Prognostic nutritional index is associated with survival after total gastrectomy for patients with gastric cancer.

Science.gov (United States)

Ishizuka, Mitsuru; Oyama, Yusuke; Abe, Akihito; Tago, Kazuma; Tanaka, Genki; Kubota, Keiichi

2014-08-01

To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC). One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival. Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001). PNI is associated with postoperative survival of patients undergoing TG for GC and is able to divide such patients into two independent groups before surgery. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Emotional pain: surviving mental health problems related to childhood experiences.

Science.gov (United States)

Holm, A L; Bégat, I; Severinsson, E

2009-09-01

Emotional pain is described as intense by women who suffer from borderline personality disorder (BPD), and a high prevalence of reported childhood abuse was found in the literature and in research. The aim of this study was to explore the experiences of women suffering from BPD with focus on emotional pain related to childhood. An explorative design was used. Data were collected from in-depth interviews consisting of women suffering from BPD (n = 13) and an interpretive content analysis was used to analyse the text. The findings revealed two main themes: 'Power' and 'Assessment of vulnerability'. The main theme 'Power' resulted in two categories: 'Surviving the feeling of being forced' and 'Surviving the feeling of having to assume responsibility'. The other main theme 'Assessment of vulnerability' had two categories: 'Surviving the feeling of being victimized' and 'Surviving the feeling of not being loved'. The findings suggest that nursing care need to develop an understanding of how these women endure their emotional pain, and try to survive as fighting spirits and how struggling became their way of life.

Treatment algorithm based on the multivariate survival analyses in patients with advanced hepatocellular carcinoma treated with trans-arterial chemoembolization.

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Hasmukh J Prajapati

Full Text Available To develop the treatment algorithm from multivariate survival analyses (MVA in patients with Barcelona clinic liver cancer (BCLC C (advanced Hepatocellular carcinoma (HCC patients treated with Trans-arterial Chemoembolization (TACE.Consecutive unresectable and non-tranplantable patients with advanced HCC, who received DEB TACE were studied. A total of 238 patients (mean age, 62.4yrs was included in the study. Survivals were analyzed according to different parameters from the time of the 1st DEB TACE. Kaplan Meier and Cox Proportional Hazard model were used for survival analysis. The SS was constructed from MVA and named BCLC C HCC Prognostic (BCHP staging system (SS.Overall median survival (OS was 16.2 months. In HCC patients with venous thrombosis (VT of large vein [main portal vein (PV, right or left PV, hepatic vein, inferior vena cava] (22.7% versus small vein (segmental/subsegmental PV (9.7% versus no VT had OSs of 6.4 months versus 20 months versus 22.8 months respectively (p<0.001. On MVA, the significant independent prognostic factors (PFs of survival were CP class, eastern cooperative oncology group (ECOG performance status (PS, single HCC<5 cm, site of VT, metastases, serum creatinine and serum alpha-feto protein. Based on these PFs, the BCHP staging system was constructed. The OSs of stages I, II and III were 28.4 months, 11.8 months and 2.4 months accordingly (p<0.001. The treatment plan was proposed according to the different stages.On MVA of patients with advanced HCC treated with TACE, significant independent prognostic factors (PFs of survival were CP class, ECOG PS, single HCC<5 cm or others, site of VT, metastases, serum creatinine and serum alpha-feto protein. New BCHP SS was proposed based on MVA data to identify the suitable advanced HCC patients for TACE treatments.

Single-Cell Analyses of ESCs Reveal Alternative Pluripotent Cell States and Molecular Mechanisms that Control Self-Renewal

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Dmitri Papatsenko

2015-08-01

Full Text Available Analyses of gene expression in single mouse embryonic stem cells (mESCs cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM. In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.

Proteomic analysis reveals the mechanisms of Mycena dendrobii promoting transplantation survival and growth of tissue culture seedlings of Dendrobium officinale.

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Xu, X B; Ma, X Y; Lei, H H; Song, H M; Ying, Q C; Xu, M J; Liu, S B; Wang, H Z

2015-06-01

Dendrobium officinale is an important traditional Chinese medicinal herb. Its seedlings generally show low survival and growth when transferred from in vitro tissue culture to a greenhouse or field environment. In this study, the effect of Mycena dendrobii on the survival and growth of D. officinale tissue culture seedlings and the mechanisms involved was explored. Mycena dendrobii were applied underneath the roots of D. officinale tissue culture seedlings. The seedling survival and growth were analysed. The root proteins induced by M. dendrobii were identified using two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF-MS). Mycena dendrobii treatment significantly enhanced survival and growth of D. officinale seedlings. Forty-one proteins induced by M. dendrobii were identified. Among them, 10 were involved in defence and stress response, two were involved in the formation of root or mycorrhizae, and three were related to the biosynthesis of bioactive constituents. These results suggest that enhancing stress tolerance and promoting new root formation induced by M. dendrobii may improve the survival and growth of D. officinale tissue culture seedlings. This study provides a foundation for future use of M. dendrobii in the large-scale cultivation of Dendrobiums. © 2015 The Society for Applied Microbiology.

Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses

DEFF Research Database (Denmark)

Brok, J.; Thorlund, K.; Gluud, C.

2008-01-01

in 80% (insufficient information size). TSA(15%) and TSA(LBHIS) found that 95% and 91% had absence of evidence. The remaining nonsignificant meta-analyses had evidence of lack of effect. CONCLUSION: TSA reveals insufficient information size and potentially false positive results in many meta......OBJECTIVES: To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random error risk and provides the required number of participants (information size) in a meta-analysis. Meta-analyses not reaching information size are analyzed with trial sequential monitoring boundaries...... analogous to interim monitoring boundaries in a single trial. STUDY DESIGN AND SETTING: We applied TSA on meta-analyses performed in Cochrane Neonatal reviews. We calculated information sizes and monitoring boundaries with three different anticipated intervention effects of 30% relative risk reduction (TSA...

Time-Series Analyses of Transcriptomes and Proteomes Reveal Molecular Networks Underlying Oil Accumulation in Canola.

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Wan, Huafang; Cui, Yixin; Ding, Yijuan; Mei, Jiaqin; Dong, Hongli; Zhang, Wenxin; Wu, Shiqi; Liang, Ying; Zhang, Chunyu; Li, Jiana; Xiong, Qing; Qian, Wei

2016-01-01

Understanding the regulation of lipid metabolism is vital for genetic engineering of canola ( Brassica napus L.) to increase oil yield or modify oil composition. We conducted time-series analyses of transcriptomes and proteomes to uncover the molecular networks associated with oil accumulation and dynamic changes in these networks in canola. The expression levels of genes and proteins were measured at 2, 4, 6, and 8 weeks after pollination (WAP). Our results show that the biosynthesis of fatty acids is a dominant cellular process from 2 to 6 WAP, while the degradation mainly happens after 6 WAP. We found that genes in almost every node of fatty acid synthesis pathway were significantly up-regulated during oil accumulation. Moreover, significant expression changes of two genes, acetyl-CoA carboxylase and acyl-ACP desaturase, were detected on both transcriptomic and proteomic levels. We confirmed the temporal expression patterns revealed by the transcriptomic analyses using quantitative real-time PCR experiments. The gene set association analysis show that the biosynthesis of fatty acids and unsaturated fatty acids are the most significant biological processes from 2-4 WAP and 4-6 WAP, respectively, which is consistent with the results of time-series analyses. These results not only provide insight into the mechanisms underlying lipid metabolism, but also reveal novel candidate genes that are worth further investigation for their values in the genetic engineering of canola.

Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

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Gareth D Westrop

Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization.

Science.gov (United States)

Verheijen, R B; Swart, L E; Beijnen, J H; Schellens, J H M; Huitema, A D R; Steeghs, N

2017-12-01

Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (C min ) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort. Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included. Using calculated C min values and a threshold of > 20 mg/L, univariate and multivariate exposure-survival analyses were performed. Sixty-one patients were included, of which 16.4% were underexposed (mean C min   20 mg/L was related to longer progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n = 35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p = 0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142). In multivariate analysis C min  > 20 mg/L was associated with hazard ratios of 0.25 (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in a pooled analysis. This study confirms that pazopanib C min  > 20 mg/L relates to better progression free survival in renal cancer and points towards a similar trend in sarcoma patients. C min monitoring of pazopanib can help identify patients with low C min for whom individualized treatment at a higher dose may be appropriate.

Special analyses reveal coke-deposit structure

International Nuclear Information System (INIS)

Albright, L.F.

1988-01-01

A scanning electron microscope (SEM) and an energy dispersive X-ray analyzer (EDAX) have been used to obtain information that clarifies the three mechanisms of coke formation in ethylene furnaces, and to analyze the metal condition at the exit of furnace. The results can be used to examine furnace operations and develop improved ethylene plant practices. In this first of four articles on the analyses of coke and metal samples, the coking mechanisms and coke deposits in a section of tube from an actual ethylene furnace (Furnace A) from a plant on the Texas Gulf Coast are discussed. The second articles in the series will analyze the condition of the tube metal in the same furnace. To show how coke deposition and metal condition dependent on the operating parameters of an ethylene furnace, the third article in the series will show the coke deposition in a Texas Gulf Coast furnace tube (Furnace B) that operated at shorter residence time. The fourth article discusses the metal condition in that furnace. Some recommendations, based on the analyses and findings, are offered in the fourth article that could help extend the life of ethylene furnace tubes, and also improve overall ethylene plant operations

Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

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James J Collins

Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

Comparative Genomics and Transcriptomics Analyses Reveal Divergent Lifestyle Features of Nematode Endoparasitic Fungus Hirsutella minnesotensis

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Lai, Yiling; Liu, Keke; Zhang, Xinyu; Zhang, Xiaoling; Li, Kuan; Wang, Niuniu; Shu, Chi; Wu, Yunpeng; Wang, Chengshu; Bushley, Kathryn E.; Xiang, Meichun; Liu, Xingzhong

2014-01-01

Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism. PMID:25359922

Phylogeographic analyses of the pampas cat (Leopardus colocola; Carnivora, Felidae) reveal a complex demographic history

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da Silva Santos, Anelisie; Trigo, Tatiane Campos; de Oliveira, Tadeu Gomes; Silveira, Leandro

2018-01-01

Abstract The pampas cat is a small felid that occurs in open habitats throughout much of South America. Previous studies have revealed intriguing patterns of morphological differentiation and genetic structure among its populations, as well as molecular evidence for hybridization with the closely related L. tigrinus. Here we report phylogeographic analyses encompassing most of its distribution (focusing particularly on Brazilian specimens, which had been poorly sampled in previous studies), using a novel dataset comprising 2,143 bp of the mitogenome, along with previously reported mtDNA sequences. Our data revealed strong population strutucture and supported a west-to-east colonization process in this species’ history. We detected two population expansion events, one older (ca. 200 thousand years ago [kya]) in western South America and another more recent (ca. 60-50 kya) in eastern areas, coinciding with the expansion of savanna environments in Brazil. Analyses including L. tigrinus individuals bearing introgressed mtDNA from L. colocola showed a complete lack of shared haplotypes between species, indicating that their hybridization was ancient. Finally, we observed a close relationship between Brazilian/Uruguayan L. colocola haplotypes and those sampled in L. tigrinus, indicating that their hybridization was likely related to the demographic expansion of L. colocola into eastern South America. PMID:29668017

SNP analyses of growth factor genes EGF, TGFβ-1, and HGF reveal haplotypic association of EGF with autism

International Nuclear Information System (INIS)

Toyoda, Takao; Nakamura, Kazuhiko; Yamada, Kazuo; Thanseem, Ismail; Anitha, Ayyappan; Suda, Shiro; Tsujii, Masatsugu; Iwayama, Yoshimi; Hattori, Eiji; Toyota, Tomoko; Miyachi, Taishi; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Kawai, Masayoshi; Sekine, Yoshimoto; Tsuchiya, Kenji; Sugihara, Gen-ichi; Ouchi, Yasuomi; Sugiyama, Toshiro; Takei, Nori; Yoshikawa, Takeo; Mori, Norio

2007-01-01

Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-β (TGFβ) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGFβ1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGFβ1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism

Global Activities and Plant Survival

DEFF Research Database (Denmark)

Bandick, Roger

2014-01-01

the highest exit rates. Moreover, the exit rates of globally engaged plants seem to be unaffected by increased foreign presence, whereas there appears to be a negative impact on the survival rates of non-exporting non-MNE plants. Finally, the result reveals that the survival ratio of plants of acquired...

Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.

Science.gov (United States)

Guyot, Patricia; Ades, A E; Ouwens, Mario J N M; Welton, Nicky J

2012-02-01

The results of Randomized Controlled Trials (RCTs) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios) with statistics based on repeated reconstructions by multiple observers. The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

Better midterm survival in women after transcatheter aortic valve implantation.

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Takagi, Hisato; Umemoto, Takuya

2017-08-01

In previous meta-analyses demonstrating better midterm overall survival in women undergoing transcatheter aortic valve implantation (TAVI), unadjusted risk and odds ratios were combined. To determine whether female gender is independently associated with better survival after TAVI, we performed a meta-analysis pooling adjusted hazard ratios (HRs) based on multivariate Cox proportional hazard regression. MEDLINE and EMBASE were searched through September 2015 using PubMed and OVID. Studies considered for inclusion met the following criteria: the study population was patients undergoing TAVI; and main outcomes included midterm (mean or median ≥6 months) overall survival or all-cause mortality in women and men. An unadjusted and/or adjusted HR of all-cause mortality for women versus men was abstracted from each individual study. Of 1347 potentially relevant articles screened initially, 16 reports of eligible studies were identified and included. A primary meta-analysis of the 9 adjusted HRs demonstrated a significantly better midterm overall survival in women than men (N.=6891; HR=0.80; 95% confidence interval [CI]: 0.65 to 0.97; P=0.03). A secondary meta-analysis adding 5 statistically non-significant unadjusted HR also indicated better survival in women (N.=8645; HR=0.83; 95% CI: 0.72 to 0.96; P=0.01). Although statistical tests for the primary meta-analysis revealed funnel plot asymmetry in favor of women, the secondary meta-analysis produced a symmetrical funnel plot. Female gender may be independently associated with better midterm overall survival after TAVI.

Lamb survival analysis from birth to weaning in Iranian Kermani sheep.

Science.gov (United States)

Barazandeh, Arsalan; Moghbeli, Sadrollah Molaei; Vatankhah, Mahmood; Hossein-Zadeh, Navid Ghavi

2012-04-01

Survival records from 1,763 Kermani lambs born between 1996 and 2004 from 294 ewes and 81 rams were used to determine genetic and non-genetic factors affecting lamb survival. Traits included were lamb survival across five periods from birth to 7, 14, 56, 70, and 90 days of age. Traits were analyzed under Weibull proportional hazard sire models. Several binary analyses were also conducted using animal models. Statistical models included the fixed class effects of sex of lamb, month and year of birth, a covariate effect of birth weight, and random genetic effects of both sire (in survival analyses) and animal (in binary analyses). The average survival to 90 days of age was 94.8%. Hazard rates ranged from 1.00 (birth to 90 days of age) to 1.73 (birth to 7 days of age) between the two sexes indicating that male lambs were at higher risk of mortality than females (P lamb survival and lamb birth weight, suggesting that viability and birth weight could be considered simultaneously in the selection programs to obtain optimal birth weight in Kermani lambs. Estimates of heritabilities from survival analyses were medium and ranged from 0.23 to 0.29. In addition, heritability estimates obtained from binary analyses were low and varied from 0.04 to 0.09. The results of this study suggest that progress in survival traits could be possible through managerial strategies and genetic selection.

Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor.

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Véronique Bertrand-Vallery

Full Text Available BACKGROUND: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. METHODOLOGY/PRINCIPAL FINDINGS: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29. Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta. CONCLUSIONS/SIGNIFICANCE: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.

Tanacetum parthenium leaf extract mediated survival protection in lethally irradiated Swiss albino mice

International Nuclear Information System (INIS)

Shetty, Prashanth; Pooja, S.; Suchetha Kumari, N.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.

2016-01-01

Search for less-toxic radioprotectors has spurred interest in the development of natural products. In Ayurveda, the traditional medicine, Tanacetum species have been used to treat ailments since ancient times throughout the world. Effects of the administration of different concentrations of Tanacetum parthenium leaf aqueous extract (TPLA), Tanacetum parthenium leaf ethanolic extract (TPLE) were investigated in Swiss albino mice. Mice (20-25 g) were randomly divided into 8 groups of ten animals each. The control group and the radiation group were treated daily with oral administration of saline for 15 days. Each subgroups of TPLA and TPLE were treated with doses of 50, 100 and 250 mg/kg daily for 15 days. On the 15th day, all were irradiated with 10 Gy whole body irradiation. Survival was observed daily up to 30th post-irradiation day. Data were analysed using the Kaplan-Meier survival curves. The significance difference in survival between control, radiation and treatment groups were observed (P < 0.001). Current studies revealed the protective effect of Tanacetum parthenium rendering high survivability in lethally irradiated mice. (author)

Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves

Directory of Open Access Journals (Sweden)

Guyot Patricia

2012-02-01

Full Text Available Abstract Background The results of Randomized Controlled Trials (RCTs on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta-analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios with statistics based on repeated reconstructions by multiple observers. Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. Conclusion The algorithm is a reliable tool for meta-analysis and cost-effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves.

Mitochondrial DNA analyses reveal low genetic diversity in Culex quinquefasciatus from residential areas in Malaysia.

Science.gov (United States)

Low, V L; Lim, P E; Chen, C D; Lim, Y A L; Tan, T K; Norma-Rashid, Y; Lee, H L; Sofian-Azirun, M

2014-06-01

The present study explored the intraspecific genetic diversity, dispersal patterns and phylogeographic relationships of Culex quinquefasciatus Say (Diptera: Culicidae) in Malaysia using reference data available in GenBank in order to reveal this species' phylogenetic relationships. A statistical parsimony network of 70 taxa aligned as 624 characters of the cytochrome c oxidase subunit I (COI) gene and 685 characters of the cytochrome c oxidase subunit II (COII) gene revealed three haplotypes (A1-A3) and four haplotypes (B1-B4), respectively. The concatenated sequences of both COI and COII genes with a total of 1309 characters revealed seven haplotypes (AB1-AB7). Analysis using tcs indicated that haplotype AB1 was the common ancestor and the most widespread haplotype in Malaysia. The genetic distance based on concatenated sequences of both COI and COII genes ranged from 0.00076 to 0.00229. Sequence alignment of Cx. quinquefasciatus from Malaysia and other countries revealed four haplotypes (AA1-AA4) by the COI gene and nine haplotypes (BB1-BB9) by the COII gene. Phylogenetic analyses demonstrated that Malaysian Cx. quinquefasciatus share the same genetic lineage as East African and Asian Cx. quinquefasciatus. This study has inferred the genetic lineages, dispersal patterns and hypothetical ancestral genotypes of Cx. quinquefasciatus. © 2013 The Royal Entomological Society.

Comparative metagenomic and metatranscriptomic analyses of microbial communities in acid mine drainage.

Science.gov (United States)

Chen, Lin-xing; Hu, Min; Huang, Li-nan; Hua, Zheng-shuang; Kuang, Jia-liang; Li, Sheng-jin; Shu, Wen-sheng

2015-07-01

The microbial communities in acid mine drainage have been extensively studied to reveal their roles in acid generation and adaption to this environment. Lacking, however, are integrated community- and organism-wide comparative gene transcriptional analyses that could reveal the response and adaptation mechanisms of these extraordinary microorganisms to different environmental conditions. In this study, comparative metagenomics and metatranscriptomics were performed on microbial assemblages collected from four geochemically distinct acid mine drainage (AMD) sites. Taxonomic analysis uncovered unexpectedly high microbial biodiversity of these extremely acidophilic communities, and the abundant taxa of Acidithiobacillus, Leptospirillum and Acidiphilium exhibited high transcriptional activities. Community-wide comparative analyses clearly showed that the AMD microorganisms adapted to the different environmental conditions via regulating the expression of genes involved in multiple in situ functional activities, including low-pH adaptation, carbon, nitrogen and phosphate assimilation, energy generation, environmental stress resistance, and other functions. Organism-wide comparative analyses of the active taxa revealed environment-dependent gene transcriptional profiles, especially the distinct strategies used by Acidithiobacillus ferrivorans and Leptospirillum ferrodiazotrophum in nutrients assimilation and energy generation for survival under different conditions. Overall, these findings demonstrate that the gene transcriptional profiles of AMD microorganisms are closely related to the site physiochemical characteristics, providing clues into the microbial response and adaptation mechanisms in the oligotrophic, extremely acidic environments.

SNP analyses of growth factor genes EGF, TGF{beta}-1, and HGF reveal haplotypic association of EGF with autism

Energy Technology Data Exchange (ETDEWEB)

Toyoda, Takao; Thanseem, Ismail; Kawai, Masayoshi; Sekine, Yoshimoto [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Yamada, Kazuo [Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama (Japan); Tsujii, Masatsugu [Faculty of Sociology, Chukyo University, Toyota, Aichi (Japan); [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan); Iwayama, Yoshimi; Hattori, Eiji; Toyota, Tomoko; Yoshikawa, Takeo [Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama (Japan); Miyachi, Taishi; Tsuchiya, Kenji; Sugihara, Gen-ichi; Matsuzaki, Hideo [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan); Iwata, Yasuhide; Suzuki, Katsuaki [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Mori, Norio [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University (Japan); Ouchi, Yasuomi [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan); [The Positron Medical Center, Hamamatsu Medical Center, Hamamatsu (Japan); Sugiyama, Toshiro [Aichi Children' s Health and Medical Center, Obu, Aichi (Japan); Takei, Nori [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan)

2007-09-07

Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-{beta} (TGF{beta}) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGF{beta}1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGF{beta}1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism.

Multivariate Analysis of the Predictors of Survival for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Focusing on Superselective Chemoembolization

International Nuclear Information System (INIS)

Ji, Suk Kyeong; Cho, Yun Ku; Ahn, Yong Sik; Kim, Mi Young; Park, Yoon Ok; Kim, Jae Kyun; Kim, Wan Tae

2008-01-01

While the prognostic factors of survival for patients with hepatocellular carcinoma (HCC) who underwent transarterial chemoembolization (TACE) are well known, the clinical significance of performing selective TACE for HCC patients has not been clearly documented. We tried to analyze the potential factors of disease-free survival for these patients, including the performance of selective TACE. A total of 151 patients with HCC who underwent TACE were retrospectively analyzed for their disease-free survival (a median follow- up of 23 months, range: 1-88 months). Univariate and multivariate analyses were performed for 20 potential factors by using the Cox proportional hazard model, including 19 baseline factors and one procedure-related factor (conventional versus selective TACE). The parameters that proved to be significant on the univariate analysis were subsequently tested with the multivariate model. Conventional or selective TACE was performed for 40 and 111 patients, respectively. Univariate and multivariate analyses revealed that tumor multiplicity, venous tumor thrombosis and selective TACE were the only three independent significant prognostic factors of disease-free survival (p = 0.002, 0.015 and 0.019, respectively). In our study, selective TACE was a favorable prognostic factor for the disease-free survival of patients with HCC who underwent TACE

Fossil-based comparative analyses reveal ancient marine ancestry erased by extinction in ray-finned fishes.

