplanted seedlings of two contrasting native evergreen shrubs—fast-growing Nevada jointfir and slow-growing blackbrush—across five burned sites in the Mojave Desert. To increase soil moisture and optimize seedling survival, we experimentally applied and evaluated soil amendments and supplemental watering. We also evaluated two herbicides that reduce competitive invasive annual grasses and two types of herbivore protection. Survival of jointfir outplanted in 2007 was 61% after 43 months, and site largely influenced survival, while herbicide containing imazapic applied more than one year after outplanting reduced survival. Reduced survival of jointfir outplanted in 2009 coincided with delayed seasonal precipitation that intensified foliar damage by small mammals. In contrast, blackbrush survival was 4% after 43 months, and was influenced by site, type of herbivore protection, and greenhouse during the 2007 outplanting, and soil amendment during 2009. Counter to expectations, we found that supplemental watering and soil amendments did not influence long-term survival of either blackbrush or jointfir. Shrub species with rapid growth rates and broad environmental tolerances, such as jointfir, make ideal candidates for outplanting, provided that seedlings are protected from herbivores. Re-introduction of species with slow growth rates and narrow environmental tolerances, such as blackbrush, requires careful consideration to optimize pre- and post-planting conditions.

  20. Precipitating Factors for Acute Heart Failure Hospitalization and Long-Term Survival.

    PubMed

    Berkovitch, Anat; Maor, Elad; Sabbag, Avi; Chernomordik, Fernando; Elis, Avishay; Arbel, Yaron; Goldenberg, Ilan; Grossman, Ehud; Klempfner, Robert

    2015-12-01

    Heart failure (HF) patients have frequent exacerbations leading to high consumption of medical services and recurrent hospitalizations.Different precipitating factors have various effects on long-term survival.We investigated 2212 patients hospitalized with a diagnosis of either acute HF or acute exacerbation of chronic HF. Patients were divided into 2 primary precipitant groups: ischemic (N = 979 [46%]) and nonischemic (N = 1233 [54%]). The primary endpoint was all-cause mortality.Multivariate analysis demonstrated that the presence of a nonischemic precipitant was associated with a favorable in-hospital outcome (OR 0.64; CI 0.43-0.94), but with a significant increase in the risk of 10-year mortality (HR 1.12; CI 1.01-1.21). Consistently, the cumulative probability of 10-year mortality was significantly higher among patients with a nonischemic versus ischemic precipitant (83% vs 90%, respectively; Log-rank P value <0.001). Subgroup analysis showed that among the nonischemic precipitant, the presence of renal dysfunction and infection were both associated with poor short-term outcomes (OR 1.56, [P < 0.001] and OR 1.35 [P < 0.001], respectively), as well as long-term (HR 1.59 [P < 0.001] and HR 1.24 [P < 0.001], respectively).Identification of precipitating factors for acute HF hospitalization has important short- and long-term implications that can be used for improved risk stratification and management. PMID:26717369

  1. The Relationship of Echocardiographic Dyssynchrony to Long-Term Survival Following Cardiac Resynchronization Therapy

    PubMed Central

    Gorcsan, John; Oyenuga, Olusegun; Habib, Phillip J.; Tanaka, Hidekazu; Adelstein, Evan C.; Hara, Hideyuki; McNamara, Dennis M.; Saba, Samir

    2010-01-01

    Background The ability of echocardiographic dyssynchrony to predict response to cardiac resynchronization therapy (CRT) has been unclear. Methods and Results A prospective, longitudinal study was designed with pre-defined dyssynchrony indices and outcome variables to test the hypothesis that baseline dyssynchrony is associated with long term survival following CRT. We studied 229 consecutive Class III–IV heart failure patients, with ejection fraction (EF) ≤35%, and QRS duration ≥120ms for CRT. Dyssynchrony before CRT was defined as: tissue Doppler velocity opposing wall delay ≥ 65 ms, 12-site standard deviation (Yu Index) ≥32ms; speckle tracking radial strain anteroseptal to posterior wall delay ≥130ms; or pulsed Doppler interventricular mechanical delay (IVMD) ≥ 40 ms. Outcome was defined as freedom from death, heart transplant or left ventricular assist device (LVAD). Of 210 patients (89%) with dyssynchrony data available, there were 62 events: 47 deaths, 9 transplants, and 6 LVADs over 4 years. Event-free survival was associated with: Yu Index (p=0.003), speckle tracking radial strain (p=0.003), and IVMD (p=0.019). When adjusted for confounding baseline variables of ischemic etiology and QRS duration, Yu Index and radial strain dyssynchrony remained independently associated with outcome (p<0.05). Lack of radial dyssynchrony was particularly associated with unfavorable outcome in those with QRS duration 120–150 ms (p=0.002). Conclusions The absence of echocardiographic dyssynchrony was associated with significantly less favorable event-free survival following CRT. Patients with narrower QRS duration who lacked dyssynchrony had the least favorable long term outcome. These observations support the relationship of dyssynchrony to CRT response. PMID:20975000

  2. Laboratory and field evidence for long-term starvation survival of microorganisms in subsurface terrestrial environments

    NASA Astrophysics Data System (ADS)

    Kieft, Thomas L.; Murphy, Ellyn M.; Amy, P. S.; Haldeman, D. L.; Ringelberg, David B.; White, David C.

    1997-07-01

    Biogeochemical modeling of groundwater flow and nutrient flux in subsurface environments indicates that inhabitant microorganisms experience severe nutrient limitation. Using laboratory and field methods, we have been testing starvation survival in subsurface microorganisms. In microcosm experiments, we have shown that strains of two commonly isolated subsurface genera, Arthrobacter and Pseudomonas, are able to maintain viability in low-nutrient, natural subsurface sediments for over one year. These non- spore-forming bacteria undergo rapid initial miniaturization followed by a stabilization of cell size. Membrane lipid phospholipid fatty acid (PLFA) profiles of the Pseudomonas are consistent with adaptation to nutrient stress; Arthrobacter apparently responds to nutrient deprivation without altering membrane PLFAs. To test survivability of microorganisms over a geologic time scale, we characterized microbial communities in a sequence of unsaturated sediments ranging in age from modern to > 780,000 years. Sediments were relatively uniform silts in eastern Washington State. Porewater ages at depth (measured by the chloride mass- balance approach) were as old as 3,600 years. Microbial abundance, biomass, and activities (measured by direct counts, culture counts, total PLFAs, and radiorespirometry) declined with sediment age. The pattern is consistent with laboratory microcosm studies of microbial survival: rapid short-term change followed by long-term survival of a proportion of cells. Even the oldest sediments evinced a small but viable microbial community. Microbial survival appeared to be a function of sediment age. Porewater age appeared to influence the makeup of surviving communities, as indicated by PLFA profiles. Sites with different porewater recharge rates and patterns of Pleistocene flooding had different communities. These and other studies provide evidence that microorganisms can survive nutrient limitation for geologic time periods.

  3. Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

    SciTech Connect

    Yang, Z.Y.; Gu, X.; Zhao, S.

    1983-12-01

    One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.

  4. A thermal control system for long-term survival of scientific instruments on lunar surface

    SciTech Connect

    Ogawa, K.; Iijima, Y.; Tanaka, S.; Sakatani, N.; Otake, H.

    2014-03-15

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  5. A thermal control system for long-term survival of scientific instruments on lunar surface

    NASA Astrophysics Data System (ADS)

    Ogawa, K.; Iijima, Y.; Sakatani, N.; Otake, H.; Tanaka, S.

    2014-03-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime -200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a "regolith mound". Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  6. Survival Response and Rearrangement of Plasmid DNA of Lactococcus lactis during Long-Term Starvation

    PubMed Central

    Kim, Woojin S.; Park, Ji Hyeon; Ren, Jun; Su, Ping; Dunn, Noel W.

    2001-01-01

    The survival response of Lactococcus lactis during long-term starvation was investigated. The cells were cultured with different levels of glucose (the sole energy source) and either were kept in the resultant spent medium or transferred to fresh medium (without glucose) for up to 2 years. The survival of the cells during starvation was not dependent on the nature of transition phase, as expected, but on the nature of medium in which the cells were kept. The proliferation of cells, despite the apparent lack of glucose, could have been due to some cells being able to utilize the small amounts of peptides still present in the spent medium or to use energy sources provided by the breakup of dead cells. The 1- and 2-year-old cultures contained cells with vastly changed morphotypes. When these isolates were examined, it was revealed that the original plasmids present in the parent were rearranged in a certain way, and an entirely new plasmid was generated. Changes were also evident in the chromosomal DNA and in gene expression. Furthermore, all of the isolates exhibited a growth advantage relative to the parent cells when grown in energy-limiting media. When they were tested against different types of stresses, they exhibited a higher resistance against the bile salt and hydrogen peroxide stresses compared to the parent. Because of the similar changes observed in the 2-year-old isolates, a similar survival strategy may be operational in those cells that survive for that length of time. PMID:11571161

  7. A thermal control system for long-term survival of scientific instruments on lunar surface.

    PubMed

    Ogawa, K; Iijima, Y; Sakatani, N; Otake, H; Tanaka, S

    2014-03-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime -200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a "regolith mound". Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system. PMID:24689621

  8. Is Long-Term Structural Priming Affected by Patterns of Experience with Individual Verbs?

    ERIC Educational Resources Information Center

    Kaschak, Michael P.; Borreggine, Kristin L.

    2008-01-01

    Several recent papers have reported long-term structural priming effects in experiments where previous patterns of experience with the double object and prepositional object constructions are shown to affect later patterns of language production for those constructions. The experiments reported in this paper address the extent to which these…

  9. Predicting long-term risk for relationship dissolution using nonparametric conditional survival trees.

    PubMed

    Kliem, Sören; Weusthoff, Sarah; Hahlweg, Kurt; Baucom, Katherine J W; Baucom, Brian R

    2015-12-01

    Identifying risk factors for divorce or separation is an important step in the prevention of negative individual outcomes and societal costs associated with relationship dissolution. Programs that aim to prevent relationship distress and dissolution typically focus on changing processes that occur during couple conflict, although the predictive ability of conflict-specific variables has not been examined in the context of other factors related to relationship dissolution. The authors examine whether emotional responding and communication during couple conflict predict relationship dissolution after controlling for overall relationship quality and individual well-being. Using nonparametric conditional survival trees, the study at hand simultaneously examined the predictive abilities of physiological (systolic and diastolic blood pressure, heart rate, cortisol) and behavioral (fundamental frequency; f0) indices of emotional responding, as well as observationally coded positive and negative communication behavior, on long-term relationship stability after controlling for relationship satisfaction and symptoms of depression. One hundred thirty-six spouses were assessed after participating in a randomized clinical trial of a relationship distress prevention program as well as 11 years thereafter; 32.5% of the couples' relationships had dissolved by follow up. For men, the only significant predictor of relationship dissolution was cortisol change score (p = .012). For women, only f0 range was a significant predictor of relationship dissolution (p = .034). These findings highlight the importance of emotional responding during couple conflict for long-term relationship stability. PMID:26192131

  10. Survival of dormant organisms after long-term exposure to the space environment

    NASA Astrophysics Data System (ADS)

    Novikova, N.; Gusev, O.; Polikarpov, N.; Deshevaya, E.; Levinskikh, M.; Alekseev, V.; Okuda, T.; Sugimoto, M.; Sychev, V.; Grigoriev, А.

    2011-05-01

    The RF SRC—Institute of Biomedical Problems, Russian Academy of Sciences, developed Biorisk hardware to study the effects of long-term exposure of dormant forms of various organisms to outer space and used it to complete a series of experiments on the Russian Module (RM) of the International Space Station (ISS). The experiments were performed using prokaryotes ( Bacillus bacteria) and eukaryotes ( Penicillium, Aspergillus, and Cladosporium fungi), as well as spores, dormant forms of higher plants, insects, lower crustaceans, and vertebrates. The biological samples were housed in two containers that were exposed to outer space for 13 or 18 months. The results of the 18-month experiment showed that, in spite of harsher temperature than in the first study, most specimens remained viable. These experiments provided evidence that not only bacterial and fungal spores but also dormant forms of organisms that reached higher levels of evolutionary development had the capability to survive a long-term exposure to outer space. This observation suggests that they can be transferred on outer walls of space platforms during interplanetary missions.

  11. Long-term survival rate of teeth receiving multidisciplinary endodontic, periodontal and prosthodontic treatments.

    PubMed

    Moghaddam, A S; Radafshar, G; Taramsari, M; Darabi, F

    2014-03-01

    Deciding whether to replace or preserve a compromised tooth, even with emerging trends in implant dentistry, is still a common dilemma for practitioners. This study sought to determine the 3- to more than 10-year survival rate of teeth that had undergone endodontic, periodontal and prosthodontic treatments. A total of 245 teeth in 87 patients were clinically and radiographically evaluated. All the teeth had received crown lengthening surgery by a single periodontist. Root canal therapy and prosthodontic procedures were rendered either by specialists or by experienced general dentists. Numbers of lost teeth were recorded and the criteria for hopeless teeth were defined. Survival rate was determined using the Kaplan-Meier estimator. Clinical indices including pocket depth (PD), bleeding index (BI), C/R ratio, position of the restoration margin relative to the gingival margin (RM-GM) and the presence of intra-canal post were compared between different survival groups (<3, 3-5, 5-10 and >10 years) using one-way analysis of variance (anova). Potential predictors of failure were determined using the Cox regression model. The mean ± s.d. of 3-, 5-, 10- and 13-year survival rates was 98 ± 1%, 96 ± 1·6%, 83·1 ± 4·5% and 51·9 ± 14·5%, respectively. The mean PD (P < 0·013), as well as C/R ratio in the mesial (P = 0·003) and distal (P = 0·007) surfaces, was significantly higher in the >10-year-survived teeth. Bleeding index and RM-GM showed no significant differences between the groups. C/R ratio and RM-GM position appeared to be the major determinants of tooth loss. The long-term survival rate of multidisciplinary-treated teeth was 83-98% in this specific sample.

  12. Laboratory and Field Evidence for Long-Term Starvation Survival of Microorganisms in Subsurface Terrestrial Environments

    SciTech Connect

    Kieft, T.L.; Murphy, E.M.; Amy, P.S.; Haldeman, D.L.; Ringelberg, D. B. |

    1997-12-31

    BIOGEOCHEMICAL MODELING OF GROUNDWATER FLOW AND NUTRIENT FLUX IN SUBSURFACE ENVIRONMENTS INDICATES THAT INHABITANT MICROORGANISMS EXPERIENCE SEVERE NUTRIENT LIMITATION. USING LABORATORY AND FIELD METHODS, WE HAVE BEEN TESTING STARVATION SURVIVAL IN SUBSURFACE MICROORGANISMS. IN MICROCOSM EXPERIMENTS, WE HAVE SHOWN THAT STRAINS OF TWO COMMONLY ISOLATED SUBSURFACE GENERA, ARTHROBACTER AND PSEUDOMONAS, ARE ABLE TO MAINTAIN VIABILITY IN LOW-NUTRIENT, NATURAL SUBSURFACE SEDIMENTS FOR OVER ONE YEAR. THESE NON-SPORE-FORMING BACTERIA UNDERGO RAPID INITIAL MINIATURIZATION FOLLOWED BY A STABILIZATION OF CELL SIZE. MEMBRANE LIPID PHOSPHOLIPID FATTY ACID (PLFA) PROFILES OF THE PSEUDOMONAS ARE CONSISTENT WITH ADAPTATION TO NUTRIENT STRESS; ARTHROBACTER APPARENTLY RESPONDS TO NUTRIENT DEPRIVATION WITHOUT ALTERING MEMBRANE PLFA. TO TEST SURVIVABILITY OF MICROORGANISMS OVER A GEOLOGIC TIME SCALE, WE CHARACTERIZED MICROBIAL COMMUNITIES IN A SEQUENCE OF UNSATURATED SEDIMENTS RANGING IN AGE FROM MODEM TO {gt}780,000 years. Sediments were relatively uniform silts in Eastern Washington State. Porewater ages at depth (measured by the chloride mass-balance approach) were as old as 3,600 years. Microbial abundance, biomass, and activities (measured by direct counts, culture counts, total PLFAs, and radiorespirometry) declined with sediment age. The pattern is consistent with laboratory microcosm studies of Microbial survival: rapid short-term change followed by long-term survival of a proportion of cells. Even the oldest sediments evinced a small but viable Microbial community. Microbial survival appeared to be a function of sediment age. Porewater age appeared to influence the markup of surviving communities, as indicated by PLFA profiles. Sites with different Porewater recharge rates and patterns of Pleistocene flooding had different communities.

  13. Extremely halophilic archaea and the issue of long-term microbial survival

    PubMed Central

    2011-01-01

    Halophilic archaebacteria (haloarchaea) thrive in environments with salt concentrations approaching saturation, such as natural brines, the Dead Sea, alkaline salt lakes and marine solar salterns; they have also been isolated from rock salt of great geological age (195–250 million years). An overview of their taxonomy, including novel isolates from rock salt, is presented here; in addition, some of their unique characteristics and physiological adaptations to environments of low water activity are reviewed. The issue of extreme long-term microbial survival is considered and its implications for the search for extraterrestrial life. The development of detection methods for subterranean haloarchaea, which might also be applicable to samples from future missions to space, is presented. PMID:21984879

  14. Successful Long-term Graft Survival of a Renal Transplantation Patient with Wiskott-Aldrich Syndrome.

    PubMed

    Kai, Kotaro; Sumida, Maki; Motoyoshi, Yaeko; Ogawa, Yuichi; Miki, Katsuyuki; Iwadoh, Kazuhiro; Sannomiya, Akihito; Murakami, Toru; Koyama, Ichiro; Kitajima, Kumiko; Nakajima, Ichiro; Morio, Tomohiro; Fuchinoue, Shohei

    2016-01-01

    Wiskott-Aldrich syndrome, a rare X-linked hereditary syndrome, is characterized by immunodeficiency, thrombocytopenia, and eczema. The underlying T-cell defect renders renal transplantation and immunosuppressive treatments uncertain. The present case exhibited the mild clinical manifestation, regarded as X-linked thrombocytopenia. He successfully underwent a living-donor ABO-compatible renal transplantation and splenectomy in 2002, and thereafter experiencing no severe rejection, serious infection, or malignancy for more than 10 years. Though IgA nephropathy was detected 8 months after transplantation, the patient's renal function and proteinuria were stable without any treatment. The present case showed a successful long-term graft survival and the importance of splenectomy added to renal transplantation. PMID:27374679

  15. The Power of Renal Function Estimation Equations for Predicting Long-Term Kidney Graft Survival

    PubMed Central

    Choi, Hoon Young; Joo, Dong Jin; Song, Mi Kyung; Kim, Myoung Soo; Park, Hyeong Cheon; Kim, Yu Seun; Kim, Beom Seok

    2016-01-01

    Abstract Evaluation of renal function using an accurate estimation equation is important for predicting long-term graft survival. We designed this retrospective cohort study to evaluate the predictive power of renal function estimation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) study equations for graft survival. We reviewed data of 3290 adult kidney transplant recipients who underwent transplantation at a single center between April 1979 and September 2012. The reliability and agreement of chronic kidney disease (CKD) stages based on the estimated glomerular filtration rate (eGFR) as calculated by the CKD-EPI and MDRD equations were evaluated using Bland–Altman plots and Cohen weighted kappa analyses. The predictive power of CKD stages as classified by each equation for graft survival was investigated using Cox regression models. Additionally, Pearson and Spearman correlation coefficients were used to reveal the relationship between graft survival and eGFR equations. Of 3290 kidney transplant recipients, 3040 were included in the analysis. The mean follow-up duration was 128.08 ± 83.54 months, and 29.8% of participants were reclassified to higher eGFR categories by the CKD-EPI equation compared to the category classification by the MDRD equation. eGFR calculated using the MDRD equation was underestimated compared to that calculated using the CKD-EPI equation, based on the Bland–Altman plot. In Cohen weighted kappa analysis, agreement across CKD stages classified using the 2 equations was reliable, but all CKD stages classified using the MDRD equation appeared to be in lower eGFR categories than those classified using the CKD-EPI equation. Pearson and Spearman correlation analyses indicated that the CKD stage as classified by the CKD-EPI equation, but not the MDRD equation, was significantly correlated with the risk of graft failure. In multivariable Cox regression analysis for

  16. Does the site of anastomosis for esophagectomy affect long-term quality of life?

    PubMed

    Wormald, J C R; Bennett, J; van Leuven, M; Lewis, M P N

    2016-01-01

    Long-term survival after esophagectomy is improving, and hence, quality of life (QOL) of these patients has become a priority. There has been extensive debate regarding the optimal site of surgical anastomosis (cervical or intrathoracic). We aimed to evaluate the impact of anastomotic site on long-term QOL postesophagectomy. Quality of life questionnaires (European Organisation for Research and Treatment of Cancer [EORTC] C-30 and OG-25) were sent to patients surviving over 3 years following esophagectomy. The data were analyzed by site of esophagogastric anastomosis: intrathoracic or cervical. EORTC C-30 data were compared against the reference population data. Of the patients, 62 responded (82%) with a median time postsurgery of 6.1 years (range 3-12 years). Patient demographics were comparable. There was no significant difference between cervical or intrathoracic anastomosis groups for functional or symptom scores, focusing on dysphagia (cervical = 8.8 vs. intrathoracic = 17.6, P = 0.24), odynophagia (cervical = 13.4 vs. intrathoracic = 16.1, P = 0.68) and swallowing problems (cervical = 8.1 vs. intrathoracic = 13.4, P = 0.32). There was no difference in overall health score between groups (cervical = 70.5 vs. intrathoracic = 71.6, P = 0.46). Overall general health score was comparable with the reference population (esophagectomy group P = 70.9 ± 22.1 vs. reference population = 71.2 ± 22.4, P = 0.93). There is no difference in long-term QOL after esophagectomy between patients with a cervical or intrathoracic anastomosis. Scores compare favorably with EORTC reference data. Survival after esophagectomy is associated with recovery of QOL in the long term, regardless of site of anastomosis and despite worse gastrointestinal-related symptoms.

  17. Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

    PubMed

    Prasad, G V Ramesh; Ananth, Sailesh; Palepu, Sneha; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S

    2016-05-01

    Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care. Their outcomes to 8 years post-transplant were compared with 702 domestic living donor and 827 deceased donor transplant recipients during this period using Kaplan-Meier survival plots and multivariate Cox regression analysis. Among many complications, notable specific events included hepatitis B or C seroconversion (7 patients), active hepatitis and/or fulminant hepatic failure (4 patients), pulmonary tuberculosis (2 patients), and a type A dissecting aortic aneurysm. Commercial transplantation was independently associated with significantly reduced death-censored kidney allograft survival (hazard ratio 3.69, 95% confidence interval 1.88-7.25) along with significantly delayed graft function and eGFR 30 ml/min/1.73 m(2) or less at 3 months post-transplant. Thus, commercial transplantation represents an important risk factor for long-term kidney allograft loss. Concerted arguments and efforts using adverse recipient outcomes among the main premises are still required in order to eradicate transplant commercialization.

  18. Early Treatment with Alglucosidase Alfa Prolongs Long Term Survival of Infants with Pompe Disease

    PubMed Central

    Kishnani, Priya S.; Corzo, Deya; Leslie, Nancy D.; Gruskin, Daniel; van der Ploeg, Ans; Clancy, John P.; Parini, Rosella; Morin, Gilles; Beck, Michael; Bauer, Mislen S.; Jokic, Mikael; Tsai, Chen-En; Tsai, Brian W.H.; Morgan, Claire; O’Meara, Tara; Richards, Susan; Tsao, Elisa C.; Mandel, Hanna

    2011-01-01

    In a previous 52-week trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 months old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alfa at either 20 mg/kg biweekly (n=8) or 40 mg/kg biweekly (n=8), for up to a total of 3 years. These children continued to exhibit the benefits of alglucosidase alfa at the age of 36 months. Cox regression analyses showed that over the entire study period, alglucosidase alfa treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, as compared to an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 mg/kg and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival, and improved cardiomyopathy. PMID:19542901

  19. Modeling the long-term kinetics of Salmonella survival on dry pet food.

    PubMed

    Lambertini, Elisabetta; Mishra, Abhinav; Guo, Miao; Cao, Huilin; Buchanan, Robert L; Pradhan, Abani K

    2016-09-01

    Due to multiple outbreaks and large-scale product recalls, Salmonella has emerged as a priority pathogen in dry pet food and treats. However, little data are available to quantify risks posed by these classes of products to both pets and their owners. Specifically, the kinetics of Salmonella survival on complex pet food matrices are not available. This study measured the long-term kinetics of Salmonella survival on a dry pet food under storage conditions commonly encountered during production, retail, and in households (aw < 0.60, 23 °C). A Salmonella enterica cocktail of 12 strains isolated from dry pet foods and treats was used to inoculate commercial dry dog food. Salmonella was enumerated on non-selective (BHI) and selective (XLD and BS) media. Results at 570 days indicated an initial relatively rapid decline (up to 54 days), followed by a much slower extended decline phase. The Weibull model provided a satisfactory fit for time series of Log-transformed Salmonella counts from all three media (δ: mean 4.65 day/Log (CFU/g); p: mean 0.364 on BHI). This study provides a survival model that can be applied in quantitative risk assessment models. PMID:27217351

  20. Long Term Non-Invasive Ventilation in Children: Impact on Survival and Transition to Adult Care

    PubMed Central

    Chatwin, Michelle; Tan, Hui-Leng; Bush, Andrew; Rosenthal, Mark; Simonds, Anita Kay

    2015-01-01

    Background The number of children receiving domiciliary ventilatory support has grown over the last few decades driven largely by the introduction and widening applications of non-invasive ventilation. Ventilatory support may be used with the intention of increasing survival, or to facilitate discharge home and/or to palliate symptoms. However, the outcome of this intervention and the number of children transitioning to adult care as a consequence of longer survival is not yet clear. Methods In this retrospective cohort study, we analysed the outcome in children (<17 years) started on home NIV at Royal Brompton Hospital over an 18 year period 1993-2011. The aim was to establish for different diagnostic groups: survival rate, likelihood of early death depending on diagnosis or discontinuation of ventilation, and the proportion transitioning to adult care. Results 496 children were commenced on home non invasive ventilation; follow-up data were available in 449 (91%). Fifty six per cent (n=254) had neuromuscular disease. Ventilation was started at a median age (IQR) 10 (3-15) years. Thirteen percent (n=59) were less than 1 year old. Forty percent (n=181) have transitioned to adult care. Twenty four percent (n=109) of patients have died, and nine percent (n=42) were able to discontinue ventilatory support. Conclusion Long term ventilation is associated with an increase in survival in a range of conditions leading to ventilatory failure in children, resulting in increasing numbers surviving to adulthood. This has significant implications for planning transition and adult care facilities. PMID:25933065

  1. Implications of subzero metabolism on long-term microbial survival in ice (Invited)

    NASA Astrophysics Data System (ADS)

    Christner, B. C.; Amato, P.; Battista, J. R.; Doyle, S. M.

    2010-12-01

    For a microorganism to remain viable over an extended period of frozen dormancy, the macromolecular damage incurred by the cell must not exceed a level where effective repair is no longer possible. Hence, survival over extended timeframes in the absence of metabolism is likely to be limited by chemical (e.g., hydrolysis and oxidation of nucleic acids; racemization of L-amino acids) and ionizing radiation-induced damage to cellular macromolecules. In freshwater and saline ice, various studies have shown that microbial cells are physically located in the aqueous interstitial veins that exist at ice grain boundaries and remain metabolically active under frozen conditions. In an effort to improve estimates for the long term limits of microbial survival in ice, we determined rates of macromolecular synthesis in cold-adapted bacteria at temperatures down to -15°C and examined their sensitivity to controlled doses of ionizing radiation (0 to 450 Gy). The purpose of this experiment was to simulate the damage which would accumulate in a cell population due to ionizing radiation in the absence of metabolic activity, allowing a prediction of cellular survival over extended dormancy versus subsistence in a metabolically active state. In experiments conducted over ≈400 days at -15°C, the rates of bacterial protein and DNA synthesis ranged from < 1 to 16 proteins cell-1 d-1 and 20 to 1600 bp cell-1 d-1, respectively, under the conditions tested. Based on the amount of bulk DNA synthesis needed to repair a known quantity of DNA damage (i.e., single- and double-stranded breaks, spontaneous hydrolysis of phosphodiester bonds, and depurination), we estimate that the viability of a dormant population of radiosensitive bacteria would be reduced by 99% after at least 600,000 years in ice. On the other hand, if microorganisms in natural ices are capable of synthesizing DNA at the lowest rates observed in the subzero laboratory experiments, our calculations imply that ionizing

  2. The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus).

    PubMed

    Shuert, Courtney; Horning, Markus; Mellish, Jo-Ann

    2015-01-01

    Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35) were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags) to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs) that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of experimental

  3. The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus)

    PubMed Central

    Shuert, Courtney; Horning, Markus; Mellish, Jo-Ann

    2015-01-01

    Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35) were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags) to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs) that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of experimental

  4. The Effect of Novel Research Activities on Long-term Survival of Temporarily Captive Steller Sea Lions (Eumetopias jubatus).

    PubMed

    Shuert, Courtney; Horning, Markus; Mellish, Jo-Ann

    2015-01-01

    Two novel research approaches were developed to facilitate controlled access to, and long-term monitoring of, juvenile Steller sea lions for periods longer than typically afforded by traditional fieldwork. The Transient Juvenile Steller sea lion Project at the Alaska SeaLife Center facilitated nutritional, physiological, and behavioral studies on the platform of temporary captivity. Temporarily captive sea lions (TJs, n = 35) were studied, and were intraperitoneally implanted with Life History Transmitters (LHX tags) to determine causes of mortality post-release. Our goal was to evaluate the potential for long-term impacts of temporary captivity and telemetry implants on the survival of study individuals. A simple open-population Cormack-Jolly-Seber mark-recapture model was built in program MARK, incorporating resightings of uniquely branded study individuals gathered by several contributing institutions. A priori models were developed to weigh the evidence of effects of experimental treatment on survival with covariates of sex, age, capture age, cohort, and age class. We compared survival of experimental treatment to a control group of n = 27 free-ranging animals (FRs) that were sampled during capture events and immediately released. Sex has previously been show to differentially affect juvenile survival in Steller sea lions. Therefore, sex was included in all models to account for unbalanced sex ratios within the experimental group. Considerable support was identified for the effects of sex, accounting for over 71% of total weight for all a priori models with delta AICc <5, and over 91% of model weight after removal of pretending variables. Overall, most support was found for the most parsimonious model based on sex and excluding experimental treatment. Models including experimental treatment were not supported after post-hoc considerations of model selection criteria. However, given the limited sample size, alternate models including effects of experimental

  5. Long-term survival in a dog with meningoencephalitis and epidural abscessation due to Actinomyces species.

    PubMed

    Song, Rachel B; Vitullo, Carina A; da Costa, Ronaldo C; Daniels, Joshua B

    2015-07-01

    A 2-year-old, female spayed Golden Retriever dog was presented to The Ohio State University Veterinary Medical Center for evaluation of ataxia, cervical pain, 1 episode of acute collapse, dull mentation, and inappetence. Physical examination revealed an elevated temperature of 39.7°C and severe cervical pain. Blood work revealed a mature neutrophilia. Cerebrospinal fluid (CSF) analysis revealed nondegenerative neutrophilic pleocytosis with no infectious agents. A presumptive diagnosis of steroid-responsive meningitis-arteritis was made, and corticosteroid therapy was started. The patient improved initially but experienced a vestibular episode characterized by falling and vertical nystagmus. A magnetic resonance imaging of the brain revealed an epidural abscess in the cervical vertebral canal and diffuse meningeal enhancement in the brain and cranial cervical spine. Abscess drainage revealed degenerate neutrophils and several filamentous, branching organisms. Culture of the initial CSF using an enrichment broth revealed growth of a Gram-positive organism 5 days after fluid collection. The isolate was identified by partial 16S ribosomal DNA sequencing as Actinomyces spp. The patient was successfully treated with long-term antibiotics. Our study reports the long-term survival after medical treatment of bacterial meningoencephalitis and epidural abscessation due to Actinomyces sp. infection in a dog. Bacterial meningoencephalitis should be included as a differential diagnosis in patients with cervical pain and fever, even when a nondegenerative neutrophilic pleocytosis is found on CSF analysis. Culture of the CSF with use of an enrichment broth should be considered in all cases of neutrophilic pleocytosis to rule out infections of the central nervous system.

  6. Long-Term Survival of Individuals Born Small and Large for Gestational Age

    PubMed Central

    Wennerström, E. Christina M.; Simonsen, Jacob; Melbye, Mads

    2015-01-01

    Background Little is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time. Methods A national cohort of 1.7 million live-born singletons in Denmark was followed during 1979–2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA) and large (LGA) gestation weight and mortality overall, by age group and birth cohort. Results Compared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30–3.64) and 1.06 (95% CI, 0.60–1.87) in 30 years and older. HR for dying among SGA adults (20–29 years) were: 1.20 (95% CI, 0.99–1.46) in years 1979–1982 and 1.61 (95% CI, 1.04–2.51) in years 1989–1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm. Conclusions Survival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life. PMID:26390219

  7. Central Versus Peripheral Pulmonary Embolism: Analysis of the Impact on the Physiological Parameters and Long-term Survival

    PubMed Central

    Alonso Martinez, José Luis; Anniccherico Sánchez, Francisco Javier; Urbieta Echezarreta, Miren Aranzazu; García, Ione Villar; Álvaro, Jorge Rojo

    2016-01-01

    Background: Studies aimed at assessing whether the emboli lodged in the central pulmonary arteries carry a worse prognosis than more peripheral emboli have yielded controversial results. Aims: To explore the impact on survival and long-term prognosis of central pulmonary embolism. Patients and Methods: Consecutive patients diagnosed with acute symptomatic pulmonary embolism by means of computed tomography (CT) angiography were evaluated at episode index and traced through the computed system of clinical recording and following-up. Central pulmonary embolism was diagnosed when thrombi were seen in the trunk or in the main pulmonary arteries and peripheral pulmonary embolism when segmental or subsegmental arteries were affected. Results: A total of 530 consecutive patients diagnosed with pulmonary embolism were evaluated; 255 patients had central pulmonary embolism and 275 patients had segmental or subsegmental pulmonary embolism. Patients with central pulmonary embolism were older, had higher plasma levels of N-terminal of the prohormone brain natriuretic peptide (NT-ProBNP), troponin I, D-dimer, alveolar-arterial gradient, and shock index (P < .001 for each one). Patients with central pulmonary embolism had an all-cause mortality of 40% while patients with segmental or subsegmental pulmonary embolism (PE) had an overall mortality of 27% and odds ratio of 1.81 [confidence interval (CI) 95% 1.16-1.9]. Survival was lower in patients with central PE than in patients with segmental or subsegmental pulmonary embolism, even after avoiding confounders (P = .018). Conclusions: Apart from a greater impact on hemodynamics, gas exchange, and right ventricular dysfunction, central pulmonary embolism associates a shorter survival and an increased long-term mortality. PMID:27114970

  8. Long-term survival and virulence of Mycobacterium leprae in amoebal cysts.

    PubMed

    Wheat, William H; Casali, Amy L; Thomas, Vincent; Spencer, John S; Lahiri, Ramanuj; Williams, Diana L; McDonnell, Gerald E; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J; Jackson, Mary

    2014-12-01

    Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs

  9. Long-term Survival and Virulence of Mycobacterium leprae in Amoebal Cysts

    PubMed Central

    Wheat, William H.; Casali, Amy L.; Thomas, Vincent; Spencer, John S.; Lahiri, Ramanuj; Williams, Diana L.; McDonnell, Gerald E.; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J.; Jackson, Mary

    2014-01-01

    Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs

  10. Long-Term Exposure to High Altitude Affects Conflict Control in the Conflict-Resolving Stage.

    PubMed

    Ma, Hailin; Wang, Yan; Wu, Jianhui; Wang, Baoxi; Guo, Shichun; Luo, Ping; Han, Buxin

    2015-01-01

    The neurocognitive basis of the effect of long-term high altitude exposure on conflict control is unclear. Event related potentials (ERPs) were recorded in a flanker task to investigate the influence of high altitude on conflict control in the high-altitude group (who had lived at high altitude for three years but were born at low altitude) and the low-altitude group (living in low altitude only). Although altitude effect was not significant at the behavioral level, ERPs showed cognitive conflict modulation. The interaction between group and trial type was significant: P3 amplitude was greater in the low-altitude group than in the high-altitude group in the incongruent trial. This result suggests that long-term exposure to high altitude affects conflict control in the conflict-resolving stage, and that attentional resources are decreased to resist the conflict control in the high-altitude group.

  11. Long-Term Exposure to High Altitude Affects Conflict Control in the Conflict-Resolving Stage

    PubMed Central

    Wu, Jianhui; Wang, Baoxi; Guo, Shichun; Luo, Ping; Han, Buxin

    2015-01-01

    The neurocognitive basis of the effect of long-term high altitude exposure on conflict control is unclear. Event related potentials (ERPs) were recorded in a flanker task to investigate the influence of high altitude on conflict control in the high-altitude group (who had lived at high altitude for three years but were born at low altitude) and the low-altitude group (living in low altitude only). Although altitude effect was not significant at the behavioral level, ERPs showed cognitive conflict modulation. The interaction between group and trial type was significant: P3 amplitude was greater in the low-altitude group than in the high-altitude group in the incongruent trial. This result suggests that long-term exposure to high altitude affects conflict control in the conflict-resolving stage, and that attentional resources are decreased to resist the conflict control in the high-altitude group. PMID:26671280

  12. Long-term Survival after Resection of HER2+ Infiltrating Ductal Carcinoma Metastasis to the Brainstem.

    PubMed

    Awad, Al-Wala; Zaidi, Hasan A; Awad, Al-Homam; Spetzler, Robert

    2016-01-01

    The central nervous system is a common site of metastatic spread from neoplasms in distant organs, including breast, bone, and lung. The decision to surgically treat these metastatic lesions is often challenging, especially in the setting of systemic disease or when eloquent brain regions are involved. Treating metastatic disease in the brainstem can be technically difficult, and in many institutions, considered a contraindication to surgical intervention, given the relatively high risk of new postoperative neurological deficits. Herein, we report a case of metastatic ductal carcinoma of the breast with spread to the pontine-medullary junction that was treated with aggressive surgical resection and chronic hormonal therapy. After surgical excision of the brainstem lesion, the patient remained asymptomatic and was maintained on trastuzumab therapy over a 10-year follow-up period, with no radiographic or clinical evidence of recurrent disease. To our knowledge, this is the first report of a patient treated for a solitary metastasis to the brainstem with long-term survival. PMID:26929889

  13. Transcriptomic response of Listeria monocytogenes during the transition to the long-term-survival phase.

    PubMed

    Wen, Jia; Deng, Xiangyu; Li, Zengxin; Dudley, Edward G; Anantheswaran, Ramaswamy C; Knabel, Stephen J; Zhang, Wei

    2011-09-01

    Listeria monocytogenes can change its cellular morphology from bacilli to cocci during the transition to the long-term-survival (LTS) phase. The LTS cells demonstrated increased baro- and thermotolerance compared to their vegetative counterparts. So far, the underlying mechanisms that trigger this morphological and physiological transition remain largely unknown. In this study, we compared the transcriptomic profiles of L. monocytogenes serotype 4b strain F2365 at different growth stages in tryptic soy broth with yeast extract (TSBYE) using a whole-genome DNA chip approach. We identified a total of 225 differentially expressed genes (≥4-fold; P < 0.05) during the transition to the LTS phase in TSBYE. Genes related to cell envelope structure, energy metabolism, and transport were most significantly upregulated in the LTS phase. The upregulation of compatible solute transporters may lead to the accumulation of cellular solutes, lowering intracellular water activity and thus increasing bacterial stress resistance during the transition to the LTS phase. The downregulation of genes associated with protein synthesis may indicate a status of metabolic dormancy of the LTS cells. The transcriptomic profiles of resuscitated LTS cells in fresh TSBYE resembled those of log-phase cells (r=0.94), as the LTS cells rapidly resume metabolic activities and transit back to log phase with decreased baro- and thermotolerance. PMID:21764970

  14. A Carboniferous non-onychophoran lobopodian reveals long-term survival of a Cambrian morphotype.

    PubMed

    Haug, Joachim T; Mayer, Georg; Haug, Carolin; Briggs, Derek E G

    2012-09-25

    Lobopodians, a nonmonophyletic assemblage of worm-shaped soft-bodied animals most closely related to arthropods, show two major morphotypes: long-legged and short-legged forms. The morphotype with stubby, conical legs has a long evolutionary history, from the early Cambrian through the Carboniferous, including the living onychophorans and tardigrades. Species with tubular lobopods exceeding the body diameter have been reported exclusively from the Cambrian; the three-dimensionally preserved Orstenotubulus evamuellerae from the uppermost middle Cambrian "Orsten" (Sweden) is the youngest long-legged lobopodian reported thus far. Here we describe a new long-legged lobopodian, Carbotubulus waloszeki gen. et sp. nov., from Mazon Creek, Illinois, USA (∼296 million years ago). This first post-Cambrian long-legged lobopodian extends the range of this morphotype by about 200 million years. The three-dimensionally preserved specimen differs significantly from the associated short-legged form Ilyodes inopinata, of which we also present new head details. The discovery of a Carboniferous long-legged lobopodian provides a more striking example of the long-term survival of Cambrian morphotypes than, for example, the occurrence of a Burgess Shale-type biota in the Ordovician of Morocco and dampens the effect of any major extinction of taxa at the end of the middle Cambrian.

  15. Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice

    PubMed Central

    Venkatesh, Aditya; Ma, Shan; Le, Yun Z.; Hall, Michael N.; Rüegg, Markus A.; Punzo, Claudio

    2015-01-01

    Retinitis pigmentosa (RP) is an inherited photoreceptor degenerative disorder that results in blindness. The disease is often caused by mutations in genes that are specific to rod photoreceptors; however, blindness results from the secondary loss of cones by a still unknown mechanism. Here, we demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) is required to slow the progression of cone death during disease and that constitutive activation of mTORC1 in cones is sufficient to maintain cone function and promote long-term cone survival. Activation of mTORC1 in cones enhanced glucose uptake, retention, and utilization, leading to increased levels of the key metabolite NADPH. Moreover, cone death was delayed in the absence of the NADPH-sensitive cell death protease caspase 2, supporting the contribution of reduced NADPH in promoting cone death. Constitutive activation of mTORC1 preserved cones in 2 mouse models of RP, suggesting that the secondary loss of cones is caused mainly by metabolic deficits and is independent of a specific rod-associated mutation. Together, the results of this study address a longstanding question in the field and suggest that activating mTORC1 in cones has therapeutic potential to prolong vision in RP. PMID:25798619

  16. A Carboniferous non-onychophoran lobopodian reveals long-term survival of a Cambrian morphotype.

    PubMed

    Haug, Joachim T; Mayer, Georg; Haug, Carolin; Briggs, Derek E G

    2012-09-25

    Lobopodians, a nonmonophyletic assemblage of worm-shaped soft-bodied animals most closely related to arthropods, show two major morphotypes: long-legged and short-legged forms. The morphotype with stubby, conical legs has a long evolutionary history, from the early Cambrian through the Carboniferous, including the living onychophorans and tardigrades. Species with tubular lobopods exceeding the body diameter have been reported exclusively from the Cambrian; the three-dimensionally preserved Orstenotubulus evamuellerae from the uppermost middle Cambrian "Orsten" (Sweden) is the youngest long-legged lobopodian reported thus far. Here we describe a new long-legged lobopodian, Carbotubulus waloszeki gen. et sp. nov., from Mazon Creek, Illinois, USA (∼296 million years ago). This first post-Cambrian long-legged lobopodian extends the range of this morphotype by about 200 million years. The three-dimensionally preserved specimen differs significantly from the associated short-legged form Ilyodes inopinata, of which we also present new head details. The discovery of a Carboniferous long-legged lobopodian provides a more striking example of the long-term survival of Cambrian morphotypes than, for example, the occurrence of a Burgess Shale-type biota in the Ordovician of Morocco and dampens the effect of any major extinction of taxa at the end of the middle Cambrian. PMID:22885062

  17. Spiritually Based Resources in Adaptation to Long-Term Prostate Cancer Survival: Perspectives of Elderly Wives

    ERIC Educational Resources Information Center

    Ka'opua, Lana Sue I.; Gotay, Carolyn C.; Boehm, Patricia S.

    2007-01-01

    Spiritually based resources (SBR) generally have a salutary effect on coping with cancer diagnosis and treatment. Few studies address this relationship in long-term cancer survivorship, however. As part of a study on long-term prostate cancer survivorship, wives' ways of coping with cancer-related issues were explored through longitudinal…

  18. Review of uncertainty sources affecting the long-term predictions of space debris evolutionary models

    NASA Astrophysics Data System (ADS)

    Dolado-Perez, J. C.; Pardini, Carmen; Anselmo, Luciano

    2015-08-01

    Since the launch of Sputnik-I in 1957, the amount of space debris in Earth's orbit has increased continuously. Historically, besides abandoned intact objects (spacecraft and orbital stages), the primary sources of space debris in Earth's orbit were (i) accidental and intentional break-ups which produced long-lasting debris and (ii) debris released intentionally during the operation of launch vehicle orbital stages and spacecraft. In the future, fragments generated by collisions are expected to become a significant source as well. In this context, and from a purely mathematical point of view, the orbital debris population in Low Earth Orbit (LEO) should be intrinsically unstable, due to the physics of mutual collisions and the relative ineffectiveness of natural sink mechanisms above~700 km. Therefore, the real question should not be "if", but "when" the exponential growth of the space debris population is supposed to start. From a practical point of view, and in order to answer the previous question, since the end of the 1980's several sophisticated long-term debris evolutionary models have been developed. Unfortunately, the predictions performed with such models, in particular beyond a few decades, are affected by considerable uncertainty. Such uncertainty comes from a relative important number of variables that being either under the partial control or completely out of the control of modellers, introduce a variability on the long-term simulation of the space debris population which cannot be captured with standard Monte Carlo statistics. The objective of this paper is to present and discuss many of the uncertainty sources affecting the long-term predictions done with evolutionary models, in order to serve as a roadmap for the uncertainty and the statistical robustness analysis of the long-term evolution of the space debris population.

  19. Long-term culture of sponge explants: conditions enhancing survival and growth, and assessment of bioactivity.

    PubMed

    de Caralt, Sònia; Agell, Gemma; Uriz, María-J

    2003-07-01

    Sponges are an important source of secondary metabolites with pharmaceutical interest. This is the main reason for the increasing interest of sponge culture recent years. The optimal culture system depends on the species to be cultured: while some species easily produce sponge aggregates after dissociation (primmorphs), others show a great capacity to regenerate after fragmentation (explants). Corticium candelabrum is a Mediterranean bacteriosponge that can undergo asexual reproduction. We have taken advantage of this capability and cultured C. candelabrum explants under several experimental conditions. To find the best conditions for obtaining functional explants, we assayed a range of conditions, including seasons of collection, culture temperature, filtered versus filtered-sterile seawater, addition of antibiotics and proportion of ectosome. We monitored the changes in shape and ultrastructure during the formation of explants. After 24 h, TEM images showed the aquiferous system disarranged, in particular at the sponge periphery. From 2 to 4 weeks later, the aquiferous system regenerated, and fragments became functional sponges (explants). Explants were cultured under two regimes: in vitro and in a closed aquarium system. Antibiotics were only added to the in vitro culture to assess their effect on the symbiotic bacteria, which remained healthy despite the presence of antibiotics. Two food regimens (marine bacteria and green algae) were assayed for their ability to satisfy the metabolic requirements of explants. We monitored explant survival and growth. Explants showed a high long-term survival rate (close to 100%). Growth rates were higher in the closed aquarium system, without antibiotic addition, and fed with algae. Explants cultures were hardly contaminated because manipulation was reduced to a minimum and we used sterilized seawater. C. candelabrum produces bioactive molecules, which may play a defensive role in the sponge and may have pharmaceutical

  20. Long-Term Survival of Fecal Indicator Bacteria in Estuarine Sediment

    NASA Astrophysics Data System (ADS)

    Ferguson, A. S.; Layton, A.; Culligan, P. J.; Kenna, T. C.; Mailloux, B. J.

    2010-12-01

    Fecal contamination of marine and freshwater environments can negatively impact water quality, leading to contaminated drinking water as well as the closure of recreational beaches and waterways. Fecal contamination is routinely assessed using fecal indicator bacteria (FIB), and even though the potential for their long-term survival or proliferation in sediments exist, information linking deposition of FIB with sediment age is scarce. We evaluate sediments as a reservoir for culturable FIB, by examining dated sediments from the lower Hudson River estuary for Escherichia coli (E. coli), enterococcus, and Bacteroides. Sediment cores were collected from in the vicinity of the George Washington (GWB) and Tappan Zee (TZB) Bridges NY. Sediment deposition ages were constrained using gamma emitting radionuclides and pollution chronology. Culturable E. coli and enterococcus were quantified using a culture-based most probable number method (ColilertTM, Idexx Laboratories). Molecular based methods were used to quantify E. coli and Bacteroides. In the GWB core, viable enterococcus or E. coli were consistently detected in sediment younger than the 1960s with maximum concentrations of 39 and 171 cells/g, respectively. In the TZB core, only enterococcus was sporadically detected in sediment younger than 1950 with a maximum concentration of 79 cells/g. Molecular Bacteroides and E. coli were detected in all core samples with a geometric mean of 4.2x104 and 1.2x105 copies/g, respectively. Results indicate that fecal bacteria can survive within estuarine sediments for decades, suggesting that sediments could be a significant and persistent source of bacterial pollution.

  1. Pediatric Cardiopulmonary Bypass Adaptations for Long-Term Survival of Baboons Undergoing Pulmonary Artery Replacement

    PubMed Central

    Whittaker, Carrie; Grist, Gary; Bert, Arthur; Brasky, Kathleen; Neighbors, Stacy; McFall, Christopher; Hilbert, Stephen L.; Drake, William B.; Cromwell, Michael; Mueller, Barbara; Lofland, Gary K.; Hopkins, Richard A.

    2010-01-01

    Abstract: Cardiopulmonary bypass (CPB) protocols of the baboon (Papio cynocephalus anubis) are limited to obtaining experimental data without concern for long-term survival. In the evaluation of pulmonary artery tissue engineered heart valves (TEHVs), pediatric CPB methods are adapted to accommodate the animals’ unique physiology enabling survival up to 6 months until elective sacrifice. Aortic access was by a 14F arterial cannula and atrial access by a single 24F venous cannula. The CPB circuit includes a 3.3 L/min flow rated oxygenator, ¼″ × ⅜″ arterial-venous loop, ⅜″ raceway, and bubble trap. The prime contains 700 mL Plasma-Lyte, 700 units heparin, 5 mL of 50% dextrose, and 20 mg amiodarone. Heparinization (200 u/kg) targets an activated clotting time of 350 seconds. Normothermic CPB was initiated at a 2.5 L/m2/min cardiac index with a mean arterial pressure of 55–80 mmHg. Weaning was monitored with transesophageal echocardiogram. Post-CPB circuit blood was re-infused. Chest tubes were removed with cessation of bleeding. Extubation was performed upon spontaneous breathing. The animals were conscious and upright 3 hours post-CPB. Bioprosthetic valves or TEHVs were implanted as pulmonary replacements in 20 baboons: weight = 27.5 ± 5.6 kg, height = 73 ± 7 cm, body surface area = 0.77 m2 ± 0.08, mean blood flow = 1.973 ± .254 L/min, core temperature = 37.1 ± .1°C, and CPB time = 60 ± 40 minutes. No acidosis accompanied CPB. Sixteen animals survived, four expired. Three died of right ventricular failure and one of an anaphylactoid reaction. Surviving animals had normally functioning replacement valves and ventricles. Baboon CPB requires modifications to include high systemic blood pressure for adequate perfusion into small coronary arteries, careful CPB weaning to prevent ventricular distention, and drug and fluid interventions to abate variable venous return related to a muscularized spleno-splanchnic venous capacity. PMID:21114226

  2. Long-term survival in acute arsenic encephalopathy. Follow-up using newer measures of electrophysiologic parameters.

    PubMed

    Fincher, R M; Koerker, R M

    1987-03-01

    A 20-year-old man survived acute massive arsenic ingestion. The resultant severe encephalopathy and peripheral neuropathy showed limited long-term recovery over the following two years. The patient's clinical course was followed using visual and auditory evoked potentials, computed tomography, electroencephalography, and electromyography.

  3. Long-Term Effects of Outpatient Geriatric Evaluation and Management on Health Care Utilization, Cost, and Survival

    ERIC Educational Resources Information Center

    Engelhardt, Joseph B.; Toseland, Ronald W.; Gao, Jian; Banks, Steven

    2006-01-01

    Purpose: The long-term effectiveness and efficiency of an outpatient geriatric evaluation and management (GEM) program was compared to usual primary care (UPC). Design and Method: A randomized controlled group design was used. Health care utilization, cost of care, and survival were assessed during a 48-month period among a sample of 160 male…

  4. Adaptation to Long-Term Prostate Cancer Survival: The Perspective of Elderly Asian/Pacific Islander Wives

    ERIC Educational Resources Information Center

    Ka'opua, Lana Sue I.; Gotay, Carolyn C.; Hannum, Meghan; Bunghanoy, Grace

    2005-01-01

    Increasingly evident is the important role of partners in patients' adaptation to diagnosis, treatment, and recovery. Yet, little is known about partners' adaptation when patients reach the benchmark known as long-term survival. This study describes elderly wives of prostate cancer survivors' perspectives of adaptation to the enduring challenges…

  5. Long-term care and hospital collaboration. To survive in a reformed healthcare system, long-term care facilities can initiate hospital-based SNFs.

    PubMed

    Hume, S K

    1993-06-01

    Establishing relationships with hospitals may be critical for long-term care facilities facing financial pressures and uncertain futures. One option is to initiate collaborative efforts to develop hospital-based skilled nursing facilities (SNFs). Hospitals, under pressure to move patients to less intensive settings and to diversify, are naturally drawn to long-term care as a related business where they can make limited personnel and financial commitments and extend their continuum of care. Before approaching hospitals to initiate collaborative efforts, long-term care providers should understand how they think and what their strengths and weaknesses are. Long-term and acute care providers have many options for collaboration, including management contracts and joint ventures. In a traditional management contract, the long-term care provider furnishes the administrator and a few key staff in exchange for direct reimbursement for those staff plus a management fee. Another option is for the long-term care facility to provide all the staff for a fee or percentage of revenue. Joint venture options are to form a subsidiary corporation to renovate a floor of the hospital or to have the hospital buy a large percentage of the long-term care facility and share the profits. All these options have potential pitfalls, including differing financial expectations and the threat of unionization at the SNF. Nevertheless, for long-term care facilities struggling under reimbursement cutbacks and other pressures, the benefits may outweigh the risks.

  6. SPORT: Does incidental durotomy affect long-term outcomes in cases of Spinal Stenosis?

    PubMed Central

    Desai, Atman; Ball, Perry A.; Bekelis, Kimon; Lurie, Jon; Mirza, Sohail K.; Tosteson, Tor D.; Weinstein, James N.