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Betancur-R, Ricardo; Ortí, Guillermo; Pyron, Robert Alexander

2015-05-01

The marine-freshwater boundary is a major biodiversity gradient and few groups have colonised both systems successfully. Fishes have transitioned between habitats repeatedly, diversifying in rivers, lakes and oceans over evolutionary time. However, their history of habitat colonisation and diversification is unclear based on available fossil and phylogenetic data. We estimate ancestral habitats and diversification and transition rates using a large-scale phylogeny of extant fish taxa and one containing a massive number of extinct species. Extant-only phylogenetic analyses indicate freshwater ancestry, but inclusion of fossils reveal strong evidence of marine ancestry in lineages now restricted to freshwaters. Diversification and colonisation dynamics vary asymmetrically between habitats, as marine lineages colonise and flourish in rivers more frequently than the reverse. Our study highlights the importance of including fossils in comparative analyses, showing that freshwaters have played a role as refuges for ancient fish lineages, a signal erased by extinction in extant-only phylogenies. © 2015 John Wiley & Sons Ltd/CNRS.

Obesity adversely affects survival in pancreatic cancer patients.

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McWilliams, Robert R; Matsumoto, Martha E; Burch, Patrick A; Kim, George P; Halfdanarson, Thorvardur R; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R

2010-11-01

Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self-reported diabetes and fasting blood glucose in the survival model. BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma (hazard ratio [HR], 1.019 for each increased unit of BMI [kg/m2], PFasting blood glucose and diabetes did not affect the results. Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. Copyright © 2010 American Cancer Society.

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

Science.gov (United States)

Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

2014-01-01

Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results.

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Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques; Pandha, Hardev S; George, Daniel J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Casey, Michelle; Serfass, Lucile; Pantuck, Allan J; Staehler, Michael

2018-01-01

Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS). Data for 615 patients randomized to sunitinib (n=309) or placebo (n=306) in the S-TRAC trial. Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade. Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy. Most subgroups of patients at high risk of recurrent renal cell carcinoma after

Survival and prognostic factors in patients treated with stereotactic radiotherapy for brain metastases

DEFF Research Database (Denmark)

Leth, Thomas; Oettingen, Gorm von; Lassen-Ramshad, Yasmin A.

2015-01-01

Abstract Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better definition of these factors...... will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven...... months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age ≥ 65 years, Performance Status ≥ 2, extracranial metastases and size of metastasis > 20 mm as independent prognostic factors related to shorter survival. No factors were independently related...

Fledgling survival increases with development time and adult survival across north and south temperate zones

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Lloyd, Penn; Martin, Thomas E.

2016-01-01

Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

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Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

UK Renal Registry 15th annual report: Chapter 5 survival and causes of death of UK adult patients on renal replacement therapy in 2011: national and centre-specific analyses.

Science.gov (United States)

Steenkamp, Retha; Shaw, Catriona; Feest, Terry

2013-01-01

These analyses examine a) survival from the start of renal replacement therapy (RRT) based on the total incident UK RRT population reported to the UK Renal Registry, b) survival of prevalent patients. Changes in survival between 1997 and 2011 are also reported. Survival was calculated for both incident and prevalent patients on RRT and compared between the UK countries after adjustment for age. Survival of incident patients (starting RRT during 2010) was calculated both from the start of RRT and from 90 days after starting RRT, both with and without censoring at transplantation. Prevalent dialysis patients were censored at transplantation; this means that the patient is considered alive up to the point of transplantation, but the patient's status post-transplant is not considered. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. The relative risk of death was calculated compared with the general UK population. The unadjusted 1 year after 90 day survival for patients starting RRT in 2010 was 87.3%, representing an increase from the previous year (86.6%). In incident patients aged 18-64 years, the unadjusted 1 year survival had risen from 86.0% in patients starting RRT in 1997 to 92.6% in patients starting RRT in 2010 and for those aged ≥65 it had increased from 63.9% to 77.0% over the same period. The age-adjusted one year survival (adjusted to age 60) of prevalent dialysis patients increased from 88.1% in the 2001 cohort to 89.8% in the 2010 cohort. Prevalent diabetic patient one year survival rose from 82.1% in the 2002 cohort to 84.7% in the 2010 cohort. The age-standardised mortality ratio for prevalent RRT patients compared with the general population was 18 for age group 30-34 and 2.5 at age 85+ years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 22% of deaths, infection and treatment withdrawal 18% each and 25% were recorded as other causes of death

CASAS: Cancer Survival Analysis Suite, a web based application.

Science.gov (United States)

Rupji, Manali; Zhang, Xinyan; Kowalski, Jeanne

2017-01-01

We present CASAS, a shiny R based tool for interactive survival analysis and visualization of results. The tool provides a web-based one stop shop to perform the following types of survival analysis:  quantile, landmark and competing risks, in addition to standard survival analysis.  The interface makes it easy to perform such survival analyses and obtain results using the interactive Kaplan-Meier and cumulative incidence plots.  Univariate analysis can be performed on one or several user specified variable(s) simultaneously, the results of which are displayed in a single table that includes log rank p-values and hazard ratios along with their significance. For several quantile survival analyses from multiple cancer types, a single summary grid is constructed. The CASAS package has been implemented in R and is available via http://shinygispa.winship.emory.edu/CASAS/. The developmental repository is available at https://github.com/manalirupji/CASAS/.

Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

Directory of Open Access Journals (Sweden)

Tod W Reeder

Full Text Available Squamate reptiles (lizards and snakes are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa. Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia. These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses without considering the possible impact of molecular data on their placement.

Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

Science.gov (United States)

Reeder, Tod W; Townsend, Ted M; Mulcahy, Daniel G; Noonan, Brice P; Wood, Perry L; Sites, Jack W; Wiens, John J

2015-01-01

Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement.

Integrated Analyses Resolve Conflicts over Squamate Reptile Phylogeny and Reveal Unexpected Placements for Fossil Taxa

Science.gov (United States)

Reeder, Tod W.; Townsend, Ted M.; Mulcahy, Daniel G.; Noonan, Brice P.; Wood, Perry L.; Sites, Jack W.; Wiens, John J.

2015-01-01

Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement. PMID:25803280

Depression and Liver Transplant Survival.

Science.gov (United States)

Meller, William; Welle, Nicole; Sutley, Kristen; Thurber, Steven

Patients who underwent liver transplantation and experienced clinical depression have heretofore evinced lower survival rates when compared to nondepressed counterparts. To investigate the hypothesis that transplant patients who seek and obtain medical treatment for depression would circumvent the prior reduced survival findings. A total of 765 patients with liver transplants were scrutinized for complications following transplantation. Further, 104 patients experienced posttransplant depression as manifested by diagnosis and treatment by medical personnel. Survival analyses were conducted comparing hazard and survival curves for these selected individuals and the remainder of transplant patients. Contrary to prior data and consistent with the aforementioned hypothesis, median survival durations, survival curves, and hazard functions (controlling for age and prolonged posttransplant survival for the depressed patients were better. The improved survival for the depressed patients may simply be related to an amelioration of depressed symptoms via antidepressant medications. However, this interpretation would only be congruent with reduced hazard, not elevated survival, beyond the norm (median) for other transplant participants. Assuming the reliability and generalization of our findings, perhaps a reasonable and compelling interpretation is that combined with the effectiveness of antidepressant medications, the seeking and receiving treatment for depression is a type of proxy measure of a more global pattern of adherence to recommended posttransplant medical regimens. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Challenges in the estimation of Net SURvival: The CENSUR working survival group.

Science.gov (United States)

Giorgi, R

2016-10-01

Net survival, the survival probability that would be observed, in a hypothetical world, where the cancer of interest would be the only possible cause of death, is a key indicator in population-based cancer studies. Accounting for mortality due to other causes, it allows cross-country comparisons or trends analysis and provides a useful indicator for public health decision-making. The objective of this study was to show how the creation and formalization of a network comprising established research teams, which already had substantial and complementary experience in both cancer survival analysis and methodological development, make it possible to meet challenges and thus provide more adequate tools, to improve the quality and the comparability of cancer survival data, and to promote methodological transfers in areas of emerging interest. The Challenges in the Estimation of Net SURvival (CENSUR) working survival group is composed of international researchers highly skilled in biostatistics, methodology, and epidemiology, from different research organizations in France, the United Kingdom, Italy, Slovenia, and Canada, and involved in French (FRANCIM) and European (EUROCARE) cancer registry networks. The expected advantages are an interdisciplinary, international, synergistic network capable of addressing problems in public health, for decision-makers at different levels; tools for those in charge of net survival analyses; a common methodology that makes unbiased cross-national comparisons of cancer survival feasible; transfer of methods for net survival estimations to other specific applications (clinical research, occupational epidemiology); and dissemination of results during an international training course. The formalization of the international CENSUR working survival group was motivated by a need felt by scientists conducting population-based cancer research to discuss, develop, and monitor implementation of a common methodology to analyze net survival in order

Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

Directory of Open Access Journals (Sweden)

Patrick N Harter

Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

Extended mitogenomic phylogenetic analyses yield new insight into crocodylian evolution and their survival of the Cretaceous-Tertiary boundary.

Science.gov (United States)

Roos, Jonas; Aggarwal, Ramesh K; Janke, Axel

2007-11-01

The mitochondrial genomes of the dwarf crocodile, Osteolaemus tetraspis, and two species of dwarf caimans, the smooth-fronted caiman, Paleosuchus trigonatus, and Cuvier's dwarf caiman, Paleosuchus palpebrosus, were sequenced and included in a mitogenomic phylogenetic study. The phylogenetic analyses, which included a total of ten crocodylian species, yielded strong support to a basal split between Crocodylidae and Alligatoridae. Osteolaemus fell within the Crocodylidae as the sister group to Crocodylus. Gavialis and Tomistoma, which joined on a common branch, constituted a sister group to Crocodylus/Osteolaemus. This suggests that extant crocodylians are organized in two families: Alligatoridae and Crocodylidae. Within the Alligatoridae there was a basal split between Alligator and a branch that contained Paleosuchus and Caiman. The analyses also provided molecular estimates of various divergences applying recently established crocodylian and outgroup fossil calibration points. Molecular estimates based on amino acid data placed the divergence between Crocodylidae and Alligatoridae at 97-103 million years ago and that between Alligator and Caiman/Paleosuchus at 65-72 million years ago. Other crocodilian divergences were placed after the Cretaceous-Tertiary boundary. Thus, according to the molecular estimates, three extant crocodylian lineages have their roots in the Cretaceous. Considering the crocodylian diversification in the Cretaceous the molecular datings suggest that the extinction of the dinosaurs was also to some extent paralleled in the crocodylian evolution. However, for whatever reason, some crocodylian lineages survived into the Tertiary.

Quantitative methods for analysing cumulative effects on fish migration success: a review.

Science.gov (United States)

Johnson, J E; Patterson, D A; Martins, E G; Cooke, S J; Hinch, S G

2012-07-01

It is often recognized, but seldom addressed, that a quantitative assessment of the cumulative effects, both additive and non-additive, of multiple stressors on fish survival would provide a more realistic representation of the factors that influence fish migration. This review presents a compilation of analytical methods applied to a well-studied fish migration, a more general review of quantitative multivariable methods, and a synthesis on how to apply new analytical techniques in fish migration studies. A compilation of adult migration papers from Fraser River sockeye salmon Oncorhynchus nerka revealed a limited number of multivariable methods being applied and the sub-optimal reliance on univariable methods for multivariable problems. The literature review of fisheries science, general biology and medicine identified a large number of alternative methods for dealing with cumulative effects, with a limited number of techniques being used in fish migration studies. An evaluation of the different methods revealed that certain classes of multivariable analyses will probably prove useful in future assessments of cumulative effects on fish migration. This overview and evaluation of quantitative methods gathered from the disparate fields should serve as a primer for anyone seeking to quantify cumulative effects on fish migration survival. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Individual social capital and survival

DEFF Research Database (Denmark)

Ejlskov, Linda; Mortensen, Rikke N; Overgaard, Charlotte

2014-01-01

BACKGROUND: The concept of social capital has received increasing attention as a determinant of population survival, but its significance is uncertain. We examined the importance of social capital on survival in a population study while focusing on gender differences. METHODS: We used data from...... a Danish regional health survey with a five-year follow-up period, 2007-2012 (n = 9288, 53.5% men, 46.5% women). We investigated the association between social capital and all-cause mortality, performing separate analyses on a composite measure as well as four specific dimensions of social capital while...... controlling for covariates. Analyses were performed with Cox proportional hazard models by which hazard ratios and 95% confidence intervals were calculated. RESULTS: For women, higher levels of social capital were associated with lower all-cause mortality regardless of age, socioeconomic status, health...

Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

Science.gov (United States)

Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

2013-07-11

FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

Modification of bacterial cell survival by postirradiation hypoxia

Energy Technology Data Exchange (ETDEWEB)

Vexler, F B; Eidus, L Kh

1986-01-27

It is shown that postirradiation hypoxia affects the survival of E.coli. Hypoxic conditions immediately after a single-dose irradiation diminish cell survival in nutrient medium. Increasing time intervals between irradiation and hypoxia decrease the efficiency of the latter, while 1 h after irradiation hypoxia does not modify the survival of irradiated cells. These findings reveal that the mechanisms of action of postirradiation hypoxia on eu- and prokaryotic cells are similar.

Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

International Nuclear Information System (INIS)

Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

2015-01-01

Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic

Effects of percutaneous endoscopic gastrostomy on survival of patients in a persistent vegetative state after stroke.

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Wu, Kunpeng; Chen, Ying; Yan, Caihong; Huang, Zhijia; Wang, Deming; Gui, Peigen; Bao, Juan

2017-10-01

To assess the effect of percutaneous endoscopic gastrostomy on short- and long-term survival of patients in a persistent vegetative state after stroke and determine the relevant prognostic factors. Stroke may lead to a persistent vegetative state, and the effect of percutaneous endoscopic gastrostomy on survival of stroke patients in a persistent vegetative state remains unclear. Prospective study. A total of 97 stroke patients in a persistent vegetative state hospitalised from January 2009 to December 2011 at the Second Hospital, University of South China, were assessed in this study. Percutaneous endoscopic gastrostomy was performed in 55 patients, and mean follow-up time was 18 months. Survival rate and risk factors were analysed. Median survival in the 55 percutaneous endoscopic gastrostomy-treated patients was 17·6 months, higher compared with 8·2 months obtained for the remaining 42 patients without percutaneous endoscopic gastrostomy treatment. Univariate analyses revealed that age, hospitalisation time, percutaneous endoscopic gastrostomy treatment status, family financial situation, family care, pulmonary infection and nutrition were significantly associated with survival. Multivariate analysis indicated that older age, no gastrostomy, poor family care, pulmonary infection and poor nutritional status were independent risk factors affecting survival. Indeed, percutaneous endoscopic gastrostomy significantly improved the nutritional status and decreased pulmonary infection rate in patients with persistent vegetative state after stroke. Interestingly, median survival time was 20·3 months in patients with no or one independent risk factors of poor prognosis (n = 38), longer compared with 8·7 months found for patients with two or more independent risk factors (n = 59). Percutaneous endoscopic gastrostomy significantly improves long-term survival of stroke patients in a persistent vegetative state and is associated with improved nutritional status

Persistent elevation of postoperative neutrophil-to-lymphocyte ratio: A better predictor of survival in gastric cancer than elevated preoperative neutrophil-to-lymphocyte ratio.

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Min, Kyueng-Whan; Kwon, Mi Jung; Kim, Dong-Hoon; Son, Byoung Kwan; Kim, Eun-Kyung; Oh, Young Ha; Wi, Young Chan

2017-10-25

Postoperative neutrophil-to-lymphocyte ratio change (NLRc) reflects the dynamic change of balance between host inflammatory response and immune response after treatment. In gastric cancer, an elevated initial NLR (iNLR) is reported to be a prognostic predictor, but the clinical application of the NLRc remains unclear. The NLRc was assessed in 734 patients undergoing total/subtotal gastrectomy and endoscopic submucosal dissection for gastric adenocarcinoma. The iNLR and NLRc were recorded within 10 days of the first diagnosis and 3-6 months after surgery, respectively. Using receiver operating characteristic (ROC) curves, we investigated the relationship between NLRc or iNLR and patient survival. The analysis revealed a higher predictive power for correlating patient survival with the NLRc compared with iNLR. NLRc was defined as negative (lower than iNLR) and positive (higher than iNLR). A positive NLRc was frequently observed in patients with advanced AJCC stage, local recurrence, distant metastasis, perineural invasion, and adjuvant chemotherapy (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between patient survival and NLRc (all p < 0.05) but no association between survival and iNLR. The NLRc could be a better indicator than iNLR for predicting survival in patients with gastric cancer.

Functional assays and metagenomic analyses reveals differences between the microbial communities inhabiting the soil horizons of a Norway spruce plantation.

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Stéphane Uroz

Full Text Available In temperate ecosystems, acidic forest soils are among the most nutrient-poor terrestrial environments. In this context, the long-term differentiation of the forest soils into horizons may impact the assembly and the functions of the soil microbial communities. To gain a more comprehensive understanding of the ecology and functional potentials of these microbial communities, a suite of analyses including comparative metagenomics was applied on independent soil samples from a spruce plantation (Breuil-Chenue, France. The objectives were to assess whether the decreasing nutrient bioavailability and pH variations that naturally occurs between the organic and mineral horizons affects the soil microbial functional biodiversity. The 14 Gbp of pyrosequencing and Illumina sequences generated in this study revealed complex microbial communities dominated by bacteria. Detailed analyses showed that the organic soil horizon was significantly enriched in sequences related to Bacteria, Chordata, Arthropoda and Ascomycota. On the contrary the mineral horizon was significantly enriched in sequences related to Archaea. Our analyses also highlighted that the microbial communities inhabiting the two soil horizons differed significantly in their functional potentials according to functional assays and MG-RAST analyses, suggesting a functional specialisation of these microbial communities. Consistent with this specialisation, our shotgun metagenomic approach revealed a significant increase in the relative abundance of sequences related glycoside hydrolases in the organic horizon compared to the mineral horizon that was significantly enriched in glycoside transferases. This functional stratification according to the soil horizon was also confirmed by a significant correlation between the functional assays performed in this study and the functional metagenomic analyses. Together, our results suggest that the soil stratification and particularly the soil resource

Survival after elective surgery for colonic cancer in Denmark

DEFF Research Database (Denmark)

Perdawid, S K; Hemmingsen, L; Boesby, S

2012-01-01

AIM: Total mesorectal excision (TME) has been shown to improve the outcome for patients with rectal cancer. In contrast, there are fewer data on complete mesocolic excision (CME) for colonic cancer. METHOD: Data from the National Colorectal Cancer Database were analysed. This includes about 95......% of all patients with colorectal cancer in Denmark. Only patients having elective surgery for colonic cancer in the period 2001-2008 were included. Overall and relative survival analyses were carried out. The study period was divided into the periods 2001-2004 and 2005-2008. RESULTS: 9149 patients were...... included for the final analysis. The overall 5-year survival rates were 0.65 in 2001-2004 and 0.66 in 2005-2008. The relative 5-year survival rates were also within 1% of each other. None of these comparisons was statistically significant. CONCLUSION: Survival following elective colon cancer surgery has...

Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

DEFF Research Database (Denmark)

Motzer, Robert J; Ravaud, Alain; Patard, Jean-Jacques

2018-01-01

BACKGROUND: Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.98; p=0.03). OBJECTIVE: To report...... sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55-0.99; p=0.04), NLR ≤3 (HR 0.72, 95% CI 0.54-0.95; p=0.02), and Fuhrman...... grade 3/4 (HR 0.73, 95% CI 0.55-0.98; p=0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66-1.28; p=0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively. CONCLUSIONS...

Meta-analysis of single-arm survival studies: a distribution-free approach for estimating summary survival curves with random effects.

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Combescure, Christophe; Foucher, Yohann; Jackson, Daniel

2014-07-10

In epidemiologic studies and clinical trials with time-dependent outcome (for instance death or disease progression), survival curves are used to describe the risk of the event over time. In meta-analyses of studies reporting a survival curve, the most informative finding is a summary survival curve. In this paper, we propose a method to obtain a distribution-free summary survival curve by expanding the product-limit estimator of survival for aggregated survival data. The extension of DerSimonian and Laird's methodology for multiple outcomes is applied to account for the between-study heterogeneity. Statistics I(2)  and H(2) are used to quantify the impact of the heterogeneity in the published survival curves. A statistical test for between-strata comparison is proposed, with the aim to explore study-level factors potentially associated with survival. The performance of the proposed approach is evaluated in a simulation study. Our approach is also applied to synthesize the survival of untreated patients with hepatocellular carcinoma from aggregate data of 27 studies and synthesize the graft survival of kidney transplant recipients from individual data from six hospitals. Copyright © 2014 John Wiley & Sons, Ltd.

A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data.

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Nasejje, Justine B; Mwambi, Henry; Dheda, Keertan; Lesosky, Maia

2017-07-28

Random survival forest (RSF) models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF) are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. In this study, we compare the random survival forest model to the conditional inference model (CIF) using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points). The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB) which consists of mainly categorical covariates with two levels (few split-points). The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

A comparison of the conditional inference survival forest model to random survival forests based on a simulation study as well as on two applications with time-to-event data

Directory of Open Access Journals (Sweden)

Justine B. Nasejje

2017-07-01

Full Text Available Abstract Background Random survival forest (RSF models have been identified as alternative methods to the Cox proportional hazards model in analysing time-to-event data. These methods, however, have been criticised for the bias that results from favouring covariates with many split-points and hence conditional inference forests for time-to-event data have been suggested. Conditional inference forests (CIF are known to correct the bias in RSF models by separating the procedure for the best covariate to split on from that of the best split point search for the selected covariate. Methods In this study, we compare the random survival forest model to the conditional inference model (CIF using twenty-two simulated time-to-event datasets. We also analysed two real time-to-event datasets. The first dataset is based on the survival of children under-five years of age in Uganda and it consists of categorical covariates with most of them having more than two levels (many split-points. The second dataset is based on the survival of patients with extremely drug resistant tuberculosis (XDR TB which consists of mainly categorical covariates with two levels (few split-points. Results The study findings indicate that the conditional inference forest model is superior to random survival forest models in analysing time-to-event data that consists of covariates with many split-points based on the values of the bootstrap cross-validated estimates for integrated Brier scores. However, conditional inference forests perform comparably similar to random survival forests models in analysing time-to-event data consisting of covariates with fewer split-points. Conclusion Although survival forests are promising methods in analysing time-to-event data, it is important to identify the best forest model for analysis based on the nature of covariates of the dataset in question.

Probabilistic Survivability Versus Time Modeling

Science.gov (United States)

Joyner, James J., Sr.

2016-01-01

This presentation documents Kennedy Space Center's Independent Assessment work completed on three assessments for the Ground Systems Development and Operations (GSDO) Program to assist the Chief Safety and Mission Assurance Officer during key programmatic reviews and provided the GSDO Program with analyses of how egress time affects the likelihood of astronaut and ground worker survival during an emergency. For each assessment, a team developed probability distributions for hazard scenarios to address statistical uncertainty, resulting in survivability plots over time. The first assessment developed a mathematical model of probabilistic survivability versus time to reach a safe location using an ideal Emergency Egress System at Launch Complex 39B (LC-39B); the second used the first model to evaluate and compare various egress systems under consideration at LC-39B. The third used a modified LC-39B model to determine if a specific hazard decreased survivability more rapidly than other events during flight hardware processing in Kennedy's Vehicle Assembly Building.

Global variations in cancer survival. Study Group on Cancer Survival in Developing Countries.