    2015-01-01

    Background Incidental durotomy is a familiar encounter during surgery for lumbar spinal stenosis. The impact of durotomy on long-term outcomes remains a matter of debate. Objective To determine the impact of durotomy on the long-term outcomes of patients in the Spine Patient Outcomes Research Trial (SPORT). Methods SPORT cohort participants with a confirmed diagnosis of spinal stenosis (SPS), without associated spondylolisthesis, undergoing standard, first-time, open decompressive laminectomy, with or without fusion, were followed from baseline at 6 weeks, and 3, 6, 12 months and yearly thereafter, at 13 spine clinics in 11 US states. Patient data from this prospectively gathered database was reviewed. As of May 2009, the mean follow-up among all analyzed patients was 43.8 months. Results 409 patients underwent first-time open laminectomy with or without fusion. 37 (9%) of these patients had an incidental durotomy. No significant differences were observed with or without durotomy in age, sex, race, body mass index, the prevalence of smoking, diabetes and hypertension, decompression level, number of levels decompressed, or whether or not an additional fusion was performed. The durotomy group had significantly increased operative duration, operative blood loss and inpatient stay. There were however, no differences in incidence of nerve root injury, mortality, additional surgeries, primary outcomes (SF-36 scores of body pain or physical function, or Oswestry disability index) at yearly follow ups to 4 years. Conclusions Incidental durotomy during first time lumbar laminectomy for spinal stenosis did not impact long-term outcomes in affected patients. PMID:25692369

  7. Predictors of long term survival after hepatic resection for hilar cholangiocarcinoma: A retrospective study of 5-year survivors

    PubMed Central

    Abd ElWahab, Mohamed; El Nakeeb, Ayman; El Hanafy, Ehab; Sultan, Ahmad M; Elghawalby, Ahmed; Askr, Waleed; Ali, Mahmoud; Abd El Gawad, Mohamed; Salah, Tarek

    2016-01-01

    AIM: To determine predictors of long term survival after resection of hilar cholangiocarcinoma (HC) by comparing patients surviving > 5 years with those who survived < 5 years. METHODS: This is a retrospective study of patients with pathologically proven HC who underwent surgical resection at the Gastroenterology Surgical Center, Mansoura University, Egypt between January 2002 and April 2013. All data of the patients were collected from the medical records. Patients were divided into two groups according to their survival: Patients surviving less than 5 years and those who survived > 5 years. RESULTS: There were 34 (14%) long term survivors (5 year survivors) among the 243 patients. Five-year survivors were younger at diagnosis than those surviving less than 5 years (mean age, 50.47 ± 4.45 vs 54.59 ± 4.98, P = 0.001). Gender, clinical presentation, preoperative drainage, preoperative serum bilirubin, albumin and serum glutamic-pyruvic transaminase were similar between the two groups. The level of CA 19-9 was significantly higher in patients surviving < 5 years (395.71 ± 31.43 vs 254.06 ± 42.19, P = 0.0001). Univariate analysis demonstrated nine variables to be significantly associated with survival > 5 year, including young age (P = 0.001), serum CA19-9 (P = 0.0001), non-cirrhotic liver (P = 0.02), major hepatic resection (P = 0.001), caudate lobe resection (P = 0.006), well differentiated tumour (P = 0.03), lymph node status (0.008), R0 resection margin (P = 0.0001) and early postoperative liver cell failure (P = 0.02). CONCLUSION: Liver status, resection of caudate lobe, lymph node status, R0 resection and CA19-9 were demonstrated to be independent risk factors for long term survival. PMID:27358676

  8. Diabetes and cardiovascular disease: Changing the focus from glycemic control to improving the long-term survival

    PubMed Central

    Wang, Cecilia C. Low; Reusch, Jane EB

    2012-01-01

    Diabetes is the fifth leading cause of death worldwide and contributes to leading causes of death, cancer and cardiovascular disease including coronary heart disease, stroke, peripheral vascular disease and other vascular disease. While glycemic management remains a cornerstone of diabetes care, the co-management of hypertension, atherosclerosis, cardiovascular risk reduction and prevention of long-term consequences associated with diabetes are now well recognized as essential to improve long-term survival. Clinical trial evidence substantiates the importance of glycemic control, LDL-cholesterol lowering therapy, blood-pressure lowering, control of albuminuria, and comprehensive approaches targeting multiple risk factors to reduce cardiovascular risk. This article presents a review of the role of diabetes in pathogenesis of atherosclerosis and cardiac dysfunction, recent evidence regarding degree of glycemic control and mortality, and available evidence for a multi-faceted approach to improve long-term outcomes for patients. PMID:23062569

  9. Factors Affecting Antioxidant Response in Fish from a Long-term Mercury-Contaminated Reservoir.

    PubMed

    Sevcikova, M; Modra, H; Blahova, J; Dobsikova, R; Kalina, J; Zitka, O; Kizek, R; Svobodova, Z

    2015-11-01

    The objective of this work was to evaluate antioxidant defence and oxidative damage in organs (liver, gills, kidney, and brain) of five fish species (Aspius aspius, Esox lucius, Sander lucioperca, Abramis brama, Rutilus rutilus) from the long-term mercury-contaminated Skalka Reservoir in the Czech Republic. Special emphasis was placed on a comprehensive assessment of the factors that may affect the antioxidant response to mercury in fish. Antioxidant enzymes (glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) did not significantly respond to mercury contamination. Levels of the analysed enzymes and oxidative damage to lipids were predominantly determined by a separate organ factor or species factor, or by the combination of both (p < 0.001). Levels of total glutathione and the reduced/oxidized glutathione ratio were influenced by mercury contamination in combination with their specific organ distribution (p < 0.001). Our results suggest that species and type of organ alone or in combination are more important factors than chronic exposure to mercury contamination with respect to effects on antioxidant defence in fish under field conditions. Our findings suggest that the main antioxidant defensive mechanism in fish from the studied long-term mercury contaminated site was the inter-tissue distribution of glutathione.

  10. Factors Affecting Antioxidant Response in Fish from a Long-term Mercury-Contaminated Reservoir.

    PubMed

    Sevcikova, M; Modra, H; Blahova, J; Dobsikova, R; Kalina, J; Zitka, O; Kizek, R; Svobodova, Z

    2015-11-01

    The objective of this work was to evaluate antioxidant defence and oxidative damage in organs (liver, gills, kidney, and brain) of five fish species (Aspius aspius, Esox lucius, Sander lucioperca, Abramis brama, Rutilus rutilus) from the long-term mercury-contaminated Skalka Reservoir in the Czech Republic. Special emphasis was placed on a comprehensive assessment of the factors that may affect the antioxidant response to mercury in fish. Antioxidant enzymes (glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) did not significantly respond to mercury contamination. Levels of the analysed enzymes and oxidative damage to lipids were predominantly determined by a separate organ factor or species factor, or by the combination of both (p < 0.001). Levels of total glutathione and the reduced/oxidized glutathione ratio were influenced by mercury contamination in combination with their specific organ distribution (p < 0.001). Our results suggest that species and type of organ alone or in combination are more important factors than chronic exposure to mercury contamination with respect to effects on antioxidant defence in fish under field conditions. Our findings suggest that the main antioxidant defensive mechanism in fish from the studied long-term mercury contaminated site was the inter-tissue distribution of glutathione. PMID:26276034

  11. Surviving the Holocaust: A Meta-Analysis of the Long-Term Sequelae of a Genocide

    ERIC Educational Resources Information Center

    Barel, Efrat; Van Ijzendoorn, Marinus H.; Sagi-Schwartz, Abraham; Bakermans-Kranenburg, Marian J.

    2010-01-01

    The current set of meta-analyses elucidates the long-term psychiatric, psychosocial, and physical consequences of the Holocaust for survivors. In 71 samples with 12,746 participants Holocaust survivors were compared with their counterparts (with no Holocaust background) on physical health, psychological well-being, posttraumatic stress symptoms,…

  12. Supercooling enables long-term transplantation survival following 4 days of liver preservation.

    PubMed

    Berendsen, Tim A; Bruinsma, Bote G; Puts, Catheleyne F; Saeidi, Nima; Usta, O Berk; Uygun, Basak E; Izamis, Maria-Louisa; Toner, Mehmet; Yarmush, Martin L; Uygun, Korkut

    2014-07-01

    The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration.

  13. Reduced Long-Term Relative Survival in Females and Younger Adults Undergoing Cardiac Surgery: A Prospective Cohort Study

    PubMed Central

    Enger, Tone Bull; Pleym, Hilde; Stenseth, Roar; Greiff, Guri; Wahba, Alexander; Videm, Vibeke

    2016-01-01

    Objectives To assess long-term survival and mortality in adult cardiac surgery patients. Methods 8,564 consecutive patients undergoing cardiac surgery in Trondheim, Norway from 2000 until censoring 31.12.2014 were prospectively followed. Observed long-term mortality following surgery was compared to the expected mortality in the Norwegian population, matched on gender, age and calendar year. This enabled assessment of relative survival (observed/expected survival rates) and relative mortality (observed/expected deaths). Long-term mortality was compared across gender, age and surgical procedure. Predictors of reduced survival were assessed with multivariate analyses of observed and relative mortality. Results During follow-up (median 6.4 years), 2,044 patients (23.9%) died. The observed 30-day, 1-, 3- and 5-year mortality rates were 2.2%, 4.4%, 8.2% and 13.8%, respectively, and remained constant throughout the study period. Comparing observed mortality to that expected in a matched sample from the general population, patients undergoing cardiac surgery showed excellent survival throughout the first seven years of follow-up (relative survival ≥ 1). Subsequently, survival decreased, which was more pronounced in females and patients undergoing other procedures than isolated coronary artery bypass grafting (CABG). Relative mortality was higher in younger age groups, females and patients undergoing aortic valve replacement (AVR). The female survival advantage in the general population was obliterated (relative mortality ratio (RMR) 1.35 (1.19–1.54), p<0.001). Increasing observed long-term mortality seen with ageing was due to population risk, and younger age was independently associated with increased relative mortality (RMR per 5 years 0.81 (0.79–0.84), p<0.001)). Conclusions Cardiac surgery patients showed comparable survival to that expected in the general Norwegian population, underlining the benefits of cardiac surgery in appropriately selected patients. The

  14. SOIL AGGREGATE STABILITY AS AFFECTED BY LONG-TERM TILLAGE AND CLAY TYPE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil aggregate stability and dispersivity depend on clay mineralogy. However, little is known about the effect of soil mineralogy on soil crustability for long-term cultivated soil. The effect of long-term tillage on aggregate stability was the objective of our study. More than 20 soil samples chara...

  15. Functional analysis of CD8 lymphocytes in long-term surviving patients after bone marrow transplantation.

    PubMed

    Divine, M; Lecouedic, J P; Gourdin, M F; Oudhriri, N; Zohair, M; Henni, T; Beaujan, F; Vernant, J P; Reyes, F; Farcet, J P

    1988-03-01

    The recovery of T-cell populations after bone marrow transplantation (BMT) is characterized by a persistent expansion of CD8 lymphocytes. Previously, we have shown that beyond 1 year posttransplantation the CD8 lymphocytes consist, to a large extent, of CD8+ HNK1+ cells that suppress, like normal CD8 lymphocytes, immunoglobulin production in vitro. We have further investigated the functional capabilities of CD8 lymphocytes, mostly HNK1+ (from 50 to 77%), in seven long-term BMT patients. As normal, patient CD8 lymphocytes do not suppress (1) phytohemagglutinin (PHA)-induced interleukin 2 (IL2) receptor expression and IL2 responsiveness by normal T cells or (2) the mixed lymphocyte reaction of donor cells. Also as normal, patient CD8 lymphocytes can be activated into potent cytotoxic effectors. Therefore, under the present experimental conditions, the increase in the absolute number of CD8 lymphocytes in the long-term BMT patients is characterized by an expansion of the CD8+ HNK1+-cell subpopulation and a normal suppressor/cytotoxic potential on a per-CD8+ cell basis. PMID:2967308

  16. Retinal Microvasculature Is Associated With Long-Term Survival in the General Adult Dutch Population.

    PubMed

    Mutlu, Unal; Ikram, M Kamran; Wolters, Frank J; Hofman, Albert; Klaver, Caroline C W; Ikram, M Arfan

    2016-02-01

    Retinal vascular diameters are associated with (sub)clinical cardiovascular disease and short-term cardiovascular mortality, but their association with long-term mortality is uncertain. We studied the association of retinal vascular diameters with cause-specific mortality in the general adult Dutch population during 25 years of follow-up. From 1990 to 1993, arteriolar and venular diameters were measured semiautomatically on digitized images in 5674 persons (mean age 68.0 years, 59% women) from the population-based Rotterdam study. Follow-up for mortality was complete till March 2015. Associations between vascular diameters and mortality were examined using Cox proportional hazards models, adjusting for age, sex, cardiovascular risk factors, and the fellow vessel diameter. During 85 770 person-years (mean±SD: 15.1±6.67), 3794 (66.8%) persons died, of whom 1034 due to cardiovascular causes. We found that narrower arterioles and wider venules were associated with higher risk of mortality (adjusted hazard ratio [95% confidence interval] per SD decrease 1.04 [1.00-1.08] and increase 1.07 [1.03-1.12], respectively). For arterioles, these associations were strongest for cardiovascular mortality, whereas venules showed consistent associations for cardiovascular and noncardiovascular mortality. Importantly, these associations remained unchanged after excluding the first 10 years of follow-up as immortal person-time. We found evidence for effect modification with stronger associations in persons <70 years (venules only) and smokers (P value for interaction<0.01). We replicated our findings in another independent cohort from the Rotterdam Study of 3106 persons with 19 880 person-years of follow-up and 144 deaths (hazard ratio for venules 1.22 [1.00-1.49]). Markers of retinal microvasculature are associated with long-term mortality in the general adult Dutch population. PMID:26628677

  17. Long-term survival outcomes of laparoscopic versus open gastrectomy for gastric cancer: a systematic review and meta-analysis.

    PubMed

    Chen, Xin-Zu; Wen, Lei; Rui, Yuan-Yi; Liu, Chao-Xu; Zhao, Qing-Chuan; Zhou, Zong-Guang; Hu, Jian-Kun

    2015-01-01

    Many meta-analyses have confirmed the technical feasibility and favorable short-term surgical outcomes of laparoscopic gastrectomy (LG) for gastric cancer patients, but the long-term survival outcome of LG remains controversial compared with open gastrectomy (OG). This study aimed to compare the 5-year overall survival (OS), recurrence, and gastric cancer-related death of LG with OG among gastric cancer patients. PubMed was searched to February 2014. The resectable gastric cancer patients who underwent curative LG or OG were eligible. The studies that compared 5-year OS, recurrence, or gastric cancer-related death in the LG and OG groups were included. A meta-analysis, meta-regression, sensitivity analysis, subgroup analysis, and stage-specific analysis were performed to estimate the survival outcome between the two groups and identify the potential confounders. Quality assessment was based on a tailored comparability scoring system. Twenty-three studies with 7336 patients were included. The score of comparability between two groups and the extent of lymphadenectomy were two independent confounders. Based on the well-balanced studies, the 5-year OS (OR = 1.07, 95% CI 0.90-1.28, P = 0.45), recurrence (OR = 0.83, 95% CI 0.68-1.02, P = 0.08), and gastric cancer-related death (OR = 0.86, 95% CI 0.65-1.13, P = 0.28) rates were comparable in LG and OG. Several subsets such as the publication year, study region, sample size, gastrectomy pattern, extent of lymphadenectomy, number of nodes harvested, and proportion of T1-2 or N0-1 did not influence the estimates, if they were well balanced. Particularly, the stage-specific estimates obtained comparable results between the two groups. Randomized controlled trials comparing LG with OG remain sparse to assess their long-term survival outcomes. The major contributions of this systematic review compared with other meta-analyses are a comprehensive collection of available long-term survival outcomes within

  18. Chronic sleep deprivation differentially affects short and long-term operant memory in Aplysia.

    PubMed

    Krishnan, Harini C; Noakes, Eric J; Lyons, Lisa C

    2016-10-01

    The induction, formation and maintenance of memory represent dynamic processes modulated by multiple factors including the circadian clock and sleep. Chronic sleep restriction has become common in modern society due to occupational and social demands. Given the impact of cognitive impairments associated with sleep deprivation, there is a vital need for a simple animal model in which to study the interactions between chronic sleep deprivation and memory. We used the marine mollusk Aplysia californica, with its simple nervous system, nocturnal sleep pattern and well-characterized learning paradigms, to assess the effects of two chronic sleep restriction paradigms on short-term (STM) and long-term (LTM) associative memory. The effects of sleep deprivation on memory were evaluated using the operant learning paradigm, learning that food is inedible, in which the animal associates a specific netted seaweed with failed swallowing attempts. We found that two nights of 6h sleep deprivation occurring during the first or last half of the night inhibited both STM and LTM. Moreover, the impairment in STM persisted for more than 24h. A milder, prolonged sleep deprivation paradigm consisting of 3 consecutive nights of 4h sleep deprivation also blocked STM, but had no effect on LTM. These experiments highlight differences in the sensitivity of STM and LTM to chronic sleep deprivation. Moreover, these results establish Aplysia as a valid model for studying the interactions between chronic sleep deprivation and associative memory paving the way for future studies delineating the mechanisms through which sleep restriction affects memory formation. PMID:27555235

  19. Chronic sleep deprivation differentially affects short and long-term operant memory in Aplysia.

    PubMed

    Krishnan, Harini C; Noakes, Eric J; Lyons, Lisa C

    2016-10-01

    The induction, formation and maintenance of memory represent dynamic processes modulated by multiple factors including the circadian clock and sleep. Chronic sleep restriction has become common in modern society due to occupational and social demands. Given the impact of cognitive impairments associated with sleep deprivation, there is a vital need for a simple animal model in which to study the interactions between chronic sleep deprivation and memory. We used the marine mollusk Aplysia californica, with its simple nervous system, nocturnal sleep pattern and well-characterized learning paradigms, to assess the effects of two chronic sleep restriction paradigms on short-term (STM) and long-term (LTM) associative memory. The effects of sleep deprivation on memory were evaluated using the operant learning paradigm, learning that food is inedible, in which the animal associates a specific netted seaweed with failed swallowing attempts. We found that two nights of 6h sleep deprivation occurring during the first or last half of the night inhibited both STM and LTM. Moreover, the impairment in STM persisted for more than 24h. A milder, prolonged sleep deprivation paradigm consisting of 3 consecutive nights of 4h sleep deprivation also blocked STM, but had no effect on LTM. These experiments highlight differences in the sensitivity of STM and LTM to chronic sleep deprivation. Moreover, these results establish Aplysia as a valid model for studying the interactions between chronic sleep deprivation and associative memory paving the way for future studies delineating the mechanisms through which sleep restriction affects memory formation.

  20. The long-term survival of Escherichia coli in river water.

    PubMed

    Flint, K P

    1987-09-01

    Escherichia coli introduced into autoclaved filtered river water survived for up to 260 d at temperatures from 4 degrees to 25 degrees C with no loss of viability. Survival times were less in water which was only filtered through either a Whatman filter paper or a 0.45 micron Millipore filter or in untreated water, suggesting that competition with the natural microbial flora of the water was the primary factor in the disappearance of the introduced bacteria. Survival was also dependent upon temperature with survival at 4 degrees C greater than 15 degrees C greater than 25 degrees C greater than 37 degrees C for any water sample. Direct counts showed that bacterial cells did not disappear as the viable count decreased. The possession of the antibiotic resistance plasmids, R1drd-19 or R144-3, did not enhance survival nor cause a faster rate of decay, indicating that the metabolic burden imposed by a plasmid was not a factor in survival under starvation conditions. There was no evidence of transfer of either plasmid at 15 degrees C or of loss of plasmid function during starvation.

  1. Survival of a very low-birthweight infant with Potter sequence on long-term hemodialysis.

    PubMed

    Miyahara, Jun; Yamamoto, Masaki; Motoshige, Kyoko; Fujita, Naoya; Ohki, Shigeru

    2016-07-01

    Recent advances in neonatal cardiorespiratory management and neonatal renal replacement therapy have led to occasional reports of favorable short-term and long-term outcomes for Potter sequence, once thought to be fatal. The present patient was a girl born at a gestational age of 34 weeks 4 days with a birthweight of 1398 g. She was diagnosed with Potter sequence complicated by pulmonary hypoplasia due to left renal agenesis and small right kidney. Hemodialysis was started because anuria persisted even after persistent pulmonary hypertension receded and cardiorespiratory status improved. Peritoneal dialysis during the clinical course failed to achieve stability because of pericatheter leakage and frequent obstruction of the peritoneal dialysis catheter; in the meantime, hemodialysis was also performed. Once bodyweight passed 3.5 kg, peritoneal dialysis became more feasible with stability; the patient was discharged at 9 months and at the time of writing was on peritoneal dialysis at home, and renal transplantation was planned.

  2. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    PubMed

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-01

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. PMID:25241741

  3. Treatment Factors Associated With Long-Term Survival Following Cytoreductive Surgery and Regional Chemotherapy for Patients with Malignant Peritoneal Mesothelioma

    PubMed Central

    Alexander, H. Richard; Bartlett, David L.; Pingpank, James F.; Libutti, Steven K.; Royal, Richard; Hughes, Marybeth S.; Holtzman, Matthew; Hanna, Nader; Turner, Keli; Beresneva, Tatiana; Zhu, Yue

    2013-01-01

    OBJECTIVES Malignant peritoneal mesothelioma (MPM) is a primary cancer that arises diffusely from the serosa of the peritoneum. Morbidity and mortality are almost invariably due to loco-regional progression; cytoreduction with intra-operative or peri-operative high dose regional chemotherapy has been established as the preferred approach in selected patients. This study was performed to identify factors associated with long-term outcome. METHODS Between January, 1992 and 2010, 211 patients with MPM treated at three major referral centers with operative cytoreduction and hyperthermic intra-operative peritoneal chemotherapy (HIPEC) were analyzed. RESULTS The median actuarial overall survival was 38.4 months; the actuarial 5 and 10 year survivals were 41% and 26%, respectively. On multivariate analysis, factors independently associated with favorable outcome were age less than 60 years (p< 0.01), complete or near complete (R0–1) versus incomplete (R2–3) resection (p< 0.02), low versus high histologic grade (P< 0.01), and the use of cisplatin versus mitomycin-C during HIPEC (p< 0.01). There was an insignificant trend towards female gender and improved survival (male Hazard Ratio: 1.46, 95% CI: 0.89–2.41, p=0.13). CONCUSIONS Operative cytoreduction with HIPEC is associated with long term survival in patients with MPM. Factors associated with survival include age, complete or near complete gross tumor resection, histologic tumor grade, and HIPEC with cisplatin. The fact that cisplatin versus mitomycin-c was independently associated with improved survival demonstrates a salutary effect for HIPEC with cisplatin in the management of patients with MPM. PMID:23489943

  4. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer

    PubMed Central

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-01-01

    Abstract Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm2/m2 for women and 40.8 cm2/m2 for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover

  5. High rates of long-term survival of deep-sea infauna in the laboratory

    NASA Astrophysics Data System (ADS)

    Weinberg, James R.

    1990-08-01

    Living bivalves ( Nucula, Thyasira), a gastropod ( Frigidoalvania brychia) and a calcareous foraminiferan ( Laticarinina pauperata), from 775 m depth in the northwest Atlantic, were maintained in the laboratory for 772 days to measure their survival. The organisms, <4 mm in size, were maintained at 1 atm and at 5°C in cups containing sediment and seawater. Over the 772 day period, 46% of all bivalves and one of two gastropods survived. Minimum estimates for survival of L. pauperata in six containers ranged from 0 to 67% for a 1-2 year period. This study demonstrates that it is feasible to maintain continental slope infauna in the laboratory for long periods of time. Such organisms could be used in experiments that examine their mobility, responses to different sediments and foods, and sizes and shapes of biogenic structures produced in sediments.

  6. Optimization of 15 parameters influencing the long-term survival of bacteria in aquatic systems

    NASA Technical Reports Server (NTRS)

    Obenhuber, D. C.

    1993-01-01

    NASA is presently engaged in the design and development of a water reclamation system for the future space station. A major concern in processing water is the control of microbial contamination. As a means of developing an optimal microbial control strategy, studies were undertaken to determine the type and amount of contamination which could be expected in these systems under a variety of changing environmental conditions. A laboratory-based Taguchi optimization experiment was conducted to determine the ideal settings for 15 parameters which influence the survival of six bacterial species in aquatic systems. The experiment demonstrated that the bacterial survival period could be decreased significantly by optimizing environmental conditions.

  7. A Simpler Creatinine Index Can Predict Long-Term Survival in Chinese Hemodialysis Patients

    PubMed Central

    Lee, Szu-Ying; Yang, Chung-Wei; Hung, Szu-Chun; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Background Low lean body mass (LBM) is an indicator of malnutrition inflammation syndrome, which is common in hemodialysis (HD) patients. The creatinine index (CI) has been validated as a reliable method to estimate LBM and evaluate the protein-energy status of HD patients. However, the traditional creatinine index formula was complex. We sought to investigate the impact of CI derived from a new simple formula on Chinese HD patient outcomes. Methods In this retrospective cohort study, we enrolled 1269 patients who initiated HD between February 1981 and February 2012 and followed them until the end of February 2013. CI was calculated using the simple creatinine kinetic model (CKM) formula. Multiple linear regression analysis and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Results The 1269 HD patients were categorized into 3 groups according to the tertiles of calculated CI between men and women. Each group consisted of 423 patients (50.6% men, 49.4% women). Patients in the highest sex-specific tertile of CI had longer overall survival (HR, 0.46; P 0.002). BMI did not significantly associate with survival after adjustment (HR,0.99; P 0.613). Conclusions CI derived from the simple CKM formula serves as a good parameter than BMI to predict the survival of HD patients. The formula could extend its convenient use in clinical practice for HD patients. PMID:27780214

  8. Soil physical and hydrological properties as affected by long-term addition of various organic amendments

    NASA Astrophysics Data System (ADS)

    Eden, Marie; Völkel, Jörg; Mercier, Vincent; Labat, Christophe; Houot, Sabine

    2014-05-01

    The use of organic residues as soil amendments in agriculture not only reduces the amount of waste needing to be disposed of; it may also lead to improvements in soil properties, including physical and hydrological ones. The present study examines a long-term experiment called "Qualiagro", run jointly by INRA and Veolia Environment in Feucherolles, France (near Paris). It was initiated in 1998 on a loess-derived silt loam (787 g/kg silt, 152 g/kg clay) and includes ten treatments: four types of organic amendments and a control (CNT) each at two levels of mineral nitrogen (N) addition: minimal (Nmin) and optimal (Nopt). The amendments include three types of compost and farmyard manure (FYM), which were applied every other year at a rate of ca. 4 t carbon ha-1. The composts include municipal solid waste compost (MSW), co-compost of green wastes and sewage sludge (GWS), and biowaste compost (BIO). The plots are arranged in a randomized block design and have a size of 450 m²; each treatment is replicated four times (total of 40 plots). Ca. 15 years after the start of the experiment soil organic carbon (OC) had continuously increased in the amended plots, while it remained stable or decreased in the control plots. This compost- or manure-induced increase in OC plays a key role, affecting numerous dependant soil properties like bulk density, porosity and water retention. The water holding capacity (WHC) of a soil is of particular interest to farmers in terms of water supply for plants, but also indicates soil quality and functionality. Addition of OC may affect WHC in different ways: carbon-induced aggregation may increase larger-pore volume and hence WHC at the wet end while increased surface areas may lead to an increased retention of water at the dry end. Consequently it is difficult to predict (e.g. with pedotransfer functions) the impact on the amount of water available for plants (PAW), which was experimentally determined for the soils, along with the entire range

  9. Cell contact as an independent factor modulating cardiac myocyte hypertrophy and survival in long-term primary culture

    NASA Technical Reports Server (NTRS)

    Clark, W. A.; Decker, M. L.; Behnke-Barclay, M.; Janes, D. M.; Decker, R. S.

    1998-01-01

    Cardiac myocytes maintained in cell culture develop hypertrophy both in response to mechanical loading as well as to receptor-mediated signaling mechanisms. However, it has been shown that the hypertrophic response to these stimuli may be modulated through effects of intercellular contact achieved by maintaining cells at different plating densities. In this study, we show that the myocyte plating density affects not only the hypertrophic response and features of the differentiated phenotype of isolated adult myocytes, but also plays a significant role influencing myocyte survival in vitro. The native rod-shaped phenotype of freshly isolated adult myocytes persists in an environment which minimizes myocyte attachment and spreading on the substratum. However, these conditions are not optimal for long-term maintenance of cultured adult cardiac myocytes. Conditions which promote myocyte attachment and spreading on the substratum, on the other hand, also promote the re-establishment of new intercellular contacts between myocytes. These contacts appear to play a significant role in the development of spontaneous activity, which enhances the redevelopment of highly differentiated contractile, junctional, and sarcoplasmic reticulum structures in the cultured adult cardiomyocyte. Although it has previously been shown that adult cardiac myocytes are typically quiescent in culture, the addition of beta-adrenergic agonists stimulates beating and myocyte hypertrophy, and thereby serves to increase the level of intercellular contact as well. However, in densely-plated cultures with intrinsically high levels of intercellular contact, spontaneous contractile activity develops without the addition of beta-adrenergic agonists. In this study, we compare the function, morphology, and natural history of adult feline cardiomyocytes which have been maintained in cultures with different levels of intercellular contact, with and without the addition of beta-adrenergic agonists

  10. Nomograms for predicting long-term survival in patients with non-metastatic nasopharyngeal carcinoma in an endemic area

    PubMed Central

    Meng, Xiang-Qi; Guo, Xiang; Qian, Chao-Nan; Wu, Pei-Hong; Huang, Pei-Yu

    2016-01-01

    Purpose Nomogram for predicting more than a 5-year survival for non-metastatic nasopharyngeal carcinoma (NPC) was lacking. This study aimed to develop the new nomograms to predict long-term survival in these patients. Results The median follow-up time for training set and test set was 95.2 months and 133.3 months, respectively. The significant predictors for death were age, gender, body mass index (BMI), T stage, N stage, lactate dehydrogenase (LDH), and radiotherapy techniques. For predicting recurrence, age, gender, T stage, LDH, and radiotherapy techniques were significant predictors, whereas age, gender, BMI, T stage, N stage and LDH were significant predictors for distant metastasis. The calibration curves showed the good agreements between nomogram-predicted and actual survival. The c-indices for predicting death, recurrence, and distant metastases between nomograms and the TNM staging system were 0.767 VS.0.686 (P<0.001), 0.655 VS.0.585 (P<0.001), and 0.881 VS.0.754 (P<0.001), respectively. These results were further confirmed in the test set. Methods On the basis of a retrospective study of 1593 patients (training set) who received radiotherapy alone or concurrent chemoradiotherapy from 2000 to 2004, significant predictors were identified and incorporated to build the nomograms. The calibration curves of nomogram-predicted survival versus the actual survival were plotted and reviewed. Bootstrap validation was performed to calculate the concordance index (c-index). These models were further validated in an independent prospective trial (test set, n=400). Conclusion The established nomograms suggest more-accurate long-term prediction for patients with non-metastatic NPC. PMID:27102440

  11. From Exit to Entry: Long-term Survival and Transmission of Salmonella

    PubMed Central

    Waldner, Landon L.; MacKenzie, Keith D.; Köster,, Wolfgang; White, Aaron P.

    2012-01-01

    Salmonella spp. are a leading cause of human infectious disease worldwide and pose a serious health concern. While we have an improving understanding of pathogenesis and the host-pathogen interactions underlying the infection process, comparatively little is known about the survival of pathogenic Salmonella outside their hosts. This review focuses on three areas: (1) in vitro evidence that Salmonella spp. can survive for long periods of time under harsh conditions; (2) observations and conclusions about Salmonella persistence obtained from human outbreaks; and (3) new information revealed by genomic- and population-based studies of Salmonella and related enteric pathogens. We highlight the mechanisms of Salmonella persistence and transmission as an essential part of their lifecycle and a prerequisite for their evolutionary success as human pathogens. PMID:25436767

  12. Hodgkin disease (1973-2002): long-term survival and cure fractions.

    PubMed

    Bouliotis, George; Bessell, Eric M

    2015-05-01

    The Nottinghamshire Lymphoma Registry contains the details of all patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a stable population of 1.1 million. The aim of this study was to investigate the relative survival and estimate the cure fraction for patients with Hodgkin disease (HD) using various cure fraction models. Five- and 10-year survival was estimated in comparison to the general population of the same age, gender and year of diagnosis. Relative survival probabilities at 10 years were 52.3% for the 1973-1982 cohort, 67.8% (1983-1992) and 75.7% (1993-2002). The estimated cured fraction (π) was 45%, 65% and 75%, respectively, for the same cohorts. There was very little excess mortality after 4 years from treatment. The prognosis of patients with HD has improved progressively within a defined unselected population over this 30-year period. In the 1993-2002 cohort the prognosis after 4 years of treatment is almost the same as for a normal population.

  13. Dryland soil chemical properties and crop yields affected by long-term tillage and cropping sequence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Information on the effect of long-term management on soil nutrients and chemical properties is scanty. We examined the 30-yr effect of tillage frequency and cropping sequence combination on dryland soil Olsen-P, K, Ca, Mg, Na, SO4-S, and Zn concentrations, pH, electrical conductivity (EC), and catio...

  14. GEOCHEMICAL AND MICROBIAL REACTIONS AFFECTING THE LONG-TERM PERFORMANCE OF IN SITU 'IRON BARRIERS'

    EPA Science Inventory

    The in situ application of granular iron (Fe0) has become popular for the destruction of halogenated organic compounds for the immobilization of specific metals in groundwater. However, a knowledge gap exists concerning the long-term performance of the Fe0-barriers. The corrosi...

  15. Long-term survival of full trisomy 13 in a 14 year old male: a case report.

    PubMed

    Imataka, G; Hagisawa, S; Nitta, A; Hirabayashi, H; Suzumura, H; Arisaka, O

    2016-03-01

    Long term survival for the cases of trisomy 13 into over a first decade is very rare. We reported here the case of a 14-year-old male karyotype with full type of trisomy 13. In this clinical phenomenon, the case had typical facial, finger and limb anomalies for trisomy 13. Arterial septal defect and patent ductus arteriosus were recognized using ultrasonography after birth. Major cerebral malformation such as holoprosencephaly or cerebellar hypoplasia were also not revealed. After 5 months of his age, artificial ventilation therapy for dyspnea associated with laryngomalacia was required. A tracheotomy was performed at 6 months of his age. After 12 years old, intractable partial epilepsy was recognized. For his partial seizures, a treatment with a combination of two anti-epileptic drugs, valproic acid and levetiracetam, were advised. Now he is alive for 14-years-old and he is the 4th longest surviving patient with full karyotype of trisomy 13. PMID:27010151

  16. Implications of subzero metabolic activity on long-term microbial survival in terrestrial and extraterrestrial permafrost.

    PubMed

    Amato, Pierre; Doyle, Shawn M; Battista, John R; Christner, Brent C

    2010-10-01

    The survival of microorganisms over extended time frames in frozen subsurface environments may be limited by chemical (i.e., via hydrolysis and oxidation) and ionizing radiation-induced damage to chromosomal DNA. In an effort to improve estimates for the survival of bacteria in icy terrestrial and extraterrestrial environments, we determined rates of macromolecular synthesis at temperatures down to -15°C in bacteria isolated from Siberian permafrost (Psychrobacter cryohalolentis K5 and P. arcticus 273-4) and the sensitivity of P. cryohalolentis to ionizing radiation. Based on experiments conducted over ≈400 days at -15°C, the rates of protein and DNA synthesis in P. cryohalolentis were <1 to 16 proteins cell(-1) d(-1) and 83 to 150 base pairs (bp) cell(-1) d(-1), respectively; P. arcticus synthesized DNA at rates of 20 to 1625 bp cell(-1) d(-1) at -15°C under the conditions tested. The dose of ionizing radiation at which 37% of the cells survive (D(37)) of frozen suspensions of P. cryohalolentis was 136 Gy, which was ∼2-fold higher (71 Gy) than identical samples exposed as liquid suspensions. Laboratory measurements of [(3)H]thymidine incorporation demonstrate the physiological potential for DNA metabolism at -15°C and suggest a sufficient activity is possible to offset chromosomal damage incurred in near-subsurface terrestrial and martian permafrost. Thus, our data imply that the longevity of microorganisms actively metabolizing within permafrost environments is not constrained by chromosomal DNA damage resulting from ionizing radiation or entropic degradation over geological time.

  17. Long-term Survival of Patients With Invasive Ultra-thin Cutaneous Melanoma

    PubMed Central

    Vecchiato, Antonella; Zonta, Elisa; Campana, Luca; Dal Bello, Giacomo; Rastrelli, Marco; Rossi, Carlo Riccardo; Alaibac, Mauro

    2016-01-01

    Abstract The incidence of cutaneous melanoma is increasing worldwide, especially for thin melanoma (Breslow ≤1 mm). Thin cutaneous melanoma has a favorable prognosis but there are few data about the prognosis of patients with ultra-thin cutaneous melanoma (Breslow ≤ 0.5 mm). Our aim was to investigate the disease-free survival among patients with invasive cutaneous melanoma with Breslow ≤ 0.5 mm after 10 years from the initial diagnosis. A retrospective review of 240 cutaneous melanoma patients with Breslow ≤ 0.5 mm was performed. Recurrence, death from cutaneous melanoma, and disease-free survival were all identified. In the whole group of patients, we observed only 2 deaths from cutaneous melanoma. Median follow-up was 13, 11 years. Among all 240 patients, 221 were alive and disease free, 2 died of cutaneous melanoma, 11 died of other non-neoplastic diseases, 5 died of other neoplastic diseases different from melanoma, and 1 patient had a local recurrence; therefore the 10-year melanoma survival rate was 99.6%. Our data indicate that death from cutaneous melanoma in the group of patients with Breslow ≤0.5 mm was a very rare event and that diagnosis at this stage dramatically decreases the risk of developing metastatic tumors to a <0.5% also after a 10-year period of follow-up. Limitation of the study includes the fact that other risk factors for melanoma, notably ulceration, and mitotic rate, were not evaluated. PMID:26765437

  18. Prognostic factors, long-term survival, and outcome of cancer patients receiving chemotherapy in the intensive care unit.

    PubMed

    Wohlfarth, Philipp; Staudinger, Thomas; Sperr, Wolfgang R; Bojic, Andja; Robak, Oliver; Hermann, Alexander; Laczika, Klaus; Carlström, Alexander; Riss, Katharina; Rabitsch, Werner; Bojic, Marija; Knoebl, Paul; Locker, Gottfried J; Obiditsch, Maria; Fuhrmann, Valentin; Schellongowski, Peter

    2014-10-01

    Prognostic factors and outcomes of cancer patients with acute organ failure receiving chemotherapy (CT) in the intensive care unit (ICU) are still incompletely described. We therefore retrospectively studied all patients who received CT in any ICU of our institution between October 2006 and November 2013. Fifty-six patients with hematologic (n = 49; 87.5 %) or solid (n = 7; 12.5 %) malignancies, of which 20 (36 %) were diagnosed in the ICU, were analyzed [m/f ratio, 33:23; median age, 47 years (IQR 32 to 62); Charlson Comorbidity Index (CCI), 3 (2 to 5); Simplified Acute Physiology Score II (SAPS II), 50 (39 to 61)]. The main reasons for admission were acute respiratory failure, acute kidney failure, and septic shock. Mechanical ventilation and vasopressors were employed in 34 patients (61 %) respectively, hemofiltration in 22 (39 %), and extracorporeal life support in 7 (13 %). Twenty-seven patients (48 %) received their first CT in the ICU. Intention of therapy was cure in 46 patients (82 %). Tumor lysis syndrome (TLS) developed in 20 patients (36 %). ICU and hospital survival was 75 and 59 %. Hospital survivors were significantly younger; had lower CCI, SAPS II, and TLS risk scores; presented less often with septic shock; were less likely to develop TLS; and received vasopressors, hemofiltration, and thrombocyte transfusions in lower proportions. After discharge, 88 % continued CT and 69 % of 1-year survivors were in complete remission. Probability of 1- and 2-year survival was 41 and 38 %, respectively. Conclusively, administration of CT in selected ICU cancer patients was feasible and associated with considerable long-term survival as well as long-term disease-free survival.

  19. Adoptive TIL Transfer in the Adjuvant Setting for Melanoma: Long-Term Patient Survival

    PubMed Central

    Khammari, Amir; Knol, Anne-Chantal; Nguyen, Jean-Michel; Bossard, Céline; Denis, Marc-Guillaume; Pandolfino, Marie-Christine; Quéreux, Gaëlle; Bercegeay, Sylvain; Dréno, Brigitte

    2014-01-01

    Two first analyses of our clinical trial on TIL as adjuvant therapy for melanoma were published in 2002 and 2007. We present here an update of the clinical results after a 17-year median followup. In this trial, disease-free patients were randomly assigned to receive either TIL/IL-2 or IL-2. The relapse-free survival (RFS) was the primary objective. Eighty-eight patients were enrolled. A new analysis performed in May 2013 did not show significant changes in RFS or OS duration. However, our first finding on the association between the number of invaded lymph nodes and TIL effectiveness was strengthened. The Cox model adjusted on this interaction showed for the first time a significant treatment effect when considering the overall population, both on the RFS and OS. Patients treated with TIL had a longer RFS (P = 0.023) or OS (P = 0.020). This study being with a very long followup (17 years), confirmed the association between TIL effectiveness and the number of invaded lymph nodes, indicating that a low tumor burden could be a crucial factor enhancing the curative effect of TIL in possible microscopic residual disease. Moreover, we confirmed that a prolonged survival was associated with the presence of specific TIL and a decrease in Foxp3 expression. PMID:24741578

  20. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy.

    PubMed

    Hammond, Suzan M; Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F; Bowerman, Melissa; Sleigh, James N; Meijboom, Katharina E; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J; Wood, Matthew J A

    2016-09-27

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  1. Long-term survival of hepatitis A virus and poliovirus type 1 in mineral water.

    PubMed

    Biziagos, E; Passagot, J; Crance, J M; Deloince, R

    1988-11-01

    The survival in mineral water of hepatitis A virus (HAV) and poliovirus type 1 was compared, under controlled experimental conditions, at 4 degrees C and room temperature. Viral infectivity titers were determined by cell culture titration, while HAV antigenicity was monitored by radioimmunoassay-endpoint titration. Both viruses persisted longest at 4 degrees C. At this temperature, after 1 year of exposure, the inactivation of either HAV or poliovirus type 1 was not important. At room temperature, poliovirus type 1 was not detected after 300 days, whereas HAV was still infectious. For both temperatures, the computed regression coefficients of best-fit lines for inactivation rates for the two viruses were significantly different. The survival of HAV was also studied at 4 degrees C and room temperature in mineral water with 5- and 50-micrograms/ml protein concentrations (i.e., purity of the virus suspension) for 120 days. As shown by a comparison of the regression coefficients for the inactivation rates, the stability of HAV in mineral water depends on protein concentration and temperature. Radioimmunoassay-endpoint titration results showed inactivation patterns similar to those of cell culture titration, with the most significant reduction in HAV antigenicity at room temperature. At the two temperatures, the infectivity of HAV declined at a faster rate than the antigenicity.

  2. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  3. Long-term Differences in Tillage and Land Use Affect Intra-aggregate Pore Heterogeneity

    SciTech Connect

    Kravchenko, A.N.; Wang, A.N.W.; Smucker, A.J.M.; Rivers, M.L.

    2012-10-25

    Recent advances in computed tomography provide measurement tools to study internal structures of soil aggregates at micrometer resolutions and to improve our understanding of specific mechanisms of various soil processes. Fractal analysis is one of the data analysis tools that can be helpful in evaluating heterogeneity of the intra-aggregate internal structures. The goal of this study was to examine how long-term tillage and land use differences affect intra-aggregate pore heterogeneity. The specific objectives were: (i) to develop an approach to enhance utility of box-counting fractal dimension in characterizing intra-aggregate pore heterogeneity; (ii) to examine intra-aggregate pores in macro-aggregates (4-6 mm in size) using the computed tomography scanning and fractal analysis, and (iii) to compare heterogeneity of intra-aggregate pore space in aggregates from loamy Alfisol soil subjected to 20 yr of contrasting management practices, namely, conventional tillage (chisel plow) (CT), no-till (NT), and native succession vegetation (NS). Three-dimensional images of the intact aggregates were obtained with a resolution of 14.6 {micro}m at the Advanced Photon Source, Argonne National Laboratory, Argonne, IL. Proposed box-counting fractal dimension normalization was successfully implemented to estimate heterogeneity of pore voxel distributions without bias associated with different porosities in soil aggregates. The aggregates from all three studied treatments had higher porosity associated with large (>100 {micro}m) pores present in their centers than in their exteriors. Pores 15 to 60 {micro}m were equally abundant throughout entire aggregates but their distributions were more heterogeneous in aggregate interiors. The CT aggregates had greater numbers of pores 15 to 60 {micro}m than NT and NS. Distribution of pore voxels belonging to large pores was most heterogeneous in the aggregates from NS, followed by NT and by CT. This result was consistent with presence of

  4. Long-term analysis of survival, fertility, and population growth rate of black bears in North Carolina

    USGS Publications Warehouse

    Brongo, L.L.; Mitchell, M.S.; Grand, J.B.

    2005-01-01

    We estimated survival, fertility, and realized and asymptotic population growth rates from 1981 to 2002 for a protected population of black bears (Ursus americanus) in the southern Appalachian Mountains. We used Akaike's information criterion to assess the time interval for averaging observations that was best for estimating vital rates for our study, given our yearly sample sizes. The temporal symmetry approach allowed us to directly assess population growth and to address all losses and gains to the population by using only capture data, offering an alternative to the logistically intensive collection of reproductive data. Models that averaged survival and fertility across 5- and 7-year time intervals were best supported by our data. Studies of black bear populations with annual sample sizes similar to ours should be of at least 5 years in duration to estimate vital rates reliably, and at least 10 years in duration to evaluate changes in population growth rate (??). We also hypothesized that survival would not track changes in ?? because ?? is influenced by both survival and fertility. The 5-year model supported our hypothesis, but the 7-year model did not. Where long-term dynamics of large, relatively stable bear populations are of interest, monitoring survival is likely to be sufficient for evaluating trends in ??. For rapidly changing, small populations, however, failure to incorporate fertility into assessments of ?? could be misleading. ?? 2005 American Society of Mammalogists.

  5. [Embryonal rhabdomyosarcoma of the middle ear: description of a case with long-term survival].

    PubMed

    Artesi, L; Sbrocca, M

    1990-01-01

    A case is described of embryonal rhabdomyosarcoma (E.R.) of the middle ear in a 4-year-old child; survival has been over 9 years. R.E. is the most common malignant tumor of the auricular region in children and is most often fatal due to locoregional extensions or secondary metastases carried through the bloodstream and lymphatic systems. The basis for treatment is a multidisciplinary approach to the disease: surgery with as broad an exeresis as possible; radiotherapy with tumor-killing doses of 5,500/6,000 rads; and polychemotherapy (Vincristina, Endoxan, Methotrexate). Such "aggressive" treatment often results in a high rate of morbidity with complications involving the blood, bones, eyes and meninx often requiring temporary suspension of treatment and prolonged hospitalization. PMID:2260443

  6. [Long-Term Survival of a Case of Quadruple Cancers with Cholangiocellular Carcinoma].

    PubMed

    Kumazu, Yuta; Yukawa, Norio; Hashimoto, Itaru; Yamada, Takanobu; Yamamoto, Naoto; Mushiake, Hiroyuki; Oshima, Takashi; Enaka, Makiko; Rino, Yasushi; Masuda, Munetaka

    2015-11-01

    The patient was an 82-year-old man, who contracted chronic hepatitis C in 1977. In 1997, he was diagnosed with intraductal papillary-mucinous neoplasm (IPMN), and was treated with surgery. In August 2005, cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC) were detected, and he underwent a subsegmentectomy of the liver. In February 2007, he had a supradiaphragmatic lymph node recurrence of CCC. It was a solitary lesion; therefore, we resected the recurrent tumor by thoracoscopic surgery. In January 2012, squamous cell lung cancer was detected and he had a thoracoscopic operation. Furthermore, in February 2015, 2HCCs were detected in S5 and S5/8 of the liver. He underwent radiofrequency ablation. Over the course of 18 years, this patient developed cancers in his pancreas, intrahepatic bile duct, liver, and lung. However, the patient has survived without recurrence because of aggressive therapy and diligent surveillance after surgery. PMID:26805198

  7. Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies

    PubMed Central

    Mordecai, Gideon J; Brettell, Laura E; Martin, Stephen J; Dixon, David; Jones, Ian M; Schroeder, Declan C

    2016-01-01

    Over the past 50 years, many millions of European honey bee (Apis mellifera) colonies have died as the ectoparasitic mite, Varroa destructor, has spread around the world. Subsequent studies have indicated that the mite's association with a group of RNA viral pathogens (Deformed Wing Virus, DWV) correlates with colony death. Here, we propose a phenomenon known as superinfection exclusion that provides an explanation of how certain A. mellifera populations have survived, despite Varroa infestation and high DWV loads. Next-generation sequencing has shown that a non-lethal DWV variant ‘type B' has become established in these colonies and that the lethal ‘type A' DWV variant fails to persist in the bee population. We propose that this novel stable host-pathogen relationship prevents the accumulation of lethal variants, suggesting that this interaction could be exploited for the development of an effective treatment that minimises colony losses in the future. PMID:26505829

  8. Superinfection exclusion and the long-term survival of honey bees in Varroa-infested colonies.

    PubMed

    Mordecai, Gideon J; Brettell, Laura E; Martin, Stephen J; Dixon, David; Jones, Ian M; Schroeder, Declan C

    2016-05-01

    Over the past 50 years, many millions of European honey bee (Apis mellifera) colonies have died as the ectoparasitic mite, Varroa destructor, has spread around the world. Subsequent studies have indicated that the mite's association with a group of RNA viral pathogens (Deformed Wing Virus, DWV) correlates with colony death. Here, we propose a phenomenon known as superinfection exclusion that provides an explanation of how certain A. mellifera populations have survived, despite Varroa infestation and high DWV loads. Next-generation sequencing has shown that a non-lethal DWV variant 'type B' has become established in these colonies and that the lethal 'type A' DWV variant fails to persist in the bee population. We propose that this novel stable host-pathogen relationship prevents the accumulation of lethal variants, suggesting that this interaction could be exploited for the development of an effective treatment that minimises colony losses in the future. PMID:26505829

  9. Influence of donor–recipient sex mismatch on long-term survival of pancreatic grafts

    PubMed Central

    Li, Zhiwei; Mei, Shengmin; Xiang, Jie; Zhou, Jie; Zhang, Qijun; Yan, Sheng; Zhou, Lin; Hu, Zhenhua; Zheng, Shusen

    2016-01-01

    To assess the role of sex mismatch on graft survival after pancreas transplantation. We evaluated 24,195 pancreas-transplant recipients reported in the Scientific Registry of Transplant Recipients over a 25-year period. Pancreatic graft survival (PGS) was analyzed according to donor–recipient sex pairing using Kaplan–Meier estimations. Hazard ratios were estimated using Cox proportional hazard models. A total of 14,187 male and 10,008 female recipients were included in final analyses. Mean follow-up was 8.3 ± 5.7 years. In multivariate analyses, neither recipient sex nor donor sex was associated with pancreatic graft failure (PGF), but donor–recipient sex mismatch (regardless of recipient sex) was an independent predictor of PGS (HR, 1.09; 95% CI, 1.04–1.14; p < 0.001). Compared with M → M sex-matched recipients in univariate analyses, M → F and F → M sex mismatches were associated with an increased risk of PGF. Adjustment for significant recipient and donor factors eliminated the association between F → M sex mismatch and PGF (HR, 1.02; 95% CI, 0.93–1.10; p = 0.752), but not M → F (1.09; 1.02–1.17; 0.020). Stratified analyses suggested that the negative effect of donor–recipient sex mismatch could be neutralized in older patients. These findings suggest that donor–recipient sex pairing should be taken into consideration in organ-allocation strategies. PMID:27403718

  10. Facilitating Long-Term Recovery from Natural Disasters: Psychosocial Programming for Tsunami-Affected Schools of Sri Lanka

    ERIC Educational Resources Information Center

    Nastasi, Bonnie K.; Jayasena, Asoka; Summerville, Meredith; Borja, Amanda P.

    2011-01-01

    This article reports the findings of a school-based intervention project conducted in the Southern Province of Sri Lanka 15 to 18 months after the December 2004 Tsunami. The work responds to the need for culturally relevant programming to address long-term psychosocial recovery of children and adolescents affected by large scale disasters. Program…

  11. Temporary treatment during primary HIV infection does not affect virologic response to subsequent long-term treatment.

    PubMed

    Grijsen, Marlous L; Wit, Ferdinand W N M; Jurriaans, Suzanne; Kroon, Frank P; Schippers, Emile F; Koopmans, Peter; Gras, Luuk; Lange, Joep M A; Prins, Jan M

    2014-01-01

    Temporary cART during primary HIV-infection (PHI) did not select for drug resistance mutations after treatment interruption and did not affect the subsequent virological response to long-term cART. Our data demonstrate that fear of drug resistance development is not a valid argument to refrain from temporary early treatment during PHI.

  12. Empowering disaster-affected communities for long-term reconstruction: intervening in Sri Lanka after the tsunami.

    PubMed

    Dominelli, Lena

    2013-01-01

    The 2004 Indian Ocean tsunami highlighted the importance of interdependencies between nations, delivery of humanitarian aid in an empowering manner, and long-term reconstruction. I examine relationships between overseas actors and local residents in tsunami-affected villages in Sri Lanka in a project initiated by the International Association of Schools of Social Work through its Rebuilding People's Lives After Disasters Network and another based on an institutional endeavour supported by Durham University because these sought to empower local communities through local, egalitarian partnerships. Lacking sufficient educational resources, capacity building in social work education has become a long-term objective.

  13. Using electrophysiology to demonstrate that cueing affects long-term memory storage over the short term.

    PubMed

    Maxcey, Ashleigh M; Fukuda, Keisuke; Song, Won S; Woodman, Geoffrey F

    2015-10-01

    As researchers who study working memory, we often assume that participants keep a representation of an object in working memory when we present a cue that indicates that the object will be tested in a couple of seconds. This intuitively accounts for how well people can remember a cued object, relative to their memory for that same object presented without a cue. However, it is possible that this superior memory does not purely reflect storage of the cued object in working memory. We tested the hypothesis that cues presented during a stream of objects, followed by a short retention interval and immediate memory test, can change how information is handled by long-term memory. We tested this hypothesis by using a family of frontal event-related potentials believed to reflect long-term memory storage. We found that these frontal indices of long-term memory were sensitive to the task relevance of objects signaled by auditory cues, even when the objects repeated frequently, such that proactive interference was high. Our findings indicate the problematic nature of assuming process purity in the study of working memory, and demonstrate that frequent stimulus repetitions fail to isolate the role of working memory mechanisms.

  14. Using electrophysiology to demonstrate that cueing affects long-term memory storage over the short term.

    PubMed

    Maxcey, Ashleigh M; Fukuda, Keisuke; Song, Won S; Woodman, Geoffrey F

    2015-10-01

    As researchers who study working memory, we often assume that participants keep a representation of an object in working memory when we present a cue that indicates that the object will be tested in a couple of seconds. This intuitively accounts for how well people can remember a cued object, relative to their memory for that same object presented without a cue. However, it is possible that this superior memory does not purely reflect storage of the cued object in working memory. We tested the hypothesis that cues presented during a stream of objects, followed by a short retention interval and immediate memory test, can change how information is handled by long-term memory. We tested this hypothesis by using a family of frontal event-related potentials believed to reflect long-term memory storage. We found that these frontal indices of long-term memory were sensitive to the task relevance of objects signaled by auditory cues, even when the objects repeated frequently, such that proactive interference was high. Our findings indicate the problematic nature of assuming process purity in the study of working memory, and demonstrate that frequent stimulus repetitions fail to isolate the role of working memory mechanisms. PMID:25604772

  15. Perioperative treatment options in resectable pancreatic cancer - how to improve long-term survival

    PubMed Central

    Sinn, Marianne; Bahra, Marcus; Denecke, Timm; Travis, Sue; Pelzer, Uwe; Riess, Hanno

    2016-01-01

    Surgery remains the only chance of cure for pancreatic cancer, but only 15%-25% of patients present with resectable disease at the time of primary diagnosis. Important goals in clinical research must therefore be to allow early detection with suitable diagnostic procedures, to further broaden operation techniques and to determine the most effective perioperative treatment of either chemotherapy and/or radiation therapy. More extensive operations involving extended pancreatectomy, portal vein resection and pancreatic resection in resectable pancreatic cancer with limited liver metastasis, performed in specialized centers seem to be the surgical procedures with a possible impact on survival. After many years of stagnation in pharmacological clinical research on advanced pancreatic ductal adenocarcinomas (PDAC) - since the approval of gemcitabine in 1997 - more effective cytotoxic substances (nab-paclitaxel) and combinations (FOLFIRINOX) are now available for perioperative treatment. Additionally, therapies with a broader mechanism of action are emerging (stroma depletion, immunotherapy, anti-inflammation), raising hopes for more effective adjuvant and neoadjuvant treatment concepts, especially in the context of “borderline resectability”. Only multidisciplinary approaches including radiology, surgery, medical and radiation oncology as the backbones of the treatment of potentially resectable PDAC may be able to further improve the rate of cure in the future. PMID:26989460

  16. Surgical Therapy for a Solitary Form of Hepatic Epithelioid Hemangioendothelioma: A Long-Term Survival Case.

    PubMed

    Oshima, Nobu; Terajima, Hiroaki; Hosotani, Ryo

    2009-01-01

    Hepatic epithelioid hemangioendothelioma (HEHE) is a rare neoplasm of vascular origin. The clinical presentation of HEHE is variable, and the therapeutic criteria are still unclear since its natural history is unpredictable. A 53-year-old woman was admitted to our hospital because she had a 2.5-cm diameter nodule in the segment V of the liver. She had undergone segmental hepatectomy for solitary HEHE in segment VII 10 years before. There had been no recurrence for the 10 years after the first operation. The tumor was diagnosed as a new lesion of HEHE by percutaneous needle liver biopsy, and thereafter repeated hepatectomy was performed. HEHE seems to be resistant to chemotherapy and radiotherapy. Either surgical resection or orthotopic liver transplantation is generally recommended as a curative treatment for this disease. However, HEHE tends to be detected in multiple lesions, and localized disease is rare. Therefore, the chance of resection is very low. Some reports do not recommend local resection because of early aggressive tumor spread even after curative resection. We herein demonstrate a rare case of HEHE in a patient who underwent repeated hepatectomy for a solitary lesion and who survived for 17 years. It is concluded that surgical resection is one of the most effective treatments for a solitary form of HEHE. PMID:21103278

  17. Surgical Therapy for a Solitary Form of Hepatic Epithelioid Hemangioendothelioma: A Long-Term Survival Case

    PubMed Central

    Oshima, Nobu; Terajima, Hiroaki; Hosotani, Ryo

    2009-01-01

    Hepatic epithelioid hemangioendothelioma (HEHE) is a rare neoplasm of vascular origin. The clinical presentation of HEHE is variable, and the therapeutic criteria are still unclear since its natural history is unpredictable. A 53-year-old woman was admitted to our hospital because she had a 2.5-cm diameter nodule in the segment V of the liver. She had undergone segmental hepatectomy for solitary HEHE in segment VII 10 years before. There had been no recurrence for the 10 years after the first operation. The tumor was diagnosed as a new lesion of HEHE by percutaneous needle liver biopsy, and thereafter repeated hepatectomy was performed. HEHE seems to be resistant to chemotherapy and radiotherapy. Either surgical resection or orthotopic liver transplantation is generally recommended as a curative treatment for this disease. However, HEHE tends to be detected in multiple lesions, and localized disease is rare. Therefore, the chance of resection is very low. Some reports do not recommend local resection because of early aggressive tumor spread even after curative resection. We herein demonstrate a rare case of HEHE in a patient who underwent repeated hepatectomy for a solitary lesion and who survived for 17 years. It is concluded that surgical resection is one of the most effective treatments for a solitary form of HEHE. PMID:21103278

  18. A fluctuating thermal regime improves long-term survival of quiescent prepupal Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Rinehart, Joseph P; Yocum, George D; Kemp, William P; Greenlee, Kendra J

    2013-06-01

    The alfalfa leafcutting bee Megachile rotundata (F.) is the primary pollinator for alfalfa seed production. Under standard management conditions, the alfalfa leafcutting bee develops to the diapausing prepupal stage under field conditions, after which they are cold-stored at a static temperature until the following spring, when temperatures are raised and development resumes. We have assessed the effects of a fluctuating thermal regime (FTR) during overwintering cold storage, where bees were exposed to a daily 1 h pulse of 20 degrees C, and compared viability and insect quality to bees stored under a static thermal regime. Our results demonstrate that implementing an FTR protocol dramatically increases the survival of cold-stored alfalfa leafcutting bees, effectively extending their shelf-life into the subsequent growing season. These findings could substantially ameliorate significant obstacles that restrict the more widespread use of this important pollinator, such as the biological constraints that restrict its use in early blooming crops, and yearly fluctuations in bee prices that add significant financial uncertainty to end users. This study also strengthens a growing body of evidence that indicates FTR protocols are superior to static thermal regime protocols for insect cold storage.

  19. A fluctuating thermal regime improves long-term survival of quiescent prepupal Megachile rotundata (Hymenoptera: Megachilidae).

    PubMed

    Rinehart, Joseph P; Yocum, George D; Kemp, William P; Greenlee, Kendra J

    2013-06-01

    The alfalfa leafcutting bee Megachile rotundata (F.) is the primary pollinator for alfalfa seed production. Under standard management conditions, the alfalfa leafcutting bee develops to the diapausing prepupal stage under field conditions, after which they are cold-stored at a static temperature until the following spring, when temperatures are raised and development resumes. We have assessed the effects of a fluctuating thermal regime (FTR) during overwintering cold storage, where bees were exposed to a daily 1 h pulse of 20 degrees C, and compared viability and insect quality to bees stored under a static thermal regime. Our results demonstrate that implementing an FTR protocol dramatically increases the survival of cold-stored alfalfa leafcutting bees, effectively extending their shelf-life into the subsequent growing season. These findings could substantially ameliorate significant obstacles that restrict the more widespread use of this important pollinator, such as the biological constraints that restrict its use in early blooming crops, and yearly fluctuations in bee prices that add significant financial uncertainty to end users. This study also strengthens a growing body of evidence that indicates FTR protocols are superior to static thermal regime protocols for insect cold storage. PMID:23865170

  20. 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.

  1. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy.

    PubMed

    Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Müller, Martin R; Brugger, Wolfram; Horger, Marius S; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans-Georg; Holderried, Tobias A; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

    2016-05-01

    Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003-2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0-3, 7-10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y. PMID:27467913

  2. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    SciTech Connect

    Kim, Wook Ha; Kim, Dong Gyu; Han, Jung Ho; Paek, Sun Ha; Chung, Hyun-Tai; Park, Chul-Kee; Kim, Chae-Yong; Kim, Yong Hwy; Kim, Jin Wook; Jung, Hee-Won

    2012-04-01

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33-78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm{sup 3} (range, 0.01-35.1 cm{sup 3}), and the mean marginal dose prescribed was 20.8 Gy (range, 12-25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 {+-} 0.4 months (95% confidence interval, 9.1-10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209-0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  3. Long term survival in patients with hepatocellular carcinoma directly invading the gastrointestinal tract: case reports and literature review.

    PubMed

    Lin, Ting-Lung; Yap, Anthony Q; Wang, Jing-Houng; Chen, Chao-Long; Iyer, Shridhar G; Low, Jee-Keem; Lin, Chih-Che; Li, Wei-Feng; Chen, Ta-Yi; Bora, Dibyajyoti; Lin, Chih-Yun; Wang, Chih-Chi

    2011-12-01

    Hepatocellular carcinoma (HCC) directly invading the gastrointestinal (GI) organs is rare and is associated with poor survival outcome. We report two patients with good long-term outcome following resection of HCC that invaded the stomach and duodenum, respectively. A literature review was conducted to elucidate the course of patients with this pathology. Two cases (57-year-old and 72-year-old males) with enlarged hepatic tumors directly invading the stomach and duodenum underwent hepatectomies with en-bloc resection of the involved organs. Both patients are still alive at 80 and 68 months following the surgery. Our literature review showed that most of the patients with this pathology have manifested, and died of persistent GI bleeding. Patients who were treated surgically had a statistically significant longer survival than those who were treated with non-surgical palliative treatments (P < 0.001). In addition, patients who were treated with surgery with curative intent tend to have a longer survival times than those who were treated with surgery to palliate the bleeding but the difference was not statistically significant (P < 0.174). Removing the tumor completely could significantly prolong the survival of patients with HCC invading the GI tract.

  4. Neutron star natal kicks and the long-term survival of star clusters

    NASA Astrophysics Data System (ADS)

    Contenta, Filippo; Varri, Anna Lisa; Heggie, Douglas C.

    2015-04-01

    We investigate the dynamical evolution of a star cluster in an external tidal field by using N-body simulations, with focus on the effects of the presence or absence of neutron star natal velocity kicks. We show that, even if neutron stars typically represent less than 2 per cent of the total bound mass of a star cluster, their primordial kinematic properties may affect the lifetime of the system by up to almost a factor of 4. We interpret this result in the light of two known modes of star cluster dissolution, dominated by either early stellar evolution mass-loss or two-body relaxation. The competition between these effects shapes the mass-loss profile of star clusters, which may either dissolve abruptly (`jumping'), in the pre-core-collapse phase, or gradually (`skiing'), after having reached core collapse.

  5. A Long-Term Psychological Observation in an Adolescent Affected with Gardner Diamond Syndrome

    PubMed Central

    Bizzi, Fabiola; Sciarretta, Lucia; D’Alessandro, Matteo; Picco, Paolo

    2016-01-01

    Gardner-Diamond syndrome (GDS) is an uncommon disease clinically characterized by a wide spectrum of psycho-emotive symptoms associated with painful ecchymoses/purpuric lesions and positivity of auto-erythrocyte sensitization skin test. Herein, a perspective clinical and psychological observation of an adolescent GDS is firstly reported focusing on her psychological features long-term monitored for a 1-year period. The administration of a standardized tools battery allowed us to define psychological features of the young patient over time and to monitored clinical course and response to treatment. PMID:27011410

  6. Factors affecting short- and long-term outcomes of manipulation under anaesthesia in patients with adhesive capsulitis of the shoulder

    PubMed Central

    Owen, John M; Sayers, Adrian E; Woods, David A

    2014-01-01

    Background The present study aimed to evaluate and determine the factors that affect short- and long-term outcome following manipulation under anaesthesia (MUA) of patients with adhesive capsulitis. Methods Patients recruited from January 1999 to January 2010 were retrospectively analyzed and classified as having primary or secondary adhesive capsulitis. All patients were assessed for range of movement (ROM) and Oxford Shoulder Scores (OSS) before and immediately postoperatively, as well as for OSS more than 1 year post MUA. Results In total, 295 patients (315 shoulders) were sequentially recruited, and information was collected at baseline, as well as at a mean follow-up of 28 days and 3.6 years. A significant improvement in OSS and ROM was noted 1 month post MUA (p < 0.0001) with females benefiting more than males (p < 0.0025). Long-term follow-up revealed that the improvement in OSS was maintained (p < 0.0001). Secondary adhesive capsulitis significantly reduced the efficacy of MUA as assessed by ROM (p < 0.0001). Other factors (age, initial ROM and OSS, and length of symptoms prior to MUA) did not significantly affect the outcome over the short- or long-term. Conclusions The findings of the present study show that all patient groups had a significantly improved ROM and OSS in the short-term with long-term maintenance of improved OSS. PMID:27582942

  7. Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas

    SciTech Connect

    Zeng, Jing; See, Alfred P.; Phallen, Jillian; Jackson, Christopher M.; Belcaid, Zineb; Ruzevick, Jacob; Durham, Nicholas; Meyer, Christian; Harris, Timothy J.; Albesiano, Emilia; Pradilla, Gustavo; Ford, Eric; Wong, John; Hammers, Hans-Joerg; Mathios, Dimitris; Tyler, Betty; Brem, Henry; Tran, Phuoc T.; Pardoll, Drew; Drake, Charles G.; and others

    2013-06-01

    Purpose: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model. Methods and Materials: We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen. Results: Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms. Conclusions: The combination of PD-1 blockade and localized

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

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

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

  9. Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

    PubMed Central

    Klyuchnikov, Evgeny; Bacher, Ulrike; Ahn, Kwang Woo; Carreras, Jeanette; Kröger, Nicolaus M.; Hari, Parameswaran N.; Ku, Grace H.; Ayala, Ernesto; Chen, Andy I.; Chen, Yi-Bin; Cohen, Jonathon B.; Freytes, César O.; Gale, Robert Peter; Kamble, Rammurti T.; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Martino, Rodrigo; Mussetti, Alberto; Savani, Bipin N.; Schouten, Harry C.; Usmani, Saad Z.; Wiernik, Peter H.; Wirk, Baldeep; Smith, Sonali M.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors. PMID:26437062

  10. Short-Term and Long-Term Survival and Virulence of Legionella pneumophila in the Defined Freshwater Medium Fraquil

    PubMed Central

    Mendis, Nilmini; McBride, Peter; Faucher, Sébastien P.

    2015-01-01

    Legionella pneumophila (Lp) is the etiological agent responsible for Legionnaires’ disease, a potentially fatal pulmonary infection. Lp lives and multiplies inside protozoa in a variety of natural and man-made water systems prior to human infection. Fraquil, a defined freshwater medium, was used as a highly reproducible medium to study the behaviour of Lp in water. Adopting a reductionist approach, Fraquil was used to study the impact of temperature, pH and trace metal levels on the survival and subsequent intracellular multiplication of Lp in Acanthamoeba castellanii, a freshwater protozoan and a natural host of Legionella. We show that temperature has a significant impact on the short- and long-term survival of Lp, but that the bacterium retains intracellular multiplication potential for over six months in Fraquil. Moreover, incubation in Fraquil at pH 4.0 resulted in a rapid decline in colony forming units, but was not detrimental to intracellular multiplication. In contrast, variations in trace metal concentrations had no impact on either survival or intracellular multiplication in amoeba. Our data show that Lp is a resilient bacterium in the water environment, remaining infectious to host cells after six months under the nutrient-deprived conditions of Fraquil. PMID:26406895

  11. Predicting long-term outcomes for children affected by HIV and AIDS: perspectives from the scientific study of children's development.

    PubMed

    Stein, Alan; Desmond, Christopher; Garbarino, James; Van IJzendoorn, Marinus H; Barbarin, Oscar; Black, Maureen M; Stein, Aryeh D; Hillis, Susan D; Kalichman, Seth C; Mercy, James A; Bakermans-Kranenburg, Marian J; Rapa, Elizabeth; Saul, Janet R; Dobrova-Krol, Natasha A; Richter, Linda M

    2014-07-01

    The immediate and short-term consequences of adult HIV for affected children are well documented. Little research has examined the long-term implications of childhood adversity stemming from caregiver HIV infection. Through overviews provided by experts in the field, together with an iterative process of consultation and refinement, we have extracted insights from the broader field of child development of relevance to predicting the long-term consequences to children affected by HIV and AIDS. We focus on what is known about the impact of adversities similar to those experienced by HIV-affected children, and for which there is longitudinal evidence. Cautioning that findings are not directly transferable across children or contexts, we examine findings from the study of parental death, divorce, poor parental mental health, institutionalization, undernutrition, and exposure to violence. Regardless of the type of adversity, the majority of children manifest resilience and do not experience any long-term negative consequences. However, a significant minority do and these children experience not one, but multiple problems, which frequently endure over time in the absence of support and opportunities for recovery. As a result, they are highly likely to suffer numerous and enduring impacts. These insights suggest a new strategic approach to interventions for children affected by HIV and AIDS, one that effectively combines a universal lattice of protection with intensive intervention targeted to selected children and families. PMID:24991899

  12. Long-term transport behavior of psychoactive compounds in sewage-affected groundwater

    NASA Astrophysics Data System (ADS)

    Nham, Hang Thuy Thi; Greskowiak, Janek; Hamann, Enrico; Meffe, Raffaella; Hass, Ulrike; Massmann, Gudrun

    2016-09-01

    The present study provides a model-based characterization of the long-term transport behavior of five psychoactive compounds (meprobamate, pyrithyldione, primidone, phenobarbital and phenylethylmalonamide) introduced into groundwater via sewage irrigation in Berlin, Germany. Compounds are still present in the groundwater despite the sewage farm closure in the year 1980. Due to the limited information on (i) compound concentrations in the source water and (ii) substance properties, a total of 180 cross-sectional model realizations for each compound were carried out, covering a large range of possible parameter combinations. Results were compared with the present-day contamination patterns in the aquifer and the most likely scenarios were identified based on a number of model performance criteria. The simulation results show that (i) compounds are highly persistent under the present field conditions, and (ii) sorption is insignificant. Thus, back-diffusion from low permeability zones appears as the main reason for the compound retardation.

  13. Dryland soil chemical properties and crop yields affected by long-term tillage and cropping sequence.

    PubMed

    Sainju, Upendra M; Allen, Brett L; Caesar-TonThat, Thecan; Lenssen, Andrew W

    2015-01-01

    Information on the effect of long-term management on soil nutrients and chemical properties is scanty. We examined the 30-year effect of tillage frequency and cropping sequence combination on dryland soil Olsen-P, K, Ca, Mg, Na, SO4-S, and Zn concentrations, pH, electrical conductivity (EC), and cation exchange capacity (CEC) at the 0-120 cm depth and annualized crop yield in the northern Great Plains, USA. Treatments were no-till continuous spring wheat (Triticum aestivum L.) (NTCW), spring till continuous spring wheat (STCW), fall and spring till continuous spring wheat (FSTCW), fall and spring till spring wheat-barley (Hordeum vulgare L., 1984-1999) followed by spring wheat-pea (Pisum sativum L., 2000-2013) (FSTW-B/P), and spring till spring wheat-fallow (STW-F, traditional system). At 0-7.5 cm, P, K, Zn, Na, and CEC were 23-60% were greater, but pH, buffer pH, and Ca were 6-31% lower in NTCW, STCW, and FSTW-B/P than STW-F. At 7.5-15 cm, K was 23-52% greater, but pH, buffer pH, and Mg were 3-21% lower in NTCW, STCW, FSTCW, FSTW-B/P than STW-F. At 60-120 cm, soil chemical properties varied with treatments. Annualized crop yield was 23-30% lower in STW-F than the other treatments. Continuous N fertilization probably reduced soil pH, Ca, and Mg, but greater crop residue returned to the soil increased P, K, Na, Zn, and CEC in NTCW and STCW compared to STW-F. Reduced tillage with continuous cropping may be adopted for maintaining long-term soil fertility and crop yields compared with the traditional system. PMID:26171303

  14. Long-Term Fluoride Release from Dental Resins Affects STRO-1+ Cell Behavior.

    PubMed

    Calarco, A; Di Salle, A; Tammaro, L; De Luca, I; Mucerino, S; Petillo, O; Riccitiello, F; Vittoria, V; Peluso, G

    2015-08-01

    Fluoride-releasing restorative dental materials can be beneficial to remineralize dentin and help prevent secondary caries. However, the effects of fluoride release from dental materials on the activity of dental pulp stem cells are not known. Here we investigate whether different fluoride release kinetics from dental resins supplemented with modified hydrotalcite (RK-F10) or fluoride-glass filler (RK-FG10) could influence the behavior of a human dental pulp stem cell subpopulation (STRO-1(+) cells) known for its ability to differentiate toward an odontoblast-like phenotype. The 2 resins, characterized by similar physicochemical properties and fluoride content, exhibited different long-term fluoride release kinetics. Our data demonstrate that long-term exposure of STRO-1(+) cells to a continuous release of a low amount of fluoride by RK-F10 increases their migratory response to transforming growth factor β1 (TGF-β1) and stromal cell-derived factor 1 (SDF-1), both important promoters of pulp stem cell recruitment. Moreover, the expression patterns of dentin sialoprotein (dspp), dentin matrix protein 1 (dmp1), osteocalcin (ocn), and matrix extracellular phosphoglycoprotein (mepe) indicate a complete odontoblast-like cell differentiation only when STRO-1(+) cells were cultured on RK-F10. On the contrary, RK-FG10, characterized by an initial fluoride release burst and reduced lifetime of the delivery, did not elicit any significant effect on both STRO-1(+) cell migration and differentiation. Taken together, our results highlight the importance of taking into account fluoride release kinetics in addition to fluoride concentration when designing new fluoride-restorative materials.

  15. Dryland soil chemical properties and crop yields affected by long-term tillage and cropping sequence.

    PubMed

    Sainju, Upendra M; Allen, Brett L; Caesar-TonThat, Thecan; Lenssen, Andrew W

    2015-01-01

    Information on the effect of long-term management on soil nutrients and chemical properties is scanty. We examined the 30-year effect of tillage frequency and cropping sequence combination on dryland soil Olsen-P, K, Ca, Mg, Na, SO4-S, and Zn concentrations, pH, electrical conductivity (EC), and cation exchange capacity (CEC) at the 0-120 cm depth and annualized crop yield in the northern Great Plains, USA. Treatments were no-till continuous spring wheat (Triticum aestivum L.) (NTCW), spring till continuous spring wheat (STCW), fall and spring till continuous spring wheat (FSTCW), fall and spring till spring wheat-barley (Hordeum vulgare L., 1984-1999) followed by spring wheat-pea (Pisum sativum L., 2000-2013) (FSTW-B/P), and spring till spring wheat-fallow (STW-F, traditional system). At 0-7.5 cm, P, K, Zn, Na, and CEC were 23-60% were greater, but pH, buffer pH, and Ca were 6-31% lower in NTCW, STCW, and FSTW-B/P than STW-F. At 7.5-15 cm, K was 23-52% greater, but pH, buffer pH, and Mg were 3-21% lower in NTCW, STCW, FSTCW, FSTW-B/P than STW-F. At 60-120 cm, soil chemical properties varied with treatments. Annualized crop yield was 23-30% lower in STW-F than the other treatments. Continuous N fertilization probably reduced soil pH, Ca, and Mg, but greater crop residue returned to the soil increased P, K, Na, Zn, and CEC in NTCW and STCW compared to STW-F. Reduced tillage with continuous cropping may be adopted for maintaining long-term soil fertility and crop yields compared with the traditional system.

  16. Long-term survival of direct and indirect restorations placed for the treatment of advanced tooth wear.

    PubMed

    Smales, Roger J; Berekally, Thomas L

    2007-03-01

    Advanced tooth wear was restored with direct resin-based composites (RBCs) in 17 patients, and with indirect ceramo-metal crowns (CMCs) and full gold crowns in 8 other patients. The mean patient age was 64.9 (8.6 SD) years, with each patient having a mean of 13.8 (5.4) restorations. In this retrospective case series study, the mean restoration age was 5.0 (3.0) years for the direct and 5.9 (2.6) years for the indirect restorations. Over 10 years, cumulative survival estimates were 62.0% for direct and 74.5% for indirect restorations (P = 0.23). Survival estimates were 58.9% for anterior RBCs and 70.3% for anterior CMCs (P = 0.06). RBCs usually failed from fractures, and CMCs from complete losses. RBC failures were usually replaced or repaired, while CMC failures often required root canal therapies or extractions. The findings from this relatively small study require confirmation by large long-term controlled clinical trials.

  17. G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts

    PubMed Central

    Peixoto, Eduardo; Messinger, Shari; Mantero, Alejandro; Padilla-Téllez, Nathalia D.; Baidal, David A.; Alejandro, Rodolfo; Ricordi, Camillo; Inverardi, Luca

    2016-01-01

    Background Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach. Methods We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia. Results The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination. Conclusion This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs. PMID:27285580

  18. The contingencies of organizational learning in long-term care: factors that affect innovation adoption.

    PubMed

    Berta, Whitney; Teare, Gary F; Gilbart, Erin; Ginsburg, Liane Soberman; Lemieux-Charles, Louise; Davis, Dave; Rappolt, Susan

    2005-01-01

    We apply the theoretical frameworks of knowledge transfer and organizational learning, and findings from studies of clinical practice guideline (CPG) implementation in health care, to develop a contingency model of innovation adoption in long-term care (LTC) facilities. Our focus is on a particular type of innovation, CPGs designed to improve the quality of LTC. Our interest in this area is founded on the premise that the ability of LTC organizations to adopt and sustain the use of innovations like CPGs is contingent on the initial capacity these institutions have to learn about them, and on the presence of factors that contribute to capacity building at each stage of innovation adoption. Based on our review of relevant theory, we develop a set of fifteen testable propositions that relate factors operating at the guideline, individual, organizational, and environmental levels in LTC institutions to stages of guideline adoption/transfer. Our model offers insights into the complexities of adopting and sustaining innovations in LTC facilities particularly, in health care organizations specifically, and in service organizations generally.

  19. The affective value of faces in patients achieving long-term seizure freedom after temporal lobectomy.

    PubMed

    Meletti, Stefano; Picardi, Angelo; De Risi, Marco; Monti, Giulia; Esposito, Vincenzo; Grammaldo, Liliana G; Di Gennaro, Giancarlo

    2014-07-01

    We investigated different aspects of facial expression evaluation in a homogeneous cohort of 42 seizure-free patients with 5 or more years of follow-up after temporal lobectomy (TL), with the aim of further characterizing the impairment in emotion and social cognition among patients. A group of healthy subjects matched for sex, age, and education served as controls. Four tasks of facial expression evaluation were used: (a) facial expression recognition, (b) rating of the intensity of facial expression, and (c) rating of valence (pleasantness) and (d) rating of arousal induced by facial expressions. Patients had a worse performance in the recognition task for all negative emotions, while no differences in intensity ratings were found. They also reported lower arousal ratings than controls for faces showing fear, anger, disgust, and neutral expressions, as well as lower valence ratings for all facial expressions except those showing happiness. Longer epilepsy duration before TL was negatively associated with ratings of arousal and intensity and positively associated with valence ratings for fearful facial expressions. This study showed that patients who become seizure-free after TL present long-term deficits in several aspects of facial expression evaluation. Longitudinal, prospective studies are needed to evaluate if social cognition improves or declines after TL.

  20. Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

    PubMed Central

    Kato, T; Kimura, T; Miyakawa, R; Fujii, A; Yamamoto, K; Kameoka, S; Nishikawa, T; Kasajima, T

    2000-01-01

    This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c- erb B-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c- erb B-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1–20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c- erb B-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies. © 2000 Cancer Research Campaign PMID:10646896

  1. [Long-term survival after surgical resection of a cancer of unknown primary site-a case report].

    PubMed

    Tsukao, Yukiko; Moon, Jeong Ho; Kobayashi, Kenji; Hyuga, Satoshi; Chono, Teruhiro; Watanabe, Risa; Matsumoto, Takashi; Takemoto, Hiroyoshi; Takachi, Ko; Nishioka, Kiyonori; Aoki, Taro; Uemura, Yoshio

    2013-11-01

    We report a case of long-term survival after combination chemotherapy and surgical resection of a cancer of unknown primary site[ CUPs]. A septuagenarian female was identified as having high blood levels of carcinoembryonic antigen (CEA) during follow-up monitoring of asthma. Endoscopy and imaging studies including computed tomography (CT) and positron emission tomography (PET)-CT revealed a malignant lymph node adjacent to the abdominal aorta; however, no other lesion was detected. Therefore, we performed CT-guided biopsy and diagnosed the lesion to be a lymph node metastasis of poorly differentiated adenocarcinoma. As we considered this as a systemic disease, the patient received 2 courses of combination chemotherapy with 5-fluorouracil( 5-FU)/cisplatin( CDDP) and achieved a partial response (PR). Later, the patient received S-1 therapy as second-line chemotherapy and S-1/irinotecan( CPT-11) as third-line chemotherapy in an outpatient clinic. However, the tumor continued to grow, and therefore, we decided to perform surgical resection. Histopathological examination of the resected specimen yielded a diagnosis of metastatic adenocarcinoma of the lymph node. The patient has been well without any signs of recurrence for more than 9 years since surgery. As CUPs is generally associated with poor prognosis, this case raises the possibility that combination therapy might improve convalescence.

  2. Long-Term Survival and Outcome in Children Admitted to Kilifi District Hospital with Convulsive Status Epilepticus

    PubMed Central

    Mung'ala Odera, Victor; Seaton, Claire; Holding, Penny; Newton, Charles R.

    2014-01-01

    Objectives. The incidence of convulsive status epilepticus (CSE) is high in Africa but the long-term outcome is unknown. We examined the neurocognitive outcome and survival of children treated for CSE in a Kenyan hospital 3 to 4 years after discharge. Methods. The frequency and nature of neurological deficits among this group of children were determined and compared to a control group. The children were screened with the Ten Questions Questionnaire for neurodevelopmental impairment if alive and those that screened positive were invited for further assessment to determine the pattern and extent of their impairment. A verbal autopsy was performed to determine the cause of death in those that died. Results. In the 119 cases followed-up, 9 (8%) died after discharge, with the majority having seizures during their fatal illness. The 110 survivors (median age 5 years) had significantly more neurological impairments on the screening compared to 282 controls (34/110 (30.9%) versus 11/282 (3.9%), OR = 11.0, 95% CI 5.3–22.8). Fifteen percent of the cases had active epilepsy. Conclusions. This study demonstrates the considerable burden of CSE in African children. Strategies to manage children with CSE that are acceptable to the community need to be explored to improve the longer-term outcome. PMID:24627807

  3. Survival outcome of radioiodine therapy in post thyroidectomy thyroid carcinoma patients: Outcome of long term follow up

    NASA Astrophysics Data System (ADS)

    Haque, F.; Nahar, N.; Sultana, S.; Nasreen, F.; Jabin, Z.; Alam, A. S. M. M.

    2016-03-01

    The overall prognosis of patients with thyroid carcinoma is excellent whenever managed following best practice guidelines. Objective: To calculate sex and age group affected by thyroid cancer; to compare between single or multiple dose of radio ablation needed after thyroidectomy and to determine the percentage of patients become disease free during their follow up. Methods: This was a retrospective study done in NINMAS, Bangladesh on 687 patients from 1984 to 2004. In all cases total or near total thyroidectomy was done before commencing radioiodine therapy. Patients TG level, neck ultrasonography, thyroid scan, whole body I131 scans, neck examination were done every six monthly/yearly. Results: Among 687 patients, female were more sufferers (68.1%) and female to male ratio was 2:1. Age group 19-40 years was mostly affected (57.8%). Most common type seen was papillary carcinoma (81.8%). After ablation 100 patients did not follow-up. Total 237 patients discontinued within 4 years. Remaining 450 patients undergone regular follow-up for 5 years and more, 394 were disease free (87.6%). Total recurrence of metastasis was 23 and 12 patients expired at different times. Conclusions: Long-term regular follow-up is necessary after radioiodine ablation to become free of disease.

  4. Early Experiences Can Alter Gene Expression and Affect Long-Term Development. Working Paper #10

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2010

    2010-01-01

    New scientific research shows that environmental influences can actually affect whether and how genes are expressed. Thus, the old ideas that genes are "set in stone" or that they alone determine development have been disproven. In fact, scientists have discovered that early experiences can determine how genes are turned on and off and even…

  5. Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients.

    PubMed

    Aubele, M; Walch, A K; Ludyga, N; Braselmann, H; Atkinson, M J; Luber, B; Auer, G; Tapio, S; Cooke, T; Bartlett, J M S

    2008-10-01

    The cytoplasmic tyrosine kinase PTK6 (BRK) shows elevated expression in approximately two-thirds of primary breast tumours, and is implicated in EGF receptor-dependent signalling and epithelial tumorigenesis. Using immunohistochemistry, we performed a retrospective study on 426 archival breast cancer samples from patients with long-term follow-up and compared the protein expression levels of PTK6, the HER receptors, Sam68 (a substrate of PTK6), and signalling proteins including MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. We show that PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of >or=240 months was directly associated with the protein expression level of PTK6 (P

  6. Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients

    PubMed Central

    Aubele, M; Walch, A K; Ludyga, N; Braselmann, H; Atkinson, M J; Luber, B; Auer, G; Tapio, S; Cooke, T; Bartlett, J M S

    2008-01-01

    The cytoplasmic tyrosine kinase PTK6 (BRK) shows elevated expression in approximately two-thirds of primary breast tumours, and is implicated in EGF receptor-dependent signalling and epithelial tumorigenesis. Using immunohistochemistry, we performed a retrospective study on 426 archival breast cancer samples from patients with long-term follow-up and compared the protein expression levels of PTK6, the HER receptors, Sam68 (a substrate of PTK6), and signalling proteins including MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. We show that PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of ⩾240 months was directly associated with the protein expression level of PTK6 (P⩽0.001), but was also inversely associated with nodal status (P⩽0.001) and tumour size (P⩽0.01). PTK6 expression in tumour tissue significantly correlated (P⩽0.05) with the expression of PTEN, MAPK, P-MAPK, and Sam68. To investigate whether these correlations may be due to molecular interactions between PTK6 and these proteins, we used protein extracts from the T47D cell line for immunoprecipitation and western blot analysis. By this, interactions could be demonstrated between PTK6 and MAPK, P-MAPK, HER2/neu, HER3, HER4, PTEN, and Sam68. On the basis of these results, we suggest that PTK6 may serve as a future target for the development of novel treatments in breast cancer. PMID:18781181

  7. Long-term perspectives for 46,XY patients affected by complete androgen insensitivity syndrome or congenital micropenis.

    PubMed

    Wisniewski, Amy B; Migeon, Claude J

    2002-08-01

    Controversy concerning optimal treatment for individuals affected by syndromes of abnormal sex differentiation can best be resolved with knowledge about long-term medical, surgical, and psychosexual outcomes of patients. Follow-up information has recently been gathered on older cohorts of the following patient groups: (1) those affected by complete androgen insensitivity syndrome (CAIS) raised female and (2) those affected by congenital micropenis raised male or female. As a group, women with CAIS were satisfied with their female gender and sexual function. However, a need for better patient education was identified for this specific population. Most patients with congenital micropenis, whether raised male or female, were satisfied with their gender. Regardless of sex of rearing, dissatisfaction with the appearance and function of the genitalia as judged by both physicians and subjects was evident. For patients with congenital micropenis, male sex of rearing was concluded to be optimal because genital reconstructive surgery is not required with this choice.

  8. Long-term contamination in a recovered area affected by a mining spill.

    PubMed

    Martín Peinado, F J; Romero-Freire, A; García Fernández, I; Sierra Aragón, M; Ortiz-Bernad, I; Simón Torres, M

    2015-05-01

    Soil pollution from the spill of Aznalcóllar mine (S Spain) was monitored by analysing polluted soils in 1998, 1999, and 2004. Following the methodology used in previous studies, in 2013 we conducted a new sampling and analysis of the soils affected by the spill and the data were compared with those of 2004. The results confirm that the pH tended to rise and concentration of pollutants tended to diminish over time. In 2013, the total concentration of pollutants was within the normal range for uncontaminated soils and close to the background concentration of the soils prior to the spill; while the soluble concentration of pollutants was clearly below the toxic level. These results indicate that remediation measures implemented have been effective. However, the removal of tailings (first remediation measure applied) was deficient and in many places the tailings were mixed with the soil. The high concentration of sulphides and metal(loid)s in the tailings gave rise to spots with very acidic and highly polluted soils devoid of vegetation. In 2013, fifteen years after the spill, these spots of bare soils remain a major source of pollution from which pollutants are scattered through the solid and liquid phases of runoff water, requiring action to immobilize pollutants and encourage the restoration of vegetation on these soils. In this type of pollution in a Mediterranean environment, the complete removal of tailings is more important than the speed at which they are removed.

  9. Long-Term Exposure to High Altitude Affects Response Inhibition in the Conflict-monitoring Stage.

    PubMed

    Ma, Hailin; Wang, Yan; Wu, Jianhui; Luo, Ping; Han, Buxin

    2015-09-01

    To investigate the effects of high-altitude exposure on response inhibition, event-related potential (ERP) components N2 and P3 were measured in Go/NoGo task. The participants included an 'immigrant' high-altitude group (who had lived at high altitude for three years but born at low altitude) and a low-altitude group (living in low altitude only). Although the behavioural data showed no significant differences between the two groups, a delayed latency of NoGo-N2 was found in the high-altitude group compared to the low-altitude group. Moreover, larger N2 and smaller P3 amplitudes were found in the high-altitude group compared to the low-altitude group, for both the Go and NoGo conditions. These findings suggest that high-altitude exposure affects response inhibition with regard to processing speed during the conflict monitoring stage. In addition, high altitude generally increases the neural activity in the matching step of information processing and attentional resources. These results may provide some insights into the neurocognitive basis of the effects on high-altitude exposure on response inhibition.

  10. Long-Term Exposure to High Altitude Affects Response Inhibition in the Conflict-monitoring Stage.

    PubMed

    Ma, Hailin; Wang, Yan; Wu, Jianhui; Luo, Ping; Han, Buxin

    2015-01-01

    To investigate the effects of high-altitude exposure on response inhibition, event-related potential (ERP) components N2 and P3 were measured in Go/NoGo task. The participants included an 'immigrant' high-altitude group (who had lived at high altitude for three years but born at low altitude) and a low-altitude group (living in low altitude only). Although the behavioural data showed no significant differences between the two groups, a delayed latency of NoGo-N2 was found in the high-altitude group compared to the low-altitude group. Moreover, larger N2 and smaller P3 amplitudes were found in the high-altitude group compared to the low-altitude group, for both the Go and NoGo conditions. These findings suggest that high-altitude exposure affects response inhibition with regard to processing speed during the conflict monitoring stage. In addition, high altitude generally increases the neural activity in the matching step of information processing and attentional resources. These results may provide some insights into the neurocognitive basis of the effects on high-altitude exposure on response inhibition. PMID:26324166

  11. Long-term cleaner fish presence affects growth of a coral reef fish.

    PubMed

    Clague, Gillian E; Cheney, Karen L; Goldizen, Anne W; McCormick, Mark I; Waldie, Peter A; Grutter, Alexandra S

    2011-12-23

    Cleaning behaviour is considered to be a classical example of mutualism. However, no studies, to our knowledge, have measured the benefits to clients in terms of growth. In the longest experimental study of its kind, over an 8 year period, cleaner fish Labroides dimidiatus were consistently removed from seven patch reefs (61-285 m(2)) and left undisturbed on nine control reefs, and the growth and parasite load of the damselfish Pomacentrus moluccensis determined. After 8 years, growth was reduced and parasitic copepod abundance was higher on fish from removal reefs compared with controls, but only in larger individuals. Behavioural observations revealed that P. moluccensis cleaned by L. dimidiatus were 27 per cent larger than nearby conspecifics. The selective cleaning by L. dimidiatus probably explains why only larger P. moluccensis individuals benefited from cleaning. This is the first demonstration, to our knowledge, that cleaners affect the growth rate of client individuals; a greater size for a given age should result in increased fecundity at a given time. The effect of the removal of so few small fish on the size of another fish species is unprecedented on coral reefs. PMID:21733872

  12. A CSTR-hollow-fiber system for continuous hydrolysis of proteins. Factors affecting long-term stability of the reactor.

    PubMed

    Deeslie, W D; Cheryan, M

    1982-01-01

    Factors affecting the long-term operational stability of a CSTR-hollow-fiber reactor for continuous hydrolysis of proteins were studied. The activity declined in a stepwise manner during a run. Declining from 92% conversion to 60% conversion in about ten hours at a space time of four minutes. Initial decay appears to be due to leakage of small active fragments of the enzyme mixture (Pronase) through the membrane, and later decay due to thermal degradation and loss of activators such as calcium through the membrane. The rate of buildup of unconverted substrate in the reaction vessel was controlled by operational variables, but did not appear to affect the reactor output or the operation of the reactor. The decay of the reactor could be partially compensated for by appropriate manipulation of the space-time variables.

  13. Prediction of Long-Term Survival in Patients with End-Stage Heart Failure Secondary to Ischemic Heart Disease: Surgical Correction and Volumetric Analysis

    PubMed Central

    Yoshida, Minoru; Hoshino, Joji; Kondo, Taichi; Isomura, Tadashi

    2015-01-01

    Purpose: Ischemic heart disease (IHD) may result in lethal conditions such as ischemic cardiomyopathy (ICM) and mitral regurgitation (MR). Methods: We hypothesized preoperative LV volume would be highly associated with long-term survival in such patients. We retrospectively evaluated effects of LV end-systolic volume index (LVESVI) on survival. Results: Patients were divided into two groups according to LVESVI; Group S (n = 19, <100 ml/m2), and L (n = 55, >100 ml/m2). There were 74 patients (male 61, female 13; 61 ± 10 y.o.). There was no statistical significance in preoperative parameters, including ejection fraction (EF), severity of MR, severity of tricuspid regurgitation (TR), and right ventricular systolic pressure (RVSP). After operation, LVESVI and severity of MR were statistically reduced in both groups. However, EF, severity of TR and RVSP were not statistically alleviated in both groups. In Group S, 5- and 10-year survival rates were 93% and 48%. In Group L, 5- and 10-year survival rates were 50% and 29%. There was a statistical difference in long-term survival between two groups. Conclusions: Preoperative LV volume would be one of the risk factors for long-term survival in patients with congestive heart failure secondary to IHD. Careful follow-up and optimal treatment should be recommended before LV dimension becomes too large. PMID:26073141

  14. Long-term survival of the Shiga toxin-producing Escherichia coli O104:H4 outbreak strain on fenugreek seeds.

    PubMed

    Knödler, Michael; Berger, Michael; Dobrindt, Ulrich

    2016-10-01

    A major outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 occurred in Germany in 2011. The epidemiological investigation revealed that a contaminated batch of fenugreek seeds (Trigonella foenum-graecum) was the most probable source of the pathogen. It was suggested that the most probable point of contamination was prior to leaving the importer, meaning that the seed contamination with STEC O104:H4 should have happened more than one year before the seeds were used for sprout production. Here, we investigated the capacity of STEC O104:H4 and closely related pathogenic as well as non-pathogenic Escherichia coli strains for long-term survival on dry fenugreek seeds. We did not observe a superior survival capacity of STEC O104:H4 on dry seeds. For none of the strains tested cultivatable cells were found without enrichment on contaminated seeds after more than 24 weeks of storage. Our findings suggest that contamination previous to the distribution from the importer may be less likely than previously assumed. We show that seeds contaminated with E. coli in extremely high numbers can be completely sterilized by a short treatment with bleach. This simple and cheap procedure does not affect the germination capacity of the seeds and could significantly improve safety in sprout production. PMID:27375259

  15. Long-term survival of the Shiga toxin-producing Escherichia coli O104:H4 outbreak strain on fenugreek seeds.

    PubMed

    Knödler, Michael; Berger, Michael; Dobrindt, Ulrich

    2016-10-01

    A major outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 occurred in Germany in 2011. The epidemiological investigation revealed that a contaminated batch of fenugreek seeds (Trigonella foenum-graecum) was the most probable source of the pathogen. It was suggested that the most probable point of contamination was prior to leaving the importer, meaning that the seed contamination with STEC O104:H4 should have happened more than one year before the seeds were used for sprout production. Here, we investigated the capacity of STEC O104:H4 and closely related pathogenic as well as non-pathogenic Escherichia coli strains for long-term survival on dry fenugreek seeds. We did not observe a superior survival capacity of STEC O104:H4 on dry seeds. For none of the strains tested cultivatable cells were found without enrichment on contaminated seeds after more than 24 weeks of storage. Our findings suggest that contamination previous to the distribution from the importer may be less likely than previously assumed. We show that seeds contaminated with E. coli in extremely high numbers can be completely sterilized by a short treatment with bleach. This simple and cheap procedure does not affect the germination capacity of the seeds and could significantly improve safety in sprout production.

  16. A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast

    PubMed Central

    Kim, Ji-Yoon; Kim, Eun-Jung; Lopez-Maury, Luis; Bähler, Jürg; Roe, Jung-Hye

    2014-01-01

    In the fission yeast Schizosaccharomyces pombe, the stationary phase-specific transcription factor Phx1 contributes to long-term survival, stress tolerance, and meiosis. We identified Phx1-dependent genes through transcriptome analysis, and further analyzed those related with carbohydrate and thiamine metabolism, whose expression decreased in Δphx1. Consistent with mRNA changes, the level of thiamine pyrophosphate (TPP) and TPP-utilizing pyruvate decarboxylase activity that converts pyruvate to acetaldehyde were also reduced in the mutant. Therefore, Phx1 appears to shift metabolic flux by diverting pyruvate from the TCA cycle and respiration to ethanol fermentation. Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival as judged by mutation and overexpression studies. These findings indicate that the Phx1-mediated long-term survival is achieved primarily through increasing the synthesis and activity of pyruvate decarboxylase. Consistent with this hypothesis, we observed that Phx1 curtailed respiration when cells entered stationary phase. Introduction of Δphx1 mutation compromised the long-lived phenotypes of Δpka1 and Δsck2 mutants that are devoid of pro-aging kinases of nutrient-signalling pathways, and of the Δpyp1 mutant with constitutively activated stress-responsive kinase Sty1. Therefore, achievement of long-term viability through both nutrient limitation and anti-stress response appears to be dependent on Phx1. PMID:25102102

  17. A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast.

    PubMed

    Kim, Ji-Yoon; Kim, Eun-Jung; Lopez-Maury, Luis; Bähler, Jürg; Roe, Jung-Hye

    2014-07-01

    In the fission yeast Schizosaccharomyces pombe, the stationary phase-specific transcription factor Phx1 contributes to long-term survival, stress tolerance, and meiosis. We identified Phx1-dependent genes through transcriptome analysis, and further analyzed those related with carbohydrate and thiamine metabolism, whose expression decreased in ∆phx1. Consistent with mRNA changes, the level of thiamine pyrophosphate (TPP) and TPP-utilizing pyruvate decarboxylase activity that converts pyruvate to acetaldehyde were also reduced in the mutant. Therefore, Phx1 appears to shift metabolic flux by diverting pyruvate from the TCA cycle and respiration to ethanol fermentation. Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival as judged by mutation and overexpression studies. These findings indicate that the Phx1-mediated long-term survival is achieved primarily through increasing the synthesis and activity of pyruvate decarboxylase. Consistent with this hypothesis, we observed that Phx1 curtailed respiration when cells entered stationary phase. Introduction of Δphx1 mutation compromised the long-lived phenotypes of Δpka1 and Δsck2 mutants that are devoid of pro-aging kinases of nutrient-signalling pathways, and of the Δpyp1 mutant with constitutively activated stress-responsive kinase Sty1. Therefore, achievement of long-term viability through both nutrient limitation and anti-stress response appears to be dependent on Phx1.

  18. A metabolic strategy to enhance long-term survival by Phx1 through stationary phase-specific pyruvate decarboxylases in fission yeast.

    PubMed

    Kim, Ji-Yoon; Kim, Eun-Jung; Lopez-Maury, Luis; Bähler, Jürg; Roe, Jung-Hye

    2014-07-01

    In the fission yeast Schizosaccharomyces pombe, the stationary phase-specific transcription factor Phx1 contributes to long-term survival, stress tolerance, and meiosis. We identified Phx1-dependent genes through transcriptome analysis, and further analyzed those related with carbohydrate and thiamine metabolism, whose expression decreased in ∆phx1. Consistent with mRNA changes, the level of thiamine pyrophosphate (TPP) and TPP-utilizing pyruvate decarboxylase activity that converts pyruvate to acetaldehyde were also reduced in the mutant. Therefore, Phx1 appears to shift metabolic flux by diverting pyruvate from the TCA cycle and respiration to ethanol fermentation. Among the four predicted genes for pyruvate decarboxylase, only the Phx1-dependent genes (pdc201+ and pdc202+) contributed to long-term survival as judged by mutation and overexpression studies. These findings indicate that the Phx1-mediated long-term survival is achieved primarily through increasing the synthesis and activity of pyruvate decarboxylase. Consistent with this hypothesis, we observed that Phx1 curtailed respiration when cells entered stationary phase. Introduction of Δphx1 mutation compromised the long-lived phenotypes of Δpka1 and Δsck2 mutants that are devoid of pro-aging kinases of nutrient-signalling pathways, and of the Δpyp1 mutant with constitutively activated stress-responsive kinase Sty1. Therefore, achievement of long-term viability through both nutrient limitation and anti-stress response appears to be dependent on Phx1. PMID:25102102

  19. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment

    PubMed Central

    Gökbuget, Nicola; Klinger, Matthias; Viardot, Andreas; Stelljes, Matthias; Neumann, Svenja; Horst, Heinz-A.; Marks, Reinhard; Faul, Christoph; Diedrich, Helmut; Reichle, Albrecht; Brüggemann, Monika; Holland, Chris; Schmidt, Margit; Einsele, Hermann; Bargou, Ralf C.; Topp, Max S.

    2015-01-01

    This long-term follow-up analysis evaluated overall survival (OS) and relapse-free survival (RFS) in a phase 2 study of the bispecific T-cell engager antibody construct blinatumomab in 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). In the primary analysis, 25 (69%) patients with relapsed/refractory ALL achieved complete remission with full (CR) or partial (CRh) hematologic recovery of peripheral blood counts within the first 2 cycles. Twenty-five patients (69%) had a minimal residual disease (MRD) response (<10−4 blasts), including 22 CR/CRh responders, 2 patients with hypocellular bone marrow, and 1 patient with normocellular bone marrow but low peripheral counts. Ten of the 36 patients (28%) were long-term survivors (OS ≥30 months). Median OS was 13.0 months (median follow-up, 32.6 months). MRD response was associated with significantly longer OS (Mantel-Byar P = .009). All 10 long-term survivors had an MRD response. Median RFS was 8.8 months (median follow-up, 28.9 months). A plateau for RFS was reached after ∼18 months. Six of the 10 long-term survivors remained relapse-free, including 4 who received allogeneic stem cell transplantation (allo-SCT) as consolidation for blinatumomab and 2 who received 3 additional cycles of blinatumomab instead of allo-SCT. Three long-term survivors had neurologic events or cytokine release syndrome, resulting in temporary blinatumomab discontinuation; all restarted blinatumomab successfully. Long-term survivors had more pronounced T-cell expansion than patients with OS <30 months. PMID:26480933

  20. An exploration of factors affecting the long term psychological impact and deterioration of mental health in flooded households.

    PubMed

    Lamond, Jessica Elizabeth; Joseph, Rotimi D; Proverbs, David G

    2015-07-01

    The long term psychological effect of the distress and trauma caused by the memory of damage and losses associated with flooding of communities remains an under researched impact of flooding. This is particularly important for communities that are likely to be repeatedly flooded where levels of mental health disorder will damage long term resilience to future flooding. There are a variety of factors that affect the prevalence of mental health disorders in the aftermath of flooding including pre-existing mental health, socio-economic factors and flood severity. However previous research has tended to focus on the short term impacts immediately following the flood event and much less focus has been given to the longer terms effects of flooding. Understanding of factors affecting the longer term mental health outcomes for flooded households is critical in order to support communities in improving social resilience. Hence, the aim of this study was to explore the characteristics associated with psychological distress and mental health deterioration over the longer term. The research examined responses from a postal survey of households flooded during the 2007 flood event across England. Descriptive statistics, correlation analysis and binomial logistic regression were applied to data representing household characteristics, flood event characteristics and post-flood stressors and coping strategies. These factors were related to reported measures of stress, anxiety, depression and mental health deterioration. The results showed that household income, depth of flooding; having to move out during reinstatement and mitigating actions are related to the prevalence of psycho-social symptoms in previously flooded households. In particular relocation and household income were the most predictive factors. The practical implication of these findings for recovery after flooding are: to consider the preferences of households in terms of the need to move out during restorative

  1. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna.

    PubMed

    Sarapultseva, Elena I; Dubrova, Yuri E

    2016-10-01

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000mGy of acute γ-rays. Exposure to 1000 and 10,000mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F0 and F1Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F0Daphnia exposed to 1000 and 10,000mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000mGy. We propose that the decreased fertility observed among the F2 progeny of parents exposed to 10,000mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F2 progeny of irradiated F0Daphnia exposed to the lower doses of acute γ-rays.

  2. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna.

    PubMed

    Sarapultseva, Elena I; Dubrova, Yuri E

    2016-10-01

    The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000mGy of acute γ-rays. Exposure to 1000 and 10,000mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F0 and F1Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F0Daphnia exposed to 1000 and 10,000mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000mGy. We propose that the decreased fertility observed among the F2 progeny of parents exposed to 10,000mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F2 progeny of irradiated F0Daphnia exposed to the lower doses of acute γ-rays. PMID:27288911

  3. Long-term sediment yield from small catchment in southern Brazil affected by land use and soil management changes.

    NASA Astrophysics Data System (ADS)

    Gomes Minella, Jean Paolo; Henrique Merten, Gustavo; Alessandra Peixoto de Barros, Claudia; Dalbianco, Leandro; Ramon, Rafael; Schlesner, Alexandre

    2015-04-01

    Soil erosion and sediment yield are the main cause of soil degradation in Brazil. Despite this, there is a lack of information about the effects of the soil management on the hydrology and sediment yield at catchment scale. This study aimed to investigate the long-term relationship between the land use and sediment yield in a small catchment with significant changes in soil management, and its impacts on soil erosion and sediment yield. To account the anthropogenic and climatic effects on sediment yield were monitored precipitation, stream flow and suspended sediment concentration during thirteen years (2002 and 2014) at 10 minutes interval and the changes that occurred each year in the land use and soil management. Despite the influence of climate on the sediment yield, the results clearly show three distinct periods affected by the land use and soil management changes during this this period. In the first four years (2002-2004) the predominant land use was the tobacco with traditional soil management, where the soils are plough every year and without winter cover crop. In this period the sediment yield reached the order of 160 t.ha-1.y-1. In the period of 2005-2009, a soil conservation program introduced the adoption of minimum tillage in the catchment and the sediment yield decrease to 70 t.ha-1.y-1. In the last period (2010-2014) there was a partial return to the traditional soil management practices with an increase trend in sediment yield. However, there was also an increase in reforestation areas with positive effect in reducing erosion and sediment yield. The magnitude order of sediment yield in this period was 100 t.ha-1.y-1. The long term sediment yield data was able to demonstrate the impact of the improved management practices in reducing soil erosion and sediment yield. The results allowed a good understanding of the changing sediment dynamics and soil erosion at catchment scale.

  4. Long term survival in a patient with variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulphate.

    PubMed

    Parry, A; Baker, I; Stacey, R; Wimalaratna, S

    2007-07-01

    Variant Creutzfeldt-Jakob disease (vCJD) is a neurodegenerative disease that principally affects young people and has a median duration of illness of 13 (range 6-39) months. vCJD is incurable and there are currently no treatments that conclusively slow the rate of disease progression. However, recent animal studies and isolated case reports have suggested that treatment with intraventricular pentosan polysulphate (PPS) may be beneficial in the treatment of patients with vCJD. We report a case of a 22-year-old male with vCJD treated 19 months after the onset of clinical symptoms with continuous intraventricular PPS (32 microg/kg/day) over a period of 31 months. Treatment with PPS appeared to be safe and well tolerated and was associated with prolonged survival (51 months) when compared to natural history studies. However, PPS treatment did not appear to arrest the progression of the disease.

  5. Long-term affected energy production of waste to energy technologies identified by use of energy system analysis

    SciTech Connect

    Muenster, M.; Meibom, P.