Science.gov (United States)

Sankaranarayanan, R; Swaminathan, R; Black, R J

1996-12-15

Population-based cancer registries from Algeria, China, Costa Rica, Cuba, India, the Philippines, and Thailand are collaborating with the International Agency for Research on Cancer in a study of cancer survival in developing countries. Comparisons with the SEER program results of the National Cancer Institute in the United States, and the EUROCARE study of survival in European countries revealed considerable differences in the survival of patients with certain tumors associated with intensive chemotherapeutic treatment regimes (Hodgkin's disease and testicular tumors), more modest differences in the survival of patients with tumors for which early diagnosis and treatment confer an improved prognosis (carcinomas of the large bowel, breast, and cervix), and only slight differences for tumors associated with poor prognosis (carcinomas of the stomach, pancreas, and lung). With limited resources to meet the challenge of the increasing incidence of cancer expected in the next few decades, health authorities in developing countries should be aware of the importance of investing in a range of cancer control activities, including primary prevention and early detection programs as well as treatment.

PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

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A. V. Seriogin

2014-08-01

Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

Directory of Open Access Journals (Sweden)

A. V. Seriogin

2009-01-01

Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

Molecular analyses reveal high species diversity of trematodes in a sub-Arctic lake

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Soldánová, Miroslava; Georgieva, Simona; Roháčováa, Jana; Knudsen, Rune; Kuhn, Jesper A.; Henriksen, Eirik H.; Siwertsson, Anna; Shaw, Jenny C.; Kuris, Armand M.; Amundsen, Per-Arne; Scholz, Tomáš; Lafferty, Kevin D.; Kostadinova, Aneta

2017-01-01

To identify trematode diversity and life-cycles in the sub-Arctic Lake Takvatn, Norway, we characterised 120 trematode isolates from mollusc first intermediate hosts, metacercariae from second intermediate host fishes and invertebrates, and adults from fish and invertebrate definitive hosts, using molecular techniques. Phylogenies based on nuclear and/or mtDNA revealed high species richness (24 species or species-level genetic lineages), and uncovered trematode diversity (16 putative new species) from five families typical in lake ecosystems (Allocreadiidae, Diplostomidae, Plagiorchiidae, Schistosomatidae and Strigeidae). Sampling potential invertebrate hosts allowed matching of sequence data for different stages, thus achieving molecular elucidation of trematode life-cycles and exploration of host-parasite interactions. Phylogenetic analyses also helped identify three major mollusc intermediate hosts (Radix balthica, Pisidium casertanum and Sphaerium sp.) in the lake. Our findings increase the known trematode diversity at the sub-Arctic Lake Takvatn, showing that digenean diversity is high in this otherwise depauperate sub-Arctic freshwater ecosystem, and indicating that sub-Arctic and Arctic ecosystems may be characterised by unique trematode assemblages.

Genetic Diversity among Rhizobium leguminosarum bv. Trifolii Strains Revealed by Allozyme and Restriction Fragment Length Polymorphism Analyses

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Demezas, David H.; Reardon, Terry B.; Watson, John M.; Gibson, Alan H.

1991-01-01

Allozyme electrophoresis and restriction fragment length polymorphism (RFLP) analyses were used to examine the genetic diversity of a collection of 18 Rhizobium leguminosarum bv. trifolii, 1 R. leguminosarum bv. viciae, and 2 R. meliloti strains. Allozyme analysis at 28 loci revealed 16 electrophoretic types. The mean genetic distance between electrophoretic types of R. leguminosarum and R. meliloti was 0.83. Within R. leguminosarum, the single strain of bv. viciae differed at an average of 0.65 from strains of bv. trifolii, while electrophoretic types of bv. trifolii differed at a range of 0.23 to 0.62. Analysis of RFLPs around two chromosomal DNA probes also delineated 16 unique RFLP patterns and yielded genetic diversity similar to that revealed by the allozyme data. Analysis of RFLPs around three Sym (symbiotic) plasmid-derived probes demonstrated that the Sym plasmids reflect genetic divergence similar to that of their bacterial hosts. The large genetic distances between many strains precluded reliable estimates of their genetic relationships. PMID:16348600

Marital Status and Survival in Patients with Carcinoid Tumors.

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Greenleaf, Erin K; Cooper, Amanda B; Hollenbeak, Christopher S

2016-01-01

Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan-Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR]), controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed) patients. Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08-1.33] and 1.34 [95% CI, 1.22-1.46], respectively) and cancer-related survival (HR, 1.15 [95% CI, 1.00-1.31] and 1.15 [95% CI, 1.03-1.29], respectively) than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08-1.33] and 1.62 [95% CI, 1.25-2.11], respectively) than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P married patients have a survival advantage after diagnosis of any carcinoid tumor, potentially reflecting better social support and financial means

Profilin-1 overexpression in MDA-MB-231 breast cancer cells is associated with alterations in proteomics biomarkers of cell proliferation, survival, and motility as revealed by global proteomics analyses.

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Coumans, Joëlle V F; Gau, David; Poljak, Anne; Wasinger, Valerie; Roy, Partha; Moens, Pierre D J

2014-12-01

Despite early screening programs and new therapeutic strategies, metastatic breast cancer is still the leading cause of cancer death in women in industrialized countries and regions. There is a need for novel biomarkers of susceptibility, progression, and therapeutic response. Global analyses or systems science approaches with omics technologies offer concrete ways forward in biomarker discovery for breast cancer. Previous studies have shown that expression of profilin-1 (PFN1), a ubiquitously expressed actin-binding protein, is downregulated in invasive and metastatic breast cancer. It has also been reported that PFN1 overexpression can suppress tumorigenic ability and motility/invasiveness of breast cancer cells. To obtain insights into the underlying molecular mechanisms of how elevating PFN1 level induces these phenotypic changes in breast cancer cells, we investigated the alteration in global protein expression profiles of breast cancer cells upon stable overexpression of PFN1 by a combination of three different proteome analysis methods (2-DE, iTRAQ, label-free). Using MDA-MB-231 as a model breast cancer cell line, we provide evidence that PFN1 overexpression is associated with alterations in the expression of proteins that have been functionally linked to cell proliferation (FKPB1A, HDGF, MIF, PRDX1, TXNRD1, LGALS1, STMN1, LASP1, S100A11, S100A6), survival (HSPE1, HSPB1, HSPD1, HSPA5 and PPIA, YWHAZ, CFL1, NME1) and motility (CFL1, CORO1B, PFN2, PLS3, FLNA, FLNB, NME2, ARHGDIB). In view of the pleotropic effects of PFN1 overexpression in breast cancer cells as suggested by these new findings, we propose that PFN1-induced phenotypic changes in cancer cells involve multiple mechanisms. Our data reported here might also offer innovative strategies for identification and validation of novel therapeutic targets and companion diagnostics for persons with, or susceptibility to, breast cancer.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

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Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

2016-01-01

Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

Multidimensional Poverty and Child Survival in India

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Mohanty, Sanjay K.

2011-01-01

Background Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. Objectives and Methodology Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. Results The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Conclusion Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population. PMID:22046384

Multidimensional poverty and child survival in India.

Directory of Open Access Journals (Sweden)

Sanjay K Mohanty

Full Text Available Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses.The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed.Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population.

Multidimensional poverty and child survival in India.

Science.gov (United States)

Mohanty, Sanjay K

2011-01-01

Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population.

Characteristics of juvenile survivors reveal spatio-temporal differences in early life stage survival of Baltic cod

DEFF Research Database (Denmark)

Huwer, Bastian; Hinrichsen, H.H.; Böttcher, U.

2014-01-01

with previous modeling studies on the survival chances of early-stage larvae and with general spatio-temporal patterns of larval prey availability suggests that differences in survival are related to food availability during the early larval stage. Results are discussed in relation to the recruitment process...

A Genetic Screen Reveals that Synthesis of 1,4-Dihydroxy-2-Naphthoate (DHNA), but Not Full-Length Menaquinone, Is Required for Listeria monocytogenes Cytosolic Survival.

Science.gov (United States)

Chen, Grischa Y; McDougal, Courtney E; D'Antonio, Marc A; Portman, Jonathan L; Sauer, John-Demian

2017-03-21

Through unknown mechanisms, the host cytosol restricts bacterial colonization; therefore, only professional cytosolic pathogens are adapted to colonize this host environment. Listeria monocytogenes is a Gram-positive intracellular pathogen that is highly adapted to colonize the cytosol of both phagocytic and nonphagocytic cells. To identify L. monocytogenes determinants of cytosolic survival, we designed and executed a novel screen to isolate L. monocytogenes mutants with cytosolic survival defects. Multiple mutants identified in the screen were defective for synthesis of menaquinone (MK), an essential molecule in the electron transport chain. Analysis of an extensive set of MK biosynthesis and respiratory chain mutants revealed that cellular respiration was not required for cytosolic survival of L. monocytogenes but that, instead, synthesis of 1,4-dihydroxy-2-naphthoate (DHNA), an MK biosynthesis intermediate, was essential. Recent discoveries showed that modulation of the central metabolism of both host and pathogen can influence the outcome of host-pathogen interactions. Our results identify a potentially novel function of the MK biosynthetic intermediate DHNA and specifically highlight how L. monocytogenes metabolic adaptations promote cytosolic survival and evasion of host immunity. IMPORTANCE Cytosolic bacterial pathogens, such as Listeria monocytogenes and Francisella tularensis , are exquisitely evolved to colonize the host cytosol in a variety of cell types. Establishing an intracellular niche shields these pathogens from effectors of humoral immunity, grants access to host nutrients, and is essential for pathogenesis. Through yet-to-be-defined mechanisms, the host cytosol restricts replication of non-cytosol-adapted bacteria, likely through a combination of cell autonomous defenses (CADs) and nutritional immunity. Utilizing a novel genetic screen, we identified determinants of L. monocytogenes cytosolic survival and virulence and identified a role

Congruence between distribution modelling and phylogeographical analyses reveals Quaternary survival of a toadflax species (Linaria elegans) in oceanic climate areas of a mountain ring range.

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Fernández-Mazuecos, Mario; Vargas, Pablo

2013-06-01

· The role of Quaternary climatic shifts in shaping the distribution of Linaria elegans, an Iberian annual plant, was investigated using species distribution modelling and molecular phylogeographical analyses. Three hypotheses are proposed to explain the Quaternary history of its mountain ring range. · The distribution of L. elegans was modelled using the maximum entropy method and projected to the last interglacial and to the last glacial maximum (LGM) using two different paleoclimatic models: the Community Climate System Model (CCSM) and the Model for Interdisciplinary Research on Climate (MIROC). Two nuclear and three plastid DNA regions were sequenced for 24 populations (119 individuals sampled). Bayesian phylogenetic, phylogeographical, dating and coalescent-based population genetic analyses were conducted. · Molecular analyses indicated the existence of northern and southern glacial refugia and supported two routes of post-glacial recolonization. These results were consistent with the LGM distribution as inferred under the CCSM paleoclimatic model (but not under the MIROC model). Isolation between two major refugia was dated back to the Riss or Mindel glaciations, > 100 kyr before present (bp). · The Atlantic distribution of inferred refugia suggests that the oceanic (buffered)-continental (harsh) gradient may have played a key and previously unrecognized role in determining Quaternary distribution shifts of Mediterranean plants. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

EGFR immunoexpression, RAS immunoexpression and their effects on survival in lung adenocarcinoma cases.

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Gundogdu, Ahmet Gokhan; Onder, Sevgen; Firat, Pinar; Dogan, Riza

2014-06-01

The impacts of epidermal growth factor receptor (EGFR) immunoexpression and RAS immunoexpression on the survival and prognosis of lung adenocarcinoma patients are debated in the literature. Twenty-six patients, who underwent pulmonary resections between 2002 and 2007 in our clinic, and whose pathologic examinations yielded adenocarcinoma, were included in the study. EGFR and RAS expression levels were examined by immunohistochemical methods. The results were compared with the survival, stage of the disease, nodal involvement, lymphovascular invasion, and pleural invasion. Nonparametric bivariate analyses were used for statistical analyses. A significant link between EGFR immunoexpression and survival has been identified while RAS immunoexpression and survival have been proven to be irrelevant. Neither EGFR, nor RAS has displayed a significant link with the stage of the disease, nodal involvement, lymphovascular invasion, or pleural invasion. Positive EGFR immunoexpression affects survival negatively, while RAS immunoexpression has no effect on survival in lung adenocarcinoma patients.

Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma

International Nuclear Information System (INIS)

Song, Jing-Jing; Zhao, Si-Jia; Fang, Juan; Ma, Da; Liu, Xiang-Qi; Chen, Xiao-Bing; Wang, Yun; Cheng, Bin; Wang, Zhi

2016-01-01

Forkhead Box P3 (Foxp3) is a regulatory T cells marker, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of Foxp3 expression with clinicopathological parameters and prognosis in oral squamous cell carcinoma (OSCC). Foxp3 expression was examined using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 273 OSCC patients. Statistical analysis was performed to evaluate the associations between Foxp3 expression, the clinicopathologic characteristics and prognostic factors in OSCC. Foxp3 protein expression was significantly associated with lymph node metastasis (P <0.01). Both univariate and multivariate analyses revealed that Foxp3 was an independent factor for both 5 years overall survival (OS) and relapse-free survival (RFS) (both P <0.01). Patients with Foxp3 overexpression had shorter OS and RFS. Our results determined that elevated Foxp3 protein expression was a predictive factor of outcome in OSCC and could act as a promising therapeutic target

Marital Status and Survival in Patients with Carcinoid Tumors

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Erin K. Greenleaf

2016-01-01

Full Text Available Background Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Methods Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan–Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR], controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed patients. Results Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08–1.33] and 1.34 [95% CI, 1.22–1.46], respectively and cancer-related survival (HR, 1.15 [95% CI, 1.00–1.31] and 1.15 [95% CI, 1.03–1.29], respectively than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08–1.33] and 1.62 [95% CI, 1.25–2.11], respectively than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P < 0.0001. Conclusions Even after controlling for other prognostic factors, married patients

Body mass index and breast cancer survival

DEFF Research Database (Denmark)

Guo, Qi; Burgess, Stephen; Turman, Constance

2017-01-01

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival...... from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between...... the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER...

Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

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Rao Nagesha AS

2009-09-01

Full Text Available Abstract Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST. They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months and long survivors (dogs with better prognosis: surviving 6 months or longer. Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the

A hemocyte gene expression signature correlated with predictive capacity of oysters to survive Vibrio infections

Directory of Open Access Journals (Sweden)

Rosa Rafael

2012-06-01

Full Text Available Abstract Background The complex balance between environmental and host factors is an important determinant of susceptibility to infection. Disturbances of this equilibrium may result in multifactorial diseases as illustrated by the summer mortality syndrome, a worldwide and complex phenomenon that affects the oysters, Crassostrea gigas. The summer mortality syndrome reveals a physiological intolerance making this oyster species susceptible to diseases. Exploration of genetic basis governing the oyster resistance or susceptibility to infections is thus a major goal for understanding field mortality events. In this context, we used high-throughput genomic approaches to identify genetic traits that may characterize inherent survival capacities in C. gigas. Results Using digital gene expression (DGE, we analyzed the transcriptomes of hemocytes (immunocompetent cells of oysters able or not able to survive infections by Vibrio species shown to be involved in summer mortalities. Hemocytes were nonlethally collected from oysters before Vibrio experimental infection, and two DGE libraries were generated from individuals that survived or did not survive. Exploration of DGE data and microfluidic qPCR analyses at individual level showed an extraordinary polymorphism in gene expressions, but also a set of hemocyte-expressed genes whose basal mRNA levels discriminate oyster capacity to survive infections by the pathogenic V. splendidus LGP32. Finally, we identified a signature of 14 genes that predicted oyster survival capacity. Their expressions are likely driven by distinct transcriptional regulation processes associated or not associated to gene copy number variation (CNV. Conclusions We provide here for the first time in oyster a gene expression survival signature that represents a useful tool for understanding mortality events and for assessing genetic traits of interest for disease resistance selection programs.

Conditional Melanoma Cancer Survival in the United States

Directory of Open Access Journals (Sweden)

Ray M. Merrill

2016-02-01

Full Text Available Beyond relative survival, which indicates the likelihood that patients will not die from causes associated with their cancer, conditional relative survival probabilities provide further useful prognostic information to cancer patients, tailored to the time already survived from diagnosis. This study presents conditional relative survival for melanoma patients in the United States, diagnosed during 2000–2008 and followed through 2012. Analyses are based on 62,803 male and 50,261 female cases in population-based cancer registries in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Five-year relative survival estimates are presented for melanoma patients who have already survived one, two, three, four, or five years after the initial diagnosis. Five- and ten-year relative survival decreases with age, stage at diagnosis, and is lower among males, Blacks, and Hispanics. Five-year conditional relative survival improves with each year already survived. The potential for improvement in five-year conditional relative survival is greatest for older age, males, Blacks, Hispanics, and in later staged cases. For local disease, five-year conditional relative survival was significantly lower in ages greater than 65 years and in Blacks. It was significantly higher in females, non-Hispanics, and married individuals. Age had a greater inverse relationship with five-year survival in later staged disease. A similar result occurred for females and married individuals. In contrast, non-Hispanics had better five-year survival if diagnosed with local or regional disease, but not distant disease.

Comparative analyses reveal different consequences of two oxidative stress inducers, gamma irradiation and potassium tellurite, in the extremophile Deinococcus radiodurans

International Nuclear Information System (INIS)

Narasimha, Anaganti; Basu, Bhakti; Apte, Shree Kumar

2014-01-01

Proteomic and mass spectrometric analyses revealed differential responses of D. radiodurans to two oxidative stressors. While both elicited oxidative stress alleviation response, major divergence was observed at the level of DNA repair, metabolic pathways and protein homeostasis. Response to gamma irradiation was focused on DNA repair and ROS scavenging but supported metabolism as well as protein homeostasis. Tellurite, induced oxidative stress alleviation but decreased reducing affected and adversely affected metabolism and protein homeostasis

Global terrestrial water storage connectivity revealed using complex climate network analyses

Science.gov (United States)

Sun, A. Y.; Chen, J.; Donges, J.

2015-07-01

Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a cutoff threshold derived from the edge-density function to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide further measures for constraining the current land surface models, especially in data sparse regions.

Survival rate of breast cancer patients in Malaysia: a population-based study.

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Abdullah, Nor Aini; Wan Mahiyuddin, Wan Rozita; Muhammad, Nor Asiah; Ali, Zainudin Mohamad; Ibrahim, Lailanor; Ibrahim Tamim, Nor Saleha; Mustafa, Amal Nasir; Kamaluddin, Muhammad Amir

2013-01-01

Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This population- based retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from 1st Jan 2000 to 31st December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan- Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.

The survival of Coxiella burnetii in soils

Science.gov (United States)

Evstigneeva, A. S.; Ul'Yanova, T. Yu.; Tarasevich, I. V.

2007-05-01

Coxiella burnetii is a pathogen of Q-fever—a widespread zoonosis. The effective adaptation of C. burnetii to intracellular existence is in contrast with its ability to survive in the environment outside the host cells and its resistance to chemical and physical agents. Its mechanism of survival remains unknown. However, its survival appears to be related to the developmental cycle of the microorganism itself, i.e., to the formation of its dormant forms. The survival of Coxiella burnetii was studied for the first time. The pathogenic microorganism was inoculated into different types of soil and cultivated under different temperatures. The survival of the pathogen was verified using a model with laboratory animals (mice). Viable C. burnetii were found in the soil even 20 days after their inoculation. The relationship between the organic carbon content in the soils and the survival of C. burnetii was revealed. Thus, the results obtained were the first to demonstrate that the soil may serve as a reservoir for the preservation and further spreading of the Q-fever pathogen in the environment, on the one hand, and reduce the risk of epidemics, on the other.

A computer program for multiple decrement life table analyses.

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Poole, W K; Cooley, P C

1977-06-01

Life table analysis has traditionally been the tool of choice in analyzing distribution of "survival" times when a parametric form for the survival curve could not be reasonably assumed. Chiang, in two papers [1,2] formalized the theory of life table analyses in a Markov chain framework and derived maximum likelihood estimates of the relevant parameters for the analyses. He also discussed how the techniques could be generalized to consider competing risks and follow-up studies. Although various computer programs exist for doing different types of life table analysis [3] to date, there has not been a generally available, well documented computer program to carry out multiple decrement analyses, either by Chiang's or any other method. This paper describes such a program developed by Research Triangle Institute. A user's manual is available at printing costs which supplements the contents of this paper with a discussion of the formula used in the program listing.

Survival of Patients with Oral Cavity Cancer in Germany

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Listl, Stefan; Jansen, Lina; Stenzinger, Albrecht; Freier, Kolja; Emrich, Katharina; Holleczek, Bernd; Katalinic, Alexander; Gondos, Adam; Brenner, Hermann

2013-01-01

The purpose of the present study was to describe the survival of patients diagnosed with oral cavity cancer in Germany. The analyses relied on data from eleven population-based cancer registries in Germany covering a population of 33 million inhabitants. Patients with a diagnosis of oral cavity cancer (ICD-10: C00-06) between 1997 and 2006 are included. Period analysis for 2002–2006 was applied to estimate five-year age-standardized relative survival, taking into account patients' sex as well as grade and tumor stage. Overall five-year relative survival for oral cavity cancer patients was 54.6%. According to tumor localization, five-year survival was 86.5% for lip cancer, 48.1% for tongue cancer and 51.7% for other regions of the oral cavity. Differences in survival were identified with respect to age, sex, tumor grade and stage. The present study is the first to provide a comprehensive overview on survival of oral cavity cancer patients in Germany. PMID:23349710

Predictive model for survival in patients with gastric cancer.

Science.gov (United States)

Goshayeshi, Ladan; Hoseini, Benyamin; Yousefli, Zahra; Khooie, Alireza; Etminani, Kobra; Esmaeilzadeh, Abbas; Golabpour, Amin

2017-12-01

Gastric cancer is one of the most prevalent cancers in the world. Characterized by poor prognosis, it is a frequent cause of cancer in Iran. The aim of the study was to design a predictive model of survival time for patients suffering from gastric cancer. This was a historical cohort conducted between 2011 and 2016. Study population were 277 patients suffering from gastric cancer. Data were gathered from the Iranian Cancer Registry and the laboratory of Emam Reza Hospital in Mashhad, Iran. Patients or their relatives underwent interviews where it was needed. Missing values were imputed by data mining techniques. Fifteen factors were analyzed. Survival was addressed as a dependent variable. Then, the predictive model was designed by combining both genetic algorithm and logistic regression. Matlab 2014 software was used to combine them. Of the 277 patients, only survival of 80 patients was available whose data were used for designing the predictive model. Mean ?SD of missing values for each patient was 4.43?.41 combined predictive model achieved 72.57% accuracy. Sex, birth year, age at diagnosis time, age at diagnosis time of patients' family, family history of gastric cancer, and family history of other gastrointestinal cancers were six parameters associated with patient survival. The study revealed that imputing missing values by data mining techniques have a good accuracy. And it also revealed six parameters extracted by genetic algorithm effect on the survival of patients with gastric cancer. Our combined predictive model, with a good accuracy, is appropriate to forecast the survival of patients suffering from Gastric cancer. So, we suggest policy makers and specialists to apply it for prediction of patients' survival.

Fissure sealants in caries prevention:a practice-based study using survival analysis

OpenAIRE

Leskinen, K. (Kaja)

2010-01-01

Abstract The purpose of this study was to analyse the effectiveness and cost of fissure sealant treatment in preventing dental caries in children in a practice-based research network using survival analysis. The survival times of first permanent molars in children were analysed in three countries: in Finland (age cohorts 1970–1972 and 1980–1982), in Sweden (1980–1982) and in Greece (1980–1982), and additionally at two municipal health centres in Finland (age cohorts 1988–1990 in Kemi...