    2010-12-15

    Affected energy production is often decisive for the outcome of consequential life-cycle assessments when comparing the potential environmental impact of products or services. Affected energy production is however difficult to determine. In this article the future long-term affected energy production is identified by use of energy system analysis. The focus is on different uses of waste for energy production. The Waste-to-Energy technologies analysed include co-combustion of coal and waste, anaerobic digestion and thermal gasification. The analysis is based on optimization of both investments and production of electricity, district heating and bio-fuel in a future possible energy system in 2025 in the countries of the Northern European electricity market (Denmark, Norway, Sweden, Finland and Germany). Scenarios with different CO{sub 2} quota costs are analysed. It is demonstrated that the waste incineration continues to treat the largest amount of waste. Investments in new waste incineration capacity may, however, be superseded by investments in new Waste-to-Energy technologies, particularly those utilising sorted fractions such as organic waste and refuse derived fuel. The changed use of waste proves to always affect a combination of technologies. What is affected varies among the different Waste-to-Energy technologies and is furthermore dependent on the CO{sub 2} quota costs and on the geographical scope. The necessity for investments in flexibility measures varies with the different technologies such as storage of heat and waste as well as expansion of district heating networks. Finally, inflexible technologies such as nuclear power plants are shown to be affected.

  6. Long-term affected energy production of waste to energy technologies identified by use of energy system analysis.

    PubMed

    Münster, M; Meibom, P

    2010-12-01

    Affected energy production is often decisive for the outcome of consequential life-cycle assessments when comparing the potential environmental impact of products or services. Affected energy production is however difficult to determine. In this article the future long-term affected energy production is identified by use of energy system analysis. The focus is on different uses of waste for energy production. The Waste-to-Energy technologies analysed include co-combustion of coal and waste, anaerobic digestion and thermal gasification. The analysis is based on optimization of both investments and production of electricity, district heating and bio-fuel in a future possible energy system in 2025 in the countries of the Northern European electricity market (Denmark, Norway, Sweden, Finland and Germany). Scenarios with different CO(2) quota costs are analysed. It is demonstrated that the waste incineration continues to treat the largest amount of waste. Investments in new waste incineration capacity may, however, be superseded by investments in new Waste-to-Energy technologies, particularly those utilising sorted fractions such as organic waste and refuse derived fuel. The changed use of waste proves to always affect a combination of technologies. What is affected varies among the different Waste-to-Energy technologies and is furthermore dependent on the CO(2) quota costs and on the geographical scope. The necessity for investments in flexibility measures varies with the different technologies such as storage of heat and waste as well as expansion of district heating networks. Finally, inflexible technologies such as nuclear power plants are shown to be affected.

  7. Long-term affected energy production of waste to energy technologies identified by use of energy system analysis.

    PubMed

    Münster, M; Meibom, P

    2010-12-01

    Affected energy production is often decisive for the outcome of consequential life-cycle assessments when comparing the potential environmental impact of products or services. Affected energy production is however difficult to determine. In this article the future long-term affected energy production is identified by use of energy system analysis. The focus is on different uses of waste for energy production. The Waste-to-Energy technologies analysed include co-combustion of coal and waste, anaerobic digestion and thermal gasification. The analysis is based on optimization of both investments and production of electricity, district heating and bio-fuel in a future possible energy system in 2025 in the countries of the Northern European electricity market (Denmark, Norway, Sweden, Finland and Germany). Scenarios with different CO(2) quota costs are analysed. It is demonstrated that the waste incineration continues to treat the largest amount of waste. Investments in new waste incineration capacity may, however, be superseded by investments in new Waste-to-Energy technologies, particularly those utilising sorted fractions such as organic waste and refuse derived fuel. The changed use of waste proves to always affect a combination of technologies. What is affected varies among the different Waste-to-Energy technologies and is furthermore dependent on the CO(2) quota costs and on the geographical scope. The necessity for investments in flexibility measures varies with the different technologies such as storage of heat and waste as well as expansion of district heating networks. Finally, inflexible technologies such as nuclear power plants are shown to be affected. PMID:20471819

  8. The effect of reverse remodeling on long-term survival in mildly symptomatic patients with heart failure receiving cardiac resynchronization therapy: Results of the REVERSE study

    PubMed Central

    Gold, Michael R.; Daubert, Claude; Abraham, William T.; Ghio, Stefano; Sutton, Martin St. John; Hudnall, John Harrison; Cerkvenik, Jeffrey; Linde, Cecilia

    2015-01-01

    BACKGROUND Cardiac resynchronization therapy (CRT) reduces mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure (HF). The magnitude of reverse remodeling predicts survival with many HF medical therapies. However, there are few studies assessing the effect of remodeling on long-term survival with CRT. OBJECTIVE The purpose of this study was to assess the effect of CRT-induced reverse remodeling on long-term survival in patients with mildly symptomatic heart failure. METHODS The REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial was a multicenter, double-blind, randomized trial of CRT in patients with mild HF. Long-term follow-up of 5 years was preplanned. The present analysis was restricted to the 353 patients who were randomized to the CRT ON group with paired echocardiographic studies at baseline and 6 months post-implantation. The left ventricular end-systolic volume index (LVESVi) was measured in the core laboratory and was an independently powered end point of the REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction trial. RESULTS A 68% reduction in mortality was observed in patients with ≥15% decrease in LVESVi compared to the rest of the patients (P = .0004). Multivariable analysis showed that the change in LVESVi was a strong independent predictor (P = .0002), with a 14% reduction in mortality for every 10% decrease in LVESVi. Other remodeling parameters such as left ventricular enddiastolic volume index and ejection fraction had a similar association with mortality. CONCLUSION The change in left ventricular end-systolic volume after 6 months of CRT is a strong independent predictor of long-term survival in mild HF. PMID:25460860

  9. Perioperative outcomes and long-term survival in clinically early-stage thymic malignancies: video-assisted thoracoscopic thymectomy versus open approaches

    PubMed Central

    Wang, Hao; Gu, Zhitao; Tan, Lijie; Fu, Jianhua; Shen, Yi; Wei, Yucheng; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background Video-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, long-term outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART). Methods Between 1994 and 2012, data of 1,117 patients having surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival. Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5% vs. 73.9%, P=0.028), resection rate (98.8% vs. 88.7%, P=0.000) and less recurrence (2.9% vs. 16.0%, P=0.000). Five-year overall survival was 92% after VATS and 92% after open thymectomy, with no significant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011). Cox proportional hazards model revealed that WHO classification, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no significant impact on long-term outcome. Conclusions This study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malignancies. And it may offer better perioperative outcomes, as well as equal oncological survival. PMID:27114834

  10. Electrical low-frequency stimulation induces long-term depression of sensory and affective components of pain in healthy man.

    PubMed

    Rottmann, Silke; Jung, Kerstin; Ellrich, Jens

    2010-04-01

    Electrical low-frequency stimulation (LFS) of nociceptive skin afferents reliably induces long-term depression (LTD) of pain. Recent experiments have assessed the effects of LTD on pain perception by using a simple one-dimensional rating scale. The psychophysical study investigated the impact of noxious LFS on the sensory and affective aspects of pain perception by multidimensional rating scales. In 20 healthy volunteers, nociceptive fibers of the left hand dorsum were electrically stimulated by a concentric electrode. Test stimulation series (15 stimuli each, 0.125Hz) were performed before (Pre) and after (Post) a conditioning LFS (1Hz, 20min) or no stimulation period (Control). Pain ratings concerning test stimulation and LFS were obtained by multidimensional assessment including Verbal rating scale of perceived stimulus intensity (VRS-I) and unpleasantness (VRS-U) and pain perception scale with sensory (SES-S) and affective items (SES-A). After the conditioning LFS, VRS-I, VRS-U, SES-S, and SES-A decreased as compared to Pre series and Control. During conditioning LFS, ratings decreased. Factor analysis of SES-S revealed sole reduction of superficial sharp pain perception after conditioning LFS in contrast to Control experiment. Perception of deep rhythmic pain decreased over time. Deep constant pain and superficial heat pain were not affected. Electrical test stimulation via concentric electrode evokes sensory as well as affective pain perception. Both components decrease during noxious, conditioning LFS and remain depressed for at least one hour. Reduction of sharp pain points to Adelta fiber mediated LTD. These results stress the analgesic potency of LTD and its possible impact on future therapy in chronic pain.

  11. Long-term trends in survival of a declining population: the case of the little owl (Athene noctua) in the Netherlands.

    PubMed

    Le Gouar, Pascaline J; Schekkerman, Hans; van der Jeugd, Henk P; Boele, Arjan; van Harxen, Ronald; Fuchs, Piet; Stroeken, Pascal; van Noordwijk, Arie J

    2011-06-01

    The little owl (Athene noctua) has declined significantly in many parts of Europe, including the Netherlands. To understand the demographic mechanisms underlying their decline, we analysed all available Dutch little owl ringing data. The data set spanned 35 years, and included more than 24,000 ringed owls, allowing detailed estimation of survival rates through multi-state capture-recapture modelling taking dispersal into account. We investigated geographical and temporal variation in age-specific survival rates and linked annual survival estimates to population growth rate in corresponding years, as well as to environmental covariates. The best model for estimating survival assumed time effects on both juvenile and adult survival rates, with average annual survival estimated at 0.258 (SE = 0.047) and 0.753 (SE = 0.019), respectively. Juvenile survival rates decreased with time whereas adult survival rates fluctuated regularly among years, low survival occurring about every 4 years. Years when the population declined were associated with low juvenile survival. More than 60% of the variation in juvenile survival was explained by the increase in road traffic intensity or in average temperature in spring, but these correlations rather reflect a gradual decrease in juvenile survival coinciding with long-term global change than direct causal effects. Surprisingly, vole dynamics did not explain the cyclic dynamics of adult survival rate. Instead, dry and cold years led to low adult survival rates. Low juvenile survival rates, that limit recruitment of first-year breeders, and the regular occurrence of years with poor adult survival, were the most important determinants of the population decline of the little owl.

  12. IDO and regulatory T cell support are critical for cytotoxic T lymphocyte-associated Ag-4 Ig-mediated long-term solid organ allograft survival.

    PubMed

    Sucher, Robert; Fischler, Klaus; Oberhuber, Rupert; Kronberger, Irmgard; Margreiter, Christian; Ollinger, Robert; Schneeberger, Stefan; Fuchs, Dietmar; Werner, Ernst R; Watschinger, Katrin; Zelger, Bettina; Tellides, George; Pilat, Nina; Pratschke, Johann; Margreiter, Raimund; Wekerle, Thomas; Brandacher, Gerald

    2012-01-01

    Costimulatory blockade of CD28-B7 interaction with CTLA4Ig is a well-established strategy to induce transplantation tolerance. Although previous in vitro studies suggest that CTLA4Ig upregulates expression of the immunoregulatory enzyme IDO in dendritic cells, the relationship of CTLA4Ig and IDO in in vivo organ transplantation remains unclear. In this study, we studied whether concerted immunomodulation in vivo by CTLA4Ig depends on IDO. C57BL/6 recipients receiving a fully MHC-mismatched BALB/c heart graft treated with CTLA4Ig + donor-specific transfusion showed indefinite graft survival (>100 d) without signs of chronic rejection or donor specific Ab formation. Recipients with long-term surviving grafts had significantly higher systemic IDO activity as compared with rejectors, which markedly correlated with intragraft IDO and Foxp3 levels. IDO inhibition with 1-methyl-dl-tryptophan, either at transplant or at postoperative day 50, abrogated CTLA4Ig + DST-induced long-term graft survival. Importantly, IDO1 knockout recipients experienced acute rejection and graft survival comparable to controls. In addition, αCD25 mAb-mediated depletion of regulatory T cells (Tregs) resulted in decreased IDO activity and again prevented CTLA4Ig + DST induced indefinite graft survival. Our results suggest that CTLA4Ig-induced tolerance to murine cardiac allografts is critically dependent on synergistic cross-linked interplay of IDO and Tregs. These results have important implications for the clinical development of this costimulatory blocker.

  13. Impact of donor-recipient sex match on long-term survival after heart transplantation in children: An analysis of 5797 pediatric heart transplants.

    PubMed

    Kemna, Mariska; Albers, Erin; Bradford, Miranda C; Law, Sabrina; Permut, Lester; McMullan, D Mike; Law, Yuk

    2016-03-01

    The effect of donor-recipient sex matching on long-term survival in pediatric heart transplantation is not well known. Adult data have shown worse survival when male recipients receive a sex-mismatched heart, with conflicting results in female recipients. We analyzed 5795 heart transplant recipients ≤ 18 yr in the Scientific Registry of Transplant Recipients (1990-2012). Recipients were stratified based on donor and recipient sex, creating four groups: MM (N = 1888), FM (N = 1384), FF (N = 1082), and MF (N = 1441). Males receiving sex-matched donor hearts had increased unadjusted allograft survival at five yr (73.2 vs. 71%, p = 0.01). However, this survival advantage disappeared with longer follow-up and when adjusted for additional risk factors by multivariable Cox regression analysis. In contrast, for females, receiving a sex-mismatched heart was associated with an 18% higher risk of allograft loss over time compared to receiving a sex-matched heart (HR 1.18, 95% CI: 1.00-1.38) and a 26% higher risk compared to sex-matched male recipients (HR 1.26, 95% CI: 1.10-1.45). Females who receive a heart from a male donor appear to have a distinct long-term survival disadvantage compared to all other groups.

  14. Long-term survivability of riprap for armoring uranium-mill tailings and covers: a literature review. [203 references

    SciTech Connect

    Lindsey, C.G.; Long, L.W.; Begej, C.W.

    1982-06-01

    Pacific Northwest Laboratory (PNL) is investigating the use of a rock armoring blanket (riprap) to mitigate wind and water erosion of an earthen radon suppression cover applied to uranium mill tailings. Because the radon suppression cover and the tailings must remain intact for up to 1000 years or longer, the riprap must withstand natural weathering forces. This report is a review of information on rock weathering and riprap durability. Chemical and physical weathering processes, rock characteristics related to durability, climatic conditions affecting the degree and rate of weathering, and testing procedures used to measure weathering susceptibilities have been reviewed. Sampling and testing techniques, as well as analyses of physical and chemical weathering susceptibilities, are necessary to evaluate rock durability. Many potential riprap materials may not be able to survive 1000 years of weathering. Available techniques for durability testing cannot adequately predict rock durability for the 1000-year period because they do not consider the issue of time (i.e., how long must riprap remain stable). This report includes an Appendix, which discusses rock weathering, written by Dr. Richard Jahns of Stanford University.

  15. Long-term survival with a stentless free-hand Batista pericardial aortic valve prosthesis: A case report

    PubMed Central

    Becerra, Valentina; Labbé, Javier; Cataldo, Anthony; Becerra, Eduardo

    2014-01-01

    INTRODUCTION Stented bovine pericardial prosthetic valves are a good option for older patients, except when there is a fragile small aortic annulus, when, if there is no contraindication to anticoagulation, a mechanical prosthesis may be indicated. PRESENTATION OF CASE We report a 72 year-old man who underwent coronary bypass grafting and aortic valve replacement with a stentless valve fashioned from bovine pericardium using the Batista technique. Despite early sternal infection and dehiscence, and renal and respiratory failure during 15 years follow-up, he remains alive and self-sufficient. Echocardiography demonstrates a well-functioning aortic valve. DISCUSSION When Batista reported his first 60 patients, concerns were raised about the surgical feasibility of constructing the valve and its long-term durability. Our case perhaps addresses both concerns. CONCLUSION Replacement of the aortic valve with a free-hand Batista pericardial valve is a feasible option in a suitable and carefully selected patient. PMID:25524300

  16. Relapsed APL patient with variant NPM-RARalpha fusion responded to arsenic trioxide-based therapy and achieved long-term survival.

    PubMed

    Chen, Yan; Gu, Ling; Zhou, Chenyan; Wu, Xueqiang; Gao, Ju; Li, Qiang; Zhu, Yiping; Jia, Cangsong; Ma, Zhigui

    2010-05-01

    The t(5;17)/NPM-RARalpha is the second variant chromosomal translocation in acute promyelocytic leukemia (APL) to be characterized and also the second most plentiful variant translocation. So far, there is a lack of information on the effectiveness of arsenic trioxide (ATO) in relapsed APL with variant RARalpha chimera including t(5;17)/NPM-RARalpha. We report here a long-term survived APL patient with variant NPM-RARalpha fusion who relapsed four times and each time responded well to ATO or ATO-based re-induction therapy. The patient had received a total of more than 3,500 mg of ATO, but showed no obvious arsenic-related toxicities. This case illustrates the long-term efficiency and safety of ATO-based therapy not only in newly diagnosed APL, but also in relapsed APL including those with variant translocations.

  17. Long-term outcome of infective endocarditis: A study on patients surviving over one year after the initial episode treated in a Finnish teaching hospital during 25 years

    PubMed Central

    Heiro, Maija; Helenius, Hans; Hurme, Saija; Savunen, Timo; Metsärinne, Kaj; Engblom, Erik; Nikoskelainen, Jukka; Kotilainen, Pirkko

    2008-01-01

    Background Only a few previous studies have focused on the long-term prognosis of the patients with infective endocarditis (IE). Our purpose was to delineate factors potentially associated with the long-term outcome of IE, recurrences of IE and requirement for late valve surgery. Methods A total of 326 episodes of IE in 303 patients were treated during 1980–2004 in the Turku University Hospital. We evaluated the long-term outcome and requirement for late valve surgery for 243 of these episodes in 226 patients who survived longer than 1 year after the initial admission. Factors associated with recurrences were analysed both for the 1-year survivors and for all 303 patients. Results The mean (SD) follow-up time for the 1-year survivors was 11.5 (7.3) years (range 25 days to 25.5 years). The overall survival was 95%, 82%, 66%, 51% and 45% at 2, 5, 10, 15 and 20 years. In age and sex adjusted multivariate analyses, significant predictors for long-term overall mortality were heart failure within 3 months of admission (HR 1.97, 95% CI 1.27 to 3.06; p = 0.003) and collagen disease (HR 2.54, 95% CI 1.25 to 5.19; p = 0.010) or alcohol abuse (HR 2.39, 95% CI 1.30 to 4.40; p = 0.005) as underlying conditions, while early surgery was significantly associated with lower overall mortality rates (HR 0.31, 95% CI 0.17 to 0.58; p < 0.001). Heart failure was also significantly associated with the long-term cardiac mortality (p = 0.032). Of all 303 patients, 20 had more than 1 disease episode. Chronic dialysis (p = 0.002), intravenous drug use (p = 0.002) and diabetes (p = 0.015) were significant risk factors for recurrent episodes of IE, but when analysed separately for the 1-year survivors, only chronic dialysis remained significant (p = 0.017). Recurrences and late valve surgery did not confer a poor prognosis. Conclusion Heart failure during the index episode of IE was the complication, which significantly predicted a poor long-term outcome. Patients who underwent surgery

  18. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  19. Age-specific survival and philopatry in three species of European ducks: a long-term study

    USGS Publications Warehouse

    Blums, P.; Mednis, A.; Bauga, I.; Nichols, J.D.; Hines, J.E.

    1996-01-01

    Capture-recapture and band recovery models were used to estimate age-specific survival probabilities for female Northern Shovelers (Anas clypeata), Common Pochards (Aythya ferina), and Tufted Ducks (Aythya.fuligula) at Engure Marsh, Latvia, in 1964-1993. We banded more than 65,100 day-old ducklings of both sexes and captured 10,211 incubating females (3,713 new bandings and 6,498 recaptures). We developed a set of 3-age capture-recapture models to estimate annual survival rates for female ducklings, yearlings (SY), and adults (ASY) using programs SURGE and SURVIV and selected parsimonious models using a method developed bv Akaike (1973). Survival rates of SY and ASY females were highest-for Tufted Ducks intermediate for Common Pochards, and lowest for Northern Shovelers. Survival rates of SY and ASY females varied in parallel for shovelers and pochards. We believe that much of the difference in survival estimates between SY and ASY birds was caused by mortality rather than permanent emigration. Estimates of day-old duckling survival, reflecting both mortality and permanent emigration, were 0.12 for shoveler, 0.06 for pochard, and 0.03 for Tufted Duck. For all species, duckling survival varied over years, but the pattern of variation was not similar to that of the other age classes. Estimates of survival using band recovery data for SY + ASY female pochards and Tufted Ducks were similar to the capture-recapturee stimates, suggestingt hat surviving females returned to the breeding marsh with probabilities approaching 1.

  20. Survival of Prokaryotic- and Eukaryotic Symbiotic Rock Inhabiting Organisms in Short- and Long-Term Space Missions

    NASA Astrophysics Data System (ADS)

    de La Torre, R.; Horneck, G.; Rabbow, E.; Rettberg, P.; Sancho, L. G.; Sanchez Iñigo, F. J.; Onofri, S.; Frias, M.; Mateo-Marti, E.; de Vera, J. P.; Cockell, C.; Olsson, K.; Demets, R.

    2010-04-01

    Three experiments allowed for the first time the demonstration and intercomparision of the high survival capacity of eukaryotic and prokaryotic symbiotic organisms in space: on a short mission (LICHENS and LITHOPANSPERMIA) and on a long mission (LIFE, EXPOSE-E).

  1. Long-term nitrogen additions increase likelihood of climate stress and affect recovery from wildfire in a lowland heath.

    PubMed

    Southon, Georgina E; Green, Emma R; Jones, Alan G; Barker, Chris G; Power, Sally A

    2012-09-01

    Increases in the emissions and associated atmospheric deposition of nitrogen (N) have the potential to cause significant changes to the structure and function of N-limited ecosystems. Here, we present the results of a long-term (13 year) experiment assessing the impacts of N addition (30 kg ha(-1)  yr(-1) ) on a UK lowland heathland under a wide range of environmental conditions, including the occurrence of prolonged natural drought episodes and a severe summer fire. Our findings indicate that elevated N deposition results in large, persistent effects on Calluna growth, phenology and chemistry, severe suppression of understorey lichen flora and changes in soil biogeochemistry. Growing season rainfall was found to be a strong driver of inter-annual variation in Calluna growth and, although interactions between N and rainfall for shoot growth were not significant until the later phase of the experiment, N addition exacerbated the extent of drought injury to Calluna shoots following naturally occurring droughts in 2003 and 2009. Following a severe wildfire at the experimental site in 2006, heathland regeneration dynamics were significantly affected by N, with a greater abundance of pioneering moss species and suppression of the lichen flora in plots receiving N additions. Significant interactions between climate and N were also apparent post fire, with the characteristic stimulation in Calluna growth in +N plots suppressed during dry years. Carbon (C) and N budgets demonstrate large increases in both above- and below-ground stocks of these elements in N-treated plots prior to the fire, despite higher levels of soil microbial activity and organic matter turnover. Although much of the organic material was removed during the fire, pre-existing treatment differences were still evident following the burn. Post fire accumulation of below-ground C and N stocks was increased rapidly in N-treated plots, highlighting the role of N deposition in ecosystem C sequestration

  2. Microstructure and Mechanical Instability of Water-Quenched U-6wt% Nb Alloy Affected by Long-Term Aging

    SciTech Connect

    Hsiung, L; Zhou, J

    2005-12-06

    A combinative approach of microhardness testing, tensile testing, and TEM microstructural analysis was employed to study the microstructure and mechanical instability of a water-quenched U-6wt.% Nb (WQ-U6Nb) alloy subjected to different aging schedules including artificial aging at 200 C, 15-year natural aging at ambient temperatures, and 15-year natural aging followed by accelerative aging at 200 C. The changes in mechanical property during and after the aging processes were examined using microhardness and tensile-testing methods. During the early stages of artificial aging at 200 C, the microhardness of WQ-U6Nb alloy increased, i.e., age hardening, as a result of the development of nanoscale modulation caused by spinodal decomposition. Coarsening of the modulated structure occurred after a prolonged aging at 200 C for 16 hours, and it led to a decrease of microhardness, i.e., age softening. Phase instability was also found to occur in WQ-U6Nb alloy that was subjected to a 15-year natural aging at ambient temperatures. The formation of partially ordered domains resulting from a spinodal modulation with an atomic-scale wavelength rendered the appearance of swirl-shape antiphase domain boundaries (APBs) observed in TEM images. Although it did not cause a significant change in microhardness, 15-year natural aging has dramatically affected the aging mechanisms of the alloy isothermally aged at 200 C. Microhardness values of the NA alloy continuously increased and no age softening was found after isothermal aging at 200 C for 96 hours as a result of the phase decomposition of partially ordered domains into Nb-depleted {alpha} phase and Nb-enriched U{sub 3}Nb ordered phase in the alloy. It is concluded that the long-term natural aging changes the transformation pathway of WQ-U6Nb, and it leads to order-disorder transformation, precipitation hardening, and ductility embrittlement of WQ-U6Nb alloy.

  3. Proliferation capacity of T-lymphocytes is affected transiently after a long-term weight gain in Beagle dogs.

    PubMed

    Van de Velde, H; Janssens, G P J; Rochus, K; Duchateau, L; Scharek-Tedin, L; Zentek, J; Nguyen, P; Cox, E; Buyse, J; Biourge, V; Hesta, M

    2013-04-15

    Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function.

  4. The effects of erythropoiesis-stimulating agents on the short-term and long-term survivals in metastatic breast cancer patients receiving chemotherapy: a SEER population-based study.

    PubMed

    Lai, Yinzhi; Ye, Zhong; Civan, Jesse M; Wang, Chun; Cristofanilli, Massimo; Mu, Zhaomei; Austin, Laura; Palazzo, Juan P; Myers, Ronald E; Yang, Hushan

    2015-09-01

    Current clinical guidelines state that the use of erythropoiesis-stimulating agents (ESAs) may be considered to treat chemotherapy-induced anemia in the non-curative setting to alleviate anemia-related symptoms. However, no convincing survival benefit has been demonstrated to support the use of ESAs in these patients. Using the comprehensive data collected in the National Cancer Institute (NCI)-surveillance epidemiology and end results (SEER) and Medicare-linked database, we analyzed the effect of ESA use on the short-term (18-month) and long-term (60-month) survival rates of chemotherapy-treated metastatic breast cancer patients. Confounding variables were adjusted using a propensity score approach. We also analyzed the effects of ESA on the survival of patients receiving trastuzumab, a commonly prescribed targeted therapy agent in treating HER2-positive tumors. Metastatic breast cancer patients who received ESA treatment exhibited similar 60-month survival rate to those without ESA treatment (22.8 vs. 24.9%, p = 0.8). ESA-treated patients had a trend toward better 18-month survival [crude hazard ratio (HR) 0.86, 95% confidence intervals (CI) 0.68-1.09, p = 0.21]. This protective effect during the first 18 months of chemotherapy became marginally significant after adjusting for the propensity of receiving ESAs (HR 0.80, 95% CI 0.63-1.01, p = 0.070). An interaction effect between ESA and trastuzumab on patient survival was noticeable but not statistically significant. ESAs did not negatively affect the long-term survival of metastatic breast cancer patients. Moreover, ESAs improved patients' survival during the first 18 months of chemotherapy treatment. These findings endorse the current clinical guideline. Given the short survival of these patients, the potential short-term beneficial effects of ESAs are clinically meaningful.

  5. Short- and long-term memory are differentially affected by metabolic inhibitors given into hippocampus and entorhinal cortex.

    PubMed

    Izquierdo, L A; Vianna, M; Barros, D M; Mello e Souza, T; Ardenghi, P; Sant'Anna, M K; Rodrigues, C; Medinam, J H; Izquierdo, I

    2000-03-01

    Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus or in the entorhinal cortex and trained in one-trial step-down inhibitory avoidance. Two retention tests were carried out in each animal, one at 1.5 h to measure short-term memory (STM) and another at 24 h to measure long-term memory (LTM). The purpose of the present study was to screen the effect on STM of various drugs previously shown to affect LTM of this task when given posttraining at the same doses that were used here. The drugs and doses were the guanylyl cyclase inhibitor LY83583 (LY, 2.5 microMg), the inhibitor of Tyr-protein kinase at low concentrations and of protein kinase G (PKG) at higher concentrations lavendustin A (LAV, 0.1 and 0.5 microMg), the PKG inhibitor KT5823 (2.0 microMg), the protein kinase C (PKC) inhibitor staurosporin (STAU, 2.5 microMg), the inhibitor of calcium/ calmodulin protein kinase II (CaMKII) KN62 (3.6 microMg), the protein kinase A (PKA) inhibitor KT5720 (0.5 microMg), and the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059 (PD, 0.05 microMg). PD was dissolved in saline; all the other drugs were dissolved in 20% dimethyl sulfoxide. In all cases the drugs affected LTM as had been described in previous papers. The drugs affected STM and LTM differentially depending on the brain structure into which they were infused. STM was inhibited by KT5720, LY, and PD given into CA1 and by STAU and KT5720 given into the entorhinal cortex. PD given into the entorhinal cortex enhanced STM. LTM was inhibited by STAU, KN62, KT5720, KT5823, and LAV (0.5 microMg) given into CA1 and by STAU, KT5720, and PD given into the entorhinal cortex. The results suggest that STM and LTM involve different physiological mechanisms but are to an extent linked. STM appears to require PKA, guanylyl cyclase, and MAPKK activity in CA1 and PKA and PKC activity in the entorhinal cortex; MAPKK seems to play an inhibitory role in STM in the entorhinal cortex. In contrast

  6. Long Term Follow-up of Children in the HIVNET 012 Perinatal HIV Prevention Trial: Five-Year Growth and Survival

    PubMed Central

    Owor, Maxensia; Mwatha, Anthony; Donnell, Deborah; Musoke, Philippa; Mmiro, Francis; Allen, Melissa; Jackson, J Brooks; Fowler, Mary Glenn; Guay, Laura A

    2014-01-01

    Objectives To describe five year growth, survival and long-term safety among children exposed to nevirapine or zidovudine in an African perinatal prevention trial, HIVNET 012. Methods All study children who were alive at eighteen months of age were eligible for an extended follow-up study. Children whose families consented were enrolled and evaluated every six months from 24 to 60 months. At each visit, history, physical exam and growth measures were taken. From these measurements Z scores based on World Health Organization (WHO) standards were computed. Serious adverse event data were collected. Data from the initial and extended follow-up cohorts were included in the analysis. Results 528 study children were alive at age 18 months, and 491 (426 HIV uninfected; 65 infected) were enrolled into the follow-up study. Both exposed but uninfected children and HIV infected children were substantially below WHO growth standards for weight and height. Head circumference Z scores for uninfected children were comparable to WHO norms. Five-year survival rates were 93% for uninfected children versus 43% for infected children. Long-term safety and growth outcomes in the two study arms were similar. Conclusions Both infected and uninfected children in the five-year HIVNET 012 follow-up showed poor height and weight growth outcomes, underscoring the need for early nutritional interventions to improve long-term growth of all infants born to HIV-infected women in resource limited settings. Likewise, the low five year survival among HIV infected children support the importance of early initiation of antiretroviral therapy. Both peripartum nevirapine and zidovudine were safe. PMID:24121753

  7. Long-term survival of Borrelia burgdorferi lacking the hibernation promotion factor homolog in the unfed tick vector.

    PubMed

    Fazzino, Lisa; Tilly, Kit; Dulebohn, Daniel P; Rosa, Patricia A

    2015-12-01

    Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic pathogen that survives in nutrient-limited environments within a tick, prior to transmission to its mammalian host. Survival under these prolonged nutrient-limited conditions is thought to be similar to survival during stationary phase, which is characterized by growth cessation and decreased protein production. Multiple ribosome-associated proteins are implicated in stationary-phase survival of Escherichia coli. These proteins include hibernation-promoting factor (HPF), which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene. BB0449 protein secondary structure modeling also predicted HPF-like structure and function. However, BB0449 protein was not localized in the ribosome-associated protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi, bb0449 transcript and BB0449 protein levels are low during various growth phases. These results are inconsistent with patterns of synthesis of HPF-like proteins in other bacterial species. In addition, two independently derived bb0449 mutants successfully completed the mouse-tick infectious cycle, indicating that bb0449 is not required for prolonged survival in the nutrient-limited environment in the unfed tick or any other stage of infection by B. burgdorferi. We suggest either that BB0449 is associated with ribosomes under specific conditions not yet identified or that BB0449 of B. burgdorferi has a function other than ribosome conformation modulation.

  8. Long-term survival of Escherichia coli in lightweight aggregate filter media of constructed wastewater treatment wetlands.

    PubMed

    Paruch, A M

    2011-01-01

    A laboratory scale experiment on the survival of Escherichia coli in samples of filter media from a horizontal subsurface flow constructed wetland treating domestic wastewater was performed. A concentration of E. coli was examined in samples collected from a wetland filter filled with lightweight aggregates (LWA). All samples testing positive for E. coli contamination were used to examine the effect of storage time on the survival of E. coli at three temperature regimes: cold (4°C), mild (10°C) and warm (22°C). It was found that the mild storage condition favoured the growth and survival of E. coli in the tested LWA media. The growth in samples of the uppermost layer of the media lasted for 5.5 months, during which E. coli reached a maximum concentration of 6.4×10(3) MPN/100 g dry matter in the media. It was also observed that E. coli had a greater capacity to survive for extended periods of time in samples collected from the upper layer of the LWA filter compared to samples taken from the deeper layers. The survival of E. coli in the shallowest samples of the wetland filter was remarkably long and unexpected, lasting for a period of over 14 months. PMID:21278480

  9. Long-Term Survival of Borrelia burgdorferi Lacking the Hibernation Promotion Factor Homolog in the Unfed Tick Vector

    PubMed Central

    Fazzino, Lisa; Dulebohn, Daniel P.

    2015-01-01

    Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic pathogen that survives in nutrient-limited environments within a tick, prior to transmission to its mammalian host. Survival under these prolonged nutrient-limited conditions is thought to be similar to survival during stationary phase, which is characterized by growth cessation and decreased protein production. Multiple ribosome-associated proteins are implicated in stationary-phase survival of Escherichia coli. These proteins include hibernation-promoting factor (HPF), which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene. BB0449 protein secondary structure modeling also predicted HPF-like structure and function. However, BB0449 protein was not localized in the ribosome-associated protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi, bb0449 transcript and BB0449 protein levels are low during various growth phases. These results are inconsistent with patterns of synthesis of HPF-like proteins in other bacterial species. In addition, two independently derived bb0449 mutants successfully completed the mouse-tick infectious cycle, indicating that bb0449 is not required for prolonged survival in the nutrient-limited environment in the unfed tick or any other stage of infection by B. burgdorferi. We suggest either that BB0449 is associated with ribosomes under specific conditions not yet identified or that BB0449 of B. burgdorferi has a function other than ribosome conformation modulation. PMID:26438790

  10. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    PubMed Central

    Gai, Xiu-juan; Wei, Yu-mei; Tao, Heng-min; An, Dian-zheng; Sun, Jia-teng; Li, Bao-sheng

    2016-01-01

    Purpose This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. Patients and methods In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). Conclusion Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation. PMID:27574452

  11. Long-term survival in laparoscopic vs open resection for colorectal liver metastases: inverse probability of treatment weighting using propensity scores

    PubMed Central

    Lewin, Joel W.; O'Rourke, Nicholas A.; Chiow, Adrian K.H.; Bryant, Richard; Martin, Ian; Nathanson, Leslie K.; Cavallucci, David J.

    2015-01-01

    Background This study compares long-term outcomes between intention-to-treat laparoscopic and open approaches to colorectal liver metastases (CLM), using inverse probability of treatment weighting (IPTW) based on propensity scores to control for selection bias. Method Patients undergoing liver resection for CLM by 5 surgeons at 3 institutions from 2000 to early 2014 were analysed. IPTW based on propensity scores were generated and used to assess the marginal treatment effect of the laparoscopic approach via a weighted Cox proportional hazards model. Results A total of 298 operations were performed in 256 patients. 7 patients with planned two-stage resections were excluded leaving 284 operations in 249 patients for analysis. After IPTW, the population was well balanced. With a median follow up of 36 months, 5-year overall survival (OS) and recurrence-free survival (RFS) for the cohort were 59% and 38%. 146 laparoscopic procedures were performed in 140 patients, with weighted 5-year OS and RFS of 54% and 36% respectively. In the open group, 138 procedures were performed in 122 patients, with a weighted 5-year OS and RFS of 63% and 38% respectively. There was no significant difference between the two groups in terms of OS or RFS. Conclusion In the Brisbane experience, after accounting for bias in treatment assignment, long term survival after LLR for CLM is equivalent to outcomes in open surgery. PMID:26902138

  12. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells

    PubMed Central

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K.

    2015-01-01

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 106 of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart. PMID:26585309

  13. Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells.

    PubMed

    Matsuo, Takehiko; Masumoto, Hidetoshi; Tajima, Shuhei; Ikuno, Takeshi; Katayama, Shiori; Minakata, Kenji; Ikeda, Tadashi; Yamamizu, Kohei; Tabata, Yasuhiko; Sakata, Ryuzo; Yamashita, Jun K

    2015-11-20

    Poor engraftment of cells after transplantation to the heart is a common and unresolved problem in the cardiac cell therapies. We previously generated cardiovascular cell sheets entirely from pluripotent stem cells with cardiomyocytes, endothelial cells and vascular mural cells. Though sheet transplantation showed a better engraftment and improved cardiac function after myocardial infarction, stacking limitation (up to 3 sheets) by hypoxia hampered larger structure formation and long-term survival of the grafts. Here we report an efficient method to overcome the stacking limitation. Insertion of gelatin hydrogel microspheres (GHMs) between each cardiovascular cell sheet broke the viable limitation via appropriate spacing and fluid impregnation with GHMs. Fifteen sheets with GHMs (15-GHM construct; >1 mm thickness) were stacked within several hours and viable after 1 week in vitro. Transplantation of 5-GHM constructs (≈2 × 10(6) of total cells) to a rat myocardial infarction model showed rapid and sustained functional improvements. The grafts were efficiently engrafted as multiple layered cardiovascular cells accompanied by functional capillary networks. Large engrafted cardiac tissues (0.8 mm thickness with 40 cell layers) successfully survived 3 months after TX. We developed an efficient method to generate thicker viable tissue structures and achieve long-term survival of the cell graft to the heart.

  14. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a Large-Scale Cohort.

    PubMed

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-03-01

    Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm²/m² for women and 40.8 cm²/m² for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia

  15. Sarcopenia is an Independent Predictor of Severe Postoperative Complications and Long-Term Survival After Radical Gastrectomy for Gastric Cancer: Analysis from a Large-Scale Cohort.

    PubMed

    Zhuang, Cheng-Le; Huang, Dong-Dong; Pang, Wen-Yang; Zhou, Chong-Jun; Wang, Su-Lin; Lou, Neng; Ma, Liang-Liang; Yu, Zhen; Shen, Xian

    2016-03-01

    Currently, the association between sarcopenia and long-term prognosis after gastric cancer surgery has not been investigated. Moreover, the association between sarcopenia and postoperative complications remains controversial. This large-scale retrospective study aims to ascertain the prevalence of sarcopenia and assess its impact on postoperative complications and long-term survival in patients undergoing radical gastrectomy for gastric cancer. From December 2008 to April 2013, the clinical data of all patients who underwent elective radical gastrectomy for gastric cancer were collected prospectively. Only patients with available preoperative abdominal CT scan within 30 days of surgery were considered for analysis. Skeletal muscle mass was determined by abdominal (computed tomography) CT scan, and sarcopenia was diagnosed by the cut-off values obtained by means of optimum stratification. Univariate and multivariate analyses evaluating risk factors of postoperative complications and long-term survival were performed. A total of 937 patients were included in this study, and 389 (41.5%) patients were sarcopenic based on the diagnostic cut-off values (34.9 cm²/m² for women and 40.8 cm²/m² for men). Sarcopenia was an independent risk factor for severe postoperative complications (OR = 3.010, P < 0.001), but not for total complications. However, sarcopenia did not show significant association with operative mortality. Moreover, sarcopenia was an independent predictor for poorer overall survival (HR = 1.653, P < 0.001) and disease-free survival (HR = 1.620, P < 0.001). Under the adjusted tumor-node-metastasis (TNM) stage, sarcopenia remained an independent risk factor for overall survival and disease-free survival in patients with TNM stage II and III, but not in patients with TNM stage I. Sarcopenia is an independent predictive factor of severe postoperative complications after radical gastrectomy for gastric cancer. Moreover, sarcopenia

  16. Factors associated with long-term survival in dogs undergoing liver lobectomy as treatment for liver tumors.

    PubMed

    Kinsey, Jessica R; Gilson, Stephen D; Hauptman, Joe; Mehler, Steve J; May, Lauren R

    2015-06-01

    The objectives of the study were to describe clinicopathologic findings in dogs that underwent surgical treatment of liver tumors and to define outcome-associated variables in this canine population. Medical records of 118 dogs that underwent liver lobectomy were reviewed. Variables were assessed via univariate and multivariate Cox regression analyses. Hazard ratios, median survival times (MSTs), and Kaplan-Meier Survival curves (KMSCs) were created for significant variables. Of the dogs with surgically addressed hepatic tumors, 93% survived to discharge. The MST was not reached. Lethargic dogs had a mortality risk 10.2 times that of non-lethargic dogs. Non-tachypneic dogs had a mortality risk 4.3 times that of tachypneic dogs. Dogs that experienced anesthetic complications had a mortality risk 100 times that of dogs that did not. We conclude that the prognosis associated with liver tumors is good. Lethargy, respiratory rate, and anesthetic complications were associated with outcome.

  17. Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

    PubMed Central

    2011-01-01

    Background Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Methods/Design Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m2) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. Discussion While clinical data indicate that excess weight for height is associated

  18. A Case of Long-term Survival of Advanced Paratesticular Rhabdomyosarcoma Treated With a Multimodal Therapy Including a Combination of Cyclophosphamide, Vincristine, Doxorubicin and Dacarbazine.

    PubMed

    Isono, Makoto; Sato, Akinori; Asano, Tomohiko

    2016-07-01

    There is no established treatment for advanced rhabdomyosarcoma (RMS) with metastases at the time of diagnosis. A 17-year-old male was referred to our hospital because of a right scrotal mass. Computed tomography showed multiple lung metastases with pleural effusion and retroperitoneal lymph node metastasis, and bone scintigraphy revealed multiple bone metastases. Right high orchiectomy was performed and the tumor was diagnosed as paratesticular embryonal RMS. He was treated with a multimodal therapy including 17 cycles of combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dacarbazine (CYVADIC) and achieved a long-term survival of 4 years. PMID:27335778

  19. Long-Term Survival on Medical Therapy Alone after Blunt-Trauma Aortic Regurgitation: Report of a New Case with Summary of 95 Others

    PubMed Central

    Murata, Mitsushige; Mahara, Keitaro; Iwanaga, Shiro; Fukuda, Keiichi

    2016-01-01

    Aortic regurgitation resulting from blunt chest trauma has been reported only 95 times, to our knowledge. The noncoronary and right coronary cusps are the cardiac structures most often injured. Although the aortic leaflets can appear to be undamaged after nonpenetrating trauma, they can have pathologic abnormalities and insufficient function. Some cases of posttraumatic aortic regurgitation progress slowly. Aortic valve replacement is the optimal treatment. We present the case of a then-62-year-old man who has lived more than 5 years after blunt-trauma aortic regurgitation. His is the only case of long-term survival on medical therapy alone among the 96 cases summarized in this report. PMID:27777534

  20. Complex interplay between intrinsic and extrinsic drivers of long-term survival trends in southern elephant seals

    PubMed Central

    de Little, Siobhan C; Bradshaw, Corey JA; McMahon, Clive R; Hindell, Mark A

    2007-01-01

    Background Determining the relative contribution of intrinsic and extrinsic factors to fluctuations in population size, trends and demographic composition is analytically complex. It is often only possible to examine the combined effects of these factors through measurements made over long periods, spanning an array of population densities or levels of food availability. Using age-structured mark-recapture models and datasets spanning five decades (1950–1999), and two periods of differing relative population density, we estimated age-specific probabilities of survival and examined the combined effects of population density and environmental conditions on juvenile survival of southern elephant seals at Macquarie Island. Results First-year survival decreased with density during the period of highest population size, and survival increased during years when the Southern Oscillation Index (SOI) anomaly (deviation from a 50-year mean) during the mother's previous foraging trip to sea was positive (i.e., El Niño). However, when environmental stochasticity and density were considered together, the effect of density on first-year survival effectively disappeared. Ignoring density effects also leads to models placing too much emphasis on the environmental conditions prevailing during the naïve pup's first year at sea. Conclusion Our analyses revealed that both the state of the environment and population density combine to modify juvenile survival, but that the degree to which these processes contributed to the variation observed was interactive and complex. This underlines the importance of evaluating the relative contribution of both the intrinsic and extrinsic factors that regulate animal populations because false conclusions regarding the importance of population regulation may be reached if they are examined in isolation. PMID:17389038

  1. Long-term survival after coronary bypass surgery. Comparison of various subsets of patients with general population.

    PubMed Central

    Greene, D G; Bunnell, I L; Arani, D T; Schimert, G; Lajos, T Z; Lee, A B; Tandon, R N; Zimdahl, W T; Bozer, J M; Kohn, R M; Visco, J P; Dean, D C; Smith, G L

    1981-01-01

    Life-table analysis consecutive cases of isolated coronary bypass surgery at the Buffalo Hospital between 1973 and 1977 showed an estimated survival of 94 per cent at five years, equal to that of an age- and sex-matched group of the US population. Subsets of these patients divided according to sex, age, number of vessels narrowed, number of segments grafted, history of myocardial infarction, ejection fraction, and presence of unstable angina have estimated survivals not statistically less in any of these subsets than that of matched cohorts of the general population. PMID:6971646

  2. Long-term survival after resection of a primary leiomyosarcoma of the innominate vein Report of a case.

    PubMed

    Illuminati, Giulio; Miraldi, Fabio; A Pacilè, Maria; Palumbo, Piero; Vietri, Francesco

    2012-10-29

    Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We report the case of a 50-year-old woman, undergoing a curative resection of the tumor. She is alive and free of disease at 88-month follow-up. Surgical excision remains the current optimal treatment able to provide a chance of cure. KEY WORDS: Late survival, Venous leiomyosarcoma.

  3. Long-term survival rates of gravity-assisted, adjustable differential pressure valves in infants with hydrocephalus.

    PubMed

    Gebert, Anna-Felicitas; Schulz, Matthias; Schwarz, Karin; Thomale, Ulrich-Wilhelm

    2016-05-01

    OBJECTIVE The use of adjustable differential pressure valves with gravity-assisted units in shunt therapy of children with hydrocephalus was reported to be feasible and promising as a way to avoid chronic overdrainage. In this single-center study, the authors' experiences in infants, who have higher rates of shunt complications, are presented. METHODS All data were collected from a cohort of infants (93 patients [37 girls and 56 boys], less than 1 year of age [mean age 4.1 ± 3.1 months]) who received their first adjustable pressure hydrocephalus shunt as either a primary or secondary implant between May 2007 and April 2012. Rates of valve and shunt failure were recorded for a total of 85 months until the end of the observation period in May 2014. RESULTS During a follow-up of 54.2 ± 15.9 months (range 26-85 months), the Kaplan-Meier rate of shunt survival was 69.2% at 1 year and 34.1% at 85 months; the Kaplan-Meier rate of valve survival was 77.8% at 1 year and 56% at 85 months. Survival rates of the shunt were significantly inferior if the patients had previous shunt surgery. During follow-up, 44 valves were exchanged in cases of infection (n = 19), occlusion (n = 14), dysfunction of the adjustment unit (n = 10), or to change the gravitational unit (n = 1). CONCLUSIONS Although a higher shunt complication rate is observed in infant populations compared with older children, reasonable survival rates demonstrate the feasibility of using this sophisticated valve technology. The gravitational unit of this valve is well tolerated and its adjustability offers the flexible application of opening pressure in an unpredictable cohort of patients. This may adequately address overdrainage-related complications from early in treatment.

  4. Long-term disease-free survival after surgical resection for multiple bone metastases from rectal cancer

    PubMed Central

    Choi, Seok Jin; Kim, Jong Hun; Lee, Min Ro; Lee, Chang Ho; Kuh, Ja Hong; Kim, Jung Ryul

    2011-01-01

    Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is usually a late manifestation of disease and is indicative of poor prognosis. We describe a patient with multiple metachronous bone metastases from lower rectal cancer who was successfully treated with multimodal treatment including surgical resections and has shown 32 mo disease-free survival. Surgical resection of metastatic bone lesion(s) from colorectal cancer may be a good treatment option in selected patients. PMID:21876853

  5. Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort.

    PubMed

    Eyster, M Elaine; Kong, Lan; Li, Menghan; Schreibman, Ian R

    2016-09-01

    We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n = 100) had a survival of 75.2%, while those infected with HIV (n = 122) had a survival of 24% (P < 0.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P = 0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990 and 2001, to 17/29 (58%) between 2002 and 2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals. Am. J. Hematol. 91:E335-E340, 2016. © 2016 Wiley Periodicals, Inc. PMID:27214557

  6. Long-term survival after resection of a primary leiomyosarcoma of the innominate vein Report of a case.

    PubMed

    Illuminati, Giulio; Miraldi, Fabio; A Pacilè, Maria; Palumbo, Piero; Vietri, Francesco

    2012-01-01

    Leiomyosarcoma of the innominate vein is a rare but usually lethal disease. We report the case of a 50-year-old woman, undergoing a curative resection of the tumor. She is alive and free of disease at 88-month follow-up. Surgical excision remains the current optimal treatment able to provide a chance of cure. KEY WORDS: Late survival, Venous leiomyosarcoma. PMID:23132461

  7. Long-term vascular access ports as a means of sedative administration in a rodent fMRI survival model.

    PubMed

    Hettinger, Patrick C; Li, Rupeng; Yan, Ji-Geng; Matloub, Hani S; Cho, Younghoon R; Pawela, Christopher P; Rowe, Daniel B; Hyde, James S

    2011-09-15

    The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in survival experiments and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8 and 12 weeks postoperatively using a 9.4T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling.

  8. Regional groundwater flow and geochemical processes within an intercratonic sedimentary basin affected by long-term episodes of freshwater

    NASA Astrophysics Data System (ADS)

    Bea, S. A.; Mayer, K. U.; Macquarrie, K. T.

    2009-12-01

    Present-day regional groundwater flow systems in intercratonic sedimentary basins are mainly driven by water table topographic gradients and recharge derived from precipitation. During a glaciation-deglaciation event; however, the migration and melting of ice sheets may alter the patterns of freshwater ingress into these basins. Under such conditions water fluxes in aquifers can be expected to be significantly modified as a result of the high hydraulic gradients beneath wet-based ice sheets. In fact, present-day hydrogeological and geochemical conditions across formerly glaciated areas may still reflect the impact of the last glaciation (around 10 ka B.P., e.g. anomalous fluid pressures in deep hydrogeologic units, changes in oxygen isotope composition, etc.). Reactive transport modeling can be used to understand the evolution of geochemical conditions of these formations and assess their suitability for hosting a deep geologic repository for used nuclear fuel. In this work, we will shed light on the effect of long-term perturbations over geologic time scales (e.g. glaciation-deglaciation events) on the hydrogeological and geochemical processes in a hypothetical sedimentary basin. Processes included in the model are density-driven flow and transport, as well as chemical reactions (aqueous complexation, mineral dissolution and precipitation including evaporites, sulfates and carbonates, cation-exchange, redox processes involving the decomposition of organic matter, and the oxidation of ferrous iron and sulfide). Transient boundary conditions are imposed in the upper part of the model to mimic ice sheet advance and retreat. Modeling hydrodynamic and geochemical processes in these basins is complex due to the presence of dense brines, hydraulic heterogeneities, continental-basin scale, permafrost and the formation of taliks., requiring robust numeric capabilities. Our preliminary results suggest that low velocities, in regions containing dense brines, are maintained

  9. Handling intensity and the short- and long-term survival of elephant seals: addressing and quantifying research effects on wild animals.

    PubMed

    McMahon, Clive; van den Hoff, John; Burton, Harry

    2005-08-01

    This study addresses the consequences of repeated human handling on the survival of an endangered phocid, the southern elephant seal and the implications for wildlife research. Southern elephant seal pups were repeatedly handled during the first six weeks of their lives. The possibility that such anthropogenic research may have altered the very parameters that were being investigated is a topical and relevant study area that we address here. Our results show that there were no measurable effects on pups that were repeatedly handled and subjected to invasive research methods with respect to survivorship in the short term (the 24-day nursing period) nor in the long term (the first year of life and beyond) and hence fitness one year after handling. In support of this conclusion we were unable to detect any significant differences in the survival rates of the most intensively handled seals and the least intensively handled seals.

  10. Effect of mu Agonists on Long-Term Survival and Recurrence in Nonsmall Cell Lung Cancer Patients

    PubMed Central

    Wang, Kai; Qu, Xiao; Wang, Ying; Shen, Hongchang; Liu, Qi; Du, Jiajun

    2015-01-01

    Abstract Opioids are widely used for postoperative analgesia. Morphine may have an effect on cell replication, migration, and cancer recurrence. However, the association of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC) patients has not been fully investigated. We retrospectively evaluated the impact of postoperative mu agonists on overall survival (OS) and disease-free survival (DFS) in early stage NSCLC patients. Patients and relevant medical information were selected from the Bio-Bank of Shandong Provincial Hospital. Difference of clinicopathologic information in postoperative mu agonists group and no mu agonists group was analyzed by χ2 test. Univariate and multivariate Cox regression analysis were conducted and represented as hazards ratio and 95% confidence interval form. The primary endpoint was OS and secondary endpoint was DFS. This retrospective study included 984 consecutive NSCLC patients who underwent surgery between January 2006 and December 2011. No significant difference existed between postoperative mu agonists usage group and no mu agonists usage group in clinicopathologic information except operation type (P = 0.041). Postoperative mu agonists usage was related to shorter OS (HR 1.514, 95% CI 1.197–1.916, P = 0.001) and shorter DFS (HR 1.415, 95% CI 1.123–1.781, P = 0.003) in the multivariate Cox regression model. For the patients who received postoperative chemotherapy or radiotherapy postoperative mu agonists also predict shorter survival (HR 1.437, 95% CI 1.041–1.982, P = 0.027). Subgroup analysis showed that administration of postoperative mu agonists was related to shorter OS, especially in males, more smoking, poor differential degree, bilobectomy or pneumonectomy, and stage III subgroup, respectively. Administration of postoperative mu agonists was related to shorter OS and DFS for the NSCLC patients who underwent surgery. PMID:26287418

  11. Anaerobic and aerobic transformations affecting stability of dewatered sludge during long-term storage in a lagoon.

    PubMed

    Lukicheva, Irina; Tian, Guanglong; Cox, Albert; Granato, Thomas; Pagilla, Krishna

    2012-01-01

    The goal of this work was to study long-term behavior of anaerobically digested and dewatered sludge (biosolids) in a lagoon under anaerobic and aerobic conditions to determine the stability of the final product as an indicator of its odor potential. Field lagoons were sampled to estimate spatial and temporal variations in the physical-chemical properties and biological stability characteristics such as volatile solids content, accumulated oxygen uptake, and soluble protein content and odorous compound assessment. The analyses of collected data suggest that the surface layer of the lagoon (depth of above 0.15 m) undergoes long-term aerobic oxidation resulting in a higher degree of stabilization in the final product. The subsurface layers (depth 0.15 m below the surface and deeper) are subjected to an anaerobic environment where the conditions favor the initial rapid organic matter degradation within approximately the first year, followed by slow degradation. PMID:22368823

  12. Impact on long-term survival of the number of lymph nodes resected in patients with pT1N0 gastric cancer after R0 resection

    PubMed Central

    Zhao, Jiuda; Du, Feng; Zhang, Yu; Kan, Jie; Dong, Li; Shen, Guoshuang; Zheng, Fangchao; Chen, Hui; Zhao, Junhui; Ji, Faxiang; Luo, Yang; Ma, Fei; Wang, Ziyi; Xu, Binghe

    2016-01-01

    Abstract Although studies on the association between the number of lymph nodes resected and prognosis in patients with pT2–4N0 stages of gastric cancer have reported consistent results, there is no consensus on the optimal number of lymph nodes to be examined for pT1N0 stage gastric cancer. The aim of this study was to evaluate the long-term effect of the number of lymph nodes removed on the outcomes of patients with pT1N0 stage gastric cancer after R0 resection. From December 2009 to December 2011, 227 patients undergoing R0 resection of pT1N0 stage gastric cancer at 4 Chinese centers were enrolled in this study. Patients were assigned to 2 groups according to the number of lymph nodes dissected (≤15 or > 15). Standard survival methods and restricted multivariable Cox regression models were applied. More women (P = 0.031) were in the ≤15 group than in the >15 group. The mean number of lymph nodes removed from women was greater than that from men (P = 0.007). The 5-year survival rate was significantly higher in the >15 lymph nodes resected group than the ≤15 group. The number of lymph nodes resected was identified as an independent prognostic factor and was significantly correlated with overall survival (OS). A lymphadenectomy with dissection of more than 15 lymph nodes improved the long-term survival of patients with pT1N0 gastric cancer after R0 resection. Therefore, it is necessary to consider removing more than 15 lymph nodes among such patients. PMID:27495062

  13. Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus.

    PubMed

    Hou, Jingang; Xue, Jianjie; Lee, Mira; Yu, Jiaojiao; Sung, Changkeun

    2014-01-01

    Ginsenosides, the secondary plant metabolites produced by Panax ginseng are responsible for the enhancing effects on learning observed following treatment with Panax ginseng. A number of studies have provided correlational evidence that cell proliferation and survival are closely associated with hippocampal-dependent learning tasks. In this study, to investigate the beneficial effects of ginsenoside Rh1 on hippocampal cells and learning, mice (6 months old) were administered ginsenoside Rh1 at a dose of 5 and 10 mg/kg/day for a period of 3 months. Saline-treated mice were used as controls. The enhancement of memory and learning in the mice was evaluated by hippocampal-dependent tasks (passive avoidance tests and Morris water maze tests) and the immunohistochemical marker of cell proliferation, bromodeoxyuridine (BrdU). In addition, the levels of brain-derived neurotrophic factor (BDNF) were measured following treatment. Based on our data, the Rh1-treated group (5 and 10 mg/kg) showed a significantly improved learning and memory ability in the passive avoidance tests compared with the control group; however, only treatment with 10 mg/kg ginsenoside Rh1 significantly promoted spatial learning ability in the Morris water maze test. Ginsenoside Rh1 significantly enhanced cell survival in the dentate gyrus of mice, although it did not enhance hippocampal cell proliferation. In addition, ginsenoside Rh1 upregulated the expression of BDNF. These findings address the potential therapeutic significance of ginsenoside Rh1 as a nutritional supplement in memory loss and neurodegenerative diseases.

  14. Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae)

    PubMed Central

    Dickel, Franziska; Freitak, Dalial; Mappes, Johanna

    2016-01-01

    Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths’ survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations. PMID:27271967

  15. Cell Adhesion and Long-Term Survival of Transplanted Mesenchymal Stem Cells: A Prerequisite for Cell Therapy

    PubMed Central

    Lee, Seahyoung; Choi, Eunhyun; Cha, Min-Ji; Hwang, Ki-Chul

    2015-01-01

    The literature provides abundant evidence that mesenchymal stem cells (MSCs) are an attractive resource for therapeutics and have beneficial effects in regenerating injured tissues due to their self-renewal ability and broad differentiation potential. Although the therapeutic potential of MSCs has been proven in both preclinical and clinical studies, several questions have not yet been addressed. A major limitation to the use of MSCs in clinical applications is their poor viability at the site of injury due to the harsh microenvironment and to anoikis driven by the loss of cell adhesion. To improve the survival of the transplanted MSCs, strategies to regulate apoptotic signaling and enhance cell adhesion have been developed, such as pretreatment with cytokines, growth factors, and antiapoptotic molecules, genetic modifications, and hypoxic preconditioning. More appropriate animal models and a greater understanding of the therapeutic mechanisms of MSCs will be required for their successful clinical application. Nevertheless, the development of stem cell therapies using MSCs has the potential to treat degenerative diseases. This review discusses various approaches to improving MSC survival by inhibiting anoikis. PMID:25722795

  16. Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae).

    PubMed

    Dickel, Franziska; Freitak, Dalial; Mappes, Johanna

    2016-01-01

    Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths' survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations.

  17. Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae).

    PubMed

    Dickel, Franziska; Freitak, Dalial; Mappes, Johanna

    2016-01-01

    Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths' survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations. PMID:27271967

  18. The predicting value of postoperative body temperature on long-term survival in patients with rectal cancer.

    PubMed

    Yu, Huichuan; Luo, Yanxin; Peng, Hui; Kang, Liang; Huang, Meijin; Luo, Shuangling; Chen, Wenhao; Yang, Zihuan; Wang, Jianping

    2015-09-01

    This study aimed to assess the association between postoperative body temperature and prognosis in patients with rectal cancer. Five hundred and seven patients with stage I to III rectal cancers were enrolled in the current study. Basal body temperature (BBT, measured at 6 am) and maximal body temperature (MBT) on each day after surgery were analyzed retrospectively. Patients were divided into two equal groups according to the median of BBT and MBT at each day. The primary end points were disease-free survival (DFS) and overall survival (OS). The univariate and multivariate analyses showed that patients with low D0-MBT (<37.4 °C) had lower 3-year DFS [adjusted hazard ratio (HR) 1.56 (95 % CI 1.08-2.24, P = 0.017)] as well as OS [adjusted HR 1.72 (95 % CI 1.05-2.82, P = 0.032)] rate as compared to those with high D0-MBT (>37.4 °C). In the subset of 318 patients with T3 stage tumor and the subgroup of 458 patients without blood transfusion as well, low D0-MBT continues to be an independent predictor of DFS/OS with an adjusted HR equal to 1.48 (95 % CI 1.02-2.24, P = 0.046)/1.68 (95 % CI 1.04-2.99, P = 0.048) and 1.45 (95 % CI 1.02-2.13, P = 0.048)/1.59 (95 % CI 1.01-2.74, P = 0.049), respectively. In addition, we found that patients have higher risk of 1-year recurrence if those were exhibiting low preoperative BBT (<36.6 °C) (17 vs. 10 %, P = 0.034). Low body temperature (D0-MBT < 37.4 °C) after surgery was an independent predictor of poor survival outcomes in patients with rectal cancer.

  19. Long-term pyrene exposure of grass shrimp, Palaemonetes pugio, affects molting and reproduction of exposed males and offspring of exposed females.

    PubMed Central

    Oberdörster, E; Brouwer, M; Hoexum-Brouwer, T; Manning, S; McLachlan, J A

    2000-01-01

    The objective of this study was to investigate the impact of long-term pyrene exposure on molting and reproduction in the model estuarine invertebrate, the grass shrimp (Palaemonetes pugio). Grass shrimp were exposed to measured concentrations of 5.1, 15.0, and 63. 4 ppb (microg/L) pyrene for 6 weeks, during which time we determined molting and survivorship. At the end of the exposure, we immediately sacrificed some of the shrimp for biomarker (CYP1A and vitellin) analyses. The remaining shrimp were used to analyze fecundity and embryo survivorship during an additional 6 weeks after termination of pyrene exposure. Male shrimp at the highest pyrene dose (63 ppb) experienced a significant delay in molting and in time until reproduction, and showed elevated ethoxycoumarin o-deethylase (ECOD) activity immediately after the 6-week exposure period. In contrast, 63 ppb pyrene did not affect these parameters in female shrimp. Females produced the same number of eggs per body weight, with high egg viability (98-100%) at all exposure levels, but with decreased survival for the offspring of the 63-ppb pyrene-exposed females. In addition, vitellin levels were elevated only in females at 63 ppb pyrene after the 6-week exposure. We hypothesize that the elevated vitellin binds pyrene and keeps it biologically unavailable to adult females, resulting in maternal transfer of pyrene to the embryos. This would account for the lack of effect of pyrene exposure on ECOD activity, molting, and reproduction in the adult females, and for reduced survival of their offspring. Images Figure 1 Figure 2 Figure 3 PMID:10903618

  20. Long-term survival of murine allogeneic bone marrow chimeras: effect of anti-lymphocyte serum and bone marrow dose

    SciTech Connect

    Norin, A.J.; Emeson, E.E.; Veith, F.J.

    1981-02-01

    Graft-vs-host disease (GVHD) and failure of donor stem cells to engraft permanently are two major obstacles to successful bone marrow transplantation. The effect of a single large dose of anti-lymphocyte serum (ALS) on mice receiving various numbers of H-2 incompatible bone marrow cells was evaluated. Most animals receiving lethal total body irradiation (TBI) and allogeneic marrow died within 45 days due to GVHD. Mice that were given ALS 6 to 24 h before TBI and bone marrow 24 h after irradiation survived in good health for more than 200 days. These cell preparations caused lethal GVHD in third party mice indicating that the lack of alloreactivity was specific to the strain in which the unresponsiveness was originally induced.

  1. Long-term cumulative survival and mechanical complications of single-tooth Ankylos Implants: focus on the abutment neck fractures

    PubMed Central

    2015-01-01

    PURPOSE To evaluate the cumulative survival rate (CSR) and mechanical complications of single-tooth Ankylos® implants. MATERIALS AND METHODS This was a retrospective clinical study that analyzed 450 single Ankylos® implants installed in 275 patients between December 2005 and December 2012. The main outcomes were survival results CSR and implant failure) and mechanical complications (screw loosening, fracture, and cumulative fracture rate [CFR]). The main outcomes were analyzed according to age, sex, implant length or diameter, bone graft, arch, and position. RESULTS The 8-year CSR was 96.9%. Thirteen (2.9%) implants failed because of early osseointegration failure in 3, marginal bone loss in 6, and abutment fracture in 4. Screw loosening occurred in 10 implants (2.2%), and 10 abutment fractures occurred. All abutment fractures were located in the neck, and concurrent screw fractures were observed. The CSR and rate of screw loosening did not differ significantly according to factors. The CFR was higher in middle-aged patients (5.3% vs 0.0% in younger and older patients); for teeth in a molar position (5.8% vs 0.0% for premolar or 1.1% for anterior position); and for larger-diameter implants (4.5% for 4.5 mm and 6.7% for 5.5 mm diameter vs 0.5% for 3.5 mm diameter) (all P<.05). CONCLUSION The Ankylos® implant is suitable for single-tooth restoration in Koreans. However, relatively frequent abutment fractures (2.2%) were observed and some fractures resulted in implant failures. Middle-aged patients, the molar position, and a large implant diameter were associated with a high incidence of abutment fracture. PMID:26813443

  2. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  3. Long-term survival in a case of stage IV carcinoma of the ovary treated with a single chemotherapeutic agent.

    PubMed

    Akbiyik, N; Solisio, E; Alexander, L

    1979-08-01

    A case of stage IV carcinoma of the ovary is presented which was treated approximately six years ago in the Department of Radiation Therapy at Queens Hospital Center. On September 12, 1972, the patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a papillary scirrhous cystadenocarcinoma of the left ovary. At the time of the operation, the patient was found to have stage IV carcinoma of the ovary due to metastases of the liver and rectum. She was scheduled to receive pelvic-abdominal postoperative radiation therapy via the moving strip technique. Unfortunately, after completion of two strips, the patient could not tolerate treatment. She then began chemotherapy with a single agent, chlorambucil.Chlorambucil, 0.2 mg/kg/day×25 days/course was administered. The patient received 18 courses. Treatment dosage on a few occasions was decreased and increased again, due to drops in hemoglobin level and white blood cell and platelet counts. At the time of this presentation, the patient has no signs or symptoms of the disease. The introduction of megavoltage radiotherapy and adjuvant chemotherapy postoperatively has significantly improved the prognosis for patients with ovarian carcinoma. However, despite progress in radiotherapy, some patients cannot sustain this kind of treatment due to the unwanted side effects. Such was the case in this patient. She was switched to chemotherapy with excellent results in response and survival, even cure.

  4. Parenteral adenoviral boost enhances BCG induced protection, but not long term survival in a murine model of bovine TB.

    PubMed

    Kaveh, Daryan A; Garcia-Pelayo, M Carmen; Webb, Paul R; Wooff, Esen E; Bachy, Véronique S; Hogarth, Philip J

    2016-07-25

    Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes. This induces significant improvement in pulmonary protection against Mycobacterium bovis over that provided by BCG when assessed in a standard 4week challenge model. However, in a stringent, year-long survival study, BCG/Ad-TB10.4 did not improve outcome over BCG, which we suggest may be due to the lack of additional memory cells (IL-2(+)) induced by boosting. These data indicate BCG-prime/parenteral-Ad-TB10.4-boost to be a promising candidate, but also highlight the need for further understanding of the mechanisms of T cell priming and associated memory using Ad delivery systems. That we were able to generate significant improvement in pulmonary protection above BCG with parenteral, rather than mucosal administration of boost vaccine is critical; suggesting that the generation of effective mucosal immunity is possible, without the risks and challenges of mucosal administration, but that further work to specifically enhance sustained protective immunity is required.

  5. Study of neuron survival on polypyrrole-embedded single-walled carbon nanotube substrates for long-term growth conditions.

    PubMed

    Hernández-Ferrer, Javier; Pérez-Bruzón, Rodolfo N; Azanza, María J; González, Mónica; Del Moral, Raquel; Ansón-Casaos, Alejandro; de la Fuente, Jesús M; Marijuan, Pedro C; Martínez, M Teresa

    2014-12-01

    Cultures of primary embryonic rat brain hippocampus neurons with supporting glia cells were carried out on different substrates containing polypyrrole (PPy) and/or single-walled carbon nanotubes (SWCNTs). Neuron adhesion, neurites and dendrites branching elongation, and development of neuron networks on substrates were followed by phase-contrast optical microscopy and quantified to state cell survival and proliferation. Suspensions of as-grown and purified SWCNTs were sprayed on a glass coverslips and PPy/SWCNTs were deposited by potentiodynamic electrochemical deposition. Cell neurotoxicity revealed by neuron death was very high for purified SWCNTs substrates in good agreement with [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) test showing lower viability on SWCNTs containing substrates compared with PPy-substrates and control samples probably due to the metal content and the carboxylic groups introduced during the purification. It is interesting to highlight that neurons grown on PPy-substrates adhere developing neurites and branching dendrites earlier even than on control cultures. On subsequent days the neurons are able to adapt to nanotube substrates developing neuron networks for 14-day cultures with similar patterns of complexity for control, PPy and PPy/SWCNT substrates. PPy/SWCNT substrates show a lower impedance value at frequencies under 1 Hz. We have come to the conclusion that glia cells and PPy added to the culture medium and substrates respectively, improve in some degree nanotube biocompatibility, cell adhesion and hence cell viability.

  6. Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats

    PubMed Central

    Shanbhag, Nagesh C.; Henning, Robert H.; Schilling, Lothar

    2016-01-01

    Occlusion of the middle cerebral artery (MCA) by an intraluminal filament is widely used to study focal brain ischemia in male Sprague-Dawley rats. However, permanent occlusion goes along with a high fatality. To overcome this drawback we designed a new filament carrying a bowling pin-shaped tip (BP-tip) and compared this with three conventionally tipped filaments. Follow-up periods were 24 h (all groups) and 72 and 120 h in BP-tip group. Ischemic damage and swelling were quantified using silver nitrate staining. Collateral flow via the posterior cerebral artery (PCA) was assessed using selective dye perfusion of the internal carotid artery. Despite a comparable decrease of brain perfusion in all groups, ischemic damage was significantly smaller in BP-tips (p < 0.05). Moreover, BP-tip significantly reduced mortality from 60% to 12.5% and widely spared the occipital region and hypothalamus from ischemic damage. Conventional but not BP-tip filaments induced vascular distortion, measured as gross displacement of the MCA origin, which correlated with occipital infarction size. Accordingly, BP-tip occluded rats showed a significantly better collateral filling of the PCA territory. Ischemic volume significantly increased in BP-tip occlusion at 72 h follow-up. BP-tip filaments offer superior survival in permanent MCA occlusion, while mimicking the course of a malignant stroke in patients. PMID:27329690

  7. Multidimensional Geriatric Prognostic Index, Based on a Geriatric Assessment, for Long-Term Survival in Older Adults in Korea

    PubMed Central

    Jung, Hee-Won; Han, Ji Won; Kim, Kayoung; Kim, Jee Hyun; Kim, Kwang-Il; Kim, Cheol-Ho

    2016-01-01

    The patient´s survival estimate is important for clinical decision-making, especially in frail patients with multimorbidities. We aimed to develop a multidimensional geriatric prognosis index (GPI) for 3- and 5-year mortality in community-dwelling elderly and to validate the GPI in a separate hospital-based population. The GPI was constructed using data for 988 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA) and cross-validated with 1109 patients who underwent a geriatric assessment at the Seoul National University Bundang Hospital (SNUBH). The GPI, with a total possible score of 8, included age, gender, activities of daily living, instrumental activities of daily living, comorbidities, mood, cognitive function, and nutritional status. During the 5-year observation period, 179 KLoSHA participants (18.1%) and 340 SNUBH patients (30.7%) died. The c-indices for 3- and 5-year mortality were 0.78 and 0.80, respectively, in the KLoSHA group and 0.73 and 0.80, respectively, in the SNUBH group. Positive linear trends were observed for GPI scores and both 3- and 5-year mortality in both groups. In conclusions, using common components of a geriatric assessment, the GPI can stratify the risk of 3- and 5-year mortality in Korean elderly people both in the community and hospital. PMID:26771562

  8. Long-term survival in an advanced gastric cancer patient treated with cetuximab in association with FOLFIRI: a case report

    PubMed Central

    Adua, Daniela; Di Fabio, Francesca; Rojas Llimpe, Fabiola Lorena; Pini, Sara

    2014-01-01

    In December 2004, a 52-year-old woman with metastatic gastric cancer was enrolled in the phase II clinical trial FOLCETUX, receiving cetuximab at an initial dose of 400 mg/m2 i.v. followed by weekly doses of 250 mg/m2, irinotecan 180 mg/m2 i.v. on day 1, LFA 100 mg/m2 i.v. followed by 5-FU 400 mg/m2 i.v. bolus and 600 mg/m2 i.v. 22-h continuous infusion on days 1 and 2 every two weeks, to a total of 17 cycles. CT and PET-CT performed after six weeks treatment failed to show any residual disease, with complete radiological response in accord to RECIST criteria and complete metabolic response. A total of 24 maintenance administrations with cetuximab alone (250 mg/m2 weekly) were performed, as foreseen by the protocol in responders. In November 2012 a clinical, radiological (CT) and metabolic (PET-CT) patient examination proved negative for recurrent disease, signifying 95 months’ progression free survival. PMID:24490046

  9. Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations

    PubMed Central

    Brito, Sara; Thompson, Kyle; Campistol, Jaume; Colomer, Jaime; Hardy, Steven A.; He, Langping; Fernández-Marmiesse, Ana; Palacios, Lourdes; Jou, Cristina; Jiménez-Mallebrera, Cecilia; Armstrong, Judith; Montero, Raquel; Artuch, Rafael; Tischner, Christin; Wenz, Tina; McFarland, Robert; Taylor, Robert W.

    2015-01-01

    Background: Mitochondrial diseases due to deficiencies in the mitochondrial oxidative phosphorylation system (OXPHOS) can be associated with nuclear genes involved in mitochondrial translation, causing heterogeneous early onset and often fatal phenotypes. Case report: The authors describe the clinical features and diagnostic workup of an infant who presented with an early onset severe encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and persistent lactic acidemia. Brain imaging revealed thinning of the corpus callosum and diffuse alteration of white matter signal. Genetic investigation confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of OXPHOS. Discussion: The patient shares multiple clinical, laboratory and radiological similarities with the 11 reported patients with mutations involving this gene, but presents with a stable clinical course without metabolic decompensations, rather than a rapidly progressive fatal course. Defects in GFM1 gene confer high susceptibility to neurologic or hepatic dysfunction and this is, to the best of our knowledge, the first described patient who has survived beyond early childhood. Reporting of such cases is essential so as to delineate the key clinical and neuroradiological features of this disease and provide a more comprehensive view of its prognosis. PMID:25852744

  10. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons.

    PubMed

    Lim, Young-Mi; Hayashi, Shigeo; Tsuda, Leo

    2012-01-01

    Sensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1) is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss. TBL1 encodes an evolutionarily conserved F-box-like and WD40 repeats-containing subunit of the nuclear receptor co-repressor/silencing mediator for retinoid and thyroid hormone receptor and other transcriptional co-repressor complexes. Here we report that a Drosophila homologue of TBL1, Ebi, is required for maintenance of photoreceptor neurons. Loss of ebi function caused late-onset neuronal apoptosis in the retina and increased sensitivity to oxidative stress. Ebi formed a complex with activator protein 1 (AP-1) and was required for repression of Drosophila pro-apoptotic and anti-apoptotic genes expression. These results suggest that Ebi/AP-1 suppresses basal transcription levels of apoptotic genes and thereby protects sensory neurons from degeneration. PMID:22666340

  11. Impact of coexisting multivessel coronary artery disease on short-term outcomes and long-term survival of patients treated with carotid stenting

    PubMed Central

    Špaček, Miloslav; Horváth, Martin; Štěchovský, Cyril; Homolová, Ingrid; Zimolová, Petra; Hájek, Petr

    2016-01-01

    Introduction Systemic atherosclerosis can result in both coronary artery disease (CAD) and carotid artery disease. Recently it has been shown that patients with CAD have a higher incidence of microembolization during carotid artery stenting (CAS), and it has been hypothesized that they could be at higher risk in this intervention. Material and methods We retrospectively evaluated an institutional registry with 437 consecutive patients who underwent coronary angiography and CAS to evaluate their short-term outcomes and long-term survival with regard to the presence of coexisting multivessel coronary artery disease (MVD). Results We performed 220 CAS procedures in MVD patients and 318 CAS procedures in non-MVD patients. The incidence of in-hospital CAS-related adverse events was 2.7% and 2.5% in the MVD and non-MVD groups, respectively (p = 0.88). At 30 days, there was no significant difference between the groups in terms of the number of patients with adverse events (hierarchically death/stroke/myocardial infarction; 8.8% vs. 5.5%; p = 0.18). The median duration of follow-up was 4.23 years. Survival free of all-cause mortality at 1, 3 and 5 years was 90% (95% CI: 86–94%), 79% (95% CI: 73–85%) and 70% (95% CI: 64–77%), and 92% (95% CI: 89–95%), 85% (95% CI: 80–90%) and 76% (95% CI: 70–82%) for the MVD and non-MVD groups (p = 0.02), respectively. Conclusions These results suggest that patients with MVD combined with carotid artery disease are probably not at higher risk of early post-CAS adverse clinical events, but they have significantly worse long-term survival rates. PMID:27478456

  12. Longer waiting times for early stage cervical cancer patients undergoing radical hysterectomy are associated with diminished long-term overall survival

    PubMed Central

    Nanthamongkolkul, Kulisara

    2015-01-01

    Objective The aim of this study was to evaluate the impact of surgical waiting time on clinical outcome in early stage cervical cancer. Methods The cohort consisted of 441 patients diagnosed with stages IA2-IB1cervical cancer who underwent radical hysterectomy and pelvic node dissection. The patients were divided into two groups based on surgical waiting time. The associations between waiting time and other potential prognostic factors with clinical outcome were evaluated. Results The median surgical waiting time was 43 days. Deep stromal invasion (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.4 to 4.6; p=0.003) and lymph node metastasis (HR, 2.9; 95% CI, 1.3 to 6.7; p=0.026) were identified as independent prognostic factors for recurrence-free survival while no prognostic significance of surgical waiting time was found (p=0.677). On multivariate analysis of overall survival (OS), only deep stromal invasion (HR, 2.6; 95% CI, 1.3 to 5.0; p=0.009) and lymph node metastasis (HR, 3.6; 95% CI, 1.5 to 8.6; p=0.009) were identified as independent prognostic factors for OS. Although OS showed no significant difference between short (≤8 weeks) and long (>8 weeks) waiting times, multivariate analysis of OS with time-varying effects revealed that a waiting time longer than 8 weeks was associated with poorer long-term survival (after 5 years; HR, 3.4; 95% CI, 1.3 to 9.2; p=0.021). Conclusion A longer surgical waiting time was associated with diminished long-term OS of early stage cervical cancer patients. PMID:26404122

  13. NGF and anti-transferrin receptor antibody conjugate: short and long-term effects on survival of cholinergic neurons in intraocular septal transplants.

    PubMed

    Granholm, A C; Bäckman, C; Bloom, F; Ebendal, T; Gerhardt, G A; Hoffer, B; Mackerlova, L; Olson, L; Söderström, S; Walus, L R

    1994-01-01

    We describe a new molecular carrier system that allows for the transport of nerve growth factor (NGF) across the blood-brain barrier (BBB), as assessed by trophic effects on intraocular forebrain transplants that contain central cholinergic neurons. The carrier system involves monoclonal antibodies (OX-26) directed against the transferrin receptor, to which NGF molecules are covalently linked. Transferrin receptors are highly concentrated on brain blood vessels and participate in the transport of iron across the BBB. Host rats with septal transplants were divided into four groups, which received OX-26-NGF, OX-26, NGF or saline intravenously at 2, 4, 6 and 8 weeks after grafting. Half of the animals were killed directly after the final injection, whereas the other half were allowed to survive for an additional 5 months. Control experiments revealed that blood vessels in mature brain grafts in oculo contained large amounts of transferrin receptors. Covalent binding of NGF to the OX-26 antibodies did not impede OX-26 binding to CNS transferrin receptors, nor did conjugation affect the bioactivity of NGF. A time-dependent increase in host brain NGF levels was found after injection of OX-26-NGF into the tail vein. Host serum contained some NGF antibodies in the short-term OX-26-NGF group that had disappeared in the long-term group; host adrenals showed no differences in wet weight or norepinephrine or epinephrine whole tissue levels in any of the groups. As previously reported, the overall growth of intraocular septal transplants was approximately twice as great in the OX-26-NGF group relative to all other groups. This difference in final size persisted unabated for at least 5 months after the last injection. Furthermore, the significantly higher numbers of choline acetyl transferase immunoreactive neurons in transplants of OX-26-NGF-treated hosts also persisted during the 5-month postinjection interval. Taken together, the data suggest that the OX-26 conjugate may be a

  14. Long-term asymmetric hearing affects cochlear implantation outcomes differently in adults with pre- and postlingual hearing loss.

    PubMed

    Boisvert, Isabelle; McMahon, Catherine M; Dowell, Richard C; Lyxell, Björn

    2015-01-01

    In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears. PMID:26043227

  15. Long-term asymmetric hearing affects cochlear implantation outcomes differently in adults with pre- and postlingual hearing loss.

    PubMed

    Boisvert, Isabelle; McMahon, Catherine M; Dowell, Richard C; Lyxell, Björn

    2015-01-01

    In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears.

  16. Long-Term Asymmetric Hearing Affects Cochlear Implantation Outcomes Differently in Adults with Pre- and Postlingual Hearing Loss

    PubMed Central

    Boisvert, Isabelle; McMahon, Catherine M.; Dowell, Richard C.; Lyxell, Björn

    2015-01-01

    In many countries, a single cochlear implant is offered as a treatment for a bilateral hearing loss. In cases where there is asymmetry in the amount of sound deprivation between the ears, there is a dilemma in choosing which ear should be implanted. In many clinics, the choice of ear has been guided by an assumption that the reorganisation of the auditory pathways caused by longer duration of deafness in one ear is associated with poorer implantation outcomes for that ear. This assumption, however, is mainly derived from studies of early childhood deafness. This study compared outcomes following implantation of the better or poorer ear in cases of long-term hearing asymmetries. Audiological records of 146 adults with bilateral hearing loss using a single hearing aid were reviewed. The unaided ear had 15 to 72 years of unaided severe to profound hearing loss before unilateral cochlear implantation. 98 received the implant in their long-term sound-deprived ear. A multiple regression analysis was conducted to assess the relative contribution of potential predictors to speech recognition performance after implantation. Duration of bilateral significant hearing loss and the presence of a prelingual hearing loss explained the majority of variance in speech recognition performance following cochlear implantation. For participants with postlingual hearing loss, similar outcomes were obtained by implanting either ear. With prelingual hearing loss, poorer outcomes were obtained when implanting the long-term sound-deprived ear, but the duration of the sound deprivation in the implanted ear did not reliably predict outcomes. Contrary to an apparent clinical consensus, duration of sound deprivation in one ear has limited value in predicting speech recognition outcomes of cochlear implantation in that ear. Outcomes of cochlear implantation are more closely related to the period of time for which the brain is deprived of auditory stimulation from both ears. PMID:26043227

  17. Health care costs, long-term survival, and quality of life following intensive care unit admission after cardiac arrest

    PubMed Central

    Graf, Jürgen; Mühlhoff, Cecile; Doig, Gordon S; Reinartz, Sebastian; Bode, Kirsten; Dujardin, Robert; Koch, Karl-Christian; Roeb, Elke; Janssens, Uwe

    2008-01-01

    Introduction The purpose of this study was to investigate the costs and health status outcomes of intensive care unit (ICU) admission in patients who present after sudden cardiac arrest with in-hospital or out-of-hospital cardiopulmonary resuscitation. Methods Five-year survival, health-related quality of life (Medical Outcome Survey Short Form-36 questionnaire, SF-36), ICU costs, hospital costs and post-hospital health care costs per survivor, costs per life year gained, and costs per quality-adjusted life year gained of patients admitted to a single ICU were assessed. Results One hundred ten of 354 patients (31%) were alive 5 years after hospital discharge. The mean health status index of 5-year survivors was 0.77 (95% confidence interval 0.70 to 0.85). Women rated their health-related quality of life significantly better than men did (0.87 versus 0.74; P < 0.05). Costs per hospital discharge survivor were 49,952 €. Including the costs of post-hospital discharge health care incurred during their remaining life span, the total costs per life year gained were 10,107 €. Considering 5-year survivors only, the costs per life year gained were calculated as 9,816 € or 14,487 € per quality-adjusted life year gained. Including seven patients with severe neurological sequelae, costs per life year gained in 5-year survivors increased by 18% to 11,566 €. Conclusion Patients who leave the hospital following cardiac arrest without severe neurological disabilities may expect a reasonable quality of life compared with age- and gender-matched controls. Quality-adjusted costs for this patient group appear to be within ranges considered reasonable for other groups of patients. PMID:18638367

  18. [Impact of acute respiratory failure on survival of COPD patients managed with long-term non-invasive ventilation and oxygen therapy].

    PubMed

    Perrin, C; Vandenbos, F; Tamisier, R; Lemoigne, F; Blaive, B

    2000-02-01

    Our study aimed to assess the impact of acute respiratory failure (ARF) on survival of patients with chronic obstructive pulmonary disease (COPD) receiving long-term oxygen therapy (LTOT) plus nasal intermittent positive pressure ventilation (NIPPV). Survival was analysed retrospectively in 24 patients with severe COPD initiated to NIPPV in addition to LTOT. Fourteen patients were established on NIPPV following exacerbation of acute respiratory failure which has required mechanical ventilation (group 1). Ten patients (group 2) have never been hospitalized for ARF. Comparison of clinical details at baseline, 6 months, 1, 2, and 3 years for the two groups failed to reveal any difference with the exception of prior episodes of ARF. The probability of survival at 3 years was 65% (95% confidence interval [CI] 43-86) for the overall population, 46% (95% CI 15-77) in group 1, and 74% (95% CI 42-105) in group 2. The difference between the two groups was statistically significant. We show that ARF requiring mechanical ventilation appears to be a factor that is negatively correlated with survival for patients treated by LTOT plus NIPPV. This data suggests that NIPPV should be tried before ARF arising in COPD patients who present a deterioration in chronic respiratory failure with hypercapnia. PMID:10756560

  19. Long-term consequences of variation in timing and manner of fry introduction on juvenile Atlantic salmon (Salmo salar) growth, survival, and life-history expression

    USGS Publications Warehouse

    Letcher, B.H.; Dubreuil, T.; O'Donnell, M. J.; Obedzinski, M.; Griswold, K.; Nislow, K.H.

    2004-01-01

    We tested the influence of introduction time and the manner of introduction on growth, survival, and life-history expression of Atlantic salmon (Salmo salar). Introduction treatments included three fry stocking times and stream rearing of embryos. Despite poor growth conditions during the early stocking period, early-stocked fish were larger throughout the entire study period, likely the result of prior residence advantage. This interpretation was reinforced by the laboratory study, where early-stocked fish outgrew late-stocked fish when reared together, but not when they were reared separately. In contrast to growth, abundance of stocked fish was greatest for fish stocked during the middle period, and this stocking group produced the greatest number of smolts. Despite smaller size, survival of stream-incubated fish was generally greater than survival of stocked fish. Introduction timing had a pronounced effect on smolt age but a weak effect on extent of parr maturation. Overall, these observations indicate that small differences (???2 weeks) in introduction time can have long-term effects on size, survival, and life-history expression. Results suggest stabilizing selection on introduction times, mediated by the interaction between prior residence (advantage to fish introduced earlier) and habitat suitability (advantage to fish introduced later). ?? 2004 NRC Canada.

  20. Long-term Survival and Late Effects among 1-year Survivors of Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Acute Leukemia and Myelodysplastic Syndromes

    PubMed Central

    Duncan, Christine N.; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A.; Hayashi, Robert J.; Hsu, Jack W.; Kamble, Rammurti T.; Kasow, Kimberly A.; Khera, Nandita; Lazarus, Hillard M.; Loren, Alison W.; Marks, David I.; Maziarz, Richard T.; Mehta, Paulette; Myers, Kasiani C.; Norkin, Maxim; Pidala, Joseph A.; Porter, David L.; Reddy, Vijay; Saber, Wael; Savani, Bipin N.; Schouten, Harry C.; Steinberg, Amir; Wall, Donna A.; Warwick, Anne B.; Wood, William A.; Yu, Lolie C.; Jacobsohn, David A.; Sorror, Mohamed L.

    2014-01-01

    We analyzed the outcomes of patients who survived disease-free for 1-year or more following second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant following disease relapse; among these 325 survived relapse-free at 1-year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplant in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least one year were 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status prior to second HCT was significantly associated with higher risk for overall mortality (HR 1.71 for patients with disease not in complete remission prior to second HCT, P<0.01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults following second transplant. Chronic GVHD was the leading cause of non-relapse mortality followed by organ failure and infection. The cumulative incidence of developing at least one of the studied late effects at 10-years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence 22%) and cataracts (20%), and in adults were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease-free for at least 1-year, many can be expected to survive long term. However, they continue to be at risk for relapse and non-relapse morbidity and mortality. Novel approaches

  1. The University of Michigan Sarcoma Survivorship Clinic: Preventing, Diagnosing, and Treating Chronic Illness for Improved Survival and Long-Term Health.

    PubMed

    Bobowski, Nina P; Baker, Laurence H

    2016-09-01

    The Children's Cancer Survivorship Study reports more chronic illnesses in sarcoma survivors than other pediatric cancers. Chemotherapy and radiation put survivors at risk for developing chronic illnesses, including heart disease, diabetes, hypertension, and kidney failure. Sarcoma survivors may have a reduced life expectancy and signs of heart disease in their 30s and 40s. Since these medical problems occur much later in the general population, they often go undetected or misdiagnosed in sarcoma survivors, creating delays in intervention and treatment. The good news is that these chronic illnesses can often be prevented or minimized. The most common adverse effect of chemotherapy and radiation is coronary artery disease (CAD). CAD has a number of risk factors, including hypertension, diabetes, obesity, and dyslipidemia. These risk factors are modifiable with lifestyle changes, including diet and exercise, and/or pharmacological intervention. By identifying and managing risk factors like hypertension early, we in turn reduce the risk for CAD and prolong survival. This is well established in the general population; there is no reason a priori not to apply it to sarcoma survivors. Sarcoma survivors should be followed by physicians who understand the late effects and outcomes of sarcoma treatment. The University of Michigan Sarcoma Survivorship Clinic provides long-term care for sarcoma survivors by preventing, diagnosing, and treating the adverse long-term physical and psychological effects associated with sarcoma survivorship. PMID:27116634

  2. The characteristics of short- and long-term surviving Shiba dogs with chronic enteropathies and the risk factors for poor outcome

    PubMed Central

    2013-01-01

    Background The objectives of this study were to investigate the differences in the characteristics of short- and long-term surviving dogs, and the factors that predict poor outcome in Shiba dogs with chronic enteropathies (CE). Methods A total of 25 Shiba dogs were included in this study, and classified as either short-term (≤6 months) survivors (Ss; n=16) or long-term (>6 months) survivors (Ls; n=9). The clinical and clinicopathological variables, histopathology, response to therapy, and outcomes were investigated between groups. Furthermore, these factors were tested for their ability to predict poor outcome. Results All CE dogs were diagnosed as having inflammatory bowel disease (IBD) with lymphocytic-plasmacytic enteritis (LPE). Age and canine inflammatory bowel disease activity index (CIBDAI) were significantly higher in the Ss group than in the Ls group (age: p = 0.035, CIBDAI: p = 0.018), as determined via univariate logistic regression analysis. According to receiver operator characteristic (ROC) curve analysis, the best predictors of poor outcome were age and CIBDAI, with the cutoffs determined as 7 years and 9 points, respectively. The majority of the cases (84%) responded to initial treatment; in particular, 75% of dogs in Ss group responded to therapy. The time to response (days) to the initial treatment in the Ss group (median 42.5 days, range: 20-91 days) was significantly shorter than that of the Ls group (median 285 days, range: 196-1026 days). Approximately half (55.5%) of the dogs in the Ls group died due to relapse of CE. Conclusions This study suggested that there is a high risk of early mortality in Shiba dogs with CE, particularly if the dogs are older (>7 years) and have a high CIBDAI score (>9 points). There appears to be a possibility of early mortality even if the initial treatment was efficacious. Furthermore, Shiba dogs with CE that become less responsive to initial therapy in the short-term (approximately 3 months) are more likely to

  3. The roles of flowering, overwinter survival and sea surface temperature in the long-term population dynamics of Zostera marina around the Isles of Scilly, UK.

    PubMed

    Potouroglou, Maria; Kenyon, Emma J; Gall, Angie; Cook, Kevan J; Bull, James C

    2014-06-30

    Interaction between biotic and abiotic drivers of dynamics is an important topic in ecology. Despite numerous short-term studies, there is a paucity of evidence about how environmental structure modifies dynamics in marine systems. We quantified Zostera marina flowering and non-flowering shoot density annually from 1996 to 2012 around the Isles of Scilly, UK, parameterizing a population dynamic model. Flowering is structured in time and space, with temperature and flowering positively associated at some locations only. We found no evidence that flower production contributes to seagrass density but 'patchiness' was positively associated with flowering in the previous year. With evidence of substantial overwinter survival, findings support the hypothesis that local populations are maintained largely through vegetative reproduction but sexual reproduction may contribute to colonisation of vacant habitat. This long-term study (1) tests validity of shorter-term investigations, (2) quantifies interaction between biotic and abiotic factors and (3) promotes seagrass as a model ecosystem. PMID:24731880

  4. Brain metastasis of ALK positive anaplastic large cell lymphoma after a long-term disease free survival in an old adult

    PubMed Central

    Wang, Cai-Xia; Wang, Hai; Li, Jie; Ma, Heng-Hui; Yu, Bo; Shi, Shan-Shan; Zhou, Xiao-Jun; Shi, Qun-Li

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin lymphoma composed of CD30-positive cells and now recognized as three different entities: primary cutaneous ALCL, primary systemic anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and primary ALK-negative (ALK-) ALCL. ALK+ ALCL is supposed to have a better prognosis than ALK- ALCL. It is rarely metastasized to other sites, especially to the central nervous system (CNS). Herein, we present a rare case of systemic ALK+ ALCL which metastasized to the brain after a long-term disease free survival in an adult. Neuroimaging revealed a well-enhanced mass in the left frontal lobe. And it was completely resected. The results of the pathological and immunohistochemical studies were consistent with the metastasized ALK+ ALCL. The clinical findings, pathologic characteristics and treatment are described. PMID:24696735

  5. The roles of flowering, overwinter survival and sea surface temperature in the long-term population dynamics of Zostera marina around the Isles of Scilly, UK.

    PubMed

    Potouroglou, Maria; Kenyon, Emma J; Gall, Angie; Cook, Kevan J; Bull, James C

    2014-06-30

    Interaction between biotic and abiotic drivers of dynamics is an important topic in ecology. Despite numerous short-term studies, there is a paucity of evidence about how environmental structure modifies dynamics in marine systems. We quantified Zostera marina flowering and non-flowering shoot density annually from 1996 to 2012 around the Isles of Scilly, UK, parameterizing a population dynamic model. Flowering is structured in time and space, with temperature and flowering positively associated at some locations only. We found no evidence that flower production contributes to seagrass density but 'patchiness' was positively associated with flowering in the previous year. With evidence of substantial overwinter survival, findings support the hypothesis that local populations are maintained largely through vegetative reproduction but sexual reproduction may contribute to colonisation of vacant habitat. This long-term study (1) tests validity of shorter-term investigations, (2) quantifies interaction between biotic and abiotic factors and (3) promotes seagrass as a model ecosystem.

  6. Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

    PubMed

    Duncan, Christine N; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; Cahn, Jean-Yves; Frangoul, Haydar A; Hayashi, Robert J; Hsu, Jack W; Kamble, Rammurti T; Kasow, Kimberly A; Khera, Nandita; Lazarus, Hillard M; Loren, Alison W; Marks, David I; Maziarz, Richard T; Mehta, Paulette; Myers, Kasiani C; Norkin, Maxim; Pidala, Joseph A; Porter, David L; Reddy, Vijay; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Steinberg, Amir; Wall, Donna A; Warwick, Anne B; Wood, William A; Yu, Lolie C; Jacobsohn, David A; Sorror, Mohamed L

    2015-01-01

    We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel

  7. Hydrogeochemical and biological processes affecting the long-term performance of an iron-based permeable reactive barrier.

    PubMed

    Zolla, Valerio; Freyria, Francesca Stefania; Sethi, Rajandrea; Di Molfetta, Antonio

    2009-01-01

    Despite the wide diffusion of zero-valent iron (Fe(0)) permeable reactive barriers (PRBs), there is still a great uncertainty about their longevity and long-term performance. The aim of this study is to investigate the biological and the hydrogeochemical processes that take place at a Fe(0) installation located in Avigliana, Italy, and to derive some general considerations about long-term performance of PRBs.The examined PRB was installed in November 2004 to remediate a chlorinated solvents plume (mainly trichloroethene and 1,2-dichloroethene). The investigation was performed during the third year of operation and included: (1) groundwater sampling and analysis for chlorinated solvents, dissolved CH(4), dissolved H(2) and major inorganic constituents; (2) Fe(0) core sampling and analysis by SEM-EDS, XRD, and FTIR spectroscopy for the organic fraction; (3) in situ permeability tests and flow field monitoring by water level measurements.The study revealed that iron passivation is negligible, as the PRB is still able to effectively treat the contaminants and to reduce their concentrations below target values. Precipitation of several inorganic compounds inside the PRB was evidenced by SEM-EDS and XRD analysis conducted on iron samples. Groundwater sampling evidenced heavy sulfate depletion and the highest reported CH(4) concentration (>5,000 microg/L) at zero-valent iron PRB sites. These are due to the intense microbial activity of sulfate-reducers and methanogens, whose proliferation was most likely stimulated by the use of a biopolymer (i.e. guar gum) as shoring fluid during the excavation of the barrier. Slug tests within the barrier evidenced an apparent hydraulic conductivity two orders of magnitude lower than the predicted value. This occurrence can be ascribed to biofouling and/or accumulation of CH(4)(g) inside the iron filings.This experience suggests that when biopolymer shoring is planned to be used, long-term column tests should be performed beforehand

  8. Chronic unpredictable stress and long-term ovariectomy affect arginine-vasopressin expression in the paraventricular nucleus of adult female mice.

    PubMed

    Grassi, D; Lagunas, N; Calmarza-Font, I; Diz-Chaves, Y; Garcia-Segura, L M; Panzica, G C

    2014-11-01

    Arginine-Vasopressin (AVP) may regulate the hypothalamic-pituitary-adrenal axis (HPA) and its effects on depressive responses. In a recent study, we demonstrated that Chronic Unpredictable Stress (CUS) depressive effects are enhanced by long-term ovariectomy (a model of post-menopause). In the present study, we investigated the effects of long-term ovariectomy and CUS on AVP expression in different subdivision of the paraventricular nucleus (PVN) of female mice. Both long-term ovariectomy and CUS affect AVP immunoreactivity in some of the PVN subnuclei of adult female mice. In particular, significant changes on AVP immunoreactivity were observed in magnocellular subdivisions, the paraventricular lateral magnocellular (PaLM) and the paraventricular medial magnocellular (PaMM), the 2 subnuclei projecting to the neurohypophysis for the hormonal regulation of body homeostasis. AVP immunoreactivity was decreased in the PaLM by both the long-term deprivation of ovarian hormones and the CUS. In contrast, AVP immunoreactivity was increased in the PaMM by CUS, whereas it was decreased by ovariectomy. Therefore, present results suggest morphological and functional differences among the PVN's subnuclei and complex interactions among CUS, gonadal hormones and AVP immunoreactivity.

  9. IL-1RAcPb signaling regulates adaptive mechanisms in neurons that promote their long-term survival following excitotoxic insults.

    PubMed

    Gosselin, David; Bellavance, Marc-André; Rivest, Serge

    2013-01-01

    Excitotoxicity is a major component of neurodegenerative diseases and is typically accompanied by an inflammatory response. Cytokines IL-1alpha and IL-1beta are key regulators of this inflammatory response and modulate the activity of numerous cell types, including neurons. IL-1RAcPb is an isoform of IL-1RAcP expressed specifically in neurons and promotes their survival during acute inflammation. Here, we investigated in vivo whether IL-1RAcPb also promotes neuronal survival in a model of excitotoxicity. Intrastriatal injection of kainic acid (KA) in mice caused a strong induction of IL-1 cytokines mRNA in the brain. The stress response of cortical neurons at 12 h post-injection, as measured by expression of Atf3, FoxO3a, and Bdnf mRNAs, was similar in WT and AcPb-deficient mice. Importantly however, a delayed upregulation in the transcription of calpastatin was significantly higher in WT than in AcPb-deficient mice. Finally, although absence of AcPb signaling had no effect on damage to neurons in the cortex at early time points, it significantly impaired their long-term survival. These data suggest that in a context of excitotoxicity, stimulation of IL-1RAcPb signaling may promote the activity of a key neuroprotective mechanism. PMID:23423359

  10. Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model

    PubMed Central

    Higginbotham, Laura; Mathews, Dave; Breeden, Cynthia A.; Song, Mingqing; Farris, Alton Brad; Larsen, Christian P.; Ford, Mandy L.; Lutz, Andrew J.; Tector, Matthew; Newell, Kenneth A.; Tector, A. Joseph; Adams, Andrew B.

    2016-01-01

    Xenotransplantation has the potential to alleviate the organ shortage that prevents many patients with end-stage renal disease from enjoying the benefits of kidney transplantation. Despite significant advances in other models, pig-to-primate kidney xenotransplantation has met limited success. Preformed anti-pig antibodies are an important component of the xenogeneic immune response. To address this, we screened a cohort of 34 rhesus macaques for anti-pig antibody levels. We then selected animals with both low and high titers of anti-pig antibodies to proceed with kidney transplant from galactose-α1,3-galactose knockout/CD55 transgenic pig donors. All animals received T-cell depletion followed by maintenance therapy with costimulation blockade (either anti-CD154 mAb or belatacept), mycophenolate mofetil, and steroid. The animal with the high titer of anti-pig antibody rejected the kidney xenograft within the first week. Low-titer animals treated with anti-CD154 antibody, but not belatacept exhibited prolonged kidney xenograft survival (>133 and >126 vs. 14 and 21 days, respectively). Long-term surviving animals treated with the anti-CD154-based regimen continue to have normal kidney function and preserved renal architecture without evidence of rejection on biopsies sampled at day 100. This description of the longest reported survival of pig-to-non-human primate kidney xenotransplantation, now >125 days, provides promise for further study and potential clinical translation. PMID:25847130

  11. [Dynamics of microbial biomass C in a black soil under long-term fertilization and related affecting factors].

    PubMed

    Li, Dongpo; Wu, Zhijie; Chen, Lijun; Zhu, Ping; Ren, Jun; Peng, Chang; Liang, Chenghua

    2004-08-01

    The effect of long-term fertilization on the dynamics of microbial biomass C in a typical black soil of Northeastern China was studied in a field trail treated by different fertilizations. The results showed that the amount of soil microbial biomass C under different fertilizations varied significantly with growth stages. It was the highest in farmyard manure (M2 and M4) treatments, with a less seasonal fluctuation, second in NPK treatment, the peak at sowing period, and the lowest in CK, the peak at wax maturity stage. No significant correlation was found between the dynamic changes of soil microbial biomass C and soil biological, physical and chemical properties in all treatments, but the correlation of soil microbial biomass C with the contents of N, P and K in plants and that of crude protein in grain was significantly positive. PMID:15573983

  12. Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in caucasian men.

    PubMed

    Hedlund, Tammy E; Maroni, Paul D; Ferucci, Paul G; Dayton, Robert; Barnes, Stephen; Jones, Kenneth; Moore, Ray; Ogden, Lorraine G; Wähälä, Kristiina; Sackett, Holly M; Gray, Karen J

    2005-06-01

    The soy isoflavones daidzein and genistein are believed to reduce prostate cancer risk in soy consumers. However, daidzein can be metabolized by the intestinal flora to form a variety of compounds with different bioactivities. In the current study, we investigated the influence of long-term dietary habits on daidzein metabolism in healthy Caucasian men (19-65 y old). A secondary goal was to compare plasma and prostatic fluid concentrations of 5 isoflavonoids: genistein, daidzein, equol, dihydrodaidzein, and O-desmethylangolensin. Baseline plasma levels of isoflavonoids were quantitated in 45 men by HPLC-electrospray ionization-MS. Participants then consumed a soy beverage daily for 1 wk, and post-soy isoflavonoid levels were quantitated in plasma and prostatic fluid. Equol was the only metabolite that appeared to be influenced by routine dietary habits. Stratified analyses revealed that men who had consumed > or =30 mg soy isoflavones/d for at least 2 y had 5.3-times the probability of producing equol than men who had consumed < or =5 mg/d (P = 0.014). Additionally, those men who consumed animal meat regularly had 4.7-times the probability of producing equol than men who did not consume meat (P = 0.023). Equol production was not linked to age, BMI, or the consumption of yogurt, dairy, fruit, or American-style fast food. Daidzein and its metabolites (but not genistein) were typically present at higher levels in prostate fluid than plasma (median = 4-13 times that in plasma). In conclusion, our data suggest that the ability of Caucasian men to produce equol is favorably influenced by the long-term consumption of high amounts of soy and the consumption of meat. Last, the high concentrations of isoflavonoids in prostatic fluid increases the potential for these compounds to have direct effects in the prostate.

  13. Daily cognitive appraisals, daily affect, and long-term depressive symptoms: the role of self-esteem and self-concept clarity in the stress process.

    PubMed

    Lee-Flynn, Sharon C; Pomaki, Georgia; Delongis, Anita; Biesanz, Jeremy C; Puterman, Eli

    2011-02-01

    The current study investigated how self-esteem and self-concept clarity are implicated in the stress process both in the short and long term. Initial and 2-year follow-up interviews were completed by 178 participants from stepfamily unions. In twice-daily structured diaries over 7 days, participants reported their main family stressor, cognitive appraisals (perceived stressor threat and stressor controllability), and negative affect. Results of multilevel modeling indicated that high self-esteem ameliorated the effect of daily negative cognitive appraisals on daily negative affect. Self-concept clarity also buffered the effect of low self-self-esteem on depressive symptoms 2 years later. Our findings point to the vulnerability of those having low self-esteem or low self-concept clarity in terms of both short- and long-term adaptation to stress. They indicate the need for the consideration of such individual differences in designing stress management interventions.

  14. Mild hypothermia facilitates the long-term survival of newborn cells in the dentate gyrus after traumatic brain injury by diminishing a pro-apoptotic microenvironment.

    PubMed

    Chen, Chong; Ma, Tie-Zhu; Wang, Li-Na; Wang, Jing-Jing; Tu, Yue; Zhao, Ming-Liang; Zhang, Sai; Sun, Hong-Tao; Li, Xiao-Hong

    2016-10-29

    Although previous research has demonstrated that traumatic brain injury (TBI) accelerates the proliferation of neural stem cells in dentate gyrus of the hippocampus, most of these newborn cells undergo apoptosis in a traumatic microenvironment. Thus, promoting the long-term survival of newborn cells during neurogenesis is a compelling goal for the treatment of TBI. In this study, we investigated whether mild hypothermia (MHT) therapy, which mitigates the multiple secondary injury cascades of TBI, enhances the survival of newborn cells. SD rats were subjected to unilateral fluid percussion injury and received MHT therapy for 4h (33.5°C). Bromodeoxyuridine (BrdU) was administered to label the mitotic cells. Spatial learning and memory were evaluated with the Morris water maze test. Brain sections were immunostained with antibodies against BrdU, DCX (a neuroblast marker) or NeuN (a mature neuron marker). The apoptosis levels in the dentate gyrus were examined with antibodies against the apoptotic proteins FAS, FASL, Bcl-2 and cleaved caspase 3. The results indicated that MHT could significantly prevent TBI-induced cognitive impairments. At 1week after injury, the density of BrdU-immunoreactive cells significantly increased in both TBI and TBI+MHT rats. At 4weeks after injury, the density of BrdU-positive cells further increased in TBI+MHT rats, whereas the density declined in the TBI rats. The density of DCX-positive cells in SGZ of the hippocampus at 1week after injury in the TBI+MHT rats was significantly greater than in the TBI rats. Moreover, the density of NeuN-positive cells in the subgranular zone at 4weeks after injury and in the granule cell layer at 7weeks after injury was significantly increased in the TBI+MHT rats. The TBI+MHT rats displayed a lower level of apoptosis in the dentate gyrus compared with the TBI rats. These data indicate that TBI could only facilitate a burst of proliferation and short-term survival of newborn cells, whereas TBI+MHT could

  15. Mild hypothermia facilitates the long-term survival of newborn cells in the dentate gyrus after traumatic brain injury by diminishing a pro-apoptotic microenvironment.

    PubMed

    Chen, Chong; Ma, Tie-Zhu; Wang, Li-Na; Wang, Jing-Jing; Tu, Yue; Zhao, Ming-Liang; Zhang, Sai; Sun, Hong-Tao; Li, Xiao-Hong

    2016-10-29

    Although previous research has demonstrated that traumatic brain injury (TBI) accelerates the proliferation of neural stem cells in dentate gyrus of the hippocampus, most of these newborn cells undergo apoptosis in a traumatic microenvironment. Thus, promoting the long-term survival of newborn cells during neurogenesis is a compelling goal for the treatment of TBI. In this study, we investigated whether mild hypothermia (MHT) therapy, which mitigates the multiple secondary injury cascades of TBI, enhances the survival of newborn cells. SD rats were subjected to unilateral fluid percussion injury and received MHT therapy for 4h (33.5°C). Bromodeoxyuridine (BrdU) was administered to label the mitotic cells. Spatial learning and memory were evaluated with the Morris water maze test. Brain sections were immunostained with antibodies against BrdU, DCX (a neuroblast marker) or NeuN (a mature neuron marker). The apoptosis levels in the dentate gyrus were examined with antibodies against the apoptotic proteins FAS, FASL, Bcl-2 and cleaved caspase 3. The results indicated that MHT could significantly prevent TBI-induced cognitive impairments. At 1week after injury, the density of BrdU-immunoreactive cells significantly increased in both TBI and TBI+MHT rats. At 4weeks after injury, the density of BrdU-positive cells further increased in TBI+MHT rats, whereas the density declined in the TBI rats. The density of DCX-positive cells in SGZ of the hippocampus at 1week after injury in the TBI+MHT rats was significantly greater than in the TBI rats. Moreover, the density of NeuN-positive cells in the subgranular zone at 4weeks after injury and in the granule cell layer at 7weeks after injury was significantly increased in the TBI+MHT rats. The TBI+MHT rats displayed a lower level of apoptosis in the dentate gyrus compared with the TBI rats. These data indicate that TBI could only facilitate a burst of proliferation and short-term survival of newborn cells, whereas TBI+MHT could

  16. Impact of immunosuppression treatment on the improvement in graft survival after deceased donor renal transplantation: a long-term cohort study.