Survival analysis of dialysis patients in selected hospitals of lahore city

International Nuclear Information System (INIS)

Ahmad, Z.; Shahzad, I.

2015-01-01

There are several reasons which are directly or indirectly relate to affect the survival time of End Stage Renal Disease (ESRD) patients. This study was done to analyse the survival rate of ESRD patients in Lahore city, and to evaluate the influence of various risk factors and prognostic factors on survival of these patients. Methods: A sample of 40 patients was taken from the Jinnah Hospital Lahore and Lahore General Hospital by using the convenience sampling technique. The Log Rank Test was used to determine the significant difference between the categories of qualitative variables of ESRD patients. Multivariate Cox Regression Analysis was used to analyse the effect of different clinical and socio-economic variables on the survival time of these patients. Results: Different qualitative variables like: age, marital status, BMI, comorbid factors, diabetes type, gender, income level, place, risk factor like diabetes, ischemic heart disease, hypertension and Hepatitis status were analysed on the basis of Log Rank Test. While age and comorbid factors were found to be statistically significant which showed that the distribution of age and comorbid factors were different. By using the Cox Regression analysis the coefficient of Mass, serum albumin and family history of diabetes were found to be significant. Conclusions: There were some of the factors which had been taken for the analysis came out less or more significant in patients of ESRD. So it was concluded that mostly clinical factors which were Mass of the Patient, Serum Albumin and Family History of Diabetes made significant contribution towards the survival status of patients. (author)

Stability of alert survivable forces during reductions

Energy Technology Data Exchange (ETDEWEB)

Canavan, G.H.

1998-01-01

The stability of current and projected strategic forces are discussed within a framework that contains elements of current US and Russian analyses. For current force levels and high alert, stability levels are high, as are the levels of potential strikes, due to the large forces deployed. As force levels drop towards those of current value target sets, the analysis becomes linear, concern shifts from stability to reconstitution, and survivable forces drop out. Adverse marginal costs generally provide disincentives for the reduction of vulnerable weapons, but the exchange of vulnerable for survivable weapons could reduce cost while increasing stability even for aggressive participants. Exchanges between effective vulnerable and survivable missile forces are studied with an aggregated, probabilistic model, which optimizes each sides` first and determines each sides` second strikes and costs by minimizing first strike costs.

Physical activity and survival in breast cancer

DEFF Research Database (Denmark)

Ammitzbøll, Gunn; Søgaard, Karen; Karlsen, Randi V

2016-01-01

PURPOSE: Knowledge about lifestyle factors possibly influencing survival after breast cancer (BC) is paramount. We examined associations between two types of postdiagnosis physical activity (PA) and overall survival after BC. PATIENTS AND METHODS: We used prospective data on 959 BC survivors from...... the Diet, Cancer, and Health cohort, all enrolled before diagnosis. Self-reported PA was measured as time per activity, and estimated metabolic equivalent task (MET)-hours per week were summed for each activity. We constructed measures for household, exercise, and total PA. The association between...... from all causes during the study period. In adjusted analyses, exercise PA above eight MET h/week compared to lower levels of activity was significantly associated with improved overall survival (HR, 0.68; confidence interval [CI]: 0.47-0.99). When comparing participation in exercise to non...

Conserved regulators of nucleolar size revealed by global phenotypic analyses.

Science.gov (United States)

Neumüller, Ralph A; Gross, Thomas; Samsonova, Anastasia A; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

2013-08-20

Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I-mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I-mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry-based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules.

Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses

Science.gov (United States)

Neumüller, Ralph A.; Gross, Thomas; Samsonova, Anastasia A.; Vinayagam, Arunachalam; Buckner, Michael; Founk, Karen; Hu, Yanhui; Sharifpoor, Sara; Rosebrock, Adam P.; Andrews, Brenda; Winston, Fred; Perrimon, Norbert

2014-01-01

Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized by increased Pol I–mediated transcription and, consequently, nucleolar hypertrophy. To map the genetic network underlying the regulation of nucleolar size and of Pol I–mediated transcription, we performed comparative, genome-wide loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and Drosophila melanogaster coupled with mass spectrometry–based analyses of the ribosomal DNA (rDNA) promoter. With this approach, we identified a set of conserved and nonconserved molecular complexes that control nucleolar size. Furthermore, we characterized a direct role of the histone information regulator (HIR) complex in repressing rRNA transcription in yeast. Our study provides a full-genome, cross-species analysis of a nuclear subcompartment and shows that this approach can identify conserved molecular modules. PMID:23962978

Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.

Science.gov (United States)

Huhn, Stefanie; da Silva Filho, Miguel I; Sanmuganantham, Tharmila; Pichulik, Tica; Catalano, Calogerina; Pardini, Barbara; Naccarati, Alessio; Polakova-Vymetálkova, Veronika; Jiraskova, Katerina; Vodickova, Ludmila; Vodicka, Pavel; Löffler, Markus W; Courth, Lioba; Wehkamp, Jan; Din, Farhat V N; Timofeeva, Maria; Farrington, Susan M; Jansen, Lina; Hemminki, Kari; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael; Dunlop, Malcolm G; Weber, Alexander N R; Försti, Asta

2018-01-01

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.

Treatment factors influencing survival in pancreatic carcinoma; Der Einfluss der Therapie auf das Ueberleben von Patienten mit Pankreaskarzinom. Eine Analyse von Einzelfaktoren

Energy Technology Data Exchange (ETDEWEB)

Warszawski, N.; Warszawski, A.; Schneider, B.M.; Roettinger, E.M. [Ulm Univ. (Germany). Abt. Radiologie 2 (Strahlentherapie); Link, K.H.; Gansauge, F. [Ulm Univ. (Germany). Abt. fuer Allgemeinchirurgie; Lutz, M.P. [Ulm Univ. (Germany). Abt. Innere Medizin 1

1999-07-01

Purpose: To identify the impact of treatment factors on overall survival in patients with pancreatic carcinoma. Patients and methods: We performed a follow-up study on 38 patients with adenocarcinoma of the pancreas treated from 1984 to 1998. 18/38 patients were resected. Irradiated volume included the primary tumor (or tumor bed) and regional lymph nodes. Thirty-seven patients received in addition chemotherapy consisting of mitoxantrone, 5-fluorouracil and cis-platin, either i.v. (14/38) or i.a. (23/38). The influence of treatment related factors on the overall survival was tested. Biologically effective dose was calculated by the linear-quadratic model ({alpha}/{beta}=25 Gy) and by losing 0.85 Gy per day starting accelerated repopulation at day 28. Results: Treatment factors influencing overall survival were resection (p=0.02), overall treatment time (p=0.03) and biologically effective dose (p<0.002). Total dose and kind of chemotherapy had no significant influence. Treatment volume had a negative correlation (r=-0.5, p=0.06) with overall survival, without any correlation between tumor size, tumor stage, and treatment volume. In multivariate analysis only biologically effective dose remained significant (p=0.02). Conclusions: Among with surgery, biologically effective dose strongly influences overall survival in patients treated for pancreatic carcinoma. Treatment volume should be kept as small as possible and all efforts should be made to avoid treatments splits in radiation therapy. (orig.) [Deutsch] Ziel: Behandlungsfaktoren zu identifizieren, die einen Einfluss auf das Ueberleben von Patienten mit Pankreaskarzinom haben. Patienten und Methode: In einer nichtrandomisierten Studie wurden 38 Patienten ausgewertet, die von 1984 bis 1998 wegen eines Adenokarzinoms des Pankreas behandelt worden waren. Bei 18/38 Patienten war eine Resektion vorgenommen worden. Das Bestrahlungsvolumen beinhaltete den Primaertumor bzw. das Tumorbett und die regionaeren Lymphknoten

Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

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Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

2008-02-10

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients.

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Keskin, Metin; Bayraktar, Adem; Sivirikoz, Emre; Yegen, Gülcin; Karip, Bora; Saglam, Esra; Bulut, Mehmet Türker; Balik, Emre

2016-02-01

The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors.Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test.A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P CRM status. Logistic regression analysis revealed that APR (P CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively).This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates.

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

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Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2016-06-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio. Copyright © 2016 the American Physiological Society.

FIRST USE OF STEREOLOGY TO QUANTIFY THE SURVIVAL OF FAT AUTOGRAFTS

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Eduardo Serna Cuéllar

2011-05-01

Full Text Available It is not usual to perform quantitative analyses on surgical materials. Rather, they are evaluated clinically, through qualitative methods, and if quantitation is done, it is on a 2-dimensional basis. In this study, the long-term survival of fat autografts (FAG in 40 subjects with facial soft tissue defects is quantified. An adipose tissue preparation from the abdomen obtained through liposuction and centrifugation is injected subcutaneously. Approximately 14 months later, the treated area is biopsied. Extensive computer-based histological analyses were performed using the stereological method in order to directly obtain three parameters: volume fraction of adipocytes in the fat tissue (VV, density (number per volume of adipocytes in the fat tissue (NV, and the mean cell volume of adipocytes (VA in each tissue sample. A set of equations based on these three quantitative parameters is produced for evaluation of the volumetric survival fraction (VSF of FAG. The presented data evidenced a 66% survival fraction at the 14-month follow-up. In routine practice, it would be sufficient to perform this volumetric analysis on the injected and biopsied fat samples to know what fraction of the FAG has survived. This is an objective method for quantifying FAG survival and will allow a standardized comparison between different research series and authors.

A spatial scan statistic for survival data based on Weibull distribution.

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Bhatt, Vijaya; Tiwari, Neeraj

2014-05-20

The spatial scan statistic has been developed as a geographical cluster detection analysis tool for different types of data sets such as Bernoulli, Poisson, ordinal, normal and exponential. We propose a scan statistic for survival data based on Weibull distribution. It may also be used for other survival distributions, such as exponential, gamma, and log normal. The proposed method is applied on the survival data of tuberculosis patients for the years 2004-2005 in Nainital district of Uttarakhand, India. Simulation studies reveal that the proposed method performs well for different survival distribution functions. Copyright © 2013 John Wiley & Sons, Ltd.

Management of hepatocellular carcinoma: an overview of major findings from meta-analyses

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Guo, Xiaozhong; Han, Guohong

2016-01-01

This paper aims to systematically review the major findings from meta-analyses comparing different treatment options for hepatocellular carcinoma (HCC). A total of 153 relevant papers were searched via the PubMed, EMBASE, and Cochrane library databases. They were classified according to the mainstay treatment modalities (i.e., liver transplantation, surgical resection, radiofrequency ablation, transarterial embolization or chemoembolization, sorafenib, and others). The primary outcome data, such as overall survival, diseases-free survival or recurrence-free survival, progression-free survival, and safety, were summarized. The recommendations and uncertainties regarding the treatment of HCC were also proposed. PMID:27167195

From basic survival analytic theory to a non-standard application

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Zimmermann, Georg

2017-01-01

Georg Zimmermann provides a mathematically rigorous treatment of basic survival analytic methods. His emphasis is also placed on various questions and problems, especially with regard to life expectancy calculations arising from a particular real-life dataset on patients with epilepsy. The author shows both the step-by-step analyses of that dataset and the theory the analyses are based on. He demonstrates that one may face serious and sometimes unexpected problems, even when conducting very basic analyses. Moreover, the reader learns that a practically relevant research question may look rather simple at first sight. Nevertheless, compared to standard textbooks, a more detailed account of the theory underlying life expectancy calculations is needed in order to provide a mathematically rigorous framework. Contents Regression Models for Survival Data Model Checking Procedures Life Expectancy Target Groups Researchers, lecturers, and students in the fields of mathematics and statistics Academics and experts work...

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

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McMahon Clive R

2007-03-01

Full Text Available Abstract 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.

Finite-size scaling of survival probability in branching processes

OpenAIRE

Garcia-Millan, Rosalba; Font-Clos, Francesc; Corral, Alvaro

2014-01-01

Branching processes pervade many models in statistical physics. We investigate the survival probability of a Galton-Watson branching process after a finite number of generations. We reveal the finite-size scaling law of the survival probability for a given branching process ruled by a probability distribution of the number of offspring per element whose standard deviation is finite, obtaining the exact scaling function as well as the critical exponents. Our findings prove the universal behavi...

Survival from tumours of the central nervous system in Danish children

DEFF Research Database (Denmark)

Erdmann, Friederike; Winther, Jeanette Falck; Dalton, Susanne Oksbjerg

2018-01-01

associations between survival and any family characteristic. Analyses by CNS tumour subtypes showed reduced survival for children with glioma when living outside of Copenhagen (HR 1.55; CI 1.03; 2.35). For embryonal CNS tumours, the number of full siblings was associated with worse survival (HR for having 3......Little is known about social inequalities in childhood cancer survival. We investigated the impact of family circumstances on survival from paediatric central nervous system (CNS) tumours in a nationwide, register-based cohort of Danish children. All children born between 1973 and 2006...... and diagnosed with a CNS tumour before the age of 20 years (N = 1,261) were followed until 10 years from diagnosis. Using Cox proportional hazards models, the impact of various family characteristics on overall survival was estimated. Hazard ratios (HRs) for all CNS tumours combined did not show strong...

Survival of Alzheimer's disease patients in Korea.

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Go, Seok Min; Lee, Kang Soo; Seo, Sang Won; Chin, Juhee; Kang, Sue J; Moon, So Young; Na, Duk L; Cheong, Hae-Kwan

2013-01-01

The natural history of Alzheimer's disease (AD) has rarely been studied in the Korean population. Our study on survival analyses in Korean AD patients potentially provides a basis for cross-cultural comparisons. We studied 724 consecutive patients from a memory disorder clinic in a tertiary hospital in Seoul, who were diagnosed as having AD between April 1995 and December 2005. Deaths were identified by the Statistics Korea database. The Kaplan-Meier method was used for survival analysis, and a Cox proportional hazard model was used to assess factors related to patient survival. The overall median survival from the onset of first symptoms and from the time of diagnosis was 12.6 years (95% confidence interval 11.7-13.4) and 9.3 years (95% confidence interval 8.7-9.9), respectively. The age of onset, male gender, history of diabetes mellitus, lower Mini-Mental State Examination score, and higher Clinical Dementia Rating score were negatively associated with survival. There was a reversal of risk of AD between early-onset and later-onset AD, 9.1 years after onset. The results of our study show a different pattern of survival compared to those studies carried out with western AD populations. Mortality risk of early-onset AD varied depending on the duration of follow-up. Copyright © 2013 S. Karger AG, Basel.

Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models.

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Gelfand, Lois A; MacKinnon, David P; DeRubeis, Robert J; Baraldi, Amanda N

2016-01-01

Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome-underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

Mediation Analysis with Survival Outcomes: Accelerated Failure Time vs. Proportional Hazards Models

Science.gov (United States)

Gelfand, Lois A.; MacKinnon, David P.; DeRubeis, Robert J.; Baraldi, Amanda N.

2016-01-01

Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored) events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH) and fully parametric accelerated failure time (AFT) approaches for illustration. Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively) under varied data conditions, some including censoring. A simulated data set illustrates the findings. Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome—underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG. Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results. PMID:27065906

Mediation Analysis with Survival Outcomes: Accelerated Failure Time Versus Proportional Hazards Models

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Lois A Gelfand

2016-03-01

Full Text Available Objective: Survival time is an important type of outcome variable in treatment research. Currently, limited guidance is available regarding performing mediation analyses with survival outcomes, which generally do not have normally distributed errors, and contain unobserved (censored events. We present considerations for choosing an approach, using a comparison of semi-parametric proportional hazards (PH and fully parametric accelerated failure time (AFT approaches for illustration.Method: We compare PH and AFT models and procedures in their integration into mediation models and review their ability to produce coefficients that estimate causal effects. Using simulation studies modeling Weibull-distributed survival times, we compare statistical properties of mediation analyses incorporating PH and AFT approaches (employing SAS procedures PHREG and LIFEREG, respectively under varied data conditions, some including censoring. A simulated data set illustrates the findings.Results: AFT models integrate more easily than PH models into mediation models. Furthermore, mediation analyses incorporating LIFEREG produce coefficients that can estimate causal effects, and demonstrate superior statistical properties. Censoring introduces bias in the coefficient estimate representing the treatment effect on outcome – underestimation in LIFEREG, and overestimation in PHREG. With LIFEREG, this bias can be addressed using an alternative estimate obtained from combining other coefficients, whereas this is not possible with PHREG.Conclusions: When Weibull assumptions are not violated, there are compelling advantages to using LIFEREG over PHREG for mediation analyses involving survival-time outcomes. Irrespective of the procedures used, the interpretation of coefficients, effects of censoring on coefficient estimates, and statistical properties should be taken into account when reporting results.

Genomic Analyses Reveal Demographic History and Temperate Adaptation of the Newly Discovered Honey Bee Subspecies Apis mellifera sinisxinyuan n. ssp.

Science.gov (United States)

Chen, Chao; Liu, Zhiguang; Pan, Qi; Chen, Xiao; Wang, Huihua; Guo, Haikun; Liu, Shidong; Lu, Hongfeng; Tian, Shilin; Li, Ruiqiang; Shi, Wei

2016-05-01

Studying the genetic signatures of climate-driven selection can produce insights into local adaptation and the potential impacts of climate change on populations. The honey bee (Apis mellifera) is an interesting species to study local adaptation because it originated in tropical/subtropical climatic regions and subsequently spread into temperate regions. However, little is known about the genetic basis of its adaptation to temperate climates. Here, we resequenced the whole genomes of ten individual bees from a newly discovered population in temperate China and downloaded resequenced data from 35 individuals from other populations. We found that the new population is an undescribed subspecies in the M-lineage of A. mellifera (Apis mellifera sinisxinyuan). Analyses of population history show that long-term global temperature has strongly influenced the demographic history of A. m. sinisxinyuan and its divergence from other subspecies. Further analyses comparing temperate and tropical populations identified several candidate genes related to fat body and the Hippo signaling pathway that are potentially involved in adaptation to temperate climates. Our results provide insights into the demographic history of the newly discovered A. m. sinisxinyuan, as well as the genetic basis of adaptation of A. mellifera to temperate climates at the genomic level. These findings will facilitate the selective breeding of A. mellifera to improve the survival of overwintering colonies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Survival of Sami cancer patients

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Leena Soininen

2012-07-01

Full Text Available Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30 and for non-Sami 1.02 (0.86–1.20, indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.

Science.gov (United States)

Yu, Qin; Hu, Liyan; Yao, Qing; Zhu, Yongqun; Dong, Na; Wang, Da-Cheng; Shao, Feng

2013-06-01

Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.

Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

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Wickramarachchi RE

2010-09-01

Full Text Available Abstract Objectives This study compares clinico-pathological features in young (50 years with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival. Materials and methods A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models. Results Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05. In both groups, the majority presented without bowel obstruction (young - 81%, older - 94%. Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p Conclusion If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.

Ortholog-based screening and identification of genes related to intracellular survival.

Science.gov (United States)

Yang, Xiaowen; Wang, Jiawei; Bing, Guoxia; Bie, Pengfei; De, Yanyan; Lyu, Yanli; Wu, Qingmin

2018-04-20

Bioinformatics and comparative genomics analysis methods were used to predict unknown pathogen genes based on homology with identified or functionally clustered genes. In this study, the genes of common pathogens were analyzed to screen and identify genes associated with intracellular survival through sequence similarity, phylogenetic tree analysis and the λ-Red recombination system test method. The total 38,952 protein-coding genes of common pathogens were divided into 19,775 clusters. As demonstrated through a COG analysis, information storage and processing genes might play an important role intracellular survival. Only 19 clusters were present in facultative intracellular pathogens, and not all were present in extracellular pathogens. Construction of a phylogenetic tree selected 18 of these 19 clusters. Comparisons with the DEG database and previous research revealed that seven other clusters are considered essential gene clusters and that seven other clusters are associated with intracellular survival. Moreover, this study confirmed that clusters screened by orthologs with similar function could be replaced with an approved uvrY gene and its orthologs, and the results revealed that the usg gene is associated with intracellular survival. The study improves the current understanding of intracellular pathogens characteristics and allows further exploration of the intracellular survival-related gene modules in these pathogens. Copyright © 2018. Published by Elsevier B.V.

On the concept of survivability, with application to spacecraft and space-based networks

International Nuclear Information System (INIS)

Castet, Jean-Francois; Saleh, Joseph H.

2012-01-01

Survivability is an important attribute and requirement for military systems. Recently, survivability has become increasingly important for public infrastructure systems as well. In this work, we bring considerations of survivability to bear on space systems. We develop a conceptual framework and quantitative analyses based on stochastic Petri nets (SPN) to characterize and compare the survivability of different space architectures. The architectures here considered are a monolith spacecraft and a space-based network. To build the stochastic Petri net models for the degradations and failures of these two architectures, we conducted statistical analyses of historical multi-state failure data of spacecraft subsystems, and we assembled these subsystems, and their SPN models, in ways to create our monolith and networked systems. Preliminary results indicate, and quantify the extent to which, a space-based network is more survivable than the monolith spacecraft with respect to on-orbit anomalies and failures. For space systems, during the design and acquisition process, different architectures are benchmarked against several metrics; we argue that if survivability is not accounted for, then the evaluation process is likely to be biased in favor of the traditional dominant design, namely the monolith spacecraft. If however in a given context, survivability is a critical requirement for a customer, the survivability framework here proposed, and the stochastic modeling capability developed, can demonstrate the extent to which a networked space architecture may better satisfy this requirement than a monolith spacecraft. These results should be of interest to operators whose space assets require high levels of survivability, especially in the light of emerging threats.

Multiple spectroscopic analyses reveal the fate and metabolism of sulfamide herbicide triafamone in agricultural environments

International Nuclear Information System (INIS)

Wang, Mengcen; Qian, Yuan; Liu, Xiaoyu; Wei, Peng; Deng, Man; Wang, Lei; Wu, Huiming; Zhu, Guonian

2017-01-01

Triafamone, a sulfamide herbicide, has been extensively utilized for weed control in rice paddies in Asia. However, its fate and transformation in the environment have not been established. Through a rice paddy microcosm-based simulation trial combined with multiple spectroscopic analyses, we isolated and identified three novel metabolites of triafamone, including hydroxyl triafamone (HTA), hydroxyl triafamone glycoside (HTAG), and oxazolidinedione triafamone (OTA). When triafamone was applied to rice paddies at a concentration of 34.2 g active ingredient/ha, this was predominantly distributed in the paddy soil and water, and then rapidly dissipated in accordance with the first-order rate model, with half-lives of 4.3–11.0 days. As the main transformation pathway, triafamone was assimilated by the rice plants and was detoxified into HTAG, whereas the rest was reduced into HTA with subsequent formation of OTA. At the senescence stage, brown rice had incurred triafamone at a concentration of 0.0016 mg/kg, but the hazard quotient was <1, suggesting that long-term consumption of the triafamone-containing brown rice is relatively safe. The findings of the present study indicate that triafamone is actively metabolized in the agricultural environment, and elucidation of the link between environmental exposure to these triazine or oxazolidinedione moieties that contain metabolites and their potential impacts is warranted. - Highlights: • Multiple spectroscopic analyses were applied to investigate agrochemicals transformation in environment. • Three novel compounds were isolated and identified as triafamone metabolites. • The fate and transformation pathway of triafamone in rice paddy were revealed. • Long-term consumption of the triafamone-containing brown rice is relatively safe. • Elucidation of environmental impacts by exposure to these triazine or oxazolidinedione metabolites is warranted. - Triafamone rapidly dissipates in agricultural environments

Transcriptome and proteomic analyses reveal multiple differences associated with chloroplast development in the spaceflight-induced wheat albino mutant mta.