    PubMed

    González-Molina, Miguel; Burgos, Dolores; Cabello, Mercedes; Ruiz-Esteban, Pedro; Rodríguez, Manuel A; Gutiérrez, Cristina; López, Verónica; Baena, Víctor; Hernández, Domingo

    2014-01-01

    We analyzed graft half-life and attrition rates in 1045 adult deceased donor kidney transplants from 1986-2001, with follow-up to 2011, grouped in two periods (1986-95 vs. 1996-01) according to immunosuppression. The Kaplan-Meier curve showed a significant increase in graft survival during 1996-2001. The uncensored real graft half-life was 10.25 years in 1986-95 and the actuarial was 14.58 years in 1996-2001 (P<0.001). The attrition rates showed a significantly greater graft loss in 1986-95, even excluding the first year from the analysis. The decline in renal function was significantly less pronounced in 1996-2001, indicating better preservation of renal function, despite the increase in donor age and stroke as the cause of donor death. The parsimonious Cox multivariate model showed donor age, acute rejection, panel reactive antibody, cold ischemia time and delayed graft function were significantly associated with a higher risk of graft loss. In contrast, the risk of graft loss fell by 21% in 1996-2001 compared with 1986-95. A similar reduction (25%) was observed when MMF treatment was entered into the multivariate model instead of study period. Long-term graft survival improved significantly in 1996-2001 compared to 1986-1995 despite older donor age. Modern immunosuppression could have contributed to the improved kidney transplant outcome.

  17. Long-term changes in food availability mediate the effects of temperature on growth, development and survival in striped marsh frog larvae: implications for captive breeding programmes

    PubMed Central

    Courtney Jones, Stephanie K.; Munn, Adam J.; Penman, Trent D.; Byrne, Phillip G.

    2015-01-01

    Food availability and temperature are known to trigger phenotypic change, but the interactive effects between these factors are only beginning to be considered. The aim of this study was to examine the independent and interactive effects of long-term stochastic food availability and water temperature on larval survivorship, growth and development of the striped marsh frog, Limnodynastes peronii. Larval L. peronii were reared in conditions of either constant or stochastic food availability and in water at three different temperatures (18, 22 and 26°C), and effects on survival, growth and development were quantified. Over the experimental period, larval growth rate was highest and survivorship lowest at the warmest temperature. However, changes in food availability mediated the effects of temperature, with slower larval growth and higher survivorship in stochastic food availability treatments. Tadpoles in the stochastic food availability treatments did not reach metamorphosis during the experimental period, suggesting that developmental stasis may have been induced by food restriction. Overall, these results demonstrate that changes in food availability alter the effects of water temperature on survival, growth and development. From an applied perspective, understanding how environmental factors interact to cause phenotypic change may assist with amphibian conservation by improving the number of tadpoles generated in captive breeding programmes. PMID:27293714

  18. Do Long-Term Changes in Organic Matter Inputs to Forest Soils Affect Dissolved Organic Matter Chemistry and Export?

    NASA Astrophysics Data System (ADS)

    Lajtha, K.; Strid, A.; Lee, B. S.

    2014-12-01

    Dissolved organic matter (DOM) production and transport play an important role in regulating organic matter (OM) distribution through a soil profile and ultimately, OM stabilization or export to aquatic systems. The contributions of varying OM inputs to the quality and amount of DOM as it passes through a soil profile remain relatively unknown. The Detrital Input and Removal Treatment (DIRT) site at the H. J. Andrews Experimental Forest in Oregon has undergone 17 years of litter, wood and root input manipulations and allows us to guage shifts in DOM chemistry induced by long-term changes to aboveground and belowground OM additions and exclusions. Using fluorescence and UV spectroscopy to characterize fluorescent properties, extent of decomposition, and sources of DOM in streams and soil solutions collected with lysimeters and soil extractions, we have assessed the importance of fresh OM inputs to DOM chemistry. Soil extracts from DIRT plots had a higher fluorescence index (FI) than lysimeter solutions or stream water. A high FI in surface water is generally interpreted as indicative of a high proportion of microbially-derived DOM. However, we suspect that the high FI in soil extracts is due to a higher proportion of non-aromatic DOM from fresh soil that microorganisms consume in transit through the soil profile to lysimeters or to streams. High redox index (RI) values were observed in lysimeters from the April 2014 sampling compared with the November 2013 sampling. These RI values show evidence of more reducing conditions at the end of the rainy season in the spring compared to the onset of the rainy season in the fall. Lysimeter water collected in No Input, No Litter, and No Root treatments contained high proportions of protein, suggesting the absence of carbon inputs changes activities of the microbial community. Observed variations reflect the viability of using fluorescent properties to explore the terrestrial-aquatic interface.

  19. Long-term psychosocial outcomes of BRCA1/BRCA2 testing: Differences across affected status and risk-reducing surgery choice

    PubMed Central

    Graves, Kristi D.; Vegella, Patti; Poggi, Elizabeth A.; Peshkin, Beth N.; Tong, Angie; Isaacs, Claudine; Finch, Clinton; Kelly, Scott; Taylor, Kathryn L.; Luta, George; Schwartz, Marc D.

    2012-01-01

    Background Numerous studies have documented the short-term impact of BRCA1/BRCA2 (BRCA1/2) testing; however, little research has examined the long-term impact of testing. We conducted the first long-term prospective study of psychosocial outcomes in a U.S. sample of women who had BRCA1/2 testing. Methods Participants were 464 women who underwent genetic testing for BRCA1/2 mutations. Prior to testing, we measured sociodemographics, clinical variables, and cancer specific and general distress. At long-term follow-up (Median=5.0 years; Range=3.4 to 9.1 years), we assessed cancer specific and genetic testing distress, perceived stress and perceived cancer risk. We evaluated the impact of BRCA1/2 test result and risk reducing surgery on long-term psychosocial outcomes. Results Among participants who had been affected with breast or ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β=0.41, P<0.0001), uncertainty (β=0.18, P<0.0001) and perceived stress (β=0.17, P=0.005) compared to women who received negative (i.e., uninformative) results. Among women unaffected with breast/ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β=0.39, P<0.0001) and lower positive testing experiences (β=0.25, P=0.008) than women with negative results. Receipt of risk-reducing surgery was associated with lower perceived cancer risk (P<0.0001). Conclusions In this first prospective long-term study in a U.S. sample, we found modestly increased distress in BRCA1/2 carriers compared to women who received uninformative or negative test results. Despite this modest increase in distress, we found no evidence of clinically significant dysfunction. Impact While a positive BRCA1/2 result remains salient among carriers years after testing, testing does not appear to impact long-term psychological dysfunction. PMID:22328347

  20. Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched environment of newborn neurons in the hippocampus.

    PubMed

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-11-01

    Hippocampal adult neurogenesis contributes to key functions of the dentate gyrus (DG), including contextual discrimination. This is due, at least in part, to the unique form of plasticity that new neurons display at a specific stage of their development when compared with the surrounding principal neurons. In addition, the contribution that newborn neurons make to dentate function can be enhanced by an increase in their numbers induced by a stimulating environment. However, signaling mechanisms that regulate these properties of newborn neurons are poorly understood. Here, we show that Ras-GRF2 (GRF2), a calcium-regulated exchange factor that can activate Ras and Rac GTPases, contributes to both of these properties of newborn neurons. Using Ras-GRF2 knockout mice and wild-type mice stereotactically injected with retrovirus containing shRNA against the exchange factor, we demonstrate that GRF2 promotes the survival of newborn neurons of the DG at approximately 1-2 weeks after their birth. GRF2 also controls the distinct form of long-term potentiation that is characteristic of new neurons of the hippocampus through its effector Erk MAP kinase. Moreover, the enhancement of neuron survival that occurs after mice are exposed to an enriched environment also involves GRF2 function. Consistent with these observations, GRF2 knockout mice display defective contextual discrimination. Overall, these findings indicate that GRF2 regulates both the basal level and environmentally induced increase of newborn neuron survival, as well as in the induction of a distinct form of synaptic plasticity of newborn neurons that contributes to distinct features of hippocampus-derived learning and memory.

  1. Long-term cardiovascular outcomes and overall survival of early-stage breast cancer patients with early discontinuation of trastuzumab: a population-based study.

    PubMed

    Gong, Inna Y; Verma, Sunil; Yan, Andrew T; Ko, Dennis T; Earle, Craig C; Tomlinson, George A; Trudeau, Maureen E; Krahn, Murray D; Krzyzanowska, Monika K; Brezden-Masley, Christine B; Gavura, Scott; Peacock, Stuart; Chan, Kelvin K W

    2016-06-01

    We critically examined long-term cardiovascular (CV) outcomes and overall survival (OS) of breast cancer (BC) patients who had cardiotoxicity during adjuvant trastuzumab treatment requiring discontinuation in a population-based sample. This was a retrospective cohort of early-stage BC patients diagnosed before 2010 and treated with trastuzumab in Ontario. Patients were stratified based on trastuzumab doses received: 1-8, 9-15, ≥16 (therapy completion). Time-dependent multivariable Cox models were used to analyze primary endpoint OS, and the following composite endpoints: hospitalization/emergency room visit for heart failure (HF) or death; non-HF CV (myocardial infarction, stroke) or death; and clinically significant relapse (palliative systemic therapy initiation >90 days after last trastuzumab dose) or death. Of the 3134 women, 6, 10, and 85 % received 1-8, 9-15, and ≥16 doses, respectively. Over 5-year median follow-up, early trastuzumab discontinuation was associated with more HF/death [1-8 doses hazard ratio (HR) 4.0, 95 % confidence interval (CI) 2.7-6.0; 9-15 doses HR 2.97, 95 % CI 2.1-4.3], non-HF/death (1-8 doses HR 4.3, 95 % CI 3.0-6.1; 9-15 doses HR 3.1, 95 % CI 2.2-4.4), clinically significant relapse/death (1-8 doses HR 3.1, 95 % CI 2.2-4.4; 9-15 doses HR 2.4, 95 % CI 1.8-3.3), and importantly lower OS (77, 80, 93 %; P < 0.001). Early discontinuation (1-8 doses HR 2.41, 95 % CI 1.5-3.8; 9-15 doses HR 2.9, 95 % CI 2.0-4.1) and clinically significant relapse (HR 34.0, 95 % CI 24.9-46.6) were both independent predictors of mortality. Of note, early discontinuation remained a critical independent predictor of OS even after adjusting for incident HF. Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival. Both adequate cancer control and optimal CV management are required to improve long-term outcomes. PMID:27271767

  2. Factors affecting the entry of for-profit providers into a price regulated market for formal long-term care services: a case study from Japan.

    PubMed

    Tokunaga, Mutsumi; Hashimoto, Hideki

    2013-01-01

    While the distinct behaviors of for-profit and non-profit providers in the healthcare market have been compared in the economic literature, their choices regarding market entry and exit have only recently been debated. Since 2000, when public Long-Term Care Insurance was introduced in Japan, for-profit providers have been able to provide formal long-term homecare services. The aim of this study is to determine which factors have affected market entry of for-profit providers under price regulation and in competition with existing non-profit providers. We used nation-wide panel data from 2002 to 2010, aggregated at the level of local public insurers (n = 1557), a basic area unit of service provision. The number of for-profit providers per elderly population in the area unit was regressed against factors related to local demand and service costs using first-difference linear regression, a fixed effects model, and Tobit regression for robustness checking. Results showed that demand (the number of eligible care recipients) and cost factors (population density and minimum wage) significantly influenced for-profit providers' choice of market entry. These findings indicate that for-profit providers will strategically choose a local market for maximizing profit. We believe that price regulation should be redesigned to incorporate quality of care and market conditions, regardless of the profit status of the providers, to ensure equal access to efficient delivery of long-term care across all regions.

  3. Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

    SciTech Connect

    Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

    2008-09-01

    Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS {>=}90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy.

  4. Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression.

    PubMed

    Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei; Zou, Xiaohui

    2013-01-01

    Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models.

  5. Stability, Survival, and Tolerability of an Auditory Osseointegrated Implant for Bone Conduction Hearing: Long-Term Follow-Up of a Randomized Controlled Trial

    PubMed Central

    den Besten, Christine A.; Stalfors, Joacim; Wigren, Stina; Blechert, Johan Ivarsson; Flynn, Mark; Eeg-Olofsson, Måns; Aggarwal, Rohini; Green, Kevin; Nelissen, Rik C.; Mylanus, Emmanuel A. M.; Hol, Myrthe K. S.

    2016-01-01

    Objective: To compare implant stability, survival, and soft tissue reactions for a novel (test) and previous generation (control) percutaneous auditory osseointegrated implant for bone conduction hearing at long-term follow-up of 5 years. Study Design: Single follow-up visit of a previously completed multicenter, randomized, controlled trial. Patients: Fifty-seven of the 77 participants of a completed randomized controlled trial on a new auditory osseointegrated implant underwent a single follow-up visit 5 years after implantation, which comprised implant stability measurements and collection of Holgers scores. Additionally, implant survival was recorded for all 77 patients from the original trial. Results: The test implant showed significantly higher implant stability quotient (ISQ) values compared with the control implant throughout the 5-year follow-up. Mean area under the curve of ISQ high from baseline to 5 years was 71.6 (standard deviation [SD] ±2.0) and 66.7 (SD ±3.4) for the test and control implant, respectively (p < 0.0001). For both implants, the mean ISQ value recorded at 5 years was higher compared with implantation (test group +2.03 [SD ±2.55, within group p < 0.0001] and control group +2.25 [SD ±4.95, within group p = 0.12]). No difference was noticed in increase from baseline between groups (p = 0.64). Furthermore, evaluation of soft tissue reactions continued to show superiority of the test implant. At the 5-year follow-up visit, one patient (2.5%) presented with a Holgers grade 2 in the test group, compared with four patients (23.5%) in the control group (p = 0.048); no patient presented with more severe soft tissue reactions. Excluding explantations, the survival rate was 95.8% for the test group and 95.0% for the control group. The corresponding rates including explantations were 93.9 and 90.0%. Conclusion: The test implant showed superiority in terms of higher mean ISQ values and less adverse soft tissue reactions, both

  6. Prostate-specific antigen nadir after high-dose-rate brachytherapy predicts long-term survival outcomes in high-risk prostate cancer

    PubMed Central

    Satoh, Takefumi; Ishiyama, Hiromichi; Tabata, Ken-ichi; Komori, Shouko; Sekiguchi, Akane; Ikeda, Masaomi; Kurosaka, Shinji; Fujita, Tetsuo; Kitano, Masashi; Hayakawa, Kazushige; Iwamura, Masatsugu

    2016-01-01

    Purpose To evaluate the prognostic value of prostate-specific antigen nadir (nPSA) after high-dose-rate (HDR) brachytherapy in clinically non-metastatic high-risk prostate cancer patients. Material and methods Data from 216 patients with high-risk or locally advanced prostate cancer who underwent HDR brachytherapy and external beam radiation therapy with long-term androgen deprivation therapy (ADT) between 2003 and 2008 were analyzed. The median prostate-specific antigen (PSA) level at diagnosis was 24 ng/ml (range: 3-338 ng/ml). The clinical stage was T1c-2a in 55 cases (26%), T2b-2c in 48 (22%), T3a in 75 (35%), and T3b-4 in 38 (17%). The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After 5 fractions, external beam radiation therapy with 10 fractions of 3 Gy was administered. All patients initially underwent neoadjuvant ADT for at least 6 months, and adjuvant ADT was continued for 36 months. The median follow-up was 7 years from the start of radiotherapy. Results The 7-year PSA relapse-free rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 94%, compared with 23% for patients with higher nPSA values (HR = 28.57; 95% CI: 12.04-66.66; p < 0.001). Multivariate analysis revealed that the nPSA value after radiotherapy was a significant independent predictor of biochemical failure, whereas pretreatment predictive values for worse biochemical control including higher level of initial PSA, Gleason score ≥ 8, positive biopsy core rate ≥ 67%, and T3b-T4, failed to reach independent predictor status. The 7-year cancer-specific survival rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 99%, compared with 82% for patients with higher nPSA values (HR = 32.25; 95% CI: 3.401-333.3; p = 0.002). Conclusions A post-radiotherapy nPSA value of ≤ 0.02 ng/ml was associated with better long-term biochemical tumor control even if patients had pretreatment predictive values for worse

  7. Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Spratt, Daniel E.; Pei, Xin; Yamada, Josh; Kollmeier, Marisa A.; Cox, Brett; Zelefsky, Michael J.

    2013-03-01

    Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-, and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date

  8. Temperature change affected groundwater quality in a confined marine aquifer during long-term heating and cooling.

    PubMed

    Saito, Takeshi; Hamamoto, Shoichiro; Ueki, Takashi; Ohkubo, Satoshi; Moldrup, Per; Kawamoto, Ken; Komatsu, Toshiko

    2016-05-01

    Global warming and urbanization together with development of subsurface infrastructures (e.g. subways, shopping complexes, sewage systems, and Ground Source Heat Pump (GSHP) systems) will likely cause a rapid increase in the temperature of relatively shallow groundwater reservoirs (subsurface thermal pollution). However, potential effects of a subsurface temperature change on groundwater quality due to changed physical, chemical, and microbial processes have received little attention. We therefore investigated changes in 34 groundwater quality parameters during a 13-month enhanced-heating period, followed by 14 months of natural or enhanced cooling in a confined marine aquifer at around 17 m depth on the Saitama University campus, Japan. A full-scale GSHP test facility consisting of a 50 m deep U-tube for circulating the heat-carrying fluid and four monitoring wells at 1, 2, 5, and 10 m from the U-tube were installed, and groundwater quality was monitored every 1-2 weeks. Rapid changes in the groundwater level in the area, especially during the summer, prevented accurate analyses of temperature effects using a single-well time series. Instead, Dual-Well Analysis (DWA) was applied, comparing variations in subsurface temperature and groundwater chemical concentrations between the thermally-disturbed well and a non-affected reference well. Using the 1 m distant well (temperature increase up to 7 °C) and the 10 m distant well (non-temperature-affected), the DWA showed an approximately linear relationships for eight components (B, Si, Li, dissolved organic carbon (DOC), Mg(2+), NH4(+), Na(+), and K(+)) during the combined 27 months of heating and cooling, suggesting changes in concentration between 4% and 31% for a temperature change of 7 °C. PMID:26938497

  9. Temperature change affected groundwater quality in a confined marine aquifer during long-term heating and cooling.

    PubMed

    Saito, Takeshi; Hamamoto, Shoichiro; Ueki, Takashi; Ohkubo, Satoshi; Moldrup, Per; Kawamoto, Ken; Komatsu, Toshiko

    2016-05-01

    Global warming and urbanization together with development of subsurface infrastructures (e.g. subways, shopping complexes, sewage systems, and Ground Source Heat Pump (GSHP) systems) will likely cause a rapid increase in the temperature of relatively shallow groundwater reservoirs (subsurface thermal pollution). However, potential effects of a subsurface temperature change on groundwater quality due to changed physical, chemical, and microbial processes have received little attention. We therefore investigated changes in 34 groundwater quality parameters during a 13-month enhanced-heating period, followed by 14 months of natural or enhanced cooling in a confined marine aquifer at around 17 m depth on the Saitama University campus, Japan. A full-scale GSHP test facility consisting of a 50 m deep U-tube for circulating the heat-carrying fluid and four monitoring wells at 1, 2, 5, and 10 m from the U-tube were installed, and groundwater quality was monitored every 1-2 weeks. Rapid changes in the groundwater level in the area, especially during the summer, prevented accurate analyses of temperature effects using a single-well time series. Instead, Dual-Well Analysis (DWA) was applied, comparing variations in subsurface temperature and groundwater chemical concentrations between the thermally-disturbed well and a non-affected reference well. Using the 1 m distant well (temperature increase up to 7 °C) and the 10 m distant well (non-temperature-affected), the DWA showed an approximately linear relationships for eight components (B, Si, Li, dissolved organic carbon (DOC), Mg(2+), NH4(+), Na(+), and K(+)) during the combined 27 months of heating and cooling, suggesting changes in concentration between 4% and 31% for a temperature change of 7 °C.

  10. Long-term survival in a rodent brain tumor model by bradykinin-enhanced intra-arterial delivery of a therapeutic herpes simplex virus vector.

    PubMed

    Rainov, N G; Dobberstein, K U; Heidecke, V; Dorant, U; Chase, M; Kramm, C M; Chiocca, E A; Breakefield, X O

    1998-01-01

    Recently, it was demonstrated that bradykinin (BK) enhances intracarotid delivery of herpes simplex virus type I (HSV) vectors to rat brain tumors, and that gene transfer takes place predominantly in the tumor periphery. The aim of the present study was to apply these findings to the treatment of experimental rat brain tumors. The HSV mutant, hrR3, which is disrupted in the ribonucleotide reductase gene, was injected intra-arterially with titers of 1 x 10(8), 1 X 10(9), and 1 x 10(10) plaque-forming units (pfu) both with and without BK into Fischer 344 rats with intracerebral, syngeneic 9L tumors. Starting on day 3 after vector administration, animals were treated by intraperitoneal injection of 60 mg/kg/day ganciclovir (GCV) or placebo. 1 x 10(10) pfu hrR3 in combination with BK and GCV treatment was able to eradicate tumors in 80% of the animals; 1 x 10(9) pfu cured 40% of the rats, and 1 x 10(8) pfu achieved an extension of survival time but no tumor cures. Control groups had 100% mortality within 30 days after injection of tumor cells, with the exception of the group with injection of 1 x 10(10) pfu of virus and GCV treatment, which had one long-term survivor. No apparent complications of this novel type of brain tumor gene therapy were encountered. In conclusion, intra-arterial injection of attenuated HSV vectors with blood-tumor barrier modification and subsequent systemic GCV application appears to be a promising approach for the treatment of malignant brain tumors.

  11. Pulmonary function changes after radiotherapy in non-small-cell lung cancer patients with long-term disease-free survival

    SciTech Connect

    Borst, Gerben R.; Jaeger, Katrien de; Belderbos, Jose; Burgers, Sjaak A.; Lebesque, Joos V. . E-mail: j.lebesque@nki.nl

    2005-07-01

    Purpose: To evaluate the changes in pulmonary function after high-dose radiotherapy (RT) for non-small-cell lung cancer in patients with a long-term disease-free survival. Methods and Materials: Pulmonary function was measured in 34 patients with inoperable non-small-cell lung cancer before RT and at 3 and 18 months of follow-up. Thirteen of these patients had a pulmonary function test (PFT) 36 months after RT. The pulmonary function parameters (forced expiratory volume in 1 s [FEV{sub 1}], diffusion capacity [T{sub lcoc}], forced vital capacity, and alveolar volume) were expressed as a percentage of normal values. Changes were expressed as relative to the pre-RT value. We evaluated the impact of chronic obstructive pulmonary disease, radiation pneumonitis, mean lung dose, and PFT results before RT on the changes in pulmonary function. Results: At 3, 18, and 36 months, a significant decrease was observed for the T{sub lcoc} (9.5%, 14.6%, and 22.0%, respectively) and the alveolar volume (5.8%, 6.6%, and 15.8%, respectively). The decrease in FEV{sub 1} was significant at 18 and 36 months (8.8% and 13.4%, respectively). No recovery of any of the parameters was observed. Chronic obstructive pulmonary disease was an important risk factor for larger PFT decreases. FEV{sub 1} and T{sub lcoc} decreases were dependent on the mean lung dose. Conclusion: A significant decrease in pulmonary function was observed 3 months after RT. No recovery in pulmonary function was seen at 18 and 36 months after RT. The decrease in pulmonary function was dependent on the mean lung dose, and patients with chronic obstructive pulmonary disease had larger reductions in the PFTs.

  12. Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease.

    PubMed

    Tewari, Priti; Martin, Paul L; Mendizabal, Adam; Parikh, Suhag H; Page, Kristin M; Driscoll, Timothy A; Malech, Harry L; Kurtzberg, Joanne; Prasad, Vinod K

    2012-09-01

    The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = 1) at our center between 1997 and 2010. SibBM and sibling cord blood were HLA matched at 6/6, whereas UCB were 5/6 (n = 5) or 6/6 (n = 1). Recipients of SibBM were conditioned with busulfan and cyclophosphamide ± anti-thymocyte globulin (ATG), whereas 6 of 7 cord blood recipients received fludarabine/busulfan/cyclophosphamide/ATG. Seven patients received granulocyte-colony stimulating factor-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but successfully underwent retransplantation with UCB. Highest acute graft-versus-host disease was grade III (n = 1). Extensive chronic graft-vs-host disease developed in 3 patients. All patients are alive with median follow-up of 70.5 months (range, 12-167 months) with high donor chimerism (>98%, n = 10; 94%, n = 1; and 92%, n = 1). Myeloablative hematopoietic stem cell transplantation led to correction of neutrophil dysfunction, durable donor chimerism, excellent survival, good quality of life, and low incidence of graft-vs-host disease regardless of graft source.

  13. Enhanced stable long-term operation of biotrickling filters treating VOCs by low-dose ozonation and its affecting mechanism on biofilm.

    PubMed

    Zhou, Qingwei; Zhang, Lili; Chen, Jianmeng; Luo, Yong; Zou, Haikui; Sun, Baochang

    2016-11-01

    For long-term operation of highly loaded biotrickling filters (BTFs), the prevention of excess biomass accumulation was essential for avoiding BTF failure. In this study, we proposed low-dose ozonation as a biomass control strategy to maintain high removal efficiencies of volatile organic compounds (VOCs) over extended operation of BTFs. To obtain an optimized biomass control strategy, the relative performance of five parallel BTFs receiving different ozone doses was determined, and the affecting mechanism of ozonation on biofilm was elucidated. Experimental results showed that the decline in ozone-free BTF performance began from day 150, which was correlated with excess biomass accumulation, abundant excretion of extracellular polymeric substances (EPS) and a decline in metabolic activity of biofilm over extended operation. Ozone of 5-10 mg m(-3) was effective in preventing excessive growth and uneven distribution of biomass, and eventually maintaining long-term stable operations. Ozone of over 20 mg m(-3) possibly inhibited microorganism growth severely, thereby deteriorating the elimination performance instead. Comparison of the biofilm EPS indicated that the presence of ozone reduce EPS contents to different extents, which was possibly beneficial for mass transfer and metabolic activity. Comparative community analysis showed that ozonation resulted in different microbial communities in the BTFs. Dyella was found to be the most abundant bacterial genera in all BTFs regardless of ozonation, indicating strong resistance to ozonation. Chryseobacterium and Burkholderia members were markedly enriched in the ozone-added biofilm, implying good adaptation to ozone presence. These findings provided an improved understanding of low-dose ozonation in maintaining a stable long-term operation of BTF. PMID:27494314

  14. Long-term feeding a plant-based diet devoid of marine ingredients strongly affects certain key metabolic enzymes in the rainbow trout liver.

    PubMed

    Véron, Vincent; Panserat, Stéphane; Le Boucher, Richard; Labbé, Laurent; Quillet, Edwige; Dupont-Nivet, Mathilde; Médale, Françoise

    2016-04-01

    Incorporation of a plant blend in the diet can affect growth parameters and metabolism in carnivorous fish. We studied for the first time the long-term (1 year) metabolic response of rainbow trout fed from first feeding with a plant-based diet totally devoid of marine ingredients. Hepatic enzymes were analyzed at enzymatic and molecular levels, at 3, 8 and 24 h after the last meal to study both the short-term effects of the last meal and long-term effects of the diet. The results were compared with those of fish fed a control diet of fish meal and fish oil. Growth, feed intake, feed efficiency and protein retention were lower in the group fed the plant-based diet. Glucokinase and pyruvate kinase activity were lower in the livers of trout fed the plant-based diet which the proportion of starch was lower than in the control diet. Glutamate dehydrogenase was induced by the plant-based diet, suggesting an imbalance of amino acids and a possible link with the lower protein retention observed. Gene expression of delta 6 desaturase was higher in fish fed the plant-based diet, probably linked to a high dietary level of linolenic acid and the absence of long-chain polyunsaturated fatty acids in vegetable oils. Hydroxymethylglutaryl-CoA synthase expression was also induced by plant-based diet because of the low rate of cholesterol in the diet. Changes in regulation mechanisms already identified through short-term nutritional experiments (<12 weeks) suggest that metabolic responses are implemented at short term and remain in the long term. PMID:26746847

  15. Factors affecting immunoreactivity in long-term storage of formalin-fixed paraffin-embedded tissue sections.

    PubMed

    Grillo, Federica; Pigozzi, Simona; Ceriolo, Paola; Calamaro, Paola; Fiocca, Roberto; Mastracci, Luca

    2015-07-01

    Antigen decay in archival formalin-fixed paraffin-embedded (FFPE) tissue sections for immunohistochemistry is a well-known phenomenon which may have repercussions on translational and research studies and length of storage time appears fundamental. The aim of this study was to evaluate all possible factors which may lead to antigen decay on a prospective standardized collection of human tissues with a panel of 14 routinely used antibodies. Serial slide sections from FFPE control tissues were stored using different methods (routine storage at room temperature, Parafilm(®) protected, paraffin coated and cold stored at 4 °C) and for different time periods: 1, 6, 9, 12, 24 and 36 months. Immunohistochemistry was performed at each time cutoff simultaneously on stored sections and on freshly cut sections using a panel of 14 antibodies. Immunoreactivity was compared with immunoreactions performed at time zero. Reduction in immunostaining was observed for a subset of antibodies (CD3, CD 31, CD117, estrogen and progesterone receptors, Ki67, p53, TTF-1, vimentin) while for others (smooth muscle actin, keratins 7, 20, AE1/AE3, 34βE12), no antigen decay was observed. Loss of antigenicity was proportional to tissue section age and was dependent on mode of storage with cold storage slides being the least affected. All antigens with reductions in immunosignal were nuclear or membranous, and they all required heat pre-treatment for antigen retrieval. In contrast to results from other studies, when pre-analytical factors are strictly controlled and standardized, antigen decay seems to be restricted to nuclear or membrane antigens which require heat antigen retrieval.

  16. The long-term impact of infant rearing background on the affective state of adult common marmosets (Callithrix jacchus)

    PubMed Central

    Ash, Hayley; Buchanan-Smith, Hannah M.

    2016-01-01

    Early life environment, including temporary family separation, can have a major influence on affective state. Using a battery of tests, the current study compared the performance of adult common marmosets (Callithrix jacchus), reared as infants under 3 different conditions: family-reared twins, family-reared animals from triplet litters where only 2 remain (2stays) and supplementary fed triplets. No significant differences were found in latency to approach and obtain food from a human or a novel object between rearing conditions, suggesting no effect on neophobia. There were no differences in cognitive bias task acquisition time, or proportion of responses to each ambiguous probe. Very minor differences were found in response to the probes, with only supplementary fed marmosets making fewer responses to the middle probe, compared to the probe nearest the rewarded stimuli. Similarly, in a test for anhedonia, no difference was found between rearing conditions in consumption of milkshake at different concentrations. There was just one very small difference in reward motivation, with only supplementary fed triplets demonstrating a lack of preference for milkshake over water at the lowest concentration. This consistent pattern of results suggests that the supplementary feeding of large litters of marmosets at this facility did not have a major effect on welfare, and is unlikely to influence performance in reward-related scientific tasks. Therefore, while family separation is not recommended, this particular practice should be used if it is necessary, such as to reduce infant mortality. Regular positive interactions with humans are also encouraged, to reduce fear and improve welfare of marmosets kept in captivity. PMID:26912940

  17. Carbon Dioxide Emissions as Affected by Alternative Long-Term Irrigation and Tillage Management Practices in the Lower Mississippi River Valley

    PubMed Central

    Smith, S. F.; Brye, K. R.

    2014-01-01

    Ensuring the sustainability of cultivated soils is an ever-increasing priority for producers in the Lower Mississippi River Valley (LMRV). As groundwater sources become depleted and environmental regulations become more strict, producers will look to alternative management practices that will ensure the sustainability and cost-effectiveness of their production systems. This study was conducted to assess the long-term (>7 years) effects of irrigation (i.e., irrigated and dryland production) and tillage (conventional and no-tillage) on estimated carbon dioxide (CO2) emissions from soil respiration during two soybean (Glycine max L.) growing seasons from a wheat- (Triticum aestivum L.-) soybean, double-cropped production system in the LMRV region of eastern Arkansas. Soil surface CO2 fluxes were measured approximately every two weeks during two soybean growing seasons. Estimated season-long CO2 emissions were unaffected by irrigation in 2011 (P > 0.05); however, during the unusually dry 2012 growing season, season-long CO2 emissions were 87.6% greater (P = 0.044) under irrigated (21.9 Mg CO2 ha−1) than under dryland management (11.7 Mg CO2 ha−1). Contrary to what was expected, there was no interactive effect of irrigation and tillage on estimated season-long CO2 emissions. Understanding how long-term agricultural management practices affect soil respiration can help improve policies for soil and environmental sustainability. PMID:25371912

  18. Carbon dioxide emissions as affected by alternative long-term irrigation and tillage management practices in the lower Mississippi River Valley.

    PubMed

    Smith, S F; Brye, K R

    2014-01-01

    Ensuring the sustainability of cultivated soils is an ever-increasing priority for producers in the Lower Mississippi River Valley (LMRV). As groundwater sources become depleted and environmental regulations become more strict, producers will look to alternative management practices that will ensure the sustainability and cost-effectiveness of their production systems. This study was conducted to assess the long-term (>7 years) effects of irrigation (i.e., irrigated and dryland production) and tillage (conventional and no-tillage) on estimated carbon dioxide (CO2) emissions from soil respiration during two soybean (Glycine max L.) growing seasons from a wheat- (Triticum aestivum L.-) soybean, double-cropped production system in the LMRV region of eastern Arkansas. Soil surface CO2 fluxes were measured approximately every two weeks during two soybean growing seasons. Estimated season-long CO2 emissions were unaffected by irrigation in 2011 (P > 0.05); however, during the unusually dry 2012 growing season, season-long CO2 emissions were 87.6% greater (P = 0.044) under irrigated (21.9 Mg CO2 ha(-1)) than under dryland management (11.7 Mg CO2 ha(-1)). Contrary to what was expected, there was no interactive effect of irrigation and tillage on estimated season-long CO2 emissions. Understanding how long-term agricultural management practices affect soil respiration can help improve policies for soil and environmental sustainability.

  19. Ethnic differences in mortality of male and female patients surviving acute myocardial infarction: long-term follow-up of 5,700 patients. The Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

    PubMed

    Harpaz, D

    1997-10-01

    In migrant countries, ethnic origin may represent a complex of cultural, behavioral and possibly genetic differences. These have been shown to influence acute myocardial infarction (AMI) incidence. How ethnic origin may affect survival after AMI is unknown. Data from 5,692 patients included in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) registry were analyzed. Patients were divided into eight different ethnic groups, according to birthplaces from five continents, representing major socio-economic and possibly some genetic variation. Mortality was analyzed after adjustment for baseline characteristics known to predict death from coronary artery disease (CAD) using Jews born in Israel as a reference. The odds ratio for in-hospital mortality was higher in women than in men, but unrelated to ethnic origin. The odds ratio for men ranged between 1.08 (95% confidence interval (CI): 0.67-1.73) for Jews born in Eastern Europe and 1.84 (95% CI: 1.07-3.15) for counterparts born in the Middle East. The odds ratio for women ranged between 0.73 in Jews born in Central Europe (95% CI: 0.35-1.50) and 1.45 (95% CI: 0.76-3.15) for Jewish women born in the Balkan countries. Among 4,686 patients surviving the hospital phase, long-term mortality rates (mean follow-up 7.1 +/- 3.5 years) were 43.3% in men and 57.6% in women. Among 3,586 surviving men, the adjusted risk ratios for 10-year mortality varied between 0.92 (95% CI: 0.72-1.18) for men born in Romania and 1.49 (95% CI: 1.07-2.09) for Israeli born Arabs. The variation among men is within the limits of statistical error. However, among 1,100 surviving women, the risk ratio for 10-year mortality differed significantly, from as low as 1.43 (95% CI: 0.84-2.41) in Jewish women born in Central Europe to as high as 2.83 (95% CI: 1.67-4.79) in counterparts born in the Middle East. The latter observations were consistent with the mortality after 3 years. Thus, ethnic origin of Israelis marginally influenced the

  20. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  1. Sphagnum peatlands as a unique habitat for the long-term survival of glacial relicts: a case study of Betula nana

    NASA Astrophysics Data System (ADS)

    Slowinski, M. M.; Slowinska, S.; Noryśkiewicz, A. M.; Lamentowicz, M.; Kołaczek, P.

    2014-12-01

    Sphagnum peatlands are characterized by distinctive vegetation, hydrology and local climate. They are very important areas for flora and fauna. In the last decade, much effort was made at better understanding of microrefugia and their important role in post-glacial migration of various plant species. The aim of this study is to explain a long-term persistence of the glacial relict Betula nana in a Sphagnum peatland in northern Poland far from the southern range of its natural distribution. We suppose that the persistence of Betula nana is driven by a) the morphology and geology of the catchment, b) the maintenance of open vegetation on the peatland surface and c) exceptional microclimatic and hydrological conditions. A detailed research was carried out on the peat profile using pollen analysis, to reconstruct the presence of open habitat on the mire during the Holocene. Furthermore, detailed monitoring of local climate, hydrology of the peatland and the surrounding area was conducted. The pollen analysis revealed a continuous presence of Betula nana in the postglacial history of the peatland. The results of local climate monitoring indicated that the mire possesses a typical microclimate, with air temperature amplitude much higher in relation to the open area, in particular during the growing season. This, in combination with the hydrology, which depends on the geology of the surrounding area, affects Betula nana population. Linje mire is a unique microrefugium sustained by local factors such as microclimate, geology, local relief and hydrology. However, it is still challenging to explain the intriguing case why this species still occurs within the study site. This work was funded by the National Science Centre grant NN306060940 and Polish-Swiss Research Programme PSPB-013/2010. This study is a contribution to the Virtual Institute of Integrated Climate and Landscape Evolution (ICLEA) of the Helmholtz Association.

  2. Effects of long-term exposure to two fungicides, pyrimethanil and tebuconazole, on survival and life history traits of Italian tree frog (Hyla intermedia).

    PubMed

    Bernabò, Ilaria; Guardia, Antonello; Macirella, Rachele; Sesti, Settimio; Crescente, Antonio; Brunelli, Elvira

    2016-03-01

    fungicides also caused a reduction in developmental rates just prior to the onset of metamorphic climax, which translated to a significant delay in timing of metamorphosis. We detected a drastic decrease in the success at metamorphosis in all exposed groups, compared to control group (86.25%). In fact, the percentage of survived larvae to GS 46, in the high and low concentrations, respectively, was only 22.5% and 36.25% in tebuconazole-exposed groups and 43.75% (50μg/L) and 56.25% (5μg/L) in pyrimethanil-exposed groups. Our findings underscore the hazardous properties of these two fungicides for non-target species in the context of ecotoxicological risk assessment. No published studies have addressed the long-term effects of tebuconazole and pyrimethanil on amphibians. To date, this is one of only a few studies documenting the effects of fungicide exposure over the whole larval development. PMID:26771902

  3. Effects of long-term exposure to two fungicides, pyrimethanil and tebuconazole, on survival and life history traits of Italian tree frog (Hyla intermedia).

    PubMed

    Bernabò, Ilaria; Guardia, Antonello; Macirella, Rachele; Sesti, Settimio; Crescente, Antonio; Brunelli, Elvira

    2016-03-01

    fungicides also caused a reduction in developmental rates just prior to the onset of metamorphic climax, which translated to a significant delay in timing of metamorphosis. We detected a drastic decrease in the success at metamorphosis in all exposed groups, compared to control group (86.25%). In fact, the percentage of survived larvae to GS 46, in the high and low concentrations, respectively, was only 22.5% and 36.25% in tebuconazole-exposed groups and 43.75% (50μg/L) and 56.25% (5μg/L) in pyrimethanil-exposed groups. Our findings underscore the hazardous properties of these two fungicides for non-target species in the context of ecotoxicological risk assessment. No published studies have addressed the long-term effects of tebuconazole and pyrimethanil on amphibians. To date, this is one of only a few studies documenting the effects of fungicide exposure over the whole larval development.

  4. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

    1981-11-01

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.

  5. Leuconostoc bacteriophages from blue cheese manufacture: long-term survival, resistance to thermal treatments, high pressure homogenization and chemical biocides of industrial application.

    PubMed

    Pujato, Silvina A; Guglielmotti, Daniela M; Ackermann, Hans-W; Patrignani, Francesca; Lanciotti, Rosalba; Reinheimer, Jorge A; Quiberoni, Andrea

    2014-05-01

    Nine Leuconostoc mesenteroides phages were isolated during blue cheese manufacture yielding faulty products with reduced eye formation. Their morphologies, restriction profiles, host ranges and long-term survival rates (25°C, 8°C, -20°C and -80°C) were analysed. Based on restriction analysis, six of them were further examined regarding resistance to physical (heat and high pressure homogenization, HPH) and chemical treatments (ethanol, sodium hypochlorite, peracetic acid, biocides A, C, E and F). According to their morphology, L. mesenteroides phages studied in the present work belonged to the Caudovirales order and Siphoviridae family. Six distinct restriction patterns were obtained with EcoRV, HindIII, ClaI and XhoI enzymes, revealing interesting phage diversity in the dairy environment. No significant reductions in phage counts were observed after ten months of storage at -20°C and -80°C, while slightly and moderate decrease in phage numbers were noticed at 8°C and 25°C, respectively. The phages subjected to heat treatments generally showed high resistance at 63°C and moderate resistance at 72°C. However, 80°C for 30 min and 90°C for 2 min led to complete inactivation of viral particles. In general, the best ethanol concentration tested was 75%, as complete inactivation for most Leuconostoc phages within 30 min of incubation was achieved. Peracetic acid, and biocides A, C, E and F were highly effective when used at the same or at a moderately lower concentration as recommended by the producer. Usually, moderate or high concentrations (600-1,600 ppm) of sodium hypochlorite were necessary to completely inactivate phage particles. Leuconostoc phages were partially inactivated by HPH treatments as remaining viral particles were found even after 8 passes at 100 MPa. This is the first report of L. mesenteroides phages isolated from an Argentinean dairy cheese plant. The results of this work could be useful for establishing the most effective physical and

  6. Leuconostoc bacteriophages from blue cheese manufacture: long-term survival, resistance to thermal treatments, high pressure homogenization and chemical biocides of industrial application.

    PubMed

    Pujato, Silvina A; Guglielmotti, Daniela M; Ackermann, Hans-W; Patrignani, Francesca; Lanciotti, Rosalba; Reinheimer, Jorge A; Quiberoni, Andrea

    2014-05-01

    Nine Leuconostoc mesenteroides phages were isolated during blue cheese manufacture yielding faulty products with reduced eye formation. Their morphologies, restriction profiles, host ranges and long-term survival rates (25°C, 8°C, -20°C and -80°C) were analysed. Based on restriction analysis, six of them were further examined regarding resistance to physical (heat and high pressure homogenization, HPH) and chemical treatments (ethanol, sodium hypochlorite, peracetic acid, biocides A, C, E and F). According to their morphology, L. mesenteroides phages studied in the present work belonged to the Caudovirales order and Siphoviridae family. Six distinct restriction patterns were obtained with EcoRV, HindIII, ClaI and XhoI enzymes, revealing interesting phage diversity in the dairy environment. No significant reductions in phage counts were observed after ten months of storage at -20°C and -80°C, while slightly and moderate decrease in phage numbers were noticed at 8°C and 25°C, respectively. The phages subjected to heat treatments generally showed high resistance at 63°C and moderate resistance at 72°C. However, 80°C for 30 min and 90°C for 2 min led to complete inactivation of viral particles. In general, the best ethanol concentration tested was 75%, as complete inactivation for most Leuconostoc phages within 30 min of incubation was achieved. Peracetic acid, and biocides A, C, E and F were highly effective when used at the same or at a moderately lower concentration as recommended by the producer. Usually, moderate or high concentrations (600-1,600 ppm) of sodium hypochlorite were necessary to completely inactivate phage particles. Leuconostoc phages were partially inactivated by HPH treatments as remaining viral particles were found even after 8 passes at 100 MPa. This is the first report of L. mesenteroides phages isolated from an Argentinean dairy cheese plant. The results of this work could be useful for establishing the most effective physical and

  7. Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival.

    PubMed

    Lee, Se Kyung; Bae, Soo Youn; Lee, Jun Ho; Lee, Hyun-Chul; Yi, Hawoo; Kil, Won Ho; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

    2015-01-01

    Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

  8. Long-Term Cold Acclimation Extends Survival Time at 0°C and Modifies the Metabolomic Profiles of the Larvae of the Fruit Fly Drosophila melanogaster

    PubMed Central

    Koštál, Vladimír; Korbelová, Jaroslava; Rozsypal, Jan; Zahradníčková, Helena; Cimlová, Jana; Tomčala, Aleš; Šimek, Petr

    2011-01-01

    Background Drosophila melanogaster is a chill-susceptible insect. Previous studies on this fly focused on acute direct chilling injury during cold shock and showed that lower lethal temperature (LLT, approximately −5°C) exhibits relatively low plasticity and that acclimations, both rapid cold hardening (RCH) and long-term cold acclimation, shift the LLT by only a few degrees at the maximum. Principal Findings We found that long-term cold acclimation considerably improved cold tolerance in fully grown third-instar larvae of D. melanogaster. A comparison of the larvae acclimated at constant 25°C with those acclimated at constant 15°C followed by constant 6°C for 2 d (15°C→6°C) showed that long-term cold acclimation extended the lethal time for 50% of the population (Lt50) during exposure to constant 0°C as much as 630-fold (from 0.137 h to 86.658 h). Such marked physiological plasticity in Lt50 (in contrast to LLT) suggested that chronic indirect chilling injury at 0°C differs from that caused by cold shock. Long-term cold acclimation modified the metabolomic profiles of the larvae. Accumulations of proline (up to 17.7 mM) and trehalose (up to 36.5 mM) were the two most prominent responses. In addition, restructuring of the glycerophospholipid composition of biological membranes was observed. The relative proportion of glycerophosphoethanolamines (especially those with linoleic acid at the sn-2 position) increased at the expense of glycerophosphocholines. Conclusion Third-instar larvae of D. melanogaster improved their cold tolerance in response to long-term cold acclimation and showed metabolic potential for the accumulation of proline and trehalose and for membrane restructuring. PMID:21957472

  9. Determining the effect of oil sands process-affected water on grazing behaviour of Daphnia magna, long-term consequences, and mechanism.

    PubMed

    Lari, Ebrahim; Wiseman, Steve; Mohaddes, Effat; Morandi, Garrett; Alharbi, Hattan; Pyle, Greg G

    2016-03-01

    Oil sands process-affected water (OSPW) is a byproduct of the extraction of bitumen in the surface-mining oil sands industry and is currently stored in on-site tailings ponds. OSPW from three oil sands companies were studied to capture some of the variability associated with OSPW characteristics. To investigate the effect and mechanism(s) of effect of OSPW on feeding behaviour, Daphnia magna were exposed to low OSPW concentrations for 24 h and monitored for their feeding rate, olfactory response and swimming activity. The Al and Si content, which are indicators of suspended particulate matter in D. magna exposed to OSPW were investigated using energy-dispersive X-ray (EDX) spectroscopy. In long-term experiments, effects of exposure to OSPW for 21 days on feeding behaviour, growth, and reproduction of D. magna were evaluated. Feeding rates were similar among the three exposure populations, yielding a 24 h IC50 of 5.3% OSPW. Results of behavioural assays suggest that OSPW impairs the chemosensory function and reduces the total activity of D. magna. In EDX spectroscopy, Al and Si were detected in the body of the exposed D. magna, suggesting that D. magna filter clay particles from the OSPW solution. Results of the long-term exposure showed that OSPW significantly inhibits feeding behaviour, suppresses growth, and reduces reproductive output of D. magna. There were no differences in the toxicity of the three samples of OSPW, which was in agreement with the fact that there were no differences in the species of dissolved organic compounds in the OSPW samples. PMID:26735738

  10. Determining the effect of oil sands process-affected water on grazing behaviour of Daphnia magna, long-term consequences, and mechanism.

    PubMed

    Lari, Ebrahim; Wiseman, Steve; Mohaddes, Effat; Morandi, Garrett; Alharbi, Hattan; Pyle, Greg G

    2016-03-01

    Oil sands process-affected water (OSPW) is a byproduct of the extraction of bitumen in the surface-mining oil sands industry and is currently stored in on-site tailings ponds. OSPW from three oil sands companies were studied to capture some of the variability associated with OSPW characteristics. To investigate the effect and mechanism(s) of effect of OSPW on feeding behaviour, Daphnia magna were exposed to low OSPW concentrations for 24 h and monitored for their feeding rate, olfactory response and swimming activity. The Al and Si content, which are indicators of suspended particulate matter in D. magna exposed to OSPW were investigated using energy-dispersive X-ray (EDX) spectroscopy. In long-term experiments, effects of exposure to OSPW for 21 days on feeding behaviour, growth, and reproduction of D. magna were evaluated. Feeding rates were similar among the three exposure populations, yielding a 24 h IC50 of 5.3% OSPW. Results of behavioural assays suggest that OSPW impairs the chemosensory function and reduces the total activity of D. magna. In EDX spectroscopy, Al and Si were detected in the body of the exposed D. magna, suggesting that D. magna filter clay particles from the OSPW solution. Results of the long-term exposure showed that OSPW significantly inhibits feeding behaviour, suppresses growth, and reduces reproductive output of D. magna. There were no differences in the toxicity of the three samples of OSPW, which was in agreement with the fact that there were no differences in the species of dissolved organic compounds in the OSPW samples.

  11. Pre-learning stress differentially affects long-term memory for emotional words, depending on temporal proximity to the learning experience.

    PubMed

    Zoladz, Phillip R; Clark, Brianne; Warnecke, Ashlee; Smith, Lindsay; Tabar, Jennifer; Talbot, Jeffery N

    2011-07-01

    Stress exerts a profound, yet complex, influence on learning and memory and can enhance, impair or have no effect on these processes. Here, we have examined how the administration of stress at different times before learning affects long-term (24-hr) memory for neutral and emotional information. Participants submerged their dominant hand into a bath of ice cold water (Stress) or into a bath of warm water (No stress) for 3 min. Either immediately (Exp. 1) or 30 min (Exp. 2) after the water bath manipulation, participants were presented with a list of 30 words varying in emotional valence. The next day, participants' memory for the word list was assessed via free recall and recognition tests. In both experiments, stressed participants exhibited greater blood pressure, salivary cortisol levels, and subjective pain and stress ratings than non-stressed participants in response to the water bath manipulation. Stress applied immediately prior to learning (Exp. 1) enhanced the recognition of positive words, while stress applied 30 min prior to learning (Exp. 2) impaired free recall of negative words. Participants' recognition of positive words in Experiment 1 was positively associated with their heart rate responses to the water bath manipulation, while participants' free recall of negative words in Experiment 2 was negatively associated with their blood pressure and cortisol responses to the water bath manipulation. These findings indicate that the differential effects of pre-learning stress on long-term memory may depend on the temporal proximity of the stressor to the learning experience and the emotional nature of the to-be-learned information.

  12. Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

    ERIC Educational Resources Information Center

    Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

    2006-01-01

    The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

  13. Human sperm chromosomes. Long-term effect of cancer treatment

    SciTech Connect

    Genesca, A.; Caballin, M.R.; Miro, R.; Benet, J.; Bonfill, X.; Egozcue, J. )

    1990-06-01

    The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.

  14. Aggressive Therapy for Patients with Non-small Cell Lung Carcinoma and Synchronous Brain-only Oligometastatic Disease is Associated with Long-term Survival

    PubMed Central

    Gray, Phillip J.; Mak, Raymond H.; Yeap, Beow Y.; Cryer, Sarah K.; Pinnell, Nancy E.; Christianson, Laura W.; Sher, David J.; Arvold, Nils D.; Baldini, Elizabeth H.; Chen, Aileen B.; Kozono, David E.; Swanson, Scott J.; Jackman, David M.; Alexander, Brian M.

    2015-01-01

    Objectives Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation. Materials and Methods We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution. Patients with T0 tumors or documented Karnofsky Performance Status <70 were excluded. Aggressive thoracic therapy (ATT) was defined as resection of the primary disease or chemoradiotherapy whose total radiation dose exceeded 45 Gy. Cox proportional hazards and competing risks models were used to analyze factors affecting survival and first recurrence in the brain. Results Sixty-six patients were included. Median follow-up was 31.9 months. Intrathoracic disease extent included 9 stage I, 10 stage II and 47 stage III patients. Thirty-eight patients received ATT, 28 did not. Patients receiving ATT were younger (median age 55 vs. 60.5 years, p=0.027) but were otherwise similar to those who did not. Receipt of ATT was associated with prolonged median overall survival (OS) (26.4 vs. 10.5 months; p<0.001) with actuarial 2-year rates of 54% vs. 26%. ATT remained associated with OS after controlling for age, thoracic stage, performance status and initial brain therapy (HR 0.40, p=0.009). On multivariate analysis, the risk of first failure in the brain was associated with receipt of ATT (HR 3.62, p=0.032) and initial combined modality brain therapy (HR 0.34, p=0.046). Conclusion Aggressive management of thoracic disease in NSCLC patients with SBO is associated with improved survival. Careful management of brain disease remains important, especially for those treated aggressively. PMID:24974152

  15. Developmental associations between short-term variability and long-term changes: Intraindividual correlation of positive and negative affect in daily life and cognitive aging.

    PubMed

    Hülür, Gizem; Hoppmann, Christiane A; Ram, Nilam; Gerstorf, Denis

    2015-07-01

    Conceptual notions and empirical evidence suggest that the intraindividual correlation (iCorr) of positive affect (PA) and negative affect (NA) is a meaningful characteristic of affective functioning. PA and NA are typically negatively correlated within-person. Previous research has found that the iCorr of PA and NA is relatively stable over time within individuals, that it differs across individuals, and that a less negative iCorr is associated with better resilience and less vulnerability. However, little is known about how the iCorr of PA and NA relates to cognitive aging. This project examined how the association between PA and NA in everyday life is associated with long-term cognitive aging trajectories. To do so, we linked microlongitudinal data on PA and NA obtained on up to 33 occasions over 6 consecutive days with macrolongitudinal data on fluid and crystallized cognitive abilities obtained over 15 years from a subsample of Berlin Aging Study participants (N = 81, mean age at the microlongitudinal study = 81 years, range 73-98; 41% women). Over and above age, gender, education, overall levels of PA and NA, and number of health conditions, a less negative iCorr of PA and NA was associated with lower levels of cognitive ability and steeper cognitive declines, particularly for fluency and knowledge abilities. We discuss possible mechanisms for this finding and argue that a less negative iCorr of PA and NA may be indicative of deficits in emotional integration that are tied to changes in crystallized aspects of cognitive abilities.