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Kui Shi

Full Text Available Chloroplast development is an integral part of plant survival and growth, and occurs in parallel with chlorophyll biosynthesis. However, little is known about the mechanisms underlying chloroplast development in hexaploid wheat. Here, we obtained a spaceflight-induced wheat albino mutant mta. Chloroplast ultra-structural observation showed that chloroplasts of mta exhibit abnormal morphology and distribution compared to wild type. Photosynthetic pigments content was also significantly decreased in mta. Transcriptome and chloroplast proteome profiling of mta and wild type were done to identify differentially expressed genes (DEGs and proteins (DEPs, respectively. In total 4,588 DEGs including 1,980 up- and 2,608 down-regulated, and 48 chloroplast DEPs including 15 up- and 33 down-regulated were identified in mta. Classification of DEGs revealed that most were involved in chloroplast development, chlorophyll biosynthesis, or photosynthesis. Besides, transcription factors such as PIF3, GLK and MYB which might participate in those pathways were also identified. The correlation analysis between DEGs and DEPs revealed that the transcript-to-protein in abundance was functioned into photosynthesis and chloroplast relevant groups. Real time qPCR analysis validated that the expression level of genes encoding photosynthetic proteins was significantly decreased in mta. Together, our results suggest that the molecular mechanism for albino leaf color formation in mta is a thoroughly regulated and complicated process. The combined analysis of transcriptome and proteome afford comprehensive information for further research on chloroplast development mechanism in wheat. And spaceflight provides a potential means for mutagenesis in crop breeding.

The Survival Processing Effect with Intentional Learning of Ad Hoc Categories

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Anastasiya Savchenko

2014-04-01

Full Text Available Previous studies have shown that memory is adapted to remember information when it is processed in a survival context. This study investigates how procedural changes in Marinho (2012 study might have led to her failure to replicate the survival mnemonic advantage. In two between-subjects design experiments, participants were instructed to learn words from ad hoc categories and to rate their relevance to a survival or a control scenario. No survival advantage was obtained in either experiment. The Adjusted Ratio of Clustering (ARC scores revealed that including the category labels made the participants rely more on the category structure of the list. Various procedural aspects of the conducted experiments are discussed as possible reasons underlying the absence of the survival effect.

Statistical reliability analyses of two wood plastic composite extrusion processes

International Nuclear Information System (INIS)

Crookston, Kevin A.; Mark Young, Timothy; Harper, David; Guess, Frank M.

2011-01-01

Estimates of the reliability of wood plastic composites (WPC) are explored for two industrial extrusion lines. The goal of the paper is to use parametric and non-parametric analyses to examine potential differences in the WPC metrics of reliability for the two extrusion lines that may be helpful for use by the practitioner. A parametric analysis of the extrusion lines reveals some similarities and disparities in the best models; however, a non-parametric analysis reveals unique and insightful differences between Kaplan-Meier survival curves for the modulus of elasticity (MOE) and modulus of rupture (MOR) of the WPC industrial data. The distinctive non-parametric comparisons indicate the source of the differences in strength between the 10.2% and 48.0% fractiles [3,183-3,517 MPa] for MOE and for MOR between the 2.0% and 95.1% fractiles [18.9-25.7 MPa]. Distribution fitting as related to selection of the proper statistical methods is discussed with relevance to estimating the reliability of WPC. The ability to detect statistical differences in the product reliability of WPC between extrusion processes may benefit WPC producers in improving product reliability and safety of this widely used house-decking product. The approach can be applied to many other safety and complex system lifetime comparisons.

Physical activity increases survival after heart valve surgery

DEFF Research Database (Denmark)

Lund, K.; Sibilitz, Kirstine Lærum; Kikkenborg Berg, Selina

2016-01-01

physical activity levels 6-12 months after heart valve surgery and (1) survival, (2) hospital readmission 18-24 months after surgery and (3) participation in exercise-based cardiac rehabilitation. METHODS: Prospective cohort study with registry data from The CopenHeart survey, The Danish National Patient......OBJECTIVES: Increased physical activity predicts survival and reduces risk of readmission in patients with coronary heart disease. However, few data show how physical activity is associated with survival and readmission after heart valve surgery. Objective were to assess the association between...... Register and The Danish Civil Registration System of 742 eligible patients. Physical activity was quantified with the International Physical Activity Questionnaire and analysed using Kaplan-Meier analysis and Cox regression and logistic regression methods. RESULTS: Patients with a moderate to high physical...

Factors associated with survival of epiploic foramen entrapment colic: a multicentre, international study.

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Archer, D C; Pinchbeck, G L; Proudman, C J

2011-08-01

Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area. © 2011 EVJ Ltd.

Ancient DNA reveals that bowhead whale lineages survived Late Pleistocene climate change and habitat shifts

DEFF Research Database (Denmark)

Foote, Andrew David; Kaschner, Kristin; Schultze, Sebastian E.

2013-01-01

that a true Arctic species, the bowhead whale (Balaena mysticetus), shifted its range and tracked its core suitable habitat northwards during the rapid climate change of the Pleistocene-Holocene transition. Late Pleistocene lineages survived into the Holocene and effective female population size increased...

Contrasting patterns of survival and dispersal in multiple habitats reveal an ecological trap in a food-caching bird.

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Norris, D Ryan; Flockhart, D T Tyler; Strickland, Dan

2013-11-01

A comprehensive understanding of how natural and anthropogenic variation in habitat influences populations requires long-term information on how such variation affects survival and dispersal throughout the annual cycle. Gray jays Perisoreus canadensis are widespread boreal resident passerines that use cached food to survive over the winter and to begin breeding during the late winter. Using multistate capture-recapture analysis, we examined apparent survival and dispersal in relation to habitat quality in a gray jay population over 34 years (1977-2010). Prior evidence suggests that natural variation in habitat quality is driven by the proportion of conifers on territories because of their superior ability to preserve cached food. Although neither adults (>1 year) nor juveniles (conifer territories, both age classes were less likely to leave high-conifer territories and, when they did move, were more likely to disperse to high-conifer territories. In contrast, survival rates were lower on territories that were adjacent to a major highway compared to territories that did not border the highway but there was no evidence for directional dispersal towards or away from highway territories. Our results support the notion that natural variation in habitat quality is driven by the proportion of coniferous trees on territories and provide the first evidence that high-mortality highway habitats can act as an equal-preference ecological trap for birds. Reproductive success, as shown in a previous study, but not survival, is sensitive to natural variation in habitat quality, suggesting that gray jays, despite living in harsh winter conditions, likely favor the allocation of limited resources towards self-maintenance over reproduction.

Overall survival and disease-free survival in endometrial cancer: prognostic factors in 276 patients

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Tejerizo-García A

2013-09-01

Full Text Available Álvaro Tejerizo-García,1 Jesús S Jiménez-López,1 José L Muñoz-González,1 Sara Bartolomé-Sotillos,1 Laura Marqueta-Marqués,1 Gregorio López-González,1 José F Pérez-Regadera Gómez21Service of Obstetrics and Gynecology, 2Radiation Oncology Service, Hospital Universitario 12 de Octubre, Madrid, SpainObjective: The aim of the study reported here was to assess the disease-free survival and overall survival of patients with endometrial cancer and to determine independent factors affecting the prognosis.Materials and methods: This was a retrospective study of a single-center clinical series of 276 patients (mean age 64 years with histologically confirmed cancer of the corpus uteri. The standard treatments were extrafascial total hysterectomy and bilateral salpingo-oophorectomy with selective pelvic/para-aortic node dissection, according to risk for recurrence. Actuarial overall survival and disease-free survival were estimated according to the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards analyses were used to assess the prognostic significance of the different variables.Results: The estimated median follow-up, determined using the inverse Kaplan–Meier method, was 45 months (95% confidence interval [CI] 41.2–48.8 for disease-free survival and 46 months (95% CI 43.0–49.0 for overall survival. The statistically significant variables affecting disease-free survival and overall survival were age, serous-papillary and clear-cell histological types, outer-half myometrial invasion, advanced International Federation of Gynecology and Obstetrics (FIGO stage, tumor grades G2 and G3, incomplete surgical resection, positive lymph nodes, lymphovascular space invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the multivariate Cox regression model, predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57–9.36, P < 0.001 and tumor grades G2 (HR 4.79, 95

Survival rates and predictors of survival among colorectal cancer patients in a Malaysian tertiary hospital.

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Magaji, Bello Arkilla; Moy, Foong Ming; Roslani, April Camilla; Law, Chee Wei

2017-05-18

Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients. This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival. Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814

Equity and child-survival strategies.

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Mulholland, Ek; Smith, L; Carneiro, I; Becher, H; Lehmann, D

2008-05-01

Recent advances in child survival have often been at the expense of increasing inequity. Successive interventions are applied to the same population sectors, while the same children in other sectors consistently miss out, leading to a trend towards increasing inequity in child survival. This is particularly important in the case of pneumonia, the leading cause of child death, which is closely linked to poverty and malnutrition, and for which effective community-based case management is more difficult to achieve than for other causes of child death. The key strategies for the prevention of childhood pneumonia are case management, mainly through Integrated Management of Childhood Illness (IMCI), and immunization, particularly the newer vaccines against Haemophilus influenzae type b (Hib) and pneumococcus. There is a tendency to introduce both interventions into communities that already have access to basic health care and preventive services, thereby increasing the relative disadvantage experienced by those children without such access. Both strategies can be implemented in such a way as to decrease rather than increase inequity. It is important to monitor equity when introducing child-survival interventions. Economic poverty, as measured by analyses based on wealth quintiles, is an important determinant of inequity in health outcomes but in some settings other factors may be of greater importance. Geography and ethnicity can both lead to failed access to health care, and therefore inequity in child survival. Poorly functioning health facilities are also of major importance. Countries need to be aware of the main determinants of inequity in their communities so that measures can be taken to ensure that IMCI, new vaccine implementation and other child-survival strategies are introduced in an equitable manner.

Variations in growth, survival and carbon isotope composition (delta(13)C) among Pinus pinaster populations of different geographic origins.

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Correia, Isabel; Almeida, Maria Helena; Aguiar, Alexandre; Alía, Ricardo; David, Teresa Soares; Pereira, João Santos

2008-10-01

To evaluate differences in growth and adaptability of maritime pine (Pinus pinaster Ait.), we studied growth, polycyclism, needle tissue carbon isotope composition (delta(13)C) as an estimate of water-use efficiency (WUE) and survival of seven populations at 10 years of age growing in a performance trial at a provenance test site in Escaroupim, Portugal. Six populations were from relatively high rainfall sites in Portugal and southwestern France (Atlantic group), and one population was from a more arid Mediterranean site in Spain. There were significant differences between some populations in total height, diameter at breast height, delta(13)C of bulk needle tissue, polycyclism and survival. A population from central Portugal (Leiria, on the Atlantic coast) was the tallest and had the lowest delta(13)C. Overall, the variation in delta(13)C was better explained by the mean minimum temperatures of the coldest month than by annual precipitation at the place of origin. Analyses of the relationships between delta(13)C and growth or survival revealed a distinct pattern for the Mediterranean population, with low delta(13)C (and WUE) associated with the lowest growth potential and reduced survival. There were significant negative correlations between delta(13)C and height or survival in the Atlantic group. Variation in polycyclism was correlated with annual precipitation at the place of origin. Some Atlantic populations maintained a high growth potential while experiencing moderate water stress. A detailed knowledge of the relationships between growth, survival and delta(13)C in contrasting environments will enhance our ability to select populations for forestry or conservation.

Effect of smoking on survival of patients with hepatocellular carcinoma.

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Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

2017-11-01

Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinicopathological characteristics and survival outcomes of invasive lobular carcinoma in different races

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Yang, Li-Yuan; Yang, Li-Peng; Zhu, Biao

2017-01-01

To investigate the clinicopathological characteristics and to determine whether there is a differential effect of race and examine survival outcomes according to race, 18,295 breast invasive lobular carcinoma (ILC) patients were identified in the Surveillance, Epidemiology, and End Result (SEER) database, which includes White patients (n=15,936), Black patients (n=1,451) and patients of other races (including American Indians/Alaskan Natives and Asian/Pacific Islanders) (n=908). The Black ILC patients presented a higher rate of advanced histological grades and American Joint Committee on Cancer (AJCC) stages, a higher rate of lymph node (LN) involvement and a lower rate of progesterone receptors (PR)-positivity than the White patients and other races. The five-year overall survival (OS) and five-year breast cancer specific survival (BCSS) were worst in the Black patients among these patients (85.5%, 76.0% and 87.7%, P<0.01; 91.1%, 84.4% and 91.6%, P<0.01). Multivariate regression analyses were performed to determine the risk hazards ratios (HR) of death for patients of the White, Black and other races. Among these patients, the Black patients had the worst survival outcomes in five-year OS and BCSS outcomes (HR=1.35, 95% confidence interval (CI) :1.20-1.51, P<0.01; HR=1.39, 95%CI:1.21-1.61, P<0.01, respectively). After a 1:1:1 matching of the three groups, the Black patients still presented worse survival outcomes in BCSS compared to White patients (HR=1.88, 95%CI: 1.14-3.10, P=0.013), however, there was no difference in OS (HR=1.35, 95%CI: 0.93-1.96, P=0.111). Difference in outcomes may partially explained by difference in histological grades, AJCC stage, LN and PR status among the three groups. In conclusion, this study revealed that the Black patients had worse five-year OS and BCSS than White and other race patients. PMID:29088785

Is Human Papillomavirus Associated with Prostate Cancer Survival?

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Mariarosa Pascale

2013-01-01

Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

A gene expression signature associated with survival in metastatic melanoma

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Mandruzzato, Susanna; Callegaro, Andrea; Turcatel, Gianluca; Francescato, Samuela; Montesco, Maria C; Chiarion-Sileni, Vanna; Mocellin, Simone; Rossi, Carlo R; Bicciato, Silvio; Wang, Ena; Marincola, Francesco M; Zanovello, Paola

2006-01-01

Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM) to identify genes associated with patient survival, and supervised principal components (SPC) to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells. PMID:17129373

A gene expression signature associated with survival in metastatic melanoma

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Rossi Carlo R

2006-11-01

Full Text Available Abstract Background Current clinical and histopathological criteria used to define the prognosis of melanoma patients are inadequate for accurate prediction of clinical outcome. We investigated whether genome screening by means of high-throughput gene microarray might provide clinically useful information on patient survival. Methods Forty-three tumor tissues from 38 patients with stage III and stage IV melanoma were profiled with a 17,500 element cDNA microarray. Expression data were analyzed using significance analysis of microarrays (SAM to identify genes associated with patient survival, and supervised principal components (SPC to determine survival prediction. Results SAM analysis revealed a set of 80 probes, corresponding to 70 genes, associated with survival, i.e. 45 probes characterizing longer and 35 shorter survival times, respectively. These transcripts were included in a survival prediction model designed using SPC and cross-validation which allowed identifying 30 predicting probes out of the 80 associated with survival. Conclusion The longer-survival group of genes included those expressed in immune cells, both innate and acquired, confirming the interplay between immunological mechanisms and the natural history of melanoma. Genes linked to immune cells were totally lacking in the poor-survival group, which was instead associated with a number of genes related to highly proliferative and invasive tumor cells.

Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007.

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Adams, Hadie; Avendaño, Javier; Raza, Shaan M; Gokaslan, Ziya L; Jallo, George I; Quiñones-Hinojosa, Alfredo

2012-05-20

Observational cross-sectional study. Using data from the population-based cancer registries of the Surveillance, Epidemiology and End Results (SEER) program, we analyzed demographic features, tumor and treatment characteristics, as well as survival rates in patients with primary malignant astrocytomas of the spinal cord (PMASC). PMASC is a rare neoplasm and is considered to carry the same dismal outcome as their cerebral counterparts. Our current knowledge is incomplete, and understanding the epidemiology, diagnosis, and optimal treatment still poses challenges. The SEER data from 1973 to 2007 were reviewed for pathologically confirmed primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord (C72.0). We compared the clinical features and outcomes of the cohort in uni- and multivariate fashion. Survival was calculated and compared using Kaplan-Meier curves and log-rank analysis. Our search criteria retrieved 135 patients diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-, and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA had a median survival time of 17 months versus 10 months in patients diagnosed with glioblastomas. Adult patients observed markedly prolonged survival compared with the pediatric group, with a 16-month versus 9-month median survival, respectively. Multivariate analysis revealed age at diagnosis, pediatric and adult age groups, sex, tumor histology, and extent of resection as significant predictors of survival. Interestingly, outcomes did not significantly change throughout the last decades or by receiving radiotherapy. Outcome for patients diagnosed with PMASC remains poor and presents an ongoing challenge for professionals in the field of neurospinal medicine and surgery. In our analyses of AA, adult patients, males, and patients undergoing radical resections were associated with increased survival. However, incidence of these lesions is low; hence, building strong

Lung cancer incidence and survival among HIV-infected and uninfected women and men.

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Hessol, Nancy A; Martínez-Maza, Otoniel; Levine, Alexandra M; Morris, Alison; Margolick, Joseph B; Cohen, Mardge H; Jacobson, Lisa P; Seaberg, Eric C

2015-06-19

To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men. Two longitudinal studies of HIV infection in the United States. Data from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses. Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time. Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

An overview of equipment survivability studies at Sandia National Laboratories (SNL)

International Nuclear Information System (INIS)

Bonzon, L.L.; Craft, Ch.M.; McCulloch, W.H.; Sebrell, W.A.

1983-01-01

The USNRC sponsors a number of programs at Sandia National Laboratories (SNL) specifically addressing safety-related equipment survivability. The major thrust of these programs has been the physical testing of equipment. Test results illustrate the importance of a dedicated equipment design effort giving particular attention to the safety implications of the equipment operation. Several equipment survivability tests here have revealed equipment design and test-related deficiencies

Association Among Blood Transfusion, Sepsis, and Decreased Long-term Survival After Colon Cancer Resection.

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Aquina, Christopher T; Blumberg, Neil; Becerra, Adan Z; Boscoe, Francis P; Schymura, Maria J; Noyes, Katia; Monson, John R T; Fleming, Fergal J

2017-08-01

To investigate the potential additive effects of blood transfusion and sepsis on colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival after colon cancer surgery. Perioperative blood transfusions are associated with infectious complications and increased risk of cancer recurrence through systemic inflammatory effects. Furthermore, recent studies have suggested an association among sepsis, subsequent systemic inflammation, and adverse cardiovascular outcomes. However, no study has investigated the association among transfusion, sepsis, and disease-specific survival in postoperative patients. The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I to III colon cancer resections from 2004 to 2011. Propensity-adjusted survival analyses assessed the association of perioperative allogeneic blood transfusion, sepsis, and 5-year colon cancer disease-specific survival, cardiovascular disease-specific survival, and overall survival. Among 24,230 patients, 29% received a transfusion and 4% developed sepsis. After risk adjustment, transfusion and sepsis were associated with worse colon cancer disease-specific survival [(+)transfusion: hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.09-1.30; (+)sepsis: HR 1.84, 95% CI 1.44-2.35; (+)transfusion/(+)sepsis: HR 2.27, 95% CI 1.87-2.76], cardiovascular disease-specific survival [(+)transfusion: HR 1.18, 95% CI 1.04-1.33; (+)sepsis: HR 1.63, 95% CI 1.14-2.31; (+)transfusion/(+)sepsis: HR 2.04, 95% CI 1.58-2.63], and overall survival [(+)transfusion: HR 1.21, 95% CI 1.14-1.29; (+)sepsis: HR 1.76, 95% CI 1.48-2.09; (+)transfusion/(+)sepsis: HR 2.36, 95% CI 2.07-2.68] relative to (-)transfusion/(-)sepsis. Additional analyses suggested an additive effect with those who both received a blood transfusion and developed sepsis having even worse survival. Perioperative blood transfusions are associated with shorter survival

Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

DEFF Research Database (Denmark)

Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

2017-01-01

We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

Hydronephrosis in patients with cervical cancer: an assessment of morbidity and survival.

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Patel, Krishna; Foster, Nathan R; Kumar, Amanika; Grudem, Megan; Longenbach, Sherri; Bakkum-Gamez, Jamie; Haddock, Michael; Dowdy, Sean; Jatoi, Aminah

2015-05-01

Hydronephrosis is a frequently observed but understudied complication in patients with cervical cancer. To better characterize hydronephrosis in cervical cancer patients, the current study sought (1) to describe hydronephrosis-associated morbidity and (2) to analyze the prognostic effect of hydronephrosis in patients with a broad range of cancer stages over time. The Mayo Clinic Tumor Registry was interrogated for all invasive cervical cancer patients seen at the Mayo Clinic from 2008 through 2013 in Rochester, Minnesota; these patients' medical records were then reviewed in detail. Two hundred seventy-nine cervical cancer patients with a median age of 49 years and a range of cancer stages were included. Sixty-five patients (23 %) were diagnosed with hydronephrosis at some point during their disease course. In univariate analyses, hydronephrosis was associated with advanced cancer stage (p hydronephrosis. All but one patient underwent stent placement or urinary diversion; hydronephrosis-related morbidity included pain, urinary tract infections, nausea and vomiting, renal failure, and urinary tract bleeding. In landmark univariate survival analyses, hydronephrosis was associated with worse survival at all time points. In landmark multivariate analyses (adjusted for patient age, stage, cancer treatment, and tumor histology), hydronephrosis was associated with a trend toward worse survival over time (hazard ratios ranged from 1.47 to 4.69). Hydronephrosis in cervical cancer patients is associated with notable morbidity. It is also associated with trends toward worse survival-even if it occurs after the original cancer diagnosis.

Comparison of Adjuvant Radiation Therapy Alone and Chemotherapy Alone in Surgically Resected Low-Grade Gliomas: Survival Analyses of 2253 Cases from the National Cancer Data Base.

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Wu, Jing; Neale, Natalie; Huang, Yuqian; Bai, Harrison X; Li, Xuejun; Zhang, Zishu; Karakousis, Giorgos; Huang, Raymond; Zhang, Paul J; Tang, Lei; Xiao, Bo; Yang, Li

2018-04-01

It is becoming increasingly common to incorporate chemotherapy (CT) with radiotherapy (RT) in the treatment of low-grade gliomas (LGGs) after surgical resection. However, there is a lack of literature comparing survival of patients who underwent RT or CT alone. The U.S. National Cancer Data Base was used to identify patients with histologically confirmed, World Health Organization grade 2 gliomas who received either RT alone or CT alone after surgery from 2004 to 2013. Overall survival (OS) was evaluated by Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and propensity-score-matched analysis. In total, 2253 patients with World Health Organization grade 2 gliomas were included, of whom 1466 (65.1%) received RT alone and 787 (34.9%) CT alone. The median OS was 98.9 months for the RT alone group and 125.8 months for the CT alone group. On multivariable analysis, CT alone was associated with a significant OS benefit compared with RT alone (hazard ratio [HR], 0.405; 95% confidence interval, 0.277-0.592; P < 0.001). On subgroup analyses, the survival advantage of CT alone over RT alone persisted across all age groups, and for the subtotal resection and biopsy groups, but not in the gross total resection group. In propensity-score-matched analysis, CT alone still showed significantly improved OS compared with RT alone (HR, 0.612; 95% confidence interval, 0.506-0.741; P < 0.001). Our results suggest that CT alone was independently associated with longer OS compared with RT alone in patients with LGGs who underwent surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Men and women show similar survival outcome in stage IV breast cancer.

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Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Survival after Out-of-Hospital Cardiac Arrest in Nursing Homes

DEFF Research Database (Denmark)

Pape, Marianne; Rajan, Shahzleen; Hansen, Steen Møller

2018-01-01

BACKGROUND: Survival among nursing home residents who suffers out-of-hospital cardiac arrest (OHCA) is sparsely studied. Deployment of automated external defibrillators (AEDs) in nursing home facilities in Denmark is unknown. We examined 30-day survival following OHCA in nursing and private home...... residents. METHODS: This register-based, nationwide, follow-up study identified OHCA-patients ≥18 years of age with a resuscitation attempt in nursing homes and private homes using Danish Cardiac Arrest Register data from June 1, 2001 to December 31, 2014. The primary outcome measure was 30-day survival....... Multiple logistic regression analyses were used to assess factors potentially associated with survival among nursing and private home residents separately. RESULTS: Of 26,999 OCHAs, 2516 (9.3%) occurred in nursing homes, and 24,483 (90.7%) in private homes. Nursing home residents were older (median 83 (Q1...

Ancient DNA analyses reveal contrasting phylogeographic patterns amongst kiwi (Apteryx spp. and a recently extinct lineage of spotted kiwi.

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Lara D Shepherd

Full Text Available The little spotted kiwi (Apteryx owenii is a flightless ratite formerly found throughout New Zealand but now greatly reduced in distribution. Previous phylogeographic studies of the related brown kiwi (A. mantelli, A. rowi and A. australis, with which little spotted kiwi was once sympatric, revealed extremely high levels of genetic structuring, with mitochondrial DNA haplotypes often restricted to populations. We surveyed genetic variation throughout the present and pre-human range of little spotted kiwi by obtaining mitochondrial DNA sequences from contemporary and ancient samples. Little spotted kiwi and great spotted kiwi (A. haastii formed a monophyletic clade sister to brown kiwi. Ancient samples of little spotted kiwi from the northern North Island, where it is now extinct, formed a lineage that was distinct from remaining little spotted kiwi and great spotted kiwi lineages, potentially indicating unrecognized taxonomic diversity. Overall, little spotted kiwi exhibited much lower levels of genetic diversity and structuring than brown kiwi, particularly through the South Island. Our results also indicate that little spotted kiwi (or at least hybrids involving this species survived on the South Island mainland until more recently than previously thought.

Benign meningiomas: primary treatment selection affects survival

International Nuclear Information System (INIS)

Condra, Kellie S.; Buatti, John M.; Mendenhall, William M.; Friedman, William A.; Marcus, Robert B.; Rhoton, Albert L.

1997-01-01

Purpose: To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. Methods and Materials: For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. Results: At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical; p = 0.0056), and Karnofsky performance status (≥80 vs. <80; p = 0.0153) as significant variables. Conclusion: Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important

Patterns and processes of Mycobacterium bovis evolution revealed by phylogenomic analyses

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Mycobacterium bovis is an important animal pathogen worldwide that parasitizes wild and domesticated vertebrate livestock as well as humans. A comparison of the five M. bovis complete genomes from UK, South Korea, Brazil and USA revealed four novel large-scale structural variations of at least 2,000...

Survival and its predictors from age 75 to 85 in men and women belonging to cohorts with marked survival differences to age 75

DEFF Research Database (Denmark)

Heikkinen, E; Kauppinen, M; Schroll, M

2016-01-01

focusing on different domains of health, functional capacity, and physical and social activities. RESULTS: The proportion of survivors to age 75 was markedly smaller among the Finnish men and women than Danish or Swedish subjects. In the local population no marked differences in survival from age 75 to 85...... among three local Nordic populations using survival data on national cohorts as background information. METHODS: The data were derived from national registers and from samples of 75-year old living in Denmark, Sweden, and Finland. The subjects were invited to take part in interviews and examinations...... were observed between the groups of men, while women survived longer than men and longer in Göteborg than in Glostrup or Jyväskylä. Univariate models revealed 12 predictors of survival. In the multivariate models, the significant predictors among men related to physical fitness, whereas among women...

Integrated in silico Analyses of Regulatory and Metabolic Networks of Synechococcus sp. PCC 7002 Reveal Relationships between Gene Centrality and Essentiality

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Hyun-Seob Song

2015-03-01

Full Text Available Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as “topologically important.” Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termed as “functionally important” genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.

51Cr - erythrocyte survival curves

International Nuclear Information System (INIS)

Paiva Costa, J. de.

1982-07-01

Sixteen patients were studied, being fifteen patients in hemolytic state, and a normal individual as a witness. The aim was to obtain better techniques for the analysis of the erythrocytes, survival curves, according to the recommendations of the International Committee of Hematology. It was used the radiochromatic method as a tracer. Previously a revisional study of the International Literature was made in its aspects inherent to the work in execution, rendering possible to establish comparisons and clarify phonomena observed in cur investigation. Several parameters were considered in this study, hindering both the exponential and the linear curves. The analysis of the survival curves of the erythrocytes in the studied group, revealed that the elution factor did not present a homogeneous answer quantitatively to all, though, the result of the analysis of these curves have been established, through listed programs in the electronic calculator. (Author) [pt

Biofilm formation enhances Helicobacter pylori survivability in vegetables.

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Ng, Chow Goon; Loke, Mun Fai; Goh, Khean Lee; Vadivelu, Jamuna; Ho, Bow

2017-04-01

To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

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Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

2016-01-01

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

Revealing climate modes in steric sea levels: lessons learned from satellite geodesy, objective analyses and ocean reanalyses

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Pfeffer, J.; Tregoning, P.; Purcell, A. P.

2017-12-01

Due to increased greenhouse gases emissions, the oceans are accumulating heat. In response to the ocean circulation and atmospheric forcing, the heat is irregularly redistributed within the oceans, causing sea level to rise at variable rates in space and time. These rates of steric expansion are extremely difficult to assess because of the sparsity of in-situ hydrographic observations available within the course of the 20th century. We compare here three methods to reconstruct the steric sea levels over the past 13, 25 and 58 years based on satellite geodesy, objective analyses and ocean reanalyses. The interannual to decadal variability of each dataset is explored with a model merging six climate indices representative of the natural variability of the ocean and climate system. Consistent regional patterns are identified for the Pacific Decadal Oscillation (PDO) and El Niño Southern Oscillation (ENSO) in all datasets at all timescales. Despite the short time coverage (13 years), the combination of satellite geodetic data (altimetry and GRACE) also reveals significant steric responses to the North Pacific Gyre Oscillation (NPGO), Indian Dipole (IOD) and Indian ocean basinwide (IOBM) mode. The richer information content in the ocean reanalyses allows us to recover the regional fingerprints of the PDO, ENSO, NPGO, IOD and IOBM, but also of the Atlantic Multidecadal Oscillation (AMO) acting over longer time scales (40 to 60 years). Therefore, ocean reanalyses, coupled with climate mode analyses, constitute innovative and promising tools to investigate the mechanisms triggering the variability of sea level rise over the past decades.

Better Rooting Procedure to Enhance Survival Rate of Field Grown Malaysian Eksotika Papaya Transformed with 1-Aminocyclopropane-1-Carboxylic Acid Oxidase Gene

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Sekeli, Rogayah; Abdullah, Janna Ong; Namasivayam, Parameswari; Muda, Pauziah; Abu Bakar, Umi Kalsom

2013-01-01

A high survival rate for transformed papaya plants when transferred to the field is useful in the quest for improving the commercial quality traits. We report in this paper an improved rooting method for the production of transformed Malaysian Eksotika papaya with high survival rate when transferred to the field. Shoots were regenerated from embryogenic calli transformed with antisense and RNAi constructs of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes using the Agrobacterium tumefaciens-mediated transformation method. Regenerated transformed shoots, each measuring approximately 3-4 cm in height, were cultured in liquid half-strength Murashige and Skoog (MS) medium or sterile distilled water, and with either perlite or vermiculite supplementation. All the culturing processes were conducted either under sterile or nonsterile condition. The results showed that rooting under sterile condition was better. Shoots cultured in half-strength MS medium supplemented with vermiculite exhibited a 92.5% rooting efficiency while perlite showed 77.5%. The survival rate of the vermiculite-grown transformed papaya plantlets after transfer into soil, contained in polybags, was 94%, and the rate after transfer into the ground was 92%. Morpho-histological analyses revealed that the tap roots were more compact, which might have contributed to the high survival rates of the plantlets. PMID:25969786

Better rooting procedure to enhance survival rate of field grown malaysian eksotika papaya transformed with 1-aminocyclopropane-1-carboxylic Acid oxidase gene.

Science.gov (United States)

Sekeli, Rogayah; Abdullah, Janna Ong; Namasivayam, Parameswari; Muda, Pauziah; Abu Bakar, Umi Kalsom

2013-01-01

A high survival rate for transformed papaya plants when transferred to the field is useful in the quest for improving the commercial quality traits. We report in this paper an improved rooting method for the production of transformed Malaysian Eksotika papaya with high survival rate when transferred to the field. Shoots were regenerated from embryogenic calli transformed with antisense and RNAi constructs of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) genes using the Agrobacterium tumefaciens-mediated transformation method. Regenerated transformed shoots, each measuring approximately 3-4 cm in height, were cultured in liquid half-strength Murashige and Skoog (MS) medium or sterile distilled water, and with either perlite or vermiculite supplementation. All the culturing processes were conducted either under sterile or nonsterile condition. The results showed that rooting under sterile condition was better. Shoots cultured in half-strength MS medium supplemented with vermiculite exhibited a 92.5% rooting efficiency while perlite showed 77.5%. The survival rate of the vermiculite-grown transformed papaya plantlets after transfer into soil, contained in polybags, was 94%, and the rate after transfer into the ground was 92%. Morpho-histological analyses revealed that the tap roots were more compact, which might have contributed to the high survival rates of the plantlets.

Long-term survival of two dogs after mitral valve plasty

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Isamu Kanemoto

2017-04-01

Full Text Available Two small 9-year-old dogs received mitral valve plasty (MVP for severe mitral regurgitation that could not be controlled via drug administration. MVP consisted of chordal reconstruction using expanded polytetrafluoroethylene (ePTFE sutures and semicircular suture annuloplasty using polypropylene sutures. In both cases, the clinical signs dramatically improved after MVP, although postoperative echocardiography revealed slight residual mitral regurgitant flow. Both dogs survived for several years after MVP without any signs of cardiac distress; one dog survived for 9 years and 1 month, and the other dog survived for 7 years and 10 months. These findings highlight the durability of ePTFE sutures as artificial chordae and the excellence of semicircular suture annuloplasty in small dogs.

Genome-wide Comparative Analyses Reveal the Dynamic Evolution of Nucleotide-Binding Leucine-Rich Repeat Gene Family among Solanaceae Plants

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Eunyoung Seo

2016-08-01

Full Text Available Plants have evolved an elaborate innate immune system against invading pathogens. Within this system, intracellular nucleotide-binding leucine-rich repeat (NLR immune receptors are known play critical roles in effector-triggered immunity (ETI plant defense. We performed genome-wide identification and classification of NLR-coding sequences from the genomes of pepper, tomato, and potato using fixed criteria. We then compared genomic duplication and evolution features. We identified intact 267, 443, and 755 NLR-encoding genes in tomato, potato, and pepper genomes, respectively. Phylogenetic analyses and classification of Solanaceae NLRs revealed that the majority of NLR super family members fell into 14 subgroups, including a TIR-NLR (TNL subgroup and 13 non-TNL subgroups. Specific subgroups have expanded in each genome, with the expansion in pepper showing subgroup-specific physical clusters. Comparative analysis of duplications showed distinct duplication patterns within pepper and among Solanaceae plants suggesting subgroup- or species-specific gene duplication events after speciation, resulting in divergent evolution. Taken together, genome-wide analyses of NLR family members provide insights into their evolutionary history in Solanaceae. These findings also provide important foundational knowledge for understanding NLR evolution and will empower broader characterization of disease resistance genes to be used for crop breeding.

Multivariate analyses to assess the effects of surgeon and hospital volume on cancer survival rates: a nationwide population-based study in Taiwan.

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Chun-Ming Chang

Full Text Available BACKGROUND: Positive results between caseloads and outcomes have been validated in several procedures and cancer treatments. However, there is limited information available on the combined effects of surgeon and hospital caseloads. We used nationwide population-based data to explore the association between surgeon and hospital caseloads and survival rates for major cancers. METHODOLOGY: A total of 11,677 patients with incident cancer diagnosed in 2002 were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity scores were used to assess the relationship between 5-year survival rates and different caseload combinations. RESULTS: Based on the Cox proportional hazard model, cancer patients treated by low-volume surgeons in low-volume hospitals had poorer survival rates, and hazard ratios ranged from 1.3 in head and neck cancer to 1.8 in lung cancer after adjusting for patients' demographic variables, co-morbidities, and treatment modality. When analyzed using the propensity scores, the adjusted 5-year survival rates were poorer for patients treated by low-volume surgeons in low-volume hospitals, compared to those treated by high-volume surgeons in high-volume hospitals (P<0.005. CONCLUSIONS: After adjusting for differences in the case mix, cancer patients treated by low-volume surgeons in low-volume hospitals had poorer 5-year survival rates. Payers may implement quality care improvement in low-volume surgeons.

Bibliometric Analyses Reveal Patterns of Collaboration between ASMS Members

Science.gov (United States)

Palmblad, Magnus; van Eck, Nees Jan

2018-03-01

We have explored the collaborative network of the current American Society for Mass Spectrometry (ASMS) membership using bibliometric methods. The analysis shows that 4249 members are connected in a single, large, co-authorship graph, including the majority of the most published authors in the field of mass spectrometry. The map reveals topographical differences between university groups and national laboratories, and that the co-authors with the strongest links have long worked together at the same location. We have collected and summarized information on the geographical distribution of members, showing a high coverage of active researchers in North America and Western Europe. Looking at research fields, we could also identify a number of new or `hot' topics among ASMS members. Interactive versions of the maps are available on-line at https://goo.gl/UBNFMQ (collaborative network) and https://goo.gl/WV25vm (research topics). [Figure not available: see fulltext.

Survival outcomes following salvage surgery for oropharyngeal squamous cell carcinoma: systematic review.

Science.gov (United States)

Kao, S S; Ooi, E H

2018-04-01

Recurrent oropharyngeal squamous cell carcinoma causes great morbidity and mortality. This systematic review analyses survival outcomes following salvage surgery for recurrent oropharyngeal squamous cell carcinoma. A comprehensive search of various electronic databases was conducted. Studies included patients with recurrent or residual oropharyngeal squamous cell carcinoma treated with salvage surgery. Primary outcomes were survival rates following salvage surgery. Secondary outcomes included time to recurrence, staging at time of recurrence, post-operative complications, and factors associated with mortality and recurrence. Methodological appraisal and data extraction were conducted as per Joanna Briggs Institute methodology. Eighteen articles were included. The two- and five-year survival rates of the patients were 52 per cent and 30 per cent respectively. Improvements in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were associated with improvements in two-year overall survival rates, with minimal change to five-year overall survival rates. Various factors were identified as being associated with long-term overall survival, thus assisting clinicians in patient counselling and selection for salvage surgery.

Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

Science.gov (United States)

Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

2016-10-03

FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

Chronic consequences of acute injuries: worse survival after discharge.

Science.gov (United States)

Shafi, Shahid; Renfro, Lindsay A; Barnes, Sunni; Rayan, Nadine; Gentilello, Larry M; Fleming, Neil; Ballard, David

2012-09-01

The Trauma Quality Improvement Program uses inhospital mortality to measure quality of care, which assumes patients who survive injury are not likely to suffer higher mortality after discharge. We hypothesized that survival rates in trauma patients who survive to discharge remain stable afterward. Patients treated at an urban Level I trauma center (2006-2008) were linked with the Social Security Administration Death Master File. Survival rates were measured at 30, 90, and 180 days and 1 and 2 years from injury among two groups of trauma patients who survived to discharge: major trauma (Abbreviated Injury Scale score ≥ 3 injuries, n = 2,238) and minor trauma (Abbreviated Injury Scale score ≤ 2 injuries, n = 1,171). Control groups matched to each trauma group by age and sex were simulated from the US general population using annual survival probabilities from census data. Kaplan-Meier and log-rank analyses conditional upon survival to each time point were used to determine changes in risk of mortality after discharge. Cox proportional hazards models with left truncation at the time of discharge were used to determine independent predictors of mortality after discharge. The survival rate in trauma patients with major injuries was 92% at 30 days posttrauma and declined to 84% by 3 years (p > 0.05 compared with general population). Minor trauma patients experienced a survival rate similar to the general population. Age and injury severity were the only independent predictors of long-term mortality given survival to discharge. Log-rank tests conditional on survival to each time point showed that mortality risk in patients with major injuries remained significantly higher than the general population for up to 6 months after injury. The survival rate of trauma patients with major injuries remains significantly lower than survival for minor trauma patients and the general population for several months postdischarge. Surveillance for early identification and treatment of

Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation: long-term results from the Bio-CAPTURE registry.

Science.gov (United States)

van den Reek, J M P A; Tummers, M; Zweegers, J; Seyger, M M B; van Lümig, P P M; Driessen, R J B; van de Kerkhof, P C M; Kievit, W; de Jong, E M G J

2015-03-01

Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P = 0.02). Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment. © 2014 European Academy of Dermatology and Venereology.

Incidence and survival from lung cancer in Greenland is comparable to survival in the Nordic countries

DEFF Research Database (Denmark)

Gelvan, Allan; Risum, Signe; Langer, Seppo W

2015-01-01

INTRODUCTION: Oncological treatment of lung cancer has been available in Greenland since 2004. We evaluated patient characteristics and survival rates for the first six years of local lung cancer treatment. METHODS: From September 2004 to August 2010, a total of 173 patients with lung cancer were...... referred to treatment at Queen Ingrid's Hospital. On 1 February 2014, treatment results, survival, and prognostic variables were analysed. RESULTS: The mean age at diagnosis was 63 years. Non-small cell lung cancer (NSCLC) was diagnosed in 145 patients (84%); 56% had squamous cell carcinoma, 34% had...... adenocarcinoma, 2% had large cell carcinoma and 8% had NSCLC not otherwise specified (NOS). In all, 28 (16%) had small cell lung cancer. A total of 142 patients (82%) received treatment; 20 underwent surgery (ten stage Ib, one stage IIa, five stage IIb, four stage IIIa); palliative chemotherapy was given to 122...

Impact of delay to treatment upon survival in 1067 patients with breast-cancer.

Science.gov (United States)

Rabinovich, M; Vallejo, C; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Lacava, J; Leone, B; Romero, A; Mickiewicz, E; Chacon, R; Estevez, R

1993-02-01

The medical records of 1067 patients with breast cancer were reviewed to evaluate the influence of delay between first symptom and first treatment upon survival. Three delay intervals were considered: 6 months. At a follow-up of 120 months, survival analyses identified a statistically significant difference (p=0.029) favoring patients with 3 months delay between first symptom and first treatment. Better survival rate for patients with a short delay would obey to a greater number of patients in favorable stages and a higher proportion of women aged 50 or older in this group.

Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.

Science.gov (United States)

Smith, Matthew R; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

2013-10-20

Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.

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

Science.gov (United States)

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

2017-09-01

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

Integrated survival analysis using an event-time approach in a Bayesian framework.

Science.gov (United States)

Walsh, Daniel P; Dreitz, Victoria J; Heisey, Dennis M

2015-02-01

Event-time or continuous-time statistical approaches have been applied throughout the biostatistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. This has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed an integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. This provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤ 4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest at birth weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data.

Integrated survival analysis using an event-time approach in a Bayesian framework

Science.gov (United States)

Walsh, Daniel P.; Dreitz, VJ; Heisey, Dennis M.

2015-01-01

Event-time or continuous-time statistical approaches have been applied throughout the biostatistical literature and have led to numerous scientific advances. However, these techniques have traditionally relied on knowing failure times. This has limited application of these analyses, particularly, within the ecological field where fates of marked animals may be unknown. To address these limitations, we developed an integrated approach within a Bayesian framework to estimate hazard rates in the face of unknown fates. We combine failure/survival times from individuals whose fates are known and times of which are interval-censored with information from those whose fates are unknown, and model the process of detecting animals with unknown fates. This provides the foundation for our integrated model and permits necessary parameter estimation. We provide the Bayesian model, its derivation, and use simulation techniques to investigate the properties and performance of our approach under several scenarios. Lastly, we apply our estimation technique using a piece-wise constant hazard function to investigate the effects of year, age, chick size and sex, sex of the tending adult, and nesting habitat on mortality hazard rates of the endangered mountain plover (Charadrius montanus) chicks. Traditional models were inappropriate for this analysis because fates of some individual chicks were unknown due to failed radio transmitters. Simulations revealed biases of posterior mean estimates were minimal (≤ 4.95%), and posterior distributions behaved as expected with RMSE of the estimates decreasing as sample sizes, detection probability, and survival increased. We determined mortality hazard rates for plover chicks were highest at birth weights and/or whose nest was within agricultural habitats. Based on its performance, our approach greatly expands the range of problems for which event-time analyses can be used by eliminating the need for having completely known fate data.

Newborn survival in Malawi: a decade of change and future implications.

Science.gov (United States)

Zimba, Evelyn; Kinney, Mary V; Kachale, Fannie; Waltensperger, Karen Z; Blencowe, Hannah; Colbourn, Tim; George, Joby; Mwansambo, Charles; Joshua, Martias; Chanza, Harriet; Nyasulu, Dorothy; Mlava, Grace; Gamache, Nathalie; Kazembe, Abigail; Lawn, Joy E

2012-07-01

Malawi is one of two low-income sub-Saharan African countries on track to meet the Millennium Development Goal (MDG 4) for child survival despite high fertility and HIV and low health worker density. With neonatal deaths becoming an increasing proportion of under-five deaths, addressing newborn survival is critical for achieving MDG 4. We examine change for newborn survival in the decade 2000-10, analysing mortality and coverage indicators whilst considering other contextual factors. We assess national and donor funding, as well as policy and programme change for newborn survival using standard analyses and tools being applied as part of a multi-country analysis. Compared with the 1990s, progress towards MDG 4 and 5 accelerated considerably from 2000 to 2010. Malawi's neonatal mortality rate (NMR) reduced slower than annual reductions in mortality for children 1-59 months and maternal mortality (NMR reduced 3.5% annually). Yet, the NMR reduced at greater pace than the regional and global averages. A significant increase in facility births and other health system changes, including increased human resources, likely contributed to this decline. High level attention for maternal health and associated comprehensive policy change has provided a platform for a small group of technical and programme experts to link in high impact interventions for newborn survival. The initial entry point for newborn care in Malawi was mainly through facility initiatives, such as Kangaroo Mother Care. This transitioned to an integrated and comprehensive approach at community and facility level through the Community-Based Maternal and Newborn Care package, now being implemented in 17 of 28 districts. Addressing quality gaps, especially for care at birth in facilities, and including newborn interventions in child health programmes, will be critical to the future agenda of newborn survival in Malawi.

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

Science.gov (United States)

Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

2015-12-01

Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells

Directory of Open Access Journals (Sweden)

Andrew Parker

2015-12-01

Full Text Available Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182 in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss.

Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials.

Science.gov (United States)

Aoyama, Toru; Kashiwabara, Kosuke; Oba, Koji; Honda, Michitaka; Sadahiro, Sotaro; Hamada, Chikuma; Maeda, Hiromichi; Mayanagi, Shuhei; Kanda, Mitsuro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

2017-11-01

The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Long survival in a patient with metastatic colorrectal carcinoma: reality or utopia?

Science.gov (United States)

Illán, Andrea; Aires, Jonathan; Quintana, Laura

2017-09-01

We report the case of a 42-year-old male patient with mucinous-type metastatic colorectal carcinoma of eight years of evolution. He has received multiple lines of cytostatic treatment with acceptable tolerance and without significant impairment in his quality of life. At present, it is estimated that the overall survival of metastatic colon cancer in cytostatic treatment is around 24 months. However, a small subset of patients may present prolonged survivals of 5 to 10 years after diagnosis, revealing heterogeneity of tumor behavior and response to treatment. Our clinical case represents a long survivor patient despite the advanced stage of his oncological mucinous-colorrectal disease, endorsed in the scientific literature as having worse rates of objective response and less survival. There are different therapeutic approaches that can achieve a significant overall survival. It is essential in clinical practice to use all drugs available to achieve increase of progression-free survival and overall survival, with maintenance of an adequate quality of life.

Neyman, Markov processes and survival analysis.

Science.gov (United States)

Yang, Grace

2013-07-01

J. Neyman used stochastic processes extensively in his applied work. One example is the Fix and Neyman (F-N) competing risks model (1951) that uses finite homogeneous Markov processes to analyse clinical trials with breast cancer patients. We revisit the F-N model, and compare it with the Kaplan-Meier (K-M) formulation for right censored data. The comparison offers a way to generalize the K-M formulation to include risks of recovery and relapses in the calculation of a patient's survival probability. The generalization is to extend the F-N model to a nonhomogeneous Markov process. Closed-form solutions of the survival probability are available in special cases of the nonhomogeneous processes, like the popular multiple decrement model (including the K-M model) and Chiang's staging model, but these models do not consider recovery and relapses while the F-N model does. An analysis of sero-epidemiology current status data with recurrent events is illustrated. Fix and Neyman used Neyman's RBAN (regular best asymptotic normal) estimates for the risks, and provided a numerical example showing the importance of considering both the survival probability and the length of time of a patient living a normal life in the evaluation of clinical trials. The said extension would result in a complicated model and it is unlikely to find analytical closed-form solutions for survival analysis. With ever increasing computing power, numerical methods offer a viable way of investigating the problem.

Identification of novel genetic markers of breast cancer survival

DEFF Research Database (Denmark)

Guo, Qi; Schmidt, Marjanka K; Kraft, Peter

2015-01-01

BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis ......BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta......-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference...... panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24...

Northern Bobwhite (Colinus virginianus Mitochondrial Population Genomics Reveals Structure, Divergence, and Evidence for Heteroplasmy.

Directory of Open Access Journals (Sweden)

Yvette A Halley

Full Text Available Herein, we evaluated the concordance of population inferences and conclusions resulting from the analysis of short mitochondrial fragments (i.e., partial or complete D-Loop nucleotide sequences versus complete mitogenome sequences for 53 bobwhites representing six ecoregions across TX and OK (USA. Median joining (MJ haplotype networks demonstrated that analyses performed using small mitochondrial fragments were insufficient for estimating the true (i.e., complete mitogenome haplotype structure, corresponding levels of divergence, and maternal population history of our samples. Notably, discordant demographic inferences were observed when mismatch distributions of partial (i.e., partial D-Loop versus complete mitogenome sequences were compared, with the reduction in mitochondrial genomic information content observed to encourage spurious inferences in our samples. A probabilistic approach to variant prediction for the complete bobwhite mitogenomes revealed 344 segregating sites corresponding to 347 total mutations, including 49 putative nonsynonymous single nucleotide variants (SNVs distributed across 12 protein coding genes. Evidence of gross heteroplasmy was observed for 13 bobwhites, with 10 of the 13 heteroplasmies involving one moderate to high frequency SNV. Haplotype network and phylogenetic analyses for the complete bobwhite mitogenome sequences revealed two divergent maternal lineages (dXY = 0.00731; FST = 0.849; P < 0.05, thereby supporting the potential for two putative subspecies. However, the diverged lineage (n = 103 variants almost exclusively involved bobwhites geographically classified as Colinus virginianus texanus, which is discordant with the expectations of previous geographic subspecies designations. Tests of adaptive evolution for functional divergence (MKT, frequency distribution tests (D, FS and phylogenetic analyses (RAxML provide no evidence for positive selection or hybridization with the sympatric scaled quail

Interspecies introgressive hybridization in spiny frogs Quasipaa (Family Dicroglossidae) revealed by analyses on multiple mitochondrial and nuclear genes.

Science.gov (United States)

Zhang, Qi-Peng; Hu, Wen-Fang; Zhou, Ting-Ting; Kong, Shen-Shen; Liu, Zhi-Fang; Zheng, Rong-Quan

2018-01-01

Introgression may lead to discordant patterns of variation among loci and traits. For example, previous phylogeographic studies on the genus Quasipaa detected signs of genetic introgression from genetically and morphologically divergent Quasipaa shini or Quasipaa spinosa . In this study, we used mitochondrial and nuclear DNA sequence data to verify the widespread introgressive hybridization in the closely related species of the genus Quasipaa , evaluate the level of genetic diversity, and reveal the formation mechanism of introgressive hybridization. In Longsheng, Guangxi Province, signs of asymmetrical nuclear introgression were detected between Quasipaa boulengeri and Q. shini . Unidirectional mitochondrial introgression was revealed from Q. spinosa to Q. shini . By contrast, bidirectional mitochondrial gene introgression was detected between Q. spinosa and Q. shini in Lushan, Jiangxi Province. Our study also detected ancient hybridizations between a female Q. spinosa and a male Q. jiulongensis in Zhejiang Province. Analyses on mitochondrial and nuclear genes verified three candidate cryptic species in Q. spinosa , and a cryptic species may also exist in Q. boulengeri . However, no evidence of introgressive hybridization was found between Q. spinosa and Q. boulengeri . Quasipaa exilispinosa from all the sampling localities appeared to be deeply divergent from other communities. Our results suggest widespread introgressive hybridization in closely related species of Quasipaa and provide a fundamental basis for illumination of the forming mechanism of introgressive hybridization, classification of species, and biodiversity assessment in Quasipaa .

Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

International Nuclear Information System (INIS)

Rumbajan, Janette Mareska; Aoki, Shigehisa; Kohashi, Kenichi; Oda, Yoshinao; Hata, Kenichiro; Saji, Tsutomu; Taguchi, Tomoaki; Tajiri, Tatsuro; Soejima, Hidenobu; Joh, Keiichiro; Maeda, Toshiyuki; Souzaki, Ryota; Mitsui, Kazumasa; Higashimoto, Ken; Nakabayashi, Kazuhiko; Yatsuki, Hitomi; Nishioka, Kenichi; Harada, Ryoko

2013-01-01

Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma

Three genetic stocks of frigate tuna Auxis thazard thazard (Lacepede, 1800) along the Indian coast revealed from sequence analyses of mitochondrial DNA D-loop region

Digital Repository Service at National Institute of Oceanography (India)

GirishKumar; Kunal, S.P.; Menezes, M.R.; Meena, R.M.

revealed from sequence analyses of mitochondrial DNA D-loop region Name of authors: 1. Girish Kumar* Biological Oceanography Division (BOD) National Institute of Oceanography (NIO) Dona Paula, Goa 403004, India. Email: girishkumar....nio@gmail.com Tel: +919766548060 2. Swaraj Priyaranjan Kunal Biological Oceanography Division (BOD) National Institute of Oceanography (NIO) Dona Paula, Goa 403004, India. Email: swar.mbt@gmail.com 3. Maria Rosalia Menezes Biological Oceanography...

Survival in systemic lupus erythematosus, 1995-2010

DEFF Research Database (Denmark)

Voss, A; Laustrup, H; Hjelmborg, J

2013-01-01

ObjectiveThe objective of this paper is to investigate survival and causes of death in a Danish lupus population.MethodsTwo hundred and fifteen SLE patients (94% Caucasians) were followed prospectively for up to 16 years. Thirty-eight patients died. Survival rate and causes of death were analysed......%) and malignancies (13%). Deaths due to infections and active SLE were rare and predominated within the first seven years after diagnosis and before age 40, while cardiovascular deaths prevailed after 20 years' follow-up.ConclusionThis study shows that despite progress in lupus management, including direct access...... to specialized hospital care and increased use of hydroxychloroquine, mortality in lupus patients is still increased. Main causes of death were active disease and infections among the young and newly diagnosed, while cardiovascular deaths prevailed in longstanding disease....

ER and PR expression and survival after endometrial cancer.

Science.gov (United States)

Smith, Deborah; Stewart, Colin J R; Clarke, Edward M; Lose, Felicity; Davies, Claire; Armes, Jane; Obermair, Andreas; Brennan, Donal; Webb, Penelope M; Nagle, Christina M; Spurdle, Amanda B

2018-02-01

To measure association between endometrial carcinoma ER and PR status and endometrial cancer (EC) survival, accounting for inter-observer variation. The intensity and proportion of tumor cell expression of ER and PR in ECs were assessed independently and semi-quantitatively by two pathologists using digital images of duplicate tumor tissue microarrays (TMAs). Cases with inconsistent initial assessment were reviewed and final scoring agreed. The association between overall and EC-specific survival and hormone receptor expression (intensity, proportion and combined) was assessed using Cox regression analysis. The C-index was used to evaluate model discrimination with addition of ER and PR status. Tumor ER and PR analysis was possible in 659 TMAs from 255 patients, and in 459 TMAs from 243 patients, respectively. Initial ER and PR scoring was consistent in 82% and 80% of cases, respectively. In multivariate analyses decreased ER and PR expression was associated with increased tumor-related mortality. Associations reached statistical significance for ER proportion score (P=0.05), ER intensity score (P=0.003), and PR combined score (P=0.04). Decreased expression of combined ER/PR expression was associated with poorer EC-specific survival than decreased expression of either hormone receptor alone (P=0.005). However, hormone receptor status did not significantly improve mortality prediction in individual cases. ER and PR expression combined, using cut-points that capture variation in scoring and across cores, is significantly associated with EC-specific survival in analyses adjusting for known prognostic factors. However, at the individual level, ER and PR expression does not improve mortality prediction. Copyright © 2017 Elsevier Inc. All rights reserved.

Integrative analysis of survival-associated gene sets in breast cancer.

Science.gov (United States)

Varn, Frederick S; Ung, Matthew H; Lou, Shao Ke; Cheng, Chao

2015-03-12

Patient gene expression information has recently become a clinical feature used to evaluate breast cancer prognosis. The emergence of prognostic gene sets that take advantage of these data has led to a rich library of information that can be used to characterize the molecular nature of a patient's cancer. Identifying robust gene sets that are consistently predictive of a patient's clinical outcome has become one of the main challenges in the field. We inputted our previously established BASE algorithm with patient gene expression data and gene sets from MSigDB to develop the gene set activity score (GSAS), a metric that quantitatively assesses a gene set's activity level in a given patient. We utilized this metric, along with patient time-to-event data, to perform survival analyses to identify the gene sets that were significantly correlated with patient survival. We then performed cross-dataset analyses to identify robust prognostic gene sets and to classify patients by metastasis status. Additionally, we created a gene set network based on component gene overlap to explore the relationship between gene sets derived from MSigDB. We developed a novel gene set based on this network's topology and applied the GSAS metric to characterize its role in patient survival. Using the GSAS metric, we identified 120 gene sets that were significantly associated with patient survival in all datasets tested. The gene overlap network analysis yielded a novel gene set enriched in genes shared by the robustly predictive gene sets. This gene set was highly correlated to patient survival when used alone. Most interestingly, removal of the genes in this gene set from the gene pool on MSigDB resulted in a large reduction in the number of predictive gene sets, suggesting a prominent role for these genes in breast cancer progression. The GSAS metric provided a useful medium by which we systematically investigated how gene sets from MSigDB relate to breast cancer patient survival. We used

Survival Strategies and Sustainability of Small and Medium Enterprises in the Oshodi-Isolo Local Government Area of Lagos State

Directory of Open Access Journals (Sweden)

Ifekwem Nkiruka

2016-12-01

Full Text Available Small and medium enterprises (SMEs play an essential role in the sustainable development of countries. They help in employment generation, industrial production increase, and export, social enrichment as well as political stability. This study investigates the survival strategies and sustainability of SMEs using selected small businesses in the Oshodi-Isolo Local Government Area, Lagos State. It examines the type of growth strategies that SMEs adopt, ascertains what influences their survival strategies as well as the challenges that hinder their growth. Fifty (50 SMEs were randomly sampled. Their owners and managers were interviewed using questionnaires. Data collected were analysed using descriptive statistics and Pearson product–moment correlation coefficient statistics. Our findings reveal that there is a statistically significant relationship between survival strategies and SMEs’ sustainability. The major implication of the findings is that maintaining small but committed and motivated employees is critical in guaranteeing the survival of the SMEs in a volatile economy. The study recommends that there be a need for orientation and educational programmes to change the mindset of business owners to enable them to graduate from sole atomistic proprietor devoid of modern scientific business practice and effective succession to corporate status with an apparatus of modern business management practices and corporate vision. Finally, the study further suggests some imperatives for policy makers concerned with promoting small businesses’ growth and sustainability in the Oshodi-Isolo Local Government Area of Lagos State.

A new scoring system for predicting survival in patients with non-small cell lung cancer

International Nuclear Information System (INIS)

Schild, Steven E; Tan, Angelina D; Wampfler, Jason A; Ross, Helen J; Yang, Ping; Sloan, Jeff A

2015-01-01

This analysis was performed to create a scoring system to estimate the survival of patients with non-small cell lung cancer (NSCLC). Data from 1274 NSCLC patients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor. Prognostic factors that were significant on both UV and MV analyses were used to develop the score. These included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking cessation. The score for each factor was determined by dividing the 5-year survival rate (%) by 10 and summing these scores to form a total score. MV models and the score were validated using bootstrapping with 1000 iterations from the original samples. The score for each prognostic factor ranged from 1 to 7 points with higher scores reflective of better survival. Total scores (sum of the scores from each independent prognostic factor) of 32–37 correlated with a 5-year survival of 8.3% (95% CI = 0–17.1%), 38–43 correlated with a 5-year survival of 20% (95% CI = 13–27%), 44–47 correlated with a 5-year survival of 48.3% (95% CI = 41.5–55.2%), 48–49 correlated to a 5-year survival of 72.1% (95% CI = 65.6–78.6%), and 50–52 correlated to a 5-year survival of 84.7% (95% CI = 79.6–89.8%). The bootstrap method confirmed the reliability of the score. Prognostic factors significantly associated with survival on both UV and MV analyses were used to construct a valid scoring system that can be used to predict survival of NSCLC patients. Optimally, this score could be used when counseling patients, and designing future trials

Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

International Nuclear Information System (INIS)

O'Higgins, N.; Brady, H.R.; Clark, C.G.

1984-01-01

A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

Estimating Probability of Default on Peer to Peer Market – Survival Analysis Approach

Directory of Open Access Journals (Sweden)

Đurović Andrija

2017-05-01

Full Text Available Arguably a cornerstone of credit risk modelling is the probability of default. This article aims is to search for the evidence of relationship between loan characteristics and probability of default on peer-to-peer (P2P market. In line with that, two loan characteristics are analysed: 1 loan term length and 2 loan purpose. The analysis is conducted using survival analysis approach within the vintage framework. Firstly, 12 months probability of default through the cycle is used to compare riskiness of analysed loan characteristics. Secondly, log-rank test is employed in order to compare complete survival period of cohorts. Findings of the paper suggest that there is clear evidence of relationship between analysed loan characteristics and probability of default. Longer term loans are more risky than the shorter term ones and the least risky loans are those used for credit card payoff.

Breast cancer data analysis for survivability studies and prediction.

Science.gov (United States)

Shukla, Nagesh; Hagenbuchner, Markus; Win, Khin Than; Yang, Jack

2018-03-01

Breast cancer is the most common cancer affecting females worldwide. Breast cancer survivability prediction is challenging and a complex research task. Existing approaches engage statistical methods or supervised machine learning to assess/predict the survival prospects of patients. The main objectives of this paper is to develop a robust data analytical model which can assist in (i) a better understanding of breast cancer survivability in presence of missing data, (ii) providing better insights into factors associated with patient survivability, and (iii) establishing cohorts of patients that share similar properties. Unsupervised data mining methods viz. the self-organising map (SOM) and density-based spatial clustering of applications with noise (DBSCAN) is used to create patient cohort clusters. These clusters, with associated patterns, were used to train multilayer perceptron (MLP) model for improved patient survivability analysis. A large dataset available from SEER program is used in this study to identify patterns associated with the survivability of breast cancer patients. Information gain was computed for the purpose of variable selection. All of these methods are data-driven and require little (if any) input from users or experts. SOM consolidated patients into cohorts of patients with similar properties. From this, DBSCAN identified and extracted nine cohorts (clusters). It is found that patients in each of the nine clusters have different survivability time. The separation of patients into clusters improved the overall survival prediction accuracy based on MLP and revealed intricate conditions that affect the accuracy of a prediction. A new, entirely data driven approach based on unsupervised learning methods improves understanding and helps identify patterns associated with the survivability of patient. The results of the analysis can be used to segment the historical patient data into clusters or subsets, which share common variable values and

B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

Science.gov (United States)

Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

2018-06-01

The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (Pcolorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P55 years) and reduced overall survival (Pcolorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in young Chinese patients with colorectal carcinoma.

Determinants of survival after liver resection for metastatic colorectal carcinoma.

Science.gov (United States)

Parau, Angela; Todor, Nicolae; Vlad, Liviu

2015-01-01

Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate

Survival and maturation rates of the African rodent Mastomys natalensis

DEFF Research Database (Denmark)

Sluydts, Vincent; Crespin, Laurent; Davis, Stephen

2008-01-01

the model fit. On the other hand we showed that maturation rates were correlated negatively with density the previous month and positively to cumulative rainfall over the past three months. Survival estimates of both adults and subadults varied seasonally, with higher estimates during the increase phase......Survival and maturation rates of female Mastomys natalensis were analysed based on a ten-year onthly capture-recapture data set. We investigated whether direct and delayed density dependent and independent (rainfall) variables accounted for the considerable variation in demographic traits....... It was estimated that seasonal and annual covariates accounted for respectively 29 and 26% of the total variation in maturation rates and respectively 17 and 11% of the variation in survival rates. Explaining the between-year differences in maturation rates with annual past rainfall or density did not improve...

CT findings associated with survival in chronic hypersensitivity pneumonitis

International Nuclear Information System (INIS)

Chung, Jonathan H.; Montner, Steven M.; Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E.; Oldham, Justin M.; Husain, Aliya N.

2017-01-01

To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

CT findings associated with survival in chronic hypersensitivity pneumonitis

Energy Technology Data Exchange (ETDEWEB)

Chung, Jonathan H.; Montner, Steven M. [University of Chicago Medical Center, Department of Radiology, Chicago, IL (United States); Adegunsoye, Ayodeji; Vij, Rekha; Noth, Imre; Strek, Mary E. [University of Chicago Medical Center, Section of Pulmonary/Critical Care, Department of Medicine, Chicago, IL (United States); Oldham, Justin M. [University of California at Davis, Section of Pulmonary/Critical Care, Department of Medicine, Sacramento, CA (United States); Husain, Aliya N. [University of Chicago Medical Center, Department of Pathology, Chicago, IL (United States)

2017-12-15

To identify CT findings in chronic hypersensitivity pneumonitis (cHP) associated with survival. Two thoracic radiologists assessed CT scans for specific imaging findings and patterns in 132 subjects with cHP. Survival analyses were performed. The majority of subjects had an inconsistent with usual interstitial pneumonitis pattern on CT (55.3%,73/132). Hypersensitivity pneumonitis (HP) diagnosis on CT was less common in those with fibrosis (66.1%, 74/112) than those without fibrosis (85%,17/20). Smoking was associated with a lower prevalence of HP on CT (p=0.04). CT features of pulmonary fibrosis, especially traction bronchiectasis (HR 8.34, 95% CI 1.98-35.21) and increased pulmonary artery (PA)/aorta ratio (HR 2.49, 95% CI 1.27-4.89) were associated with worse survival, while ground-glass opacity (HR 0.31, 95% CI 0.12-0.79) was associated with improved survival. Survival association with imaging was less pronounced after adjustment for gender, age and physiology score. A substantial proportion of cHP cases have a non-HP-like appearance. Ground-glass opacity, pulmonary fibrosis features and elevated PA/aorta ratio on CT likely reflect varying degrees of disease severity in cHP and may inform future clinical prediction models. (orig.)

Toxigenic potential and heat survival of spore-forming bacteria isolated from bread and ingredients.

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De Bellis, Palmira; Minervini, Fiorenza; Di Biase, Mariaelena; Valerio, Francesca; Lavermicocca, Paola; Sisto, Angelo

2015-03-16

Fifty-four spore-forming bacterial strains isolated from bread ingredients and bread, mainly belonging to the genus Bacillus (including Bacillus cereus), together with 11 reference strains were investigated to evaluate their cytotoxic potential and heat survival in order to ascertain if they could represent a risk for consumer health. Therefore, we performed a screening test of cytotoxic activity on HT-29 cells using bacterial culture filtrates after growing bacterial cells in Brain Heart Infusion medium and in the bread-based medium Bread Extract Broth (BEB). Moreover, immunoassays and PCR analyses, specifically targeting already known toxins and related genes of B. cereus, as well as a heat spore inactivation assay were carried out. Despite of strain variability, the results clearly demonstrated a high cytotoxic activity of B. cereus strains, even if for most of them it was significantly lower in BEB medium. Cytotoxic activity was also detected in 30% of strains belonging to species different from B. cereus, although, with a few exceptions (e.g. Bacillus simplex N58.2), it was low or very low. PCR analyses detected the presence of genes involved in the production of NHE, HBL or CytK toxins in B. cereus strains, while genes responsible for cereulide production were not detected. Production of NHE and HBL toxins was also confirmed by specific immunoassays only for B. cereus strains even if PCR analyses revealed the presence of related toxin genes also in some strains of other species. Viable spore count was ascertained after a heat treatment simulating the bread cooking process. Results indicated that B. amyloliquefaciens strains almost completely survived the heat treatment showing less than 2 log-cycle reductions similarly to two strains of B. cereus group III and single strains belonging to Bacillus subtilis, Bacillus mojavensis and Paenibacillus spp. Importantly, spores from strains of the B. cereus group IV exhibited a thermal resistance markedly lower than B

Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

International Nuclear Information System (INIS)

Crispo, Anna; Esposito, Emanuela; Amore, Alfonso; Di Bonito, Maurizio; Botti, Gerardo; Montella, Maurizio; Barba, Maddalena; D’Aiuto, Giuseppe; De Laurentiis, Michelino; Grimaldi, Maria; Rinaldo, Massimo; Caolo, Giuseppina; D’Aiuto, Massimiliano; Capasso, Immacolata

2013-01-01

Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology

Survival study of enterotoxigenic Escherichia colistrain in seawater and wastewater microcosms.

Science.gov (United States)

Boukef Ben Omrane, I; El Bour, M; Mejri, S; Mraouna, R; Got, P; Troussellier, M; Boudabous, A

2011-01-01

In order to survey osmotic and oligotrophic stress consequence on pathogenic enterobacteria discharged in marine areas, we examined enterotoxigenic Escherichia coli (ETEC) and a reference (Ecoli O126:B16) strains during their survival (47 days) in wastewater microcosms, submerged in natural seawater and maintained in laboratory conditions. The results revealed that the survival time for the two strains was prolonged when bacterial cells were previously incubated in wastewater, with less cellular membrane damage. In addition, the wild clinical E. coli strain showed a better survival capacity than the reference E. coli strain one. For both, we noted some modifications in biochemical profiles relatively to the initial state, notably when they were previously incubated in wastewater microcosm.

The validity of EORTC GBM prognostic calculator on survival of GBM patients in the West of Scotland.

Science.gov (United States)

Teo, Mario; Clark, Brian; MacKinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

2014-06-01

It is now accepted that the addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) significantly improves survival. In 2008, a subanalysis of the original study data was performed, and an online "GBM Calculator" was made available on the European Organisation for Research and Treatment of Cancer (EORTC) website allowing users to estimate patients' survival outcomes. We tested this calculator against actual local survival data to validate its use in our patients. Prospectively collected clinical data were analysed on 105 consecutive patients receiving concurrent chemoradiotherapy following surgical treatment of GBM between December 2004 and February 2009. Using the EORTC online calculator, survival outcomes were generated for these patients and compared with their actual survival. The median overall survival for the entire cohort was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival of 65.7% and 19%, respectively. This is in comparison to the median overall predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and 39.5%, respectively. Case by case analysis also showed that the survival was overestimated in nearly 80% of patients. Subgroup analyses showed similar overestimation of patients' survival, except calculator Model 3 which utilised MGMT status. Use of the EORTC GBM prognostic calculator would have overestimated the survival of the majority of our patients with GBM. Uncertainty exists as to the cause of overestimation in the cohort although local socioeconomic factors might play a role. The different calculator models yielded different outcomes and the "best" predictor of survival for the cohort under study utilised the tumour MGMT status. We would strongly encourage similar local studies of validity testing prior to employing the online prognostic calculator for other population groups.

Survival analysis

International Nuclear Information System (INIS)

Badwe, R.A.

1999-01-01

The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

Parental crime and the safety and survival of small children

NARCIS (Netherlands)

van Gaalen, R.

2016-01-01

In this study the association between having a criminal parent and the safety and survival of small children is analysed. From the System of Social Statistical Datasets (SSD) hosted by Statistics Netherlands, we retrieve information on 10 complete birth cohorts (2000-2009; 1.9 million) of children

Surviving a cluster collapse: risk aversion as a core value

NARCIS (Netherlands)

Schiele, Holger; Hospers, Gerrit J.; van der Zee, D.J.

2012-01-01

Purpose – This paper analyses firms, which survived in a collapsed regional cluster. The target is to analyze whether the principles for enduring success identified researching success factors of very old firms also apply in such an environment. Design/methodology/approach – The authors conduct a

An overview of equipment survivability studies at Sandia National Labs. (SNL): Chapter 3

International Nuclear Information System (INIS)

Bonzon, L.L.; Craft, C.M.; McCulloch, W.H.; Sebrell, W.A.

1983-01-01

The USNRC sponsors a number of programs at Sandia National Laboratories (SNL) specifically addressing safety-related equipment survivability. The major thrust of these programs has been the physical testing of equipment. Test results illustrate the importance of a dedicated equipment design effort giving particular attention to the safety implications of the equipment operation. Several equipment survivability tests here have revealed equipment design and test-related deficiencies

Orphan caribou, Rangifer tarandus, calves: A re-evaluation of overwinter survival data

Science.gov (United States)

Joly, Kyle

2000-01-01

Low sample size and high variation within populations reduce power of statistical tests. These aspects of statistical power appear to have affected an analysis comparing overwinter survival rates of non-orphan and orphan Caribou (Rangifer tarandus) calves by an earlier study for the Porcupine Caribou Herd. A re-evaluation of the data revealed that conclusions about a lack of significant difference in the overwinter survival rates between orphan and non-orphan calves were premature.

Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons.

Directory of Open Access Journals (Sweden)

Liviu Aron

2010-04-01

Full Text Available The mechanisms underlying the selective death of substantia nigra (SN neurons in Parkinson disease (PD remain elusive. While inactivation of DJ-1, an oxidative stress suppressor, causes PD, animal models lacking DJ-1 show no overt dopaminergic (DA neuron degeneration in the SN. Here, we show that aging mice lacking DJ-1 and the GDNF-receptor Ret in the DA system display an accelerated loss of SN cell bodies, but not axons, compared to mice that only lack Ret signaling. The survival requirement for DJ-1 is specific for the GIRK2-positive subpopulation in the SN which projects exclusively to the striatum and is more vulnerable in PD. Using Drosophila genetics, we show that constitutively active Ret and associated Ras/ERK, but not PI3K/Akt, signaling components interact genetically with DJ-1. Double loss-of-function experiments indicate that DJ-1 interacts with ERK signaling to control eye and wing development. Our study uncovers a conserved interaction between DJ-1 and Ret-mediated signaling and a novel cell survival role for DJ-1 in the mouse. A better understanding of the molecular connections between trophic signaling, cellular stress and aging could uncover new targets for drug development in PD.

Genome and metagenome enabled analyses reveal new insight into the global biogeography and potential urea utilization in marine Thaumarchaeota.

Science.gov (United States)

Ahlgren, N.; Parada, A. E.; Fuhrman, J. A.

2016-02-01

Marine Thaumarchaea are an abundant, important group of marine microbial communities as they fix carbon, oxidize ammonium, and thus contribute to key N and C cycles in the oceans. From an enrichment culture, we have sequenced the complete genome of a new Thaumarchaeota strain, SPOT01. Analysis of this genome and other Thaumarchaeal genomes contributes new insight into its role in N cycling and clarifies the broader biogeography of marine Thaumarchaeal genera. Phylogenomics of Thaumarchaeota genomes reveal coherent separation into clusters roughly equivalent to the genus level, and SPOT01 represents a new genus of marine Thaumarchaea. Competitive fragment recruitment of globally distributed metagenomes from TARA, Ocean Sampling Day, and those generated from a station off California shows that the SPOT01 genus is often the most abundant genus, especially where total Thaumarchaea are most abundant in the overall community. The SPOT01 genome contains urease genes allowing it to use an alternative form of N. Genomic and metagenomic analysis also reveal that among planktonic genomes and populations, the urease genes in general are more frequently found in members of the SPOT01 genus and another genus dominant in deep waters, thus we predict these two genera contribute most significantly to urea utilization among marine Thaumarchaea. Recruitment also revealed broader biogeographic and ecological patterns of the putative genera. The SPOT01 genus was most abundant at colder temperatures (45 degrees). The genus containing Nitrosopumilus maritimus had the highest temperature range, and the genus containing Candidatus Nitrosopelagicus brevis was typically most abundant at intermediate temperatures and intermediate latitudes ( 35-45 degrees). Together these genome and metagenome enabled analyses provide significant new insight into the ecology and biogeochemical contributions of marine archaea.

Metagenomic Analysis of Hot Springs in Central India Reveals Hydrocarbon Degrading Thermophiles and Pathways Essential for Survival in Extreme Environments

Science.gov (United States)

Saxena, Rituja; Dhakan, Darshan B.; Mittal, Parul; Waiker, Prashant; Chowdhury, Anirban; Ghatak, Arundhuti; Sharma, Vineet K.

2017-01-01

Extreme ecosystems such as hot springs are of great interest as a source of novel extremophilic species, enzymes, metabolic functions for survival and biotechnological products. India harbors hundreds of hot springs, the majority of which are not yet explored and require comprehensive studies to unravel their unknown and untapped phylogenetic and functional diversity. The aim of this study was to perform a large-scale metagenomic analysis of three major hot springs located in central India namely, Badi Anhoni, Chhoti Anhoni, and Tattapani at two geographically distinct regions (Anhoni and Tattapani), to uncover the resident microbial community and their metabolic traits. Samples were collected from seven distinct sites of the three hot spring locations with temperature ranging from 43.5 to 98°C. The 16S rRNA gene amplicon sequencing of V3 hypervariable region and shotgun metagenome sequencing uncovered a unique taxonomic and metabolic diversity of the resident thermophilic microbial community in these hot springs. Genes associated with hydrocarbon degradation pathways, such as benzoate, xylene, toluene, and benzene were observed to be abundant in the Anhoni hot springs (43.5–55°C), dominated by Pseudomonas stutzeri and Acidovorax sp., suggesting the presence of chemoorganotrophic thermophilic community with the ability to utilize complex hydrocarbons as a source of energy. A high abundance of genes belonging to methane metabolism pathway was observed at Chhoti Anhoni hot spring, where methane is reported to constitute >80% of all the emitted gases, which was marked by the high abundance of Methylococcus capsulatus. The Tattapani hot spring, with a high-temperature range (61.5–98°C), displayed a lower microbial diversity and was primarily dominated by a nitrate-reducing archaeal species Pyrobaculum aerophilum. A higher abundance of cell metabolism pathways essential for the microbial survival in extreme conditions was observed at Tattapani. Taken together

Denosumab and Bone Metastasis–Free Survival in Men With Nonmetastatic Castration-Resistant Prostate Cancer: Exploratory Analyses by Baseline Prostate-Specific Antigen Doubling Time

Science.gov (United States)

Smith, Matthew R.; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

2013-01-01

Purpose Denosumab, an anti–RANK ligand monoclonal antibody, significantly increases bone metastasis–free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. Patients and Methods A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. Results In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Conclusion Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression. PMID:24043751

Proteomic and physiological analyses reveal the role of exogenous spermidine on cucumber roots in response to Ca(NO3)2 stress.

Science.gov (United States)

Du, Jing; Guo, Shirong; Sun, Jin; Shu, Sheng

2018-05-01

The mechanism of exogenous Spd-induced Ca(NO 3 ) 2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO 3 ) 2 stress resistance. Ca(NO 3 ) 2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO 3 ) 2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO 3 ) 2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO 3 ) 2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO 3 ) 2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H 2 O 2 and MDA, were detected after exogenous Spd application during Ca(NO 3 ) 2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO 3 ) 2 stress tolerance mediated by exogenous Spd.

Farm-by-farm analysis of microsatellite, mtDNA and SNP genotype data reveals inbreeding and crossbreeding as threats to the survival of a native Spanish pig breed.

Science.gov (United States)

Herrero-Medrano, J M; Megens, H J; Crooijmans, R P; Abellaneda, J M; Ramis, G

2013-06-01

The Chato Murciano (CM), a pig breed from the Murcia region in the southeastern region of Spain, is a good model for endangered livestock populations. The remaining populations are bred on approximately 15 small farms, and no herdbook exists. To assess the genetic threats to the integrity and survival of the CM breed, and to aid in designing a conservation program, three genetic marker systems - microsatellites, SNPs and mtDNA - were applied across the majority of the total breeding stock. In addition, mtDNA and SNPs were genotyped in breeds that likely contributed genetically to the current CM gene pool. The analyses revealed the levels of genetic diversity within the range of other European local breeds (H(e) = 0.53). However, when the eight farms that rear at least 10 CM pigs were independently analyzed, high levels of inbreeding were found in some. Despite the evidence for recent crossbreeding with commercial breeds on a few farms, the entire breeding stock remains readily identifiable as CM, facilitating the design of traceability assays. The genetic management of the breed is consistent with farm size, farm owner and presence of other pig breeds on the farm, demonstrating the highly ad hoc nature of current CM breeding. The results of genetic diversity and substructure of the entire breed, as well as admixture and crossbreeding obtained in the present study, provide a benchmark to develop future conservation strategies. Furthermore, this study demonstrates that identifying farm-based practices and farm-based breeding stocks can aid in the design of a sustainable breeding program for minority breeds. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

High serum uric acid concentration predicts poor survival in patients with breast cancer.

Science.gov (United States)

Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

2017-10-01

Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors of survival in surgically treated patients of spinal metastasis

Directory of Open Access Journals (Sweden)

Pravin Padalkar

2011-01-01

Full Text Available Background: The spinal metastasis occurs in up to 40% of cancer patient. We compared the Tokuhashi and Tomita scoring systems, two commonly used scoring systems for prognosis in spinal metastases. We also assessed the different variables separately with respect to their value in predicting postsurgical life expectancy. Finally, we suggest criteria for selecting patients for surgery based on the postoperative survival pattern. Materials and Methods: We retrospectively analyzed 102 patients who had been operated for metastatic disease of the spine. Predictive scoring was done according to the scoring systems proposed by Tokuhashi and Tomita. Overall survival was assessed using Kaplan-Meier survival analysis. Using the log rank test and Cox regression model we assessed the value of the individual components of each scoring system for predicting survival in these patients. Result: The factors that were most significantly associated with survival were the general condition score (Karnofsky Performance Scale (P=.000, log rank test, metastasis to internal organs (P=.0002 log rank test, and number of extraspinal bone metastases (P=.0058. Type of primary tumor was not found to be significantly associated with survival according to the revised Tokuhashi scoring system (P=.9131, log rank test. Stepwise logistic regression revealed that the Tomita score correlated more closely with survival than the Tokuhashi score. Conclusion: The patient′s performance status, extent of visceral metastasis, and extent of bone metastases are significant predictors of survival in patients with metastatic disease. Both revised Tokuhashi and Tomita scores were significantly correlated with survival. A revised Tokuhashi score of 7 or more and a Tomita score of 6 or less indicated >50% chance of surviving 6 months postoperatively. We recommend that the Tomita score be used for prognostication in patients who are contemplating surgery, as it is simpler to score and has a higher

Blowfly puparia in a hermetic container: survival under decreasing oxygen conditions.

Science.gov (United States)

Mądra-Bielewicz, Anna; Frątczak-Łagiewska, Katarzyna; Matuszewski, Szymon

2017-09-01

Despite widely accepted standards for sampling and preservation of insect evidence, unrepresentative samples or improperly preserved evidence are encountered frequently in forensic investigations. Here, we report the results of laboratory studies on the survival of Lucilia sericata and Calliphora vomitoria (Diptera: Calliphoridae) intra-puparial forms in hermetic containers, which were stimulated by a recent case. It is demonstrated that the survival of blowfly intra-puparial forms inside airtight containers is dependent on container volume, number of puparia inside, and their age. The survival in both species was found to increase with an increase in the volume of air per 1 mg of puparium per day of development in a hermetic container. Below 0.05 ml of air, no insect survived, and above 0.2 ml of air per 1 mg of puparium per day, survival reached its maximum. These results suggest that blowflies reveal a single, general pattern of survival under decreasing oxygen conditions and that this pattern is a product of number of developing insects, their age and the initial amount of available air. Implications for forensic entomology are discussed.

On the analysis of clonogenic survival data: Statistical alternatives to the linear-quadratic model

International Nuclear Information System (INIS)

Unkel, Steffen; Belka, Claus; Lauber, Kirsten

2016-01-01

The most frequently used method to quantitatively describe the response to ionizing irradiation in terms of clonogenic survival is the linear-quadratic (LQ) model. In the LQ model, the logarithm of the surviving fraction is regressed linearly on the radiation dose by means of a second-degree polynomial. The ratio of the estimated parameters for the linear and quadratic term, respectively, represents the dose at which both terms have the same weight in the abrogation of clonogenic survival. This ratio is known as the α/β ratio. However, there are plausible scenarios in which the α/β ratio fails to sufficiently reflect differences between dose-response curves, for example when curves with similar α/β ratio but different overall steepness are being compared. In such situations, the interpretation of the LQ model is severely limited. Colony formation assays were performed in order to measure the clonogenic survival of nine human pancreatic cancer cell lines and immortalized human pancreatic ductal epithelial cells upon irradiation at 0-10 Gy. The resulting dataset was subjected to LQ regression and non-linear log-logistic regression. Dimensionality reduction of the data was performed by cluster analysis and principal component analysis. Both the LQ model and the non-linear log-logistic regression model resulted in accurate approximations of the observed dose-response relationships in the dataset of clonogenic survival. However, in contrast to the LQ model the non-linear regression model allowed the discrimination of curves with different overall steepness but similar α/β ratio and revealed an improved goodness-of-fit. Additionally, the estimated parameters in the non-linear model exhibit a more direct interpretation than the α/β ratio. Dimensionality reduction of clonogenic survival data by means of cluster analysis was shown to be a useful tool for classifying radioresistant and sensitive cell lines. More quantitatively, principal component analysis allowed

Experiential Strategies for the Survival of Small Cities in Europe

DEFF Research Database (Denmark)

Allingham, Peter

2009-01-01

The aim of the article is to analyse, discuss and evaluate different methods of branding applied in experiential strategies for the survival of small cities in Europe. After the introduction that refers to the advent of the experience economy in the post-Fordist era, the article introduces various...... branding methods applied in experiential strategies. Then follows an analysis of how these branding methods are applied in experiential strategies for the development and survival of two small cities in Germany, Dresden and Wolfsburg, in which car production and city development have been combined....... The article concludes with an evaluation of the branding methods, which includes considerations of whether they can be used as models of survival for other small European cities. The evaluation refers to recent views on the question of representation and authenticity, and the role of cultural heritage...

Visceral fat area predicts survival in patients with advanced hepatocellular carcinoma treated with tyrosine kinase inhibitors.

Science.gov (United States)

Nault, Jean-Charles; Pigneur, Frédéric; Nelson, Anaïs Charles; Costentin, Charlotte; Tselikas, Lambros; Katsahian, Sandrine; Diao, Guoqing; Laurent, Alexis; Mallat, Ariane; Duvoux, Christophe; Luciani, Alain; Decaens, Thomas

2015-10-01

Anthropometric measurements have been linked to resistance to anti-angiogenic treatment and survival. Patients with advanced hepatocellular carcinoma treated with sorafenib or brivanib in 2008-2011 were included in this retrospective study. Anthropometric measurements were assessed using computed tomography and were correlated with drug toxicity, radiological response, and overall survival. 52 patients were included, Barcelona Clinic Liver Classification B (38%) and C (62%), with a mean value of α-fetoprotein of 29,554±85,654 ng/mL, with a median overall survival of 10.5 months. Sarcopenia was associated with a greater rate of hand-foot syndrome (P=0.049). Modified Response Evaluation Criteria In Solid Tumours (mRECIST) and Choi criteria were significantly associated with survival, but RECIST criteria were not. An absence of hand-foot syndrome and high-visceral fat area were associated with progressive disease as assessed by RECIST and mRECIST criteria. In multivariate analyses, high visceral fat area (HR=3.6; P=0.002), low lean body mass (HR=2.4; P=0.015), and presence of hand-foot syndrome (HR=1.8; P=0.004) were significantly associated with overall survival. In time-dependent multivariate analyses; only high visceral fat area was associated with survival. Visceral fat area is associated with survival and seems to be a predictive marker for primary resistance to tyrosine kinase inhibitors in patients with advanced hepatocellular carcinoma. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

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Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

2016-01-01

In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti

Network survivability performance

Science.gov (United States)

1993-11-01

This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

Direct Survival Analysis: a new stock assessment method

Directory of Open Access Journals (Sweden)

Eduardo Ferrandis

2007-03-01

Full Text Available In this work, a new stock assessment method, Direct Survival Analysis, is proposed and described. The parameter estimation of the Weibull survival model proposed by Ferrandis (2007 is obtained using trawl survey data. This estimation is used to establish a baseline survival function, which is in turn used to estimate the specific survival functions in the different cohorts considered through an adaptation of the separable model of the fishing mortality rates introduced by Pope and Shepherd (1982. It is thus possible to test hypotheses on the evolution of survival during the period studied and to identify trends in recruitment. A link is established between the preceding analysis of trawl survey data and the commercial catch-at-age data that are generally obtained to evaluate the population using analytical models. The estimated baseline survival, with the proposed versions of the stock and catch equations and the adaptation of the Separable Model, may be applied to commercial catch-at-age data. This makes it possible to estimate the survival corresponding to the landing data, the initial size of the cohort and finally, an effective age of first capture, in order to complete the parameter model estimation and consequently the estimation of the whole survival and mortality, along with the reference parameters that are useful for management purposes. Alternatively, this estimation of an effective age of first capture may be obtained by adapting the demographic structure of trawl survey data to that of the commercial fleet through suitable selectivity models of the commercial gears. The complete model provides the evaluation of the stock at any age. The coherence (and hence the mutual “calibration” between the two kinds of information may be analysed and compared with results obtained by other methods, such as virtual population analysis (VPA, in order to improve the diagnosis of the state of exploitation of the population. The model may be

Perioperative Outcomes and Long-term Survival in Clinically Early-stage Thymic 
Malignancies: Video-assisted Thoracoscopic Thymectomy versus Open Approaches

Directory of Open Access Journals (Sweden)

Hao WANG

2016-07-01

Full Text Available Background and objective Video-assisted thoracoscopic surgery (VATS theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II thymic malignancies. However, longterm 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<0.001 and less recurrence (2.9% vs 16.0%, P<0.001. 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. Conclusion 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.

Prognostic value of biochemical variables for survival after surgery for metastatic bone disease of the extremities.

Science.gov (United States)

Sørensen, Michala Skovlund; Hovgaard, Thea Bechman; Hindsø, Klaus; Petersen, Michael Mørk

2017-03-01

Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables. In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C-reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses. Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 10 9 /L, neutrophil 5.68 × 10 9 /L, lymphocyte 1.37 × 10 9 /L, C-reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors. We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex. © 2016 Wiley Periodicals, Inc.

Incidence, treatment, and survival patterns for sacral chordoma in the United States, 1974-2011

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Esther Yu

2016-09-01

Full Text Available IntroductionSacral chordomas represent one half of all chordomas, a rare neoplasm of notochordal remnants. Current NCCN guidelines recommend surgical resection with or without adjuvant radiotherapy, or definitive radiation for unresectable cases. Recent advances in radiation for chordomas include conformal photon and proton beam radiation. We investigated incidence, treatment, and survival outcomes to observe any trends in response to improvements in surgical and radiation techniques over a near 40 year time period.Materials and Methods345 microscopically confirmed cases of sacral chordoma were identified between 1974 and 2011 from the Surveillance, Epidemiology, and End Results (SEER program of the National Cancer Institute. Cases were divided into three cohorts by calendar year, 1974-1989, 1990-1999, and 2000-2011, as well as into two groups by age less than or equal to 65 versus greater than 65 to investigate trends over time and age via Chi-square analysis. Kaplan-Meier analyses were performed to determine effects of treatment on survival. Multivariate Cox regression analysis was performed to determine predictors of overall survival.Results5-year overall survival for the entire cohort was 60.0%. Overall survival correlated significantly with treatment modality, with 44% surviving at 5 years with no treatment, 52% with radiation alone, 82% surgery alone, and 78% surgery and radiation (p<.001. Age greater than 65 was significantly associated with non-surgical management with radiation alone or no treatment (p<.001. Relatively fewer patients received radiation between 2000 and 2011 compared to prior time periods (p=.03 versus surgery, for which rates which did not vary significantly over time (p=.55. However, 5-year overall survival was not significantly different by time period. Age group and treatment modality were predictive for overall survival on multivariate analysis (p<.001. ConclusionSurgery remains an important component in the

ATHENA/INTRA analyses for ITER, NSSR-2

International Nuclear Information System (INIS)

Shen, Kecheng; Eriksson, John; Sjoeberg, A.

1999-02-01

The present report is a summary report including thermal-hydraulic analyses made at Studsvik Eco and Safety AB for the ITER NSSR-2 safety documentation. The objective of the analyses was to reveal the safety characteristics of various heat transfer systems at specified operating conditions and to indicate the conditions for which there were obvious risks of jeopardising the structural integrity of the coolant systems. In the