  16. Effect of long-term aging on microstructure and local behavior in the heat-affected zone of a Ni–Cr–Mo–V steel welded joint

    SciTech Connect

    Zhu, Ming-Liang Wang, De-Qiang; Xuan, Fu-Zhen

    2014-01-15

    Evolution of microstructure, micro-hardness and micro-tensile strength behavior was investigated in the heat-affected zone of a Ni–Cr–Mo–V steel welded joint after the artificial aging at 350 °C for 3000 h. After detailed characterization of microstructures in optical microscopy, scanning electron microscopy and transmission electron microscopy, it is revealed that the change of martensite–bainite constituent promotes more homogeneous microstructure distribution. The aging treatment facilitates redistribution of carbon and chromium elements along the welded joint, and the micro-hardness is increased slightly through the welds due to enrichment of carbon. The types of precipitates in the weldment mainly include M{sub 3}C, MC, M{sub 2}C and M{sub 23}C{sub 6}. The carbides in base metal, weld metal and coarse-grained heat-affected zone are prone to change from ellipsoidal to platelet form whereas more uniform spherical carbides are observed in the fine-grained zone. Precipitation and coarsening of M{sub 23}C{sub 6} near the fusion line, and formation of MC and M{sub 2}C, are responsible for the tensile strength decrease and its smooth distribution in the aged heat-affected zone. This implies that the thermal aging can relieve strength mismatch in the weldments. - Highlights: • Microstructure homogeneity improved in HAZ after long-term aging. • Tensile strength decreased in HAZ due to precipitation and coarsening of M{sub 23}C{sub 6}. • Strength mismatch in NiCrMoV steel welds was relieved after aging at 350 °C × 3000 h.

  17. Association between psychopathology and problems of psychosocial functioning in the long-term outcome of patients diagnosed with schizophrenic, schizoaffective and affective disorders.

    PubMed

    Bottlender, Ronald; Strauss, Anton; Möller, Hans-Jürgen

    2013-03-01

    Mental health problems do significantly impact on a person's functioning. In the past, problems with psychosocial functioning were mainly associated with the diagnoses of schizophrenia. However, nowadays it is clear that impaired psychosocial functioning is also a common phenomenon in people suffering from affective disorders. Only few studies have investigated psychosocial functioning in patients with affective, schizoaffective and schizophrenic disorders in the long-term and in a comparative approach. In the present study, we analysed the association between psychopathology and psychosocial functioning. This question is relevant as symptom remission and sufficient levels of functioning are considered as important indicators of patients' recovery from their mental health problems. The here reported findings refer to the data of a sample of 177 patients with life-time diagnoses belonging to the schizophrenic, schizoaffective or affective spectrum according to the ICD-10 criteria. Psychopathological, socio-demographic and other illness-related variables were assessed at the index hospitalisation and at the 15-year follow-up evaluation. In the present study, psychopathology is focused on data assessed with the PANSS (Positive and Negative Syndrome Scale). Information about patients' psychosocial functioning was assessed by using a modified and extended version of the WHO disability assessment scale (WHO-DAS-M). The association between psychosocial functioning and psychopathology was analysed by correlation analyses with the total sample and diagnostic subsamples. The consistency of correlations across the diagnostic groups and domains of psychosocial functioning was calculated. Findings revealed for all diagnostic groups that higher levels of psychopathology were associated with higher levels of problems in psychosocial functioning in various domains. Though there seem to be some differences between psychopathological dimensions and their effects on different aspects

  18. Long-term results of adrenalectomy in patients with aldosterone-producing adenomas: multivariate analysis of factors affecting unresolved hypertension and review of the literature.

    PubMed

    Lumachi, Franco; Ermani, Mario; Basso, Stefano M M; Armanini, Decio; Iacobone, Maurizio; Favia, Gennaro

    2005-10-01

    The long-term surgical cure rate of patients with primary aldosteronism varies widely, and causes of persistent hypertension are not completely established. We reviewed retrospectively charts from 98 patients (range, 19-70 years old) with aldosterone-producing adenomas who underwent unilateral adrenalectomy. At a median follow-up of 81 months (range, 18-186 months), the mean blood pressure values improved in 95 out of 98 (96.9%) patients, although hypertension was cured only in 71 out of 98 (72.4%) patients. Multivariate analysis using a logistic regression model adjusted for duration of follow-up showed that only age of the patients and duration of the disease independently correlated with unresolved hypertension. The cumulative odds ratio (OR), obtained using the logistic regression function, was 5.38 (95% CI 1.78-16.22), and the OR of single variables were 1.32 (95% CI 0.36-19.83) and 4.56 (95% CI 1.41-14.78), respectively. By using discriminant analysis to derive a classification function for the prediction of unresolved hypertension, a maximum predictive power of 75 per cent was achieved. In conclusion, in patients with an aldosterone-producing adenoma undergoing surgery, the combination of age and duration of hypertension gave the best predictive power of a linear classification function and represented the main independent risk factors affecting hypertension cure rate. PMID:16468537

  19. The interpretation of long-term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials.

    PubMed

    Langley, R G; Reich, K

    2013-12-01

    Psoriasis is a chronic disease requiring long-term therapy, which makes finding treatments with favourable long-term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long-term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow-up methods and handling of missing data. Various trial designs and data handling methods are used in long-term studies of biologic psoriasis treatments. Responder analyses in long-term trials can be conducted in responder enrichment, re-treated nonresponder or intent-to-treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last-observation-carried-forward, as-observed analysis and anytime analysis. Long-term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions.

  20. The interpretation of long-term trials of biologic treatments for psoriasis: trial designs and the choices of statistical analyses affect ability to compare outcomes across trials.

    PubMed

    Langley, R G; Reich, K

    2013-12-01

    Psoriasis is a chronic disease requiring long-term therapy, which makes finding treatments with favourable long-term safety and efficacy profiles crucial. The goal of this review is to provide the background needed to evaluate properly long-term studies of biologic treatments for psoriasis. Firstly, important elements of design and analysis strategies are described. Secondly, data from published trials of biologic therapies for psoriasis are reviewed in light of the design and analysis choices implemented in the studies. Published reports of clinical trials of biologic treatments (adalimumab, alefacept, etanercept, infliximab or ustekinumab) that lasted 33 weeks or longer and included efficacy results and statistical analysis were reviewed. Study designs and statistical analyses were evaluated and summarized, emphasizing patient follow-up methods and handling of missing data. Various trial designs and data handling methods are used in long-term studies of biologic psoriasis treatments. Responder analyses in long-term trials can be conducted in responder enrichment, re-treated nonresponder or intent-to-treat trials. Missing data can be handled in four ways, including, from most to least conservative, nonresponder imputation, last-observation-carried-forward, as-observed analysis and anytime analysis. Long-term clinical trials have shown that adalimumab, alefacept, etanercept, infliximab and ustekinumab are efficacious for psoriasis treatment; however, without common standards for these trials, direct comparisons of these agents are difficult. Understanding differences in trial design and data handling is essential to make informed treatment decisions. PMID:23937204

  1. Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

    PubMed

    Tamburrino, Federica; Gibertoni, Dino; Rossi, Cesare; Scarano, Emanuela; Perri, Annamaria; Montanari, Francesca; Fantini, Maria Pia; Pession, Andrea; Tartaglia, Marco; Mazzanti, Laura

    2015-11-01

    RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS-MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty-three patients showed GH deficiency after pharmacological tests, and were GH-treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was -2.6 ± 1.3 SDS, and mean basal IGF1 levels were -2.0 ± 1.1 SDS. Long-term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height-gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from -2.43 to -0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.

  2. Can resistant coral-Symbiodinium associations enable coral communities to survive climate change? A study of a site exposed to long-term hot water input.

    PubMed

    Keshavmurthy, Shashank; Meng, Pei-Jie; Wang, Jih-Terng; Kuo, Chao-Yang; Yang, Sung-Yin; Hsu, Chia-Min; Gan, Chai-Hsia; Dai, Chang-Feng; Chen, Chaolun Allen

    2014-01-01

    Climate change has led to a decline in the health of corals and coral reefs around the world. Studies have shown that, while some corals can cope with natural and anthropogenic stressors either through resistance mechanisms of coral hosts or through sustainable relationships with Symbiodinium clades or types, many coral species cannot. Here, we show that the corals present in a reef in southern Taiwan, and exposed to long-term elevated seawater temperatures due to the presence of a nuclear power plant outlet (NPP OL), are unique in terms of species and associated Symbiodinium types. At shallow depths (<3 m), eleven coral genera elsewhere in Kenting predominantly found with Symbiodinium types C1 and C3 (stress sensitive) were instead hosting Symbiodinium type D1a (stress tolerant) or a mixture of Symbiodinium type C1/C3/C21a/C15 and Symbiodinium type D1a. Of the 16 coral genera that dominate the local reefs, two that are apparently unable to associate with Symbiodinium type D1a are not present at NPP OL at depths of <3 m. Two other genera present at NPP OL and other locations host a specific type of Symbiodinium type C15. These data imply that coral assemblages may have the capacity to maintain their presence at the generic level against long-term disturbances such as elevated seawater temperatures by acclimatization through successful association with a stress-tolerant Symbiodinium over time. However, at the community level it comes at the cost of some coral genera being lost, suggesting that species unable to associate with a stress-tolerant Symbiodinium are likely to become extinct locally and unfavorable shifts in coral communities are likely to occur under the impact of climate change.

  3. Archaeal dominated ammonia-oxidizing communities in Icelandic grassland soils are moderately affected by long-term N fertilization and geothermal heating

    PubMed Central

    Daebeler, Anne; Abell, Guy C. J.; Bodelier, Paul L. E.; Bodrossy, Levente; Frampton, Dion M. F.; Hefting, Mariet M.; Laanbroek, Hendrikus J.

    2012-01-01

    The contribution of ammonia-oxidizing bacteria and archaea (AOB and AOA, respectively) to the net oxidation of ammonia varies greatly between terrestrial environments. To better understand, predict and possibly manage terrestrial nitrogen turnover, we need to develop a conceptual understanding of ammonia oxidation as a function of environmental conditions including the ecophysiology of associated organisms. We examined the discrete and combined effects of mineral nitrogen deposition and geothermal heating on ammonia-oxidizing communities by sampling soils from a long-term fertilization site along a temperature gradient in Icelandic grasslands. Microarray, clone library and quantitative PCR analyses of the ammonia monooxygenase subunit A (amoA) gene accompanied by physico-chemical measurements of the soil properties were conducted. In contrast to most other terrestrial environments, the ammonia-oxidizing communities consisted almost exclusively of archaea. Their bacterial counterparts proved to be undetectable by quantitative polymerase chain reaction suggesting AOB are only of minor relevance for ammonia oxidation in these soils. Our results show that fertilization and local, geothermal warming affected detectable ammonia-oxidizing communities, but not soil chemistry: only a subset of the detected AOA phylotypes was present in higher temperature soils and AOA abundance was increased in the fertilized soils, while soil physio-chemical properties remained unchanged. Differences in distribution and structure of AOA communities were best explained by soil pH and clay content irrespective of temperature or fertilizer treatment in these grassland soils, suggesting that these factors have a greater potential for ecological niche-differentiation of AOA in soil than temperature and N fertilization. PMID:23060870

  4. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.

    PubMed

    Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C; Thomas, Marvin L; Clark, Tannia; Lewis, Billeta G; Hoyt, Robert F; Eckhaus, Michael; Pierson, Richard N; Belli, Aaron J; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A; Ayares, David; Horvath, Keith A

    2016-04-05

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days.

  5. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.

    PubMed

    Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C; Thomas, Marvin L; Clark, Tannia; Lewis, Billeta G; Hoyt, Robert F; Eckhaus, Michael; Pierson, Richard N; Belli, Aaron J; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A; Ayares, David; Horvath, Keith A

    2016-01-01

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. PMID:27045379

  6. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft

    PubMed Central

    Mohiuddin, Muhammad M.; Singh, Avneesh K.; Corcoran, Philip C.; Thomas III, Marvin L.; Clark, Tannia; Lewis, Billeta G.; Hoyt, Robert F.; Eckhaus, Michael; Pierson III, Richard N.; Belli, Aaron J.; Wolf, Eckhard; Klymiuk, Nikolai; Phelps, Carol; Reimann, Keith A.; Ayares, David; Horvath, Keith A.

    2016-01-01

    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46.hTBM), that were transplanted into baboons. Our immunomodulatory drug regimen includes induction with anti-thymocyte globulin and αCD20 antibody, followed by maintenance with mycophenolate mofetil and an intensively dosed αCD40 (2C10R4) antibody. Median (298 days) and longest (945 days) graft survival in five consecutive recipients using this regimen is significantly prolonged over our recently established survival benchmarks (180 and 500 days, respectively). Remarkably, the reduction of αCD40 antibody dose on day 100 or after 1 year resulted in recrudescence of anti-pig antibody and graft failure. In conclusion, genetic modifications (GTKO.hCD46.hTBM) combined with the treatment regimen tested here consistently prevent humoral rejection and systemic coagulation pathway dysregulation, sustaining long-term cardiac xenograft survival beyond 900 days. PMID:27045379

  7. Soil microbial biomass and community structure affected by repeated additions of sewage sludge in four Swedish long-term field experiments

    NASA Astrophysics Data System (ADS)

    Börjesson, G.; Kätterer, T.; Kirchmann, H.

    2012-04-01

    Soil organic matter is a key attribute of soil fertility. The pool of soil organic C can be increased, either by mineral fertilisers or by adding organic amendments such as sewage sludge. Sewage sludge has positive effects on agricultural soils through the supply of organic matter and essential plant nutrients, but sludge may also contain unwanted heavy metals, xenobiotic substances and pathogens. One obvious effect of long-term sewage sludge addition is a decrease in soil pH, caused by N mineralisation followed by nitrification, sulphate formation and presence of organic acids with the organic matter added. The objective of this study was to investigate the effect of sewage sludge on the microbial biomass and community structure. Materials and methods We analysed soil samples from four sites where sewage sludge has been repeatedly applied in long-term field experiments situated in different parts of Sweden; Ultuna (59°49'N, 17°39'E, started 1956), Lanna (58°21'N, 13°06'E, started 1997-98), Petersborg (55°32'N, 13°00'E, started 1981) and Igelösa (55°45'N, 13°18'E, started 1981). In these four experiments, at least one sewage sludge treatment is included in the experimental design. In the Ultuna experiment, all organic fertilisers, including sewage sludge, are applied every second year, corresponding to 4 ton C ha-1. The Lanna experiment has a similar design, with 8 ton dry matter ha-1 applied every second year. Lanna also has an additional treatment in which metal salts (Cd, Cu, Ni and Zn) are added together with sewage sludge. At Petersborg and Igelösa, two levels of sewage sludge (4 or 12 ton dry matter ha-1 every 4th year) are compared with three levels of NPK fertiliser (0 N, ½ normal N and normal N). Topsoil samples (0-20 cm depth) from the four sites were analysed for total C, total N, pH and PLFAs (phospholipid fatty acids). In addition, crop yields were recorded. Results At all four sites, sewage sludge has had a positive effect on crop yields

  8. Extent of Surgery Affects Survival for Papillary Thyroid Cancer

    PubMed Central

    Bilimoria, Karl Y.; Bentrem, David J.; Ko, Clifford Y.; Stewart, Andrew K.; Winchester, David P.; Talamonti, Mark S.; Sturgeon, Cord

    2007-01-01

    Background: The extent of surgery for papillary thyroid cancers (PTC) remains controversial. Consensus guidelines have recommended total thyroidectomy for PTC ≥1 cm; however, no study has supported this recommendation based on a survival advantage. The objective of this study was to examine whether the extent of surgery affects outcomes for PTC and to determine whether a size threshold could be identified above which total thyroidectomy is associated with improved outcomes. Methods: From the National Cancer Data Base (1985–1998), 52,173 patients underwent surgery for PTC. Survival was estimated by the Kaplan-Meier method and compared using log-rank tests. Cox Proportional Hazards modeling stratified by tumor size was used to assess the impact of surgical extent on outcomes and to identify a tumor size threshold above which total thyroidectomy is associated with an improvement in recurrence and long-term survival rates. Results: Of the 52,173 patients, 43,227 (82.9%) underwent total thyroidectomy, and 8946 (17.1%) underwent lobectomy. For PTC <1 cm extent of surgery did not impact recurrence or survival (P = 0.24, P = 0.83). For tumors ≥1 cm, lobectomy resulted in higher risk of recurrence and death (P = 0.04, P = 0.009). To minimize the influence of larger tumors, 1 to 2 cm lesions were examined separately: lobectomy again resulted in a higher risk of recurrence and death (P = 0.04, P = 0.04). Conclusions: The results of this study demonstrate that total thyroidectomy results in lower recurrence rates and improved survival for PTC ≥1.0 cm compared with lobectomy. This is the first study to demonstrate that total thyroidectomy for PTC ≥1.0 cm improves outcomes. PMID:17717441

  9. The long-term survival of in vitro engineered nervous tissue derived from the specific neural differentiation of mouse embryonic stem cells.

    PubMed

    Dubois-Dauphin, Michel L; Toni, Nicolas; Julien, Stéphanie D; Charvet, Igor; Sundstrom, Lars E; Stoppini, Luc

    2010-09-01

    Embryonic stem cells (ESCs) offer attractive prospective as potential source of neurons for cell replacement therapy in human neurodegenerative diseases. Besides, ESCs neural differentiation enables in vitro tissue engineering for fundamental research and drug discovery aimed at the nervous system. We have established stable and long-term three-dimensional (3D) culture conditions which can be used to model long latency and complex neurodegenerative diseases. Mouse ESCs-derived neural progenitor cells generated by MS5 stromal cells induction, result in strictly neural 3D cultures of about 120-mum thick, whose cells expressed mature neuronal, astrocytes and myelin markers. Neurons were from the glutamatergic and gabaergic lineages. This nervous tissue was spatially organized in specific layers resembling brain sub-ependymal (SE) nervous tissue, and was maintained in vitro for at least 3.5 months with great stability. Electron microscopy showed the presence of mature synapses and myelinated axons, suggesting functional maturation. Electrophysiological activity revealed biological signals involving action potential propagation along neuronal fibres and synaptic-like release of neurotransmitters. The rapid development and stabilization of this 3D cultures model result in an abundant and long-lasting production that is compatible with multiple and productive investigations for neurodegenerative diseases modeling, drug and toxicology screening, stress and aging research.

  10. Importance of early and deeper responses to long-term survival in CML patients: Implications of BCR-ABL testing in management of CML in Indian setting

    PubMed Central

    Agarwal, Mohan B.

    2014-01-01

    The prognosis of patients with chronic myeloid leukemia (CML) has changed radically since the advent of imatinib mesylate, a selective inhibitor of BCR-ABL tyrosine kinase. Shortly thereafter, more potent BCR-ABL inhibitors (dasatinib and nilotinib) were introduced for use in patients resistant to or intolerant of imatinib. All three drugs are now approved for initial therapy for chronic phase CML. Response to tyrosine kinase inhibitor (TKI) treatment is assessed with standardized quantitative reverse transcriptase polymerase chain reaction (Q-RTPCR) and/or cytogenetics at 3, 6 and 12 months. Clinical trials have clearly demonstrated that early and deeper cytogenetic and molecular response to TKI therapy is associated with lower rate of disease progression and improved long-term outcomes. In recent times, molecular response as determined by BCR-ABL transcript levels at defined time points is rapidly gaining popularity as a predictive marker for subsequent outcomes in CML. Optimal response is defined as BCR-ABL transcript levels of ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward while >10% at 6 months and >1% from 12 months onward define failure. Patients who do not achieve molecular milestones at 3 or 6 months with 3 months being highly predictive are less likely to achieve cytogenetic responses eventually; early identification of such patients who have a low probability of achieving an adequate response are thus candidates for alternative treatment. Review of literature by electronic search of MEDline, Google Scholar was done using keywords and data was identified and systematically evaluated. PMID:25006277

  11. Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study

    PubMed Central

    Bagshaw, Sean M; Laupland, Kevin B; Doig, Christopher J; Mortis, Garth; Fick, Gordon H; Mucenski, Melissa; Godinez-Luna, Tomas; Svenson, Lawrence W; Rosenal, Tom

    2005-01-01

    Introduction Severe acute renal failure (sARF) is associated with considerable morbidity, mortality and use of healthcare resources; however, its precise epidemiology and long-term outcomes have not been well described in a non-specified population. Methods Population-based surveillance was conducted among all adult residents of the Calgary Health Region (population 1 million) admitted to multidisciplinary and cardiovascular surgical intensive care units between May 1 1999 and April 30 2002. Clinical records were reviewed and outcome at 1 year was assessed. Results sARF occurred in 240 patients (11.0 per 100,000 population/year). Rates were highest in males and older patients (≥65 years of age). Risk factors for development of sARF included previous heart disease, stroke, pulmonary disease, diabetes mellitus, cancer, connective tissue disease, chronic renal dysfunction, and alcoholism. The annual mortality rate was 7.3 per 100,000 population with rates highest in males and those ≥65 years. The 28-day, 90-day, and 1-year case-fatality rates were 51%, 60%, and 64%, respectively. Increased Charlson co-morbidity index, presence of liver disease, higher APACHE II score, septic shock, and need for continuous renal replacement therapy were independently associated with death at 1 year. Renal recovery occurred in 78% (68/87) of survivors at 1 year. Conclusion sARF is common and males, older patients, and those with underlying medical conditions are at greatest risk. Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year. PMID:16280066

  12. Medical Status of 219 Children with Biliary Atresia Surviving Long-Term with their Native Livers: Results from a North American Multicenter Consortium

    PubMed Central

    Ng, Vicky Lee; Haber, Barbara H.; Magee, John C.; Miethke, Alexander; Murray, Karen F.; Michail, Sonia; Karpen, Saul J.; Kerkar, Nanda; Molleston, JeanP.; Romero, Rene; Rosenthal, Philip; Schwarz, Kathleen B.; Shneider, Benjamin L.; P.Turmelle, Yumirle; Alonso, Estella M.; Sherker, Averell H.; Sokol, Ronald J.

    2014-01-01

    Objectives To examine the medical status of children with biliary atresia (BA) with their native livers after hepatic portoenterostomy (HPE) surgery. Study design The Childhood Liver Disease Research and Education Network (ChiLDREN) database was utilized to examine subjects with BA living with their native livers 5 or more years after HPE and to describe the prevalence of subjects with BA with an “ideal” outcome, defined as no clinical evidence of chronic liver disease, normal liver biochemical indices (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, platelet count, total bilirubin, International Normalized Ratio, and albumin) and normal Health-Related Quality of Life (HRQOL) 5 or more years after HPE. Results Children with BA (n=219; 43% male) with median age 9.7 years were studied. Median age at HPE was 56 (range 7-125) days. Median age- and sex-adjusted height and weight Z-scores at 5 year follow-up were 0.487 (interquartile range [IQR]: -0.27 to 1.02) and 0.00 (IQR: -0.74 to 0.70), respectively. During the 12 preceding months, cholangitis and bone fractures occurred in 17% and 5.5%, respectively. HRQOL was reported normal by 53% of patients. However, only 1.8% met the study definition of “ideal” outcome. Individual tests of liver synthetic function (TB, Alb, and INR) were normal in 75%, 85% and 73% of the study cohort. Conclusion Cholangitis and fractures in long-term survivors underscore the importance of ongoing medical surveillance. Over 98% of this North American cohort of subjects with BA living with native livers 5 or more years after HPE have clinical or biochemical evidence of chronic liver disease. PMID:25015575

  13. Utility of cardiac magnetic resonance imaging, echocardiography and electrocardiography for the prediction of clinical response and long-term survival following cardiac resynchronisation therapy.

    PubMed

    Ellims, Andris H; Pfluger, Heinz; Elsik, Maros; Butler, Michelle J; Hare, James L; Taylor, Andrew J

    2013-08-01

    Cardiac resynchronisation therapy (CRT) can reduce symptoms, hospitalisations, and mortality in patients with severe left ventricular (LV) systolic dysfunction and electro-mechanical dyssynchrony. Unfortunately, approximately 30 % of eligible patients fail to respond to CRT. This study prospectively compared electrocardiography (ECG), echocardiography, and cardiac magnetic resonance (CMR) imaging for the prediction of response to CRT. We performed ECG, echocardiography and CMR on 46 patients prior to planned CRT implantation. Patients were divided into predicted responder and non-responder groups using previously described criteria for each modality. Changes in indicators of CRT response were recorded 6 months post-implantation, and later for transplant-free survival. Less dyspnoea, lower levels of N-terminal pro-brain natriuretic peptide, more LV reverse remodelling, and longer transplant-free survival were observed in predicted responders compared to predicted non-responders using each of the three modalities (p < 0.05 for each comparison). Additionally, for patients with QRS duration <150 ms and/or non-left bundle branch block (non-LBBB) QRS morphology, CMR predicted both clinical response and improved longer term transplant-free survival (80 % transplant-free survival in predicted responders vs. 20 % in predicted non-responders, p = 0.04). ECG and cardiac imaging techniques predict improvements in markers of response following CRT with similar accuracy. However, for CRT candidates with shorter, non-LBBB QRS complexes, a subgroup known to derive less benefit from CRT, CMR may predict those who are more likely to gain both symptomatic and survival benefits.

  14. Radiation Use and Long-Term Survival in Breast Cancer Patients With T1, T2 Primary Tumors and One to Three Positive Axillary Lymph Nodes

    SciTech Connect

    Buchholz, Thomas A. Woodward, Wendy A.; Duan Zhigang; Fang Shenying; Oh, Julia L.; Tereffe, Welela; Strom, Eric A.; Perkins, George H.; Yu, T.-K.; Hunt, Kelly K.; Meric-Bernstam, Funda; Hortobagyi, Gabriel N.; Giordano, Sharon H.

    2008-07-15

    Background: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. Methods and Materials: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). Results: Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. Conclusions: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.

  15. Macitentan, a dual endothelin receptor antagonist, in combination with temozolomide leads to glioblastoma regression and long-term survival in mice

    PubMed Central

    Kim, Sun-Jin; Lee, Ho Jeong; Kim, Mark Seungwook; Choi, Hyun Jin; He, Junqin; Wu, Qiuyu; Aldape, Kenneth; Weinberg, Jeffrey S.; Alfred Yung, W. K.; Conrad, Charles A.; Langley, Robert R.; Lehembre, François; Regenass, Urs; Fidler, Isaiah J.

    2016-01-01

    Purpose The objective of the study was to determine whether astrocytes and brain endothelial cells protect glioma cells from temozolomide (TMZ) through an endothelin-dependent signaling mechanism and to examine the therapeutic efficacy of the dual endothelin receptor antagonist, macitentan, in orthotopic models of human glioblastoma. Experimental Design We evaluated several endothelin receptor antagonists for their ability to inhibit astrocyte- and brain endothelial cell-induced protection of glioma cells from TMZ in chemoprotection assays. We compared survival in nude mice bearing orthotopically implanted LN-229 glioblastomas or TMZ-resistant (LN-229Res and D54Res) glioblastomas that were treated with macitentan, TMZ, or both. Tumor burden was monitored weekly with bioluminescence imaging. The effect of therapy on cell division, apoptosis, tumor-associated vasculature, and pathways associated with cell survival was assessed by immunofluorescent microscopy. Results Only dual endothelin receptor antagonism abolished astrocyte- and brain endothelial cell-mediated protection of glioma cells from TMZ. In five independent survival studies, including TMZ-resistant glioblastomas, 46 of 48 (96%) mice treated with macitentan plus TMZ had no evidence of disease (P<0.0001), whereas all mice in other groups died. In another analysis, macitentan plus TMZ therapy was stopped in 16 mice after other groups had died. Only 3 of 16 mice eventually developed recurrent disease, 2 of which responded to additional cycles of macitentan plus TMZ. Macitentan downregulated proteins associated with cell division and survival in glioma cells and associated endothelial cells, which enhanced their sensitivity to TMZ. Conclusions Macitentan plus TMZ are well tolerated, produce durable responses, and warrant clinical evaluation in glioblastoma patients. PMID:26106074

  16. Nitrite survival and nitrous oxide production of denitrifying phosphorus removal sludges in long-term nitrite/nitrate-fed sequencing batch reactors.

    PubMed

    Wang, Yayi; Zhou, Shuai; Ye, Liu; Wang, Hong; Stephenson, Tom; Jiang, Xuxin

    2014-12-15

    Nitrite-based phosphorus (P) removal could be useful for innovative biological P removal systems where energy and carbon savings are a priority. However, using nitrite for denitrification may cause nitrous oxide (N2O) accumulation and emissions. A denitrifying nitrite-fed P removal system [Formula: see text] was successfully set up in a sequencing batch reactor (SBR) and was run for 210 days. The maximum pulse addition of nitrite to [Formula: see text] was 11 mg NO2(-)-N/L in the bulk, and a total of 34 mg NO2(-)-N/L of nitrite was added over three additions. Fluorescent in situ hybridization results indicated that the P-accumulating organisms (PAOs) abundance was 75 ± 1.1% in [Formula: see text] , approximately 13.6% higher than that in a parallel P removal SBR using nitrate [Formula: see text] . Type II Accumulibacter (PAOII) (unable to use nitrate as an electron acceptor) was the main PAOs species in [Formula: see text] , contributing 72% to total PAOs. Compared with [Formula: see text] , [Formula: see text] biomass had enhanced nitrite/free nitrous acid (FNA) endurance, as demonstrated by its higher nitrite denitrification and P uptake rates. N2O accumulated temporarily in [Formula: see text] after each pulse of nitrite. Peak N2O concentrations in the bulk for [Formula: see text] were generally 6-11 times higher than that in [Formula: see text] ; these accumulations were rapidly denitrified to nitrogen gases. N2O concentration increased rapidly in nitrate-cultivated biomass when 5 or 10 mg NO2(-)-N/L per pulse was added. Whereas, N2O accumulation did not occur in nitrite-cultivated biomass until up to 30 mg NO2(-)-N/L per pulse was added. Long-term acclimation to nitrite and pulse addition of nitrite in [Formula: see text] reduced the risk of nitrite accumulation, and mitigated N2O accumulation and emissions from denitrifying P removal by nitrite.

  17. Decreased survival of glioma patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile and cordless phones.

    PubMed

    Carlberg, Michael; Hardell, Lennart

    2014-10-16

    On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a "possible", human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997-2003 and 2007-2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2-2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4-2.9 and cordless phone use HR = 3.4, 95% CI = 1.04-11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007-1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999-1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.

  18. Clinical evaluation of osseointegrated implants in Tokyo Dental College Hospital (third report): long-term observation of functioning survival rate of fixtures.

    PubMed

    Miyashita, Yuko; Arataki, Tomohiko; Nomura, Takao; Suzuki, Hiroki; Atsuta, Syunichi; Hotta, Hiromi; Shimamura, Ichiro; Adachi, Yasushi; Kishi, Masataka

    2003-08-01

    The objective of this report was to review 365 cases of Brånemark Implant Bridge including 1,444 fixtures in patients of Tokyo Dental College Chiba Hospital. The term of implantation was divided into several phases; less than 1 year, from 1 year to 3 years, from 3 years to 5 years, from 5 years to 7 years, from 7 years to 10 years, more than 10 years, and the survival rate was calculated for each phase. The removal rate of fixture after connecting the superstructure was 13% in maxillary cases and 2% in mandibular cases. The functioning survival rate in maxillary cases slightly decreased from 91% in less than 1 year to 87% after more than 10 years; however, the functioning survival rate in mandibular cases was about 99% in all periods. The removal rate of fixtures per patient was 23% in maxillary cases and 6% in mandibular ones. The average removal number of fixtures was 1.8 in maxillary cases and 1.2 in mandibular ones. The removal of the fixture occurred most frequently at less than 1 year in maxillary cases, but there was no tendency for a pattern of removal of fixture in mandibular cases.

  19. Impact of different cryoprotectants on the survival of freeze-dried Lactobacillus rhamnosus and Lactobacillus casei/paracasei during long-term storage.

    PubMed

    Jofré, A; Aymerich, T; Garriga, M

    2015-01-01

    The production of long shelf-life highly concentrated dried probiotic/starter cultures is of paramount importance for the food industry. The aim of the present study was to evaluate the protective effect of glucose, lactose, trehalose, and skim milk applied alone or combined upon the survival of potentially probiotic Lactobacillus rhamnosus CTC1679, Lactobacillus casei/paracasei CTC1677 and L. casei/paracasei CTC1678 during freeze-drying and after 39 weeks of storage at 4 and 22 °C. Immediately after freeze-drying, the percentage of survivors was very high (≥ 94%) and only slight differences were observed among strains and cryoprotectants. In contrast, during storage, survival in the dried state depended on the cryoprotectant, temperature and strain. For all the protectants assayed, the stability of the cultures was remarkably higher when stored under refrigeration (4 °C). Under these conditions, skim milk alone or supplemented with trehalose or lactose showed the best performance (reductions ≤ 0.9 log units after 39 weeks of storage). The lowest survival was observed during non-refrigerated storage and with glucose and glucose plus milk; no viable cells left at the end of the storage period. Thus, freeze-drying in the presence of appropriate cryoprotectants allows the production of long shelf-life highly concentrated dried cultures ready for incorporation in high numbers into food products as starter/potential probiotic cultures.

  20. Air-dried cells from the anhydrobiotic insect, Polypedilum vanderplanki, can survive long term preservation at room temperature and retain proliferation potential after rehydration.

    PubMed

    Watanabe, Kazuyo; Imanishi, Shigeo; Akiduki, Gaku; Cornette, Richard; Okuda, Takashi

    2016-08-01

    Pv11, a cell line derived from the anhydrobiotic insect, Polypedilum vanderplanki, was preserved in a dry form (only 6% residual moisture) at room temperature for up to 251 days and restarted proliferating after rehydration. A previous study already reported survival of Pv11 cells after desiccation, but without subsequent proliferation. Here, the protocol was improved to increase survival and achieve proliferation of Pv11 cells after dry storage. The method basically included preincubation, desiccation and rehydration processes and each step was investigated. So far, preincubation in a 600 mM trehalose solution for 48 h before dehydration was the most favourable preconditioning to achieve successful dry preservation of Pv11 cells, allowing about 16% of survival after rehydration and subsequent cell proliferation. Although the simple air-dry method established for Pv11 cells here was not applicable for successful dry-preservation of other insect cell lines, Pv11 is the first dry-preservable animal cell line and will surely contribute not only to basic but also applied sciences. PMID:27207249

  1. Long term survival with stereotactic ablative radiotherapy (SABR) versus thoracoscopic sublobar lung resection in elderly people: national population based study with propensity matched comparative analysis

    PubMed Central

    Paul, Subroto; Lee, Paul C; Mao, Jialin; Isaacs, Abby J

    2016-01-01

    Objectives To compare cancer specific survival after thoracoscopic sublobar lung resection and stereotactic ablative radiotherapy (SABR) for tumors ≤2 cm in size and thoracoscopic resection (sublobar resection or lobectomy) and SABR for tumors ≤5 cm in size. Design National population based retrospective cohort study with propensity matched comparative analysis. Setting Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare database in the United States. Participants Patients aged ≥66 with lung cancer undergoing SABR or thoracoscopic lobectomy or sublobar resection from 1 Oct 2007 to 31 June 2012 and followed up to 31 December 2013. Main outcome measures Cancer specific survival after SABR or thoracoscopic surgery for lung cancer. Results 690 (275 (39.9%) SABR and 415 (60.1%) thoracoscopic sublobar lung resection) and 2967 (714 (24.1%) SABR and 2253 (75.9%) thoracoscopic resection) patients were included in primary and secondary analyses. The average age of the entire cohort was 76. Follow-up of the entire cohort ranged from 0 to 6.25 years, with an average of three years. In the primary analysis of patients with tumors sized ≤2 cm, 37 (13.5%) undergoing SABR and 44 (10.6%) undergoing thoracoscopic sublobar resection died from lung cancer, respectively. The cancer specific survival diverged after one year, but in the matched analysis (201 matched patients in each group) there was no significant difference between the groups (SABR v sublobar lung resection mortality: hazard ratio 1.32, 95% confidence interval 0.77 to 2.26; P=0.32). Estimated cancer specific survival at three years after SABR and thoracoscopic sublobar lung resection was 82.6% and 86.4%, respectively. The secondary analysis (643 matched patients in each group) showed that thoracoscopic resection was associated with improved cancer specific survival over SABR in patients with tumors sized ≤5 cm (SABR v resection mortality: hazard ratio 2.10, 1.52 to 2.89; P<0

  2. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  3. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).

    PubMed

    Hanfstein, B; Müller, M C; Hehlmann, R; Erben, P; Lauseker, M; Fabarius, A; Schnittger, S; Haferlach, C; Göhring, G; Proetel, U; Kolb, H-J; Krause, S W; Hofmann, W-K; Schubert, J; Einsele, H; Dengler, J; Hänel, M; Falge, C; Kanz, L; Neubauer, A; Kneba, M; Stegelmann, F; Pfreundschuh, M; Waller, C F; Branford, S; Hughes, T P; Spiekermann, K; Baerlocher, G M; Pfirrmann, M; Hasford, J; Saußele, S; Hochhaus, A

    2012-09-01

    In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL(IS)) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1-10% BCR-ABL(IS) (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ≤1% BCR-ABL(IS) (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ≤35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABL(IS) (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ≤1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks. PMID:22446502

  4. A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis

    PubMed Central

    Fruscio, R; Colombo, N; Lissoni, A A; Garbi, A; Fossati, R; Ieda', N; Torri, V; Mangioni, C

    2008-01-01

    To test the feasibility and efficacy of epirubicin and ifosfamide added to first-line chemotherapy with cisplatin and paclitaxel in a phase II randomised clinical trial. Patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP) or cisplatin/paclitaxel/ifosfamide (CIP) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms and the median number of cycles per patient was six. Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm. Response rates were 85% (95% confidence interval (CI) 77–93%) in the CIP arm and 90% (95% CI 84–96%) in the CEP arm; complete response rates were 48 and 52%. After a median follow-up of 82 months, median overall survival (OS) was 51 and 65 months; 5-year survival rates were respectively 43 and 50%. In this clinical trial, both regimens showed good efficacy, but toxicity was heavier with the CIP regimen. Considering that more than 50% of patients were suboptimally debulked after the first surgery, OS seems to be longer than is commonly reported. This unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach. PMID:18253120

  5. Survival in air of Mytilus trossulus following long-term exposure to spilled Exxon Valdez crude oil in Prince William Sound.

    PubMed

    Thomas, R E; Harris, P M; Rice, S D

    1999-01-01

    Mussels, Mytilus trossulus, were sampled in 1996 from beaches in Prince William Sound (PWS) which contained residual oil resulting from the Exxon Valdez oil spill of March 1989, and from one beach which had been lightly oiled in 1989, but contained no residual oil in 1996. The latter mussels served as un-oiled references. Mussels were also collected from Tee Harbor, Southeast Alaska, to be used as an additional reference group. Where the size of the individuals in the resident population would permit, two size groups were sampled, 32-35 and 18-20 mm in length. Polynuclear aromatic hydrocarbon (PAH) concentrations in mussel tissue, and air survival time were determined for each group of mussels. Total PAH concentrations were significantly greater in tissue of mussels from oiled beds (0.6-2.0 micrograms g-1) than from references (0.01-0.12 microgram g-1) (P < 0.01). Oil-exposed mussels had significantly lower LT50 values (P < 0.05) for air survival than reference groups. Tolerance of small mussels to air exposure was significantly greater (P < 0.01) than large mussels in both the unoiled reference and oil exposed groups.

  6. Survival in air of Mytilus trossulus following long-term exposure to spilled Exxon Valdez crude oil in Prince William Sound.

    PubMed

    Thomas, R E; Harris, P M; Rice, S D

    1999-01-01

    Mussels, Mytilus trossulus, were sampled in 1996 from beaches in Prince William Sound (PWS) which contained residual oil resulting from the Exxon Valdez oil spill of March 1989, and from one beach which had been lightly oiled in 1989, but contained no residual oil in 1996. The latter mussels served as un-oiled references. Mussels were also collected from Tee Harbor, Southeast Alaska, to be used as an additional reference group. Where the size of the individuals in the resident population would permit, two size groups were sampled, 32-35 and 18-20 mm in length. Polynuclear aromatic hydrocarbon (PAH) concentrations in mussel tissue, and air survival time were determined for each group of mussels. Total PAH concentrations were significantly greater in tissue of mussels from oiled beds (0.6-2.0 micrograms g-1) than from references (0.01-0.12 microgram g-1) (P < 0.01). Oil-exposed mussels had significantly lower LT50 values (P < 0.05) for air survival than reference groups. Tolerance of small mussels to air exposure was significantly greater (P < 0.01) than large mussels in both the unoiled reference and oil exposed groups. PMID:10190039

  7. Validation of long-term survival prediction for scheduled abdominal aortic aneurysm repair with an independent calculator using only pre-operative variables.

    PubMed

    Carlisle, J B; Danjoux, G; Kerr, K; Snowden, C; Swart, M

    2015-06-01

    We observed survival after scheduled repair of abdominal aortic aneurysm in 1096 patients for a median (IQR [range]) of 3.0 (1.5-5.8 [0-15]) years: 943 patients had complete data, 250 of whom died. We compared discrimination and calibration of an external model with the Kaplan-Meier model generated from the study data. Integrated Brier misclassification scores for both models at 1-5 postoperative years were 0.04, 0.08, 0.11, 0.13 and 0.16, respectively. Harrel's concordance index at 1-5 postoperative years was 0.73, 0.71, 0.68, 0.67 and 0.66, respectively. Groups with median 5-year predicted mortality of 40% (n = 251), 18% (n = 414) and 8% (n = 164) had lower observed mortality than 114 patients with 70% predicted mortality, hazard ratio (95% CI): 0.58 (0.37-0.76), p = 0.0031; 0.30 (0.19-0.48), p = 1.7 × 10(-12) and 0.19 (0.13-0.27), p = 1.3 × 10(-10) , respectively, test for trend p = 5.6 × 10(-15) . Survival predicted by the external calculator was similar to the Kaplan-Meier estimate.

  8. Impact of local surgical treatment on survival in young women with T1 breast cancer: long-term results of a population-based cohort.

    PubMed

    Jeon, Ye Won; Choi, Jung Eun; Park, Heung Kyu; Kim, Ku Sang; Lee, Jee Yeon; Suh, Young Jin

    2013-04-01

    The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0-131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750-1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620-1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982-2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755-2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy. PMID:23456232

  9. Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

    SciTech Connect

    Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

    2003-02-24

    As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.

  10. Peritoneal solitary fibrous tumour (SFT): long-term survival of recurrent and metastasised SFT treated with cytoreductive surgery and intraperitoneal chemotherapy.

    PubMed

    Peixoto Callejo, Isabel

    2009-04-01

    This study reports a case of a SFT of the peritoneum in a 44-year-old white man that recurred 3 years after the initial surgical removal of the tumour. The patient recurred diffusely, developing a pattern of sarcomatosis and hepatic metastasis and was treated by surgical cytoreduction followed by intraoperative peritoneal hyperthermic chemotherapy (IPHC). Subsequently, he developed pulmonary metastases and was treated with palliative chemotherapy. The patient persisted with recurrent and distant disease, although it was reduced and stabilised, allowing his survival for the last 3 years since the extended surgery. New treatment strategies for a rare disease such as this one have first to be described in order to improve patient follow-up.

  11. A long-term mesocosm study on the settlement and survival of juvenile European lobster Homarus gammarus L. in four natural substrata.

    PubMed

    Linnane; Mazzoni; Mercer

    2000-06-01

    To date, the natural substratum preferences of early benthic phase (EBP) European lobsters (Homarus gammarus) remain largely unknown. This study utilised a large scale mesocosm experiment to determine if the animal favours cobble ground, similar to its American counterpart (Homarus americanus), or has other substratum preferences. Postlarvae were provided with the choice of settling on four natural substrata: sand, coralline algae, mussel shell and cobble. Over a nine month period, the number and size of juveniles on each substratum was recorded, with loss of chelipeds used as an indication of social interaction. After a 30 day period, a non-random distribution of lobsters was observed on the four substrata. Juveniles were more abundant in substrata which provided pre-existing shelter in the form of interstitial spaces, i.e. cobble and mussel shell, than in sand or coralline algae. The survival of individuals from postlarvae to 30 day old juveniles ranged from 5 to 14% with surviving benthic recruits showing a clear mode at 6-8 mm carapace length (CL) in size distribution. The density of lobsters per m(2) of cobble remained relatively constant (18/m(2)) throughout the study period while the density of juveniles on mussel shell decreased significantly (35 to 5/m(2)). The size distribution of lobsters on each substratum also varied with time. By the conclusion of the trial, lobsters found in mussel shell had a mode of 8-10 mm CL within a range of 6-14 mm CL while those in cobble had a mode of 10-12 mm CL within a range of 8-24 mm CL. Overall, the results underline the importance of shelter-providing habitat such as cobble or crevice-type substrata to EBP European lobsters. They also confirm that for a shelter-dwelling animal such as a lobster, the physical structure of the habitat is a key factor in determining both the size and number of its inhabitants. PMID:10817827

  12. Impact of combined pulmonary fibrosis and emphysema on surgical complications and long-term survival in patients undergoing surgery for non-small-cell lung cancer

    PubMed Central

    Hata, Atsushi; Sekine, Yasuo; Kota, Ohashi; Koh, Eitetsu; Yoshino, Ichiro

    2016-01-01

    Purpose The outcome of radical surgery for lung cancer was investigated in patients with combined pulmonary fibrosis and emphysema (CPFE). Methods A retrospective chart review involved 250 patients with lung cancer who underwent pulmonary resection at Tokyo Women’s Medical University Yachiyo Medical Center between 2008 and 2012. Based on the status of nontumor-bearing lung evaluated by preoperative computed tomography (CT), the patients were divided into normal, emphysema, interstitial pneumonia (IP), and CPFE groups, and their clinical characteristics and surgical outcome were analyzed. Results The normal, emphysema, IP, and CPFE groups comprised 124 (49.6%), 108 (43.2%), seven (2.8%), and eleven (4.4%) patients, respectively. The 5-year survival rate of the CPFE group (18.7%) was significantly lower than that of the normal (77.5%) and emphysema groups (67.1%) (P<0.0001 and P=0.0027, respectively) but equivalent to that of the IP group (44.4%) (P=0.2928). In a subset analysis of cancer stage, the 5-year overall survival rate of the CPFE group in stage I (n=8, 21.4%) was also lower than that of the normal group and emphysema group in stage I (n=91, 84.9% and n=70, 81.1%; P<0.0001 and P<0.0001, respectively). During entire observation period, the CPFE group was more likely to die of respiratory failure (27.2%) compared with the normal and emphysema groups (P<0.0001). Multivariate analysis of prognostic factors using Cox proportional hazard model identified CPFE as an independent risk factor (P=0.009). Conclusion CPFE patients have a poorer prognosis than those with emphysema alone or with normal lung on CT finding. The intensive evaluation of preoperative CT images is important, and radical surgery for lung cancer should be decided carefully when patients concomitantly harbor CPFE, because of unfavorable prognosis. PMID:27354784

  13. Long-term data reveal a population decline of the tropical lizard Anolis apletophallus, and a negative affect of el nino years on population growth rate.

    PubMed

    Stapley, Jessica; Garcia, Milton; Andrews, Robin M

    2015-01-01

    Climate change threatens biodiversity worldwide, however predicting how particular species will respond is difficult because climate varies spatially, complex factors regulate population abundance, and species vary in their susceptibility to climate change. Studies need to incorporate these factors with long-term data in order to link climate change to population abundance. We used 40 years of lizard abundance data and local climate data from Barro Colorado Island to ask how climate, total lizard abundance and cohort-specific abundance have changed over time, and how total and cohort-specific abundance relate to climate variables including those predicted to make the species vulnerable to climate change (i.e. temperatures exceeding preferred body temperature). We documented a decrease in lizard abundance over the last 40 years, and changes in the local climate. Population growth rate was related to the previous years' southern oscillation index; increasing following cooler-wetter, la niña years, decreasing following warmer-drier, el nino years. Within-year recruitment was negatively related to rainfall and minimum temperature. This study simultaneously identified climatic factors driving long-term population fluctuations and climate variables influencing short-term annual recruitment, both of which may be contributing to the population decline and influence the population's future persistence.

  14. A Limited Antigen-Specific Cellular Response Is Sufficient for the Early Control of Mycobacterium tuberculosis in the Lung but Is Insufficient for Long-Term Survival

    PubMed Central

    Turner, Joanne; Dobos, Karen M.; Keen, Marc A; Frank, Anthony A.; Ehlers, Stefan; Orme, Ian M.; Belisle, John T.; Cooper, Andrea M.

    2004-01-01

    Mice that were transgenic for a T-cell receptor (TCR) specific for ovalbumin peptide323-339 (DO11.10) were able to survive an infection with Mycobacterium tuberculosis for approximately 80 days. This limited early control of infection was associated with gamma interferon production, inducible nitric oxide synthase expression within the lung, and an influx of clonotypic lymphocytes. The control of M. tuberculosis was lost in DO11.10 mice bred in a rag mutant background, demonstrating that the immune responsiveness was recombinase dependent and likely to be associated with the expression of an alternative α TCR by DO11.10 mice. A characterization of the antigen specificity in DO11.10 TCR transgenic mice demonstrated that the specificity was limited and dominated by the 26-kDa (Rv1411c) lipoprotein of M. tuberculosis. This study identifies this lipoprotein as an important and potent inducer of protective T cells within the lungs of mice infected with M. tuberculosis and therefore as a possible target for vaccination. PMID:15213116

  15. Predicting future threats to the long-term survival of Gila Trout using a high-resolution simulation of climate change

    SciTech Connect

    Kennedy, Thomas L.; Gutzler, David S.; Leung, Lai R.

    2008-11-20

    Regional climates are a major factor in determining the distribution of many species. Anthropogenic inputs of greenhouse gases into the atmosphere have been predicted to cause rapid climatic changes in the next 50-100 years. Species such as the Gila Trout (Onchorhynchus gilae) that have small ranges, limited dispersal capabilities, and narrow physiological tolerances will become increasingly susceptible to extinction as their climate envelope changes. This study uses a regional climate change simulation (Leung et al. 2004) to determine changes in the climate envelope for Gila Trout, which is sensitive to maximum temperature, associated with a plausible scenario for greenhouse gas increases. The model predicts approximately a 2° C increase in temperature and a doubling by the mid 21st Century in the annual number of days during which temperature exceeds 37°C, and a 25% increase in the number of days above 32°C, across the current geographical range of Gila Trout. At the same time summer rainfall decreases by more than 20%. These climate changes would reduce their available habitat by decreasing the size of their climate envelope. Warmer temperatures coupled with a decrease in summer precipitation would also tend to increase the intensity and frequency of forest fires that are a major threat to their survival. The climate envelope approach utilized here could be used to assess climate change threats to other rare species with limited ranges and dispersal capabilities.

  16. Long-term survival of a patient with small cell carcinoma of the stomach with metachronous lung metastases treated by multimodal therapy: a case report.

    PubMed

    Aoyagi, Keishiro; Kizaki, Junya; Isobe, Taro; Akagi, Yoshito

    2015-12-01

    A 69-year-old man was referred to our institution for treatment of gastric cancer. Type 2 gastric cancer was found on the anterior wall of the lower body of the stomach.The patient underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction with curative resection. The tumor was diagnosed as a small cell carcinoma of the stomach. Recurrence occurred in the lung after surgery. The patient underwent several chemoradiation therapy regimens, including cisplatin + irinotecan + radiation, S-1 + paclitaxel, amrubicin, carboplatin + etoposide, nogitecan, and docetaxel for lung metastases and radiation for brain and bone metastases for 43 months. He finally died of brain metastases 74 months after surgery (47 months after recognition of the lung metastases). Long continuous multimodal treatment including surgery, regimens for small cell lung cancer, S-1, taxanes, and radiation was thought to prolong the survival of this man with small cell carcinoma of the stomach. PMID:26943449

  17. The use of contrast media in deceased kidney donors does not affect initial graft function or graft survival.

    PubMed

    Vigneau, C; Fulgencio, J-P; Godier, A; Chalem, Y; El Metaoua, S; Rondeau, E; Tuppin, P; Bonnet, F

    2006-09-01

    Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival according to the method used to diagnose brain death. Data from 9921 cadaveric kidneys, transplanted between 1 January 1998 and 31 December 2003, were retrieved from the French National Registry for organ donation. We defined RFR as the number of days for the recipient to reach a plasma creatinine less than 250 mumol/l, and/or a 24-h urine output greater than 1000 ml. RFR and 1-year and long-term graft survival were compared between four different donor groups (according to ICMI and diabetes mellitus). A total of 41.5% of deceased donors received ICMI before organ procurement and 1.95% of them were diabetic. History of ICMI or diabetes in the donor did not influence RFR or 1-year graft survival. Long-term graft survival was decreased in the group of patients transplanted with a diabetic graft as compared to patients transplanted with a non-diabetic graft (P=0.001). History of ICMI in the donor did not affect long-term graft survival in the non-diabetic donor group (P=0.2); however, in the diabetic group, ICMI tended to decrease long-term graft survival (P=0.056). ICMI did not affect RFR or graft survival in non-diabetic deceased donors. However, its use in diabetic deceased donors requires further study.

  18. Anti-CD45 Pretargeted Radioimmunotherapy using Bismuth-213: High Rates of Complete Remission and Long-Term Survival in a Mouse Myeloid Leukemia Xenograft Model

    SciTech Connect

    Pagel, John M; Kenoyer, Aimee L; Back, Tom; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Park, Steven I; Frayo, Shani; Axtman, Amanda; Orgun, Nural; Orozoco, Johnnie; Shenoi, Jaideep; Lin, Yukang; Gopal, Ajay K; Green, Damian J; Appelbaum, Frederick R; Press, Oliver W

    2011-07-21

    Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path-length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with Acute Myeloid Leukemia (AML). Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5 ± 1.1% of the injected dose of 213Bi was delivered per gram of tumor. α imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of 213Bi- or 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for >100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of AML.

  19. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study.

    PubMed

    Park, Jun Seok; Sakai, Yoshiharu; Simon, Ng Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-05-01

    Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer.An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate.The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively.Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer.

  20. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study.

    PubMed

    Park, Jun Seok; Sakai, Yoshiharu; Simon, Ng Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-05-01

    Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer.An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate.The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively.Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  1. Long-term effect of the North Carolina graduated driver licensing system on licensed driver crash incidence: a 5-year survival analysis.

    PubMed

    Masten, Scott V; Foss, Robert D

    2010-11-01

    Several studies document the success of graduated driver licensing (GDL) systems in reducing young teen crash rates, but it is not yet clear whether any portion of the crash reduction is achieved by producing more capable drivers. The purpose of this study was to determine whether young teen drivers licensed under the North Carolina GDL system remain crash-free longer than those licensed prior to GDL, independent of the crude reductions in exposure (i.e., decreasing and delaying licensure) that may be responsible for most documented effects of GDL. Survival analysis was used to compare retrospective cohorts of 16-17 year olds before (n=105,569) and after (n=327,054) the North Carolina GDL system was implemented. The crash incidence of GDL-licensed 16-17 year olds (combined) was 10% lower than that for pre-GDL teens for at least 5 years after being licensed to drive independently (hazard ratio [HR]=0.90; 95% confidence interval [CI]=0.89, 0.91). However, more refined analysis revealed the reductions to only be among females (7%; HR=0.93; CI=0.91, 0.94) and males (15%; HR=0.85, CI=0.84, 0.87) licensed at age 16 and not among females (0%; HR=1.00; CI=0.95, 1.06) and males (0%; HR=1.00; CI=0.92, 1.09) licensed at age 17. Sixteen-year-old drivers licensed under the North Carolina GDL system experienced lower first-crash incidence during the first 5 years of unsupervised driving than did those licensed under the previous system. The benefits are greater for males, who tend to have higher crash rates. The findings contradict conventional wisdom that the entire benefit of GDL results merely from decreasing or delaying licensure among young drivers.

  2. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

    PubMed Central

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B

    2016-01-01

    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  3. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  4. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  5. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  6. Concentration-Dependent Effects of Rhodiola Rosea on Long-Term Survival and Stress Resistance of Yeast Saccharomyces Cerevisiae: The Involvement of YAP 1 and MSN2/4 Regulatory Proteins.

    PubMed

    Bayliak, Maria M; Burdyliuk, Nadia I; Izers'ka, Lilia I; Lushchak, Volodymyr I

    2014-01-01

    Concentration-dependent effects of aqueous extract from R. rosea root on long-term survival and stress resistance of budding yeast Saccharomyces cerevisiae were studied. At low concentrations, R. rosea aqueous extract extended yeast chronological lifespan, enhanced oxidative stress resistance of stationary-phase cells and resistance to number stressors in exponentially growing cultures. At high concentrations, R. rosea extract sensitized yeast cells to stresses and shortened yeast lifespan. These biphasic concentration-responses describe a common hormetic phenomenon characterized by a low-dose stimulation and a high-dose inhibition. Yeast pretreatment with low doses of R. rosea extract enhanced yeast survival and prevented protein oxidation under H2O2-induced oxidative stress. Positive effect of R. rosea extract on yeast survival under heat shock exposure was not accompanied with changes in antioxidant enzyme activities and levels of oxidized proteins. The deficiency in transcriptional regulators, Msn2/Msn4 and Yap1, abolished the positive effect of low doses of R. rosea extract on yeast viability under stress challenges. Potential involvement of Msn2/Msn4 and Yap1 regulatory proteins in realization of R. rosea beneficial effects is discussed.

  7. Focal Radiation Therapy Combined with 4-1BB Activation and CTLA-4 Blockade Yields Long-Term Survival and a Protective Antigen-Specific Memory Response in a Murine Glioma Model

    PubMed Central

    Belcaid, Zineb; Phallen, Jillian A.; Zeng, Jing; See, Alfred P.; Mathios, Dimitrios; Gottschalk, Chelsea; Nicholas, Sarah; Kellett, Meghan; Ruzevick, Jacob; Jackson, Christopher; Albesiano, Emilia; Durham, Nicholas M.; Ye, Xiaobu; Tran, Phuoc T.; Tyler, Betty; Wong, John W.; Brem, Henry; Pardoll, Drew M.; Drake, Charles G.; Lim, Michael

    2014-01-01

    Background Glioblastoma (GBM) is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4) blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137) is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model. Methods GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors. Results Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response. Conclusion Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in

  8. Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease.

    PubMed

    Chiu, W-H; Depboylu, C; Hermanns, G; Maurer, L; Windolph, A; Oertel, W H; Ries, V; Höglinger, G U

    2015-08-01

    Non-motor symptoms such as hyposmia and depression are often observed in Parkinson's disease (PD) and can precede the onset of motor symptoms for years. The underlying pathological alterations in the brain are not fully understood so far. Dysregulation of adult neurogenesis in the dentate gyrus of the hippocampus and the olfactory bulb has been recently suggested to be implicated in non-motor symptoms of PD. However, there is so far no direct evidence to support the relationship of non-motor symptoms and the modulation of adult neurogenesis following dopamine depletion and/or dopamine replacement. In this study, we investigated the long-term effects of l-DOPA and pramipexole, a dopamine agonist, in a mouse model of bilateral intranigral 6-OHDA lesion, in order to assess the impact of adult neurogenesis on non-motor behavior. We found that l-DOPA and pramipexole can normalize decreased neurogenesis in the hippocampal dentate gyrus and the periglomerular layer of the olfactory bulb caused by a 6-OHDA lesion. Interestingly, pramipexole showed an antidepressant and anxiolytic effect in the forced swim test and social interaction test. However, there was no significant change in learning and memory function after dopamine depletion and dopamine replacement, respectively.

  9. Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease.

    PubMed

    Chiu, W-H; Depboylu, C; Hermanns, G; Maurer, L; Windolph, A; Oertel, W H; Ries, V; Höglinger, G U

    2015-08-01

    Non-motor symptoms such as hyposmia and depression are often observed in Parkinson's disease (PD) and can precede the onset of motor symptoms for years. The underlying pathological alterations in the brain are not fully understood so far. Dysregulation of adult neurogenesis in the dentate gyrus of the hippocampus and the olfactory bulb has been recently suggested to be implicated in non-motor symptoms of PD. However, there is so far no direct evidence to support the relationship of non-motor symptoms and the modulation of adult neurogenesis following dopamine depletion and/or dopamine replacement. In this study, we investigated the long-term effects of l-DOPA and pramipexole, a dopamine agonist, in a mouse model of bilateral intranigral 6-OHDA lesion, in order to assess the impact of adult neurogenesis on non-motor behavior. We found that l-DOPA and pramipexole can normalize decreased neurogenesis in the hippocampal dentate gyrus and the periglomerular layer of the olfactory bulb caused by a 6-OHDA lesion. Interestingly, pramipexole showed an antidepressant and anxiolytic effect in the forced swim test and social interaction test. However, there was no significant change in learning and memory function after dopamine depletion and dopamine replacement, respectively. PMID:25839898

  10. Out of sight - Profiling soil characteristics, nutrients and microbial communities affected by organic amendments down to one meter in a long-term maize cultivation experiment

    NASA Astrophysics Data System (ADS)

    Lehtinen, Taru; Mikkonen, Anu; Zavattaro, Laura; Grignani, Carlo; Baumgarten, Andreas; Spiegel, Heide

    2016-04-01

    Soil characteristics, nutrients and microbial activity in the deeper soil layers are topics not of-ten covered in agricultural studies since the main interest lies within the most active topsoils and deep soils are more time-consuming to sample. Studies have shown that deep soil does matter, although biogeochemical cycles are not fully understood yet. The main aim of this study is to investigate the soil organic matter dynamics, nutrients and microbial community composition in the first meter of the soil profiles in the long-term maize cropping system ex-periment Tetto Frati, in the vicinity of the Po River in Northern Italy. The trial site lies on a deep, calcareous, free-draining soil with a loamy texture. The following treatments have been applied since 1992: 1) maize for silage with 250 kg mineral N ha-1 (crop residue removal, CRR), 2) maize for grain with 250 kg mineral N ha-1 (crop residue incorporation, CRI), 3) maize for silage with 250 kg bovine slurry N ha-1 (SLU), 4) maize for silage with 250 kg farm yard manure N ha-1 (FYM). Soil characteristics (pH, carbonate content, soil organic carbon (SOC), aggregate stability (WSA)), and nutrients (total nitrogen (Nt), CAL-extractable phos-phorous (P) and potassium (K), potential N mineralisation) were investigated. Bacteri-al community composition was investigated with Ion PGM high-throughput sequencing at the depth of 8000 sequences per sample. Soil pH was moderately alkaline in all soil samples, in-creasing with increasing soil depth, as the carbonate content increased. SOC was significantly higher in the treatments with organic amendments (CRI, SLU and FYM) compared to CRR in 0-25 cm (11.1, 11.6, 14.7 vs. 9.8 g kg-1, respectively), but not in the deeper soil. At 50-75 cm soil depth FYM treatment revealed higher WSA compared to CRR, as well as higher CAL-extractable K (25 and 15 mg kg-1, respectively) and potential N mineralisation (11.30 and 8.78 mg N kg-1 7d-1, respectively). At 75-100 cm soil depth, SLU and

  11. Variable wind, pack ice, and prey dispersion affect the long-term adequacy of protected areas for an Arctic sea duck.

    PubMed

    Lovvorn, James R; Anderson, Eric M; Rocha, Aariel R; Larned, William W; Grebmeier, Jacqueline M; Cooper, Lee W; Kolts, Jason M; North, Christopher A

    2014-03-01

    With changing climate, delineation of protected areas for sensitive species must account for long-term variability and geographic shifts of key habitat elements. Projecting the future adequacy of protected areas requires knowing major factors that drive such changes, and how readily the animals adjust to altered resources. In the Arctic, the viability of habitats for marine birds and mammals often depends on sea ice to dissipate storm waves and provide platforms for resting. However, some wind conditions (including weak winds during extreme cold) can consolidate pack ice into cover so dense that air-breathing divers are excluded from the better feeding areas. Spectacled Eiders (Somateria fischeri) winter among leads (openings) in pack ice in areas where densities of their bivalve prey are quite high. During winter 2009, however, prevailing winds created a large region of continuous ice with inadequate leads to allow access to areas of dense preferred prey. Stable isotope and fatty acid biomarkers indicated that, under these conditions, the eiders did not diversify their diet to include abundant non-bivalve taxa but did add a smaller, less preferred, bivalve species. Consistent with a computer model of eider energy balance, the body fat of adult eiders in 2009 was 33-35% lower than on the same date (19 March) in 2001 when ice conditions allowed access to higher bivalve densities. Ice cover data suggest that the eiders were mostly excluded from areas of high bivalve density from January to March in about 30% of 14 winters from 1998 to 2011. Thus, even without change in total extent of ice, shifts in prevailing winds can alter the areal density of ice to reduce access to important habitats. Because changes in wind-driven currents can also rearrange the dispersion of prey, the potential for altered wind patterns should be an important concern in projecting effects of climate change on the adequacy of marine protected areas for diving endotherms in the Arctic. PMID

  12. Variable wind, pack ice, and prey dispersion affect the long-term adequacy of protected areas for an Arctic sea duck.

    PubMed

    Lovvorn, James R; Anderson, Eric M; Rocha, Aariel R; Larned, William W; Grebmeier, Jacqueline M; Cooper, Lee W; Kolts, Jason M; North, Christopher A

    2014-03-01

    With changing climate, delineation of protected areas for sensitive species must account for long-term variability and geographic shifts of key habitat elements. Projecting the future adequacy of protected areas requires knowing major factors that drive such changes, and how readily the animals adjust to altered resources. In the Arctic, the viability of habitats for marine birds and mammals often depends on sea ice to dissipate storm waves and provide platforms for resting. However, some wind conditions (including weak winds during extreme cold) can consolidate pack ice into cover so dense that air-breathing divers are excluded from the better feeding areas. Spectacled Eiders (Somateria fischeri) winter among leads (openings) in pack ice in areas where densities of their bivalve prey are quite high. During winter 2009, however, prevailing winds created a large region of continuous ice with inadequate leads to allow access to areas of dense preferred prey. Stable isotope and fatty acid biomarkers indicated that, under these conditions, the eiders did not diversify their diet to include abundant non-bivalve taxa but did add a smaller, less preferred, bivalve species. Consistent with a computer model of eider energy balance, the body fat of adult eiders in 2009 was 33-35% lower than on the same date (19 March) in 2001 when ice conditions allowed access to higher bivalve densities. Ice cover data suggest that the eiders were mostly excluded from areas of high bivalve density from January to March in about 30% of 14 winters from 1998 to 2011. Thus, even without change in total extent of ice, shifts in prevailing winds can alter the areal density of ice to reduce access to important habitats. Because changes in wind-driven currents can also rearrange the dispersion of prey, the potential for altered wind patterns should be an important concern in projecting effects of climate change on the adequacy of marine protected areas for diving endotherms in the Arctic.

  13. Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice.

    PubMed

    Baca, Michael; Allan, Andrea M; Partridge, L Donald; Wilson, Michael C

    2013-09-26

    Genes and environmental conditions interact in the development of cognitive capacities and each plays an important role in neuropsychiatric disorders such as attention deficit/hyperactivity disorder (ADHD) and schizophrenia. Multiple studies have indicated that the gene for the SNARE protein SNAP-25 is a candidate susceptibility gene for ADHD, as well as schizophrenia, while maternal smoking is a candidate environmental risk factor for ADHD. We utilized mice heterozygous for a Snap25 null allele and deficient in SNAP-25 expression to model genetic effects in combination with prenatal exposure to nicotine to explore genetic and environmental interactions in synaptic plasticity and behavior. We show that SNAP-25 deficient mice exposed to prenatal nicotine exhibit hyperactivity and deficits in social interaction. Using a high frequency stimulus electrophysiological paradigm for long-term depression (LTD) induction, we examined the roles of dopaminergic D2 receptors (D2Rs) and cannabinoid CB1 receptors (CB1Rs), both critical for LTD induction in the striatum. We found that prenatal exposure to nicotine in Snap25 heterozygote null mice produced a deficit in the D2R-dependent induction of LTD, although CB1R regulation of plasticity was not impaired. We also show that prenatal nicotine exposure altered the affinity and/or receptor coupling of D2Rs, but not the number of these receptors in heterozygote null Snap25 mutants. These results refine the observations made in the coloboma mouse mutant, a proposed mouse model of ADHD, and illustrate how gene×environmental influences can interact to perturb neural functions that regulate behavior.

  14. Long-term, six-dimensional live-cell imaging for the mouse preimplantation embryo that does not affect full-term development.

    PubMed

    Yamagata, Kazuo; Suetsugu, Rinako; Wakayama, Teruhiko

    2009-06-01

    Mammalian preimplantation embryonic development is achieved by tightly coordinated regulation of a great variety of temporal and spatial changes. Therefore, it would be valuable to analyze these events three-dimensionally and dynamically. We have previously developed a live-cell imaging method based on the expression of fluorescent proteins, using mRNA injection and time-lapse florescence microscopy. However, with conventional fluorescent microscopy, three-dimensional images could not be obtained due to the thickness of the embryos and the optical problem in which ;out-of focus blur' cannot be eliminated. Moreover, as the repeated exposure of intense excitation light to the cell yields phototoxicity, long-term observation was detrimental to embryonic development. Here, we improved our imaging system to enable six-dimensional live-cell imaging of mouse preimplantation embryos (x, y and z axes, time-lapse, multicolor and multisample). Importantly, by improving the imaging devices and optimizing the conditions for imaging, such as intensity of excitation and time intervals for image acquisition, the procedure itself was not detrimental to full-term development, although it is a prolonged imaging process. For example, live pups were obtained from embryos to which two different wavelengths of excitation (488 and 561 nm) were applied at 7.5-min intervals for about 70 h, and 51 images were acquired in the z axis at each time point; thus, a total of 56,814 fluorescent images were taken. All the pups were healthy, reproductively normal and not transgenic. Thus, this live-cell imaging technology is safe for full-term mouse development. This offers a novel approach for developmental and reproductive research in that it enables both retrospective and prospective analyses of development. It might also be applicable to assessment of embryo quality in fields such as human reproductive technology and production animal research.

  15. Developmental Associations between Short-Term Variability and Long-Term Changes: Intraindividual Correlation of Positive and Negative Affect in Daily Life and Cognitive Aging

    ERIC Educational Resources Information Center

    Hülür, Gizem; Hoppmann, Christiane A.; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    Conceptual notions and empirical evidence suggest that the intraindividual correlation (iCorr) of positive affect (PA) and negative affect (NA) is a meaningful characteristic of affective functioning. PA and NA are typically negatively correlated within-person. Previous research has found that the iCorr of PA and NA is relatively stable over time…

  16. Long term complications of diabetes

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000327.htm Long term complications of diabetes To use the sharing ... sores and infections. If it goes on too long, your toes, foot, or leg may need to ...

  17. Abdominal Pain, Long-Term

    MedlinePlus

    MENU Return to Web version Abdominal Pain, Long-term See complete list of charts. Ongoing or recurrent abdominal pain, also called chronic pain, may be difficult to diagnose, causing frustration for ...

  18. Long-term biomass research

    SciTech Connect

    Not Available

    1981-03-01

    Some of DOE's long term R and D programs for biomass are summarized in this article. These include research efforts in the fields of anaerobic digestion, energy farming, short rotation cultivation and aquatic farming. (DMC)

  19. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  20. [Taiwan long-term care insurance and the evolution of long-term care in Japan].

    PubMed

    Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu

    2010-08-01

    The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

  1. Environmental and Genetic Preconditioning for Long-Term Anoxia Responses Requires AMPK in Caenorhabditis elegans

    PubMed Central

    LaRue, Bobby L.; Padilla, Pamela A.

    2011-01-01

    Background Preconditioning environments or therapeutics, to suppress the cellular damage associated with severe oxygen deprivation, is of interest to our understanding of diseases associated with oxygen deprivation. Wildtype C. elegans exposed to anoxia enter into a state of suspended animation in which energy-requiring processes reversibly arrest. C. elegans at all developmental stages survive 24-hours of anoxia exposure however, the ability of adult hermaphrodites to survive three days of anoxia significantly decreases. Mutations in the insulin-like signaling receptor (daf-2) and LIN-12/Notch (glp-1) lead to an enhanced long-term anoxia survival phenotype. Methodology/Principal Findings In this study we show that the combined growth environment of 25°C and a diet of HT115 E. coli will precondition adult hermaphrodites to survive long-term anoxia; many of these survivors have normal movement after anoxia treatment. Animals fed the drug metformin, which induces a dietary-restriction like state in animals and activates AMPK in mammalian cell culture, have a higher survival rate when exposed to long-term anoxia. Mutations in genes encoding components of AMPK (aak-2, aakb-1, aakb-2, aakg-2) suppress the environmentally and genetically induced long-term anoxia survival phenotype. We further determine that there is a correlation between the animals that survive long-term anoxia and increased levels of carminic acid staining, which is a fluorescent dye that incorporates in with carbohydrates such as glycogen. Conclusions/Significance We conclude that small changes in growth conditions such as increased temperature and food source can influence the physiology of the animal thus affecting the responses to stress such as anoxia. Furthermore, this supports the idea that metformin should be further investigated as a therapeutic tool for treatment of oxygen-deprived tissues. Finally, the capacity for an animal to survive long bouts of severe oxygen deprivation is likely

  2. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  3. Factors affecting survival following radical mastectomy.

    PubMed

    Freund, H; Grover, N B; Durst, A L

    1978-01-01

    Data on 17 potentially useful factors from 152 women undergoing radical mastectomy for operable breast cancer were analyzed in order to determine the effect of each on survival and their relative importance. Only four, clinical stage, clinical and pathological lymph node involvement, and appearance of recurrence and metastases, proved to be of significant prognostic value. Axillary nodal involvement was the main single determinant of survival. Multiple regression analysis, based on factor analysis of the original input variables, was able to account for 34% of the variance in survival and is thus of only very limited use as a predictive instrument in the clinical management of prospective patients. PMID:651367

  4. A Case Report of Long-Term Survival following Hepatic Arterial Infusion of L-Folinic Acid Modulated 5-Fluorouracil Combined with Intravenous Irinotecan and Cetuximab Followed by Hepatectomy in a Patient with Initially Unresectable Colorectal Liver Metastases

    PubMed Central

    Van Bael, Kobe; Jansen, Yanina; Seremet, Teofila; Engels, Benedikt; Delvaux, Georges

    2015-01-01

    A 43-year-old women admitted to our hospital for weight loss, anorexia, and abdominal pain was diagnosed with sigmoid neoplasm and multiple bilobar liver metastases. This patient received six cycles of systemic FOLFOX prior to a laparoscopically assisted anterior resection of the rectosigmoid for a poorly differentiated invasive adenocarcinoma T2N2M1, K-RAS negative (wild type). Hepatic arterial infusion (HAI) of L-folinic acid modulated 5-fluorouracil (LV/5-FU) with intravenous (iv) irinotecan (FOLFIRI) and cetuximab as adjuvant therapy resulted in a complete metabolic response (CR) with CEA normalization. A right hepatectomy extended to segment IV was performed resulting in (FDG-)PET negative remission for 7 months. Solitary intrahepatic recurrence was effectively managed by local radiofrequent ablation following 6c FOLFIRI plus cetuximab iv. Multiple lung lesions and recurrence of pulmonary and local lymph node metastases were successfully treated with fractionated stereotactic radiotherapy (50 Gy) and iv LV/5-FU/oxaliplatin (FOLFOX) plus cetuximab finally switched to panitumumab with CR as a result. At present the patient is in persistent complete remission of her stage IV colorectal cancer, more than 5 years after initial diagnosis of the advanced disease. Multidisciplinary treatment with HAI of chemotherapy (LV/5-FU + CPT-11) plus EGFR-inhibitor can achieve CR of complex unresectable LM and can even result in hepatectomy with possible long-term survival. PMID:26064730

  5. Long-Term Treatment Outcomes of Patients Infected With Hepatitis C Virus: A Systematic Review and Meta-analysis of the Survival Benefit of Achieving a Sustained Virological Response

    PubMed Central

    Simmons, Bryony; Saleem, Jawaad; Heath, Katherine; Cooke, Graham S.; Hill, Andrew

    2015-01-01

    Background. Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with nonresponders in a range of populations. Methods. An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and populations coinfected with human immunodeficiency virus. The adjusted hazard ratio (95% confidence interval [CI]) for mortality in patients achieving SVR vs non-SVR, and pooled estimates for the 5-year mortality in each group were calculated. Results. 31 studies (n = 33 360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (interquartile range, 4.9–7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR vs non-SVR was 0.50 (95% CI, .37–.67) in the general population, 0.26 (95% CI, .18–.74) in the cirrhotic group, and 0.21 (.10–.45) in the coinfected group. The pooled 5-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all 3 populations. Conclusions. The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of populations infected with hepatitis C virus. PMID:25987643

  6. Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

    PubMed

    Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

    2013-01-01

    In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

  7. Long-term Survival Outcomes Following Internal Mammary Node Irradiation in Stage II-III Breast Cancer: Results of a Large Retrospective Study With 12-Year Follow-up

    SciTech Connect

    Chang, Jee Suk; Park, Won; Kim, Yong Bae; Lee, Ik Jae; Keum, Ki Chang; Lee, Chang Geol; Choi, Doo Ho; Suh, Chang-Ok; Huh, Seung Jae

    2013-08-01

    Purpose: To examine the effect of internal mammary node irradiation (IMNI) on disease-free survival (DFS) and overall survival (OS) in breast cancer patients treated with modified radical mastectomy and postoperative radiation therapy. Methods and Materials: Between 1994 and 2002, 396 patients with stage II-III breast cancer were treated with postmastectomy radiation therapy with (n=197) or without (n=199) IMNI. Patients who received neoadjuvant chemotherapy were excluded. IMNI was administered at the clinical discretion of the treating physician. Median RT dose was 50.4 Gy (range, 45.0-59.4 Gy) in 28 fractions, with inclusion of the supraclavicular fossa in 96% of patients. Adjuvant chemotherapy was administered to 99.7% of the patients and endocrine therapy to 53%. Results: The median follow-up was 149 months (range, 124-202). IMNI patients had more advanced nodal stage and non-high grade tumors than those without IMNI (P<.001). Otherwise, disease and treatment characteristics were well balanced. The 10-year DFS with and without IMNI was 65% and 57%, respectively (P=.05). Multivariate analysis demonstrated that IMNI was an independent, positive predictor of DFS (hazard ratio [HR], 0.70; P=.02). Benefits of IMNI in DFS were seen most apparently in N2 patients (HR, 0.44; 95% confidence interval [CI], 0.26-0.74) and inner/central tumors (HR, 0.55; 95% CI, 0.34-0.90). The 10-year OS with and without IMNI was 72% and 66%, respectively (P=.62). The 10-year DFS and OS were 61%, and 69%, respectively. Conclusions: Internal mammary node irradiation significantly improved DFS in postmastectomy breast cancer patients. Pending long-term results from randomized trials, treatment of internal mammary nodes should be considered in postmastectomy radiation therapy.

  8. Myeloablative Anti-CD20 Radioimmunotherapy +/- High-Dose Chemotherapy Followed by Autologous Stem Cell Support for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival

    PubMed Central

    Schreiber, Susanne; Schmidt, Burkhard; Wester, Hans-Jürgen; Schwaiger, Markus; Peschel, Christian; von Schilling, Christoph

    2013-01-01

    Background Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival. Methods Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (131I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine 131I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years. Results 6.956-19.425GBq of 131I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS. Conclusion Myeloablative RIT with 131I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging. PMID:23765188

  9. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Gettinger, Scott N.; Horn, Leora; Gandhi, Leena; Spigel, David R.; Antonia, Scott J.; Rizvi, Naiyer A.; Powderly, John D.; Heist, Rebecca S.; Carvajal, Richard D.; Jackman, David M.; Sequist, Lecia V.; Smith, David C.; Leming, Philip; Carbone, David P.; Pinder-Schenck, Mary C.; Topalian, Suzanne L.; Hodi, F. Stephen; Sosman, Jeffrey A.; Sznol, Mario; McDermott, David F.; Pardoll, Drew M.; Sankar, Vindira; Ahlers, Christoph M.; Salvati, Mark; Wigginton, Jon M.; Hellmann, Matthew D.; Kollia, Georgia D.; Gupta, Ashok K.; Brahmer, Julie R.

    2015-01-01

    Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non–small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients and Methods Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Results Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Conclusion Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing. PMID:25897158

  10. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    PubMed

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting. PMID:10613451

  11. Do governance, equity characteristics, and venture capital nvolvement affect long-term wealth creation in U.S. health care and biotechnology IPOs?

    PubMed

    Williams, David R; Duncan, W Jack; Ginter, Peter M; Shewchuk, Richard M

    2006-01-01

    Agency theory remains the dominant means of examining governance issues and ownership characteristics related to large organizations. Research in these areas within large organizations has increased our understanding, yet little is known about the influence that these mechanisms and characteristics have had on IPO firm performance. This study tests an agency perspective that venture capital involvement, governance and equity characteristics affect health care and biotechnology IPO firm performance. Our results indicate that there is no correlation between these factors and health care and biotechnology IPO wealth creation. For these entrepreneurs, our findings suggest a contingent approach for the use of these mechanisms.

  12. Interfering with post-learning hippocampal activity does not affect long-term consolidation of a context fear memory outside the hippocampus.

    PubMed

    Gulbrandsen, Tine L; Sparks, Fraser T; Sutherland, Robert J

    2013-03-01

    There are still uncertainties about the role of the hippocampus (HPC) in memory consolidation. One theory, systems consolidation, states that the HPC is required for the initial storage of certain memories that subsequently become established in non-HPC networks through a lengthy process, involving an interaction with the HPC. A similar process may underlie the ability of multiple, distributed learning episodes of contextual fear conditioning to create a HPC-independent context fear memory, in a memory task that does not undergo systems consolidation with the mere passage of time [5]. The current study examined whether post-learning HPC activity is necessary to establish these HPC-independent context memories through distributed learning episodes. Rats received either three or six context conditioning sessions over the course of three days. The HPC-dependence of context memories was assessed using multisite, temporary inactivation of the HPC using ropivacaine during retention testing. We established that six conditioning sessions, but not three, created a memory that could be retrieved while the HPC was inactive. To directly test our hypothesis, HPC was inactivated after half of the six context-shock pairings in an independent group of rats. The rats were then tested for retention of context fear in the absence of HPC activity. Post-learning inactivation of the HPC did not affect the establishment of a HPC-independent context memory. These results favor the idea that at least one memory system outside the HPC can acquire context memories independently. PMID:23201356

  13. Temperature affects long-term productivity and quality attributes of day-neutral strawberry for a space life-support system

    NASA Astrophysics Data System (ADS)

    Massa, Gioia D.; Chase, Elaine; Santini, Judith B.; Mitchell, Cary A.

    2015-04-01

    Strawberry (Fragaria x ananassa L.) is a promising candidate crop for space life-support systems with desirable sensory quality and health attributes. Day-neutral cultivars such as 'Seascape' are adaptable to a range of photoperiods, including short days that would save considerable energy for crop lighting without reductions in productivity or yield. Since photoperiod and temperature interact to affect strawberry growth and development, several diurnal temperature regimes were tested under a short photoperiod of 10 h per day for effects on yield and quality attributes of 'Seascape' strawberry during production cycles longer than 270 days. The coolest day/night temperature regime, 16°/8 °C, tended to produce smaller numbers of larger fruit than did the intermediate temperature range of 18°/10 °C or the warmest regime, 20°/12 °C, both of which produced similar larger numbers of smaller fruit. The intermediate temperature regime produced the highest total fresh mass of berries over an entire production cycle. Independent experiments examined either organoleptic or physicochemical quality attributes. Organoleptic evaluation indicated that fruit grown under the coolest temperature regime tended to score the highest for both hedonic preference and descriptive evaluation of sensory attributes related to sweetness, texture, aftertaste, and overall approval. The physicochemical quality attributes Brix, pH, and sugar/acid ratio were highest for fruits harvested from the coolest temperature regime and lower for those from the warmer temperature regimes. The cool-regime fruits also were lowest in titratable acidity. The yield parameters fruit number and size oscillated over the course of a production cycle, with a gradual decline in fruit size under all three temperature regimes. Brix and titratable acidity both decreased over time for all three temperature treatments, but sugar/acid ratio remained highest for the cool temperature regime over the entire production

  14. Drug loading and elution from a phosphorylcholine polymer-coated coronary stent does not affect long-term stability of the coating in vivo.

    PubMed

    Lewis, Andrew L; Willis, Sean L; Small, Sharon A; Hunt, Stuart R; O'byrne, Vincent; Stratford, Peter W

    2004-01-01

    A drug eluting coronary stent was developed for use in preclinical and clinical trial evaluation. The stent was coated with a phosphorylcholine (PC)-based polymer coating containing the cell migration inhibitor batimastat. A pharmacokinetic study was conducted in a rabbit iliac model using (14)C-radiolabeled version of the drug; this showed the drug release to be first order with 94% of it being released within 28 days. Unloaded and drug-loaded stents were implanted in a porcine coronary artery model; a number were explanted at 5 days and scanning electron microscopy was used to show that the presence of the drug did not affect the rate of stent endothelialization. The remainder of the stents were removed after 6 months and the stents carefully removed from the arterial tissue. Fourier-transform infrared (FT-IR) spectroscopy (both attenuated total reflectance and microscopic imaging) was used to show the presence of the PC coating on control unloaded, drug-loaded and explanted stents, providing evidence that the coating was still present. This was further confirmed by use of atomic force microscopy (AFM) amplitude-phase, distance (a-p,d) curves which generated the characteristic traces of the PC coating. Further AFM depth-profiling techniques found that the thicknesses of the PC coatings on an control unloaded stent was 252+/-19 nm, on an control batimastat-loaded stent 906+/-224 nm and on an explanted stent 405+/-224 nm. The increase in thickness after the drug-loading process was a consequence of drug incorporation in the film, and the return to the unloaded dimensions for the explanted sample indicative of elution of the drug from the coating. The drug delivery PC coating was therefore found to be stable following elution of the drug and after 6 months implantation in vivo. PMID:15472385

  15. Impact of hospital type and treatment on long-term survival among patients with FIGO Stage IIIC epithelial ovarian cancer: follow-up through two recurrences and three treatment lines in search for predictors for survival.

    PubMed

    Szczesny, W; Vistad, I; Kaern, J; Nakling, J; Tropé, C; Paulsen, T

    2016-01-01

    The purpose of this study was to investigate the impact of hospital type determined at primary treatment and find possible predictors of survival in a cohort of patients with advanced epithelial ovarian cancer (EOC) who recurred twice and received three lines of treatment during eight-year follow-up. Using the Norwegian Cancer Registry, the authors identified 174 women with FIGO Stage IIIC EOC diagnosed in 2002. First-line treatment consisted of up-front debulking surgery and chemotherapy, received in either a teaching hospital (TH, n = 84) or a non-teaching hospital (NTH, n = 90). After recurrence all patients in Norway are equally consulted at TH. Survival determined for three time intervals (TI): TI-1, from end date of first-line treatment to first recurrence or death, TI-2, from beginning of second-line treatment until second recurrence or death, and TI-3, from beginning of third-line treatment to death or end of follow-up. Extensive surgery carried out in TH followed by at least six cycles of platinol-taxan chemotherapy resulted in longer survival in the TH group during TI-1. Altogether, the majority of those who receive treatment for recurrences were primary better debulked with following platinol-taxane chemotherapy. Survival in TI-2 was influenced by platinol-sensitivity. During TI-3 the majority (96%) had good performance status and their mean age at primary diagnosis at either hospital type was 57 years. Extensive primary surgery at TH, platinol sensitivity, age, and performance status were predictors of survival in this cohort. PMID:27352555

  16. Cushing's syndrome: a structured short- and long-term management plan for patients in remission.

    PubMed

    Ragnarsson, Oskar; Johannsson, Gudmundur

    2013-11-01

    One hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing's syndrome (CS), body composition and lipid, carbohydrate and protein metabolism are dramatically affected and psychopathology and cognitive dysfunction are frequently observed. Untreated patients with CS have a grave prognosis with an estimated 5-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy. Recent data indicate that the adverse metabolic consequences of CS are present for years after successful treatment.In addition, recent studies have demonstrated that health-related quality of life and cognitive function are impaired in patients with CS in long-term remission. The focus of specialised care should therefore be not only on the diagnostic work-up and the early postoperative management but also on the long-term follow-up. In this paper, we review the long-term consequences in patients with CS in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically-treated patients with CS, each phase distinguished by specific challenges: the immediate postoperative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialised care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and detect possible recurrence of CS. PMID:23985132

  17. Temperature affects long-term productivity and quality attributes of day-neutral strawberry for a space life-support system.

    PubMed

    Massa, Gioia D; Chase, Elaine; Santini, Judith B; Mitchell, Cary A

    2015-04-01

    Strawberry (Fragaria x ananassa L.) is a promising candidate crop for space life-support systems with desirable sensory quality and health attributes. Day-neutral cultivars such as 'Seascape' are adaptable to a range of photoperiods, including short days that would save considerable energy for crop lighting without reductions in productivity or yield. Since photoperiod and temperature interact to affect strawberry growth and development, several diurnal temperature regimes were tested under a short photoperiod of 10 h per day for effects on yield and quality attributes of 'Seascape' strawberry during production cycles longer than 270 days. The coolest day/night temperature regime, 16°/8 °C, tended to produce smaller numbers of larger fruit than did the intermediate temperature range of 18°/10 °C or the warmest regime, 20°/12 °C, both of which produced similar larger numbers of smaller fruit. The intermediate temperature regime produced the highest total fresh mass of berries over an entire production cycle. Independent experiments examined either organoleptic or physicochemical quality attributes. Organoleptic evaluation indicated that fruit grown under the coolest temperature regime tended to score the highest for both hedonic preference and descriptive evaluation of sensory attributes related to sweetness, texture, aftertaste, and overall approval. The physicochemical quality attributes Brix, pH, and sugar/acid ratio were highest for fruits harvested from the coolest temperature regime and lower for those from the warmer temperature regimes. The cool-regime fruits also were lowest in titratable acidity. The yield parameters fruit number and size oscillated over the course of a production cycle, with a gradual decline in fruit size under all three temperature regimes. Brix and titratable acidity both decreased over time for all three temperature treatments, but sugar/acid ratio remained highest for the cool temperature regime over the entire production

  18. Temperature affects long-term productivity and quality attributes of day-neutral strawberry for a space life-support system.

    PubMed

    Massa, Gioia D; Chase, Elaine; Santini, Judith B; Mitchell, Cary A

    2015-04-01

    Strawberry (Fragaria x ananassa L.) is a promising candidate crop for space life-support systems with desirable sensory quality and health attributes. Day-neutral cultivars such as 'Seascape' are adaptable to a range of photoperiods, including short days that would save considerable energy for crop lighting without reductions in productivity or yield. Since photoperiod and temperature interact to affect strawberry growth and development, several diurnal temperature regimes were tested under a short photoperiod of 10 h per day for effects on yield and quality attributes of 'Seascape' strawberry during production cycles longer than 270 days. The coolest day/night temperature regime, 16°/8 °C, tended to produce smaller numbers of larger fruit than did the intermediate temperature range of 18°/10 °C or the warmest regime, 20°/12 °C, both of which produced similar larger numbers of smaller fruit. The intermediate temperature regime produced the highest total fresh mass of berries over an entire production cycle. Independent experiments examined either organoleptic or physicochemical quality attributes. Organoleptic evaluation indicated that fruit grown under the coolest temperature regime tended to score the highest for both hedonic preference and descriptive evaluation of sensory attributes related to sweetness, texture, aftertaste, and overall approval. The physicochemical quality attributes Brix, pH, and sugar/acid ratio were highest for fruits harvested from the coolest temperature regime and lower for those from the warmer temperature regimes. The cool-regime fruits also were lowest in titratable acidity. The yield parameters fruit number and size oscillated over the course of a production cycle, with a gradual decline in fruit size under all three temperature regimes. Brix and titratable acidity both decreased over time for all three temperature treatments, but sugar/acid ratio remained highest for the cool temperature regime over the entire production

  19. Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes

    PubMed Central

    Jensen, Line; Gejl, Kasper D; Ørtenblad, Niels; Nielsen, Jakob L; Bech, Rune D; Nygaard, Tobias; Sahlin, Kent; Frandsen, Ulrik

    2015-01-01

    The aim was to determine if the metabolic adaptations, particularly PGC-1α and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg−1·min−1, n = 15) completed 4 h cycling at ∼56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg−1·dw−1) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1α, TFAM, NRF-1, COX-IV, PPAR-α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained. PMID:25677542

  20. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  1. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    SciTech Connect

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  2. High genetic differentiation in the alpine plant Campanula alpina Jacq. (Campanulaceae): evidence for glacial survival in several Carpathian regions and long-term isolation between the Carpathians and the Alps.

    PubMed

    Ronikier, M; Cieślak, E; Korbecka, G

    2008-04-01

    A survey of amplified fragment length polymorphism (AFLP) and chloroplast DNA (cpDNA) variation was conducted to elucidate the phylogeography of Campanula alpina, a key species of silicicolous alpine grasslands in the Carpathians with a disjunct distribution in the Eastern European Alps. The Carpathians experienced a different glacial history from the Alps: local glaciers were present only in the highest massifs, while alpine habitats extended over larger areas related to their present distribution in this region. We asked: (i) whether in the Carpathians a high-mountain plant exhibits a complex phylogeographical structure or rather signatures of recent migrations, and (ii) whether the disjunct part of the species' distribution in the Alps resulted from a recent colonization from the Carpathians or from a restricted expansion from separate Eastern Alpine refugia. Our study revealed a clear phylogeographical pattern in AFLPs supported by congruent groups of distinct cpDNA haplotypes. Highest genetic differentiation was observed between the Alps and the Carpathians, indicating a long-term isolation between populations from these two mountain ranges. Further genetic division within the Carpathians suggests that current species' distribution is composed of several groups which have been isolated from each other for a long period. One genetic break separates Western from Southeastern Carpathian material, which is in line with a classical biogeographical boundary. A further, strongly supported genetic group was identified at the southwestern edge of the Carpathian arch. In the Eastern Alps, genetic traces of glacial survival in separate refugial areas in the calcareous northern part and the siliceous central part were found.

  3. Offspring size at weaning affects survival to recruitment and reproductive performance of primiparous gray seals

    PubMed Central

    Bowen, William D; den Heyer, Cornelia E; McMillan, Jim I; Iverson, Sara J

    2015-01-01

    Offspring size affects survival and subsequent reproduction in many organisms. However, studies of offspring size in large mammals are often limited to effects on juveniles because of the difficulty of following individuals to maturity. We used data from a long-term study of individually marked gray seals (Halichoerus grypus; Fabricius, 1791) to test the hypothesis that larger offspring have higher survival to recruitment and are larger and more successful primiparous mothers than smaller offspring. Between 1998 and 2002, 1182 newly weaned female pups were branded with unique permanent marks on Sable Island, Canada. Each year through 2012, all branded females returning to the breeding colony were identified in weekly censuses and a subset were captured and measured. Females that survived were significantly longer offspring than those not sighted, indicating size-selective mortality between weaning and recruitment. The probability of female survival to recruitment varied among cohorts and increased nonlinearly with body mass at weaning. Beyond 51.5 kg (mean population weaning mass) weaning mass did not influence the probability of survival. The probability of female survival to recruitment increased monotonically with body length at weaning. Body length at primiparity was positively related to her body length and mass at weaning. Three-day postpartum mass (proxy for birth mass) of firstborn pups was also positively related to body length of females when they were weaned. However, females that were longer or heavier when they were weaned did not wean heavier firstborn offspring. PMID:25897381

  4. Long-term RNA persistence in postmortem contexts

    PubMed Central

    2013-01-01

    Ribonucleic acids (RNA) are generally considered fragile molecules that are readily degraded. However, there is growing documentation of long-term (from days to centuries) RNA persistence in a variety of contexts and tissue types, and as such a number of academic disciplines are beginning to exploit degraded RNA. While the reasons for its survival are not fully understood, there are several plausible mechanisms that would safeguard this molecule against degradation. However, after examining the literature available on the postmortem instability and decay mechanisms of RNA, it has become clear that limited experimental studies and no reviews offer an overview of these mechanisms. Hence in this review we outline molecular reasons for RNA surviving long-term postmortem, and provide specific examples of RNA survival in forensic, archival and archaeological contexts. A better understanding of the mechanisms of RNA decay will be crucial for developing expectations on its long-term survival. PMID:23618361

  5. Long-term consequences of anorexia nervosa.

    PubMed

    Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof

    2013-07-01

    Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

  6. Association between P-glycoprotein and lymphoid antigen expression on myeloblasts versus therapy response and survival in de novo acute myeloid leukemia: long-term follow-up results.

    PubMed

    Machaczka, Maciej; Wahlin, Björn Engelbrekt; Piatkowska-Jakubas, Beata; Rucinska, Malgorzata; Jurczak, Wojciech; Balana-Nowak, Agnieszka; Klimkowska, Monika; Hägglund, Hans; Skotnicki, Aleksander B

    2012-09-01

    P-glycoprotein (PGP) over-expression on malignant cells is associated with poor prognosis and treatment outcome due to the development of a multidrug resistance phenotype. In this study, we analyzed the correlation between expression of PGP and lymphoid antigens (Ly) on leukemic myeloblasts versus response to therapy and survival in acute myeloid leukemia (AML). Fifty-one consecutive patients, aged 16-75 (median age 44.6 years), diagnosed with de novo AML between 1997 and 2000, and who received at least one induction chemotherapy course, were enrolled in the study. Expression of PGP on ≥ 10% of the myeloblasts (PGP(+)AML) at the time of diagnosis was observed in 21 patients (41%). The complete remission rate did not differ between PGP(+) (13/21) and PGP(-) (20/30) patients (62 vs. 67%). Twelve of the 51 patients (24%) were still alive after a median follow-up time of 11.5 years (range 10.7-13.1). The Ly(+)AML patients showed significantly better overall survival compared with Ly(-)AML patients (8/18 vs. 4/33 patients alive at the last follow-up, P = 0.003). The subgroup of patients with co-expression of PGP and Ly also showed better overall survival compared with PGP(+)AML patients without Ly expression (4/8 vs. 0/13 patients alive at the last follow-up; P = 0.04). Our results suggest that expression of lymphoid antigens on PGP(+) myeloblasts in AML can positively affect survival in AML patients, mainly due to a decreased relapse risk and better survival. Although the small number of patient may be perceived as a limitation of the study, the long follow-up period strengthens its value. Further prospective trials are needed to obtain more information concerning the association between PGP and lymphoid antigens in AML, which would put our results in their ultimate proper context.

  7. Long-term outcomes in multiple gestations.

    PubMed

    Rand, Larry; Eddleman, Keith A; Stone, Joanne

    2005-06-01

    Children born from a multiple gestation are at increased risk for cerebral palsy, learning disability, and language and neurobehavioral deficits. With the increased incidence of multiple pregnancies and use of assisted reproductive technology (ART), these issues are more commonly affecting parents. Long-term outcomes are a critical part of preconceptual and early pregnancy counseling for parents faced with a multiple gestation or considering ART, and the provider should be well versed on issues surrounding zygosity, gestational age, higher-order multiples, and the effects of options such as multifetal pregnancy reduction. PMID:15922795

  8. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  9. Long-term prognostic impact of the attenuated plaque in patients with acute coronary syndrome.

    PubMed

    Okura, Hiroyuki; Kataoka, Toru; Yoshiyama, Minoru; Yoshikawa, Junichi; Yoshida, Kiyoshi

    2016-01-01

    Several intravascular ultrasound studies have reported that culprit lesion-attenuated plaque (AP) is related to slow flow/no reflow after percutaneous coronary intervention (PCI). Long-term prognostic impact of the AP is unknown. The aim of this study was to investigate acute and long-term clinical impact of the AP in patients with acute coronary syndrome (ACS). A total of 110 ACS patients who underwent successful PCI were enrolled. Acute and long-term clinical outcomes were compared between patients with AP (AP group: n = 73) and those without AP (non-AP group: n = 37). Long-term cardiac event was defined as a composite of death and ACS. Baseline characteristics in 2 groups were similar. AP was associated with higher TIMI frame count immediately after the first balloon inflation. After thrombectomy and intracoronary drug administration, final TIMI frame count became similar between AP and non-AP group. Although AP was associated with higher incidence of fatal arrhythmia during hospitalization, in-hospital mortality did not differ between the 2 groups. During follow-up (median 6.2 years), cardiac event-free survival did not differ between the 2 groups. Despite the initial unfavorable effect on coronary reflow, presence of AP did not affect acute as well as long-term clinical outcome in patients with ACS. PMID:25183306

  10. Re-Evaluating Neonatal-Age Models for Ungulates: Does Model Choice Affect Survival Estimates?

    PubMed Central

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  11. Re-evaluating neonatal-age models for ungulates: does model choice affect survival estimates?

    PubMed

    Grovenburg, Troy W; Monteith, Kevin L; Jacques, Christopher N; Klaver, Robert W; DePerno, Christopher S; Brinkman, Todd J; Monteith, Kyle B; Gilbert, Sophie L; Smith, Joshua B; Bleich, Vernon C; Swanson, Christopher C; Jenks, Jonathan A

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001-2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  12. Re-evaluating neonatal-age models for ungulates: Does model choice affect survival estimates?

    USGS Publications Warehouse

    Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  13. Re-evaluating neonatal-age models for ungulates: does model choice affect survival estimates?

    PubMed

    Grovenburg, Troy W; Monteith, Kevin L; Jacques, Christopher N; Klaver, Robert W; DePerno, Christopher S; Brinkman, Todd J; Monteith, Kyle B; Gilbert, Sophie L; Smith, Joshua B; Bleich, Vernon C; Swanson, Christopher C; Jenks, Jonathan A

    2014-01-01

    New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001-2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

  14. Multiple Weather Factors Affect Apparent Survival of European Passerine Birds

    PubMed Central

    Salewski, Volker; Hochachka, Wesley M.; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  15. Multiple weather factors affect apparent survival of European passerine birds.

    PubMed

    Salewski, Volker; Hochachka, Wesley M; Fiedler, Wolfgang

    2013-01-01

    Weather affects the demography of animals and thus climate change will cause local changes in demographic rates. In birds numerous studies have correlated demographic factors with weather but few of those examined variation in the impacts of weather in different seasons and, in the case of migrants, in different regions. Using capture-recapture models we correlated weather with apparent survival of seven passerine bird species with different migration strategies to assess the importance of selected facets of weather throughout the year on apparent survival. Contrary to our expectations weather experienced during the breeding season did not affect apparent survival of the target species. However, measures for winter severity were associated with apparent survival of a resident species, two short-distance/partial migrants and a long-distance migrant. Apparent survival of two short distance migrants as well as two long-distance migrants was further correlated with conditions experienced during the non-breeding season in Spain. Conditions in Africa had statistically significant but relatively minor effects on the apparent survival of the two long-distance migrants but also of a presumably short-distance migrant and a short-distance/partial migrant. In general several weather effects independently explained similar amounts of variation in apparent survival for the majority of species and single factors explained only relatively low amounts of temporal variation of apparent survival. Although the directions of the effects on apparent survival mostly met our expectations and there are clear predictions for effects of future climate we caution against simple extrapolations of present conditions to predict future population dynamics. Not only did weather explains limited amounts of variation in apparent survival, but future demographics will likely be affected by changing interspecific interactions, opposing effects of weather in different seasons, and the potential for

  16. [Long-term-management of organ transplant recipients].

    PubMed

    Bürger, Christin; Schmidt, Martina; Maschmeier, Miriam; Stella, Jaqueline; Hüsing, Anna; Wilms, Christian; Schmidt, Hartmut Hans-Jürgen; Kabar, Iyad

    2016-07-01

    Due to advances in immunosuppressive therapy and surgical techniques, survival rates after solid organ transplantation have constantly improved over the last decades. In long-term care after transplantation, physicians need to focus as much on diagnosis and treatment of allograft-related complications as they should consider comorbidities and evaluate risk-factors and adverse events of immunosuppressive agents to prevent secondary diseases. In particular, cardiovascular and metabolic diseases, malignancy and infection play a major role in long-term survival. Therefore, screening of organ transplant recipients in regard to these complications and adverse events is a crucial part of follow up in these patients. PMID:27359310

  17. Long-term developmental outcomes of low birth weight infants.

    PubMed

    Hack, M; Klein, N K; Taylor, H G

    1995-01-01

    Advances in neonatal medicine have resulted in the increased survival of infants at lower and lower birth weight. While these medical success stories highlight the power of medical technology to save many of the tiniest infants at birth, serious questions remain about how these infants will develop and whether they will have normal, productive lives. Low birth weight children can be born at term or before term and have varying degrees of social and medical risk. Because low birth weight children are not a homogeneous group, they have a broad spectrum of growth, health, and developmental outcomes. While the vast majority of low birth weight children have normal outcomes, as a group they generally have higher rates of subnormal growth, illnesses, and neurodevelopmental problems. These problems increase as the child's birth weight decreases. With the exception of a small minority of low birth weight children with mental retardation and/or cerebral palsy, the developmental sequelae for most low birth weight infants include mild problems in cognition, attention, and neuromotor functioning. Long-term follow-up studies conducted on children born in the 1960s indicated that the adverse consequences of being born low birth weight were still apparent in adolescence. Adverse sociodemographic factors negatively affect developmental outcomes across the continuum of low birth weight and appear to have far greater effects on long-term cognitive outcomes than most of the biological risk factors. In addition, the cognitive defects associated with social or environmental risks become more pronounced as the child ages. Enrichment programs for low birth weight children seem to be most effective for the moderately low birth weight child who comes from a lower socioeconomic group. Continued research and attempts to decrease the rate of low birth weight and associated perinatal medical sequelae are of primary importance. Ongoing documentation of the long-term outcome of low birth weight

  18. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  19. Long-term equilibrium tides

    NASA Astrophysics Data System (ADS)

    Shaffer, John A.; Cerveny, Randall S.

    1998-08-01

    Extreme equilibrium tides, or ``hypertides,'' are computed in a new equilibrium tidal model combining algorithms of a version of the Chapront ELP-2000/82 Lunar Theory with the BER78 Milankovitch astronomical expansions. For the recent past, a high correspondence exists between computed semidiurnal tide levels and a record of coastal flooding demonstrating that astronomical alignment is a potential influence on such flooding. For the Holocene and near future, maximum tides demonstrate cyclic variations with peaks at near 5000 B.P. and 4000 A.P. On the late Quaternary timescale, variations in maximum equilibrium tide level display oscillations with periods of approximately 10,000, 100,000 and 400,000 years, because of precessional shifts in tidal maxima between vernal and autumnal equinoxes. While flooding occurs under the combined effects of tides and storms via ``storm surges,'' the most extensive flooding will occur with the coincidence of storms and the rarer hypertides and is thus primarily influenced by hypertides. Therefore we suggest that astronomical alignment's relationship to coastal flooding is probabilistic rather than deterministic. Data derived from this model are applicable to (1) archaeological and paleoclimatic coastal reconstructions, (2) long-term planning, for example, radioactive waste site selection, (3) sealevel change and paleoestuarine studies or (4) ocean-meteorological interactions.

  20. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  1. Long-term effects of tetanus toxoid inoculation on the demography and life expectancy of the Cayo Santiago rhesus macaques.

    PubMed

    Kessler, Matthew J; Hernández Pacheco, Raisa; Rawlins, Richard G; Ruiz-Lambrides, Angelina; Delgado, Diana L; Sabat, Alberto M

    2015-02-01

    Tetanus was a major cause of mortality in the free-ranging population of rhesus monkeys on Cayo Santiago prior to 1985 when the entire colony was given its first dose of tetanus toxoid. The immediate reduction in mortality that followed tetanus toxoid inoculation (TTI) has been documented, but the long-term demographic effects of eliminating tetanus infections have not. This study uses the Cayo Santiago demographic database to construct comparative life tables 12 years before, and 12 years after, TTI. Life tables and matrix projection models are used to test for differences in: (i) survival among all individuals as well as among social groups, (ii) long-term fitness of the population, (iii) age distribution, (iv) reproductive value, and (v) life expectancy. A retrospective life table response experiment (LTRE) was performed to determine which life cycle transition contributed most to observed changes in long-term fitness of the population post-TTI. Elimination of clinical tetanus infections through mass inoculation improved the health and well-being of the monkeys. It also profoundly affected the population by increasing survivorship and long-term fitness, decreasing the differences in survival rates among social groups, shifting the population's age distribution towards older individuals, and increasing reproductive value and life expectancy. These findings are significant because they demonstrate the long-term effects of eradicating a major cause of mortality at a single point in time on survival, reproduction, and overall demography of a naturalistic population of primates.

  2. Emotional behavior in long-term marriage.

    PubMed

    Carstensen, L L; Gottman, J M; Levenson, R W

    1995-03-01

    In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction. In older couples, the resolution of conflict was less emotionally negative and more affectionate than in middle-aged marriages. Differences between husbands and wives and between happy and unhappy marriages were also found. Wives were more affectively negative than husbands, whereas husbands were more defensive than wives, and unhappy marriages involved greater exchange of negative affect than happy marriages.

  3. Analysis of Long-term Outcomes of 3200 Liver Transplantations Over Two Decades

    PubMed Central

    Busuttil, Ronald W.; Farmer, Douglas G.; Yersiz, Hasan; Hiatt, Jonathan R.; McDiarmid, Sue V.; Goldstein, Leonard I.; Saab, Sammy; Han, Steven; Durazo, Francisco; Weaver, Michael; Cao, Carlos; Chen, Tony; Lipshutz, Gerald S.; Holt, Curtis; Gordon, Sherilyn; Gornbein, Jeffery; Amersi, Farin; Ghobrial, Rafik M.

    2005-01-01

    Objective: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. Methods: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. Results: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992–2001) versus the era I (1984–1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. Conclusions: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be

  4. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  5. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  6. 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. PMID:19486379

  7. Long-term oxygen therapy: battling breathlessness.

    PubMed

    Wick, Jeannette Y

    2012-12-01

    Approximately 1 million of the 1.4 million Americans (71%) receiving long-term oxygen therapy (LTOT) are Medicare beneficiaries, confirming that LTOT is most often prescribed for individuals 65 years of age or older. Although several conditions create a need for supplemental oxygen, the majority of patients have chronic obstructive pulmonary disease (COPD). People with healthy lungs can extract the oxygen from air, while those with damaged lungs need higher oxygen concentrations. They can supplement their oxygen using one of three options: high-pressure oxygen tanks, liquid oxygen, or oxygen concentrators. The multicenter Nocturnal Oxygen Therapy Trial and the smaller Medical Research Council study identified LTOT as an intervention that improved survival in patients with COPD or chronic respiratory failure, approximately doubling survival at 19 months in patients who were adherent to oxygen. Despite its advantages, LTOT is plagued with problems: compliance with clinical guidelines, patient adherence, and cost. Fires associated with smoking in the vicinity of supplemental oxygen are the leading cause of residential fire deaths in the United States.

  8. Early life triclocarban exposure during lactation affects neonate rat survival.

    PubMed

    Kennedy, Rebekah C M; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A; Hu, Pan; Bae, Jiyoung; Gee, Nancy A; Lasley, Bill L; Zhao, Ling; Chen, Jiangang

    2015-01-01

    Triclocarban (3,4,4'-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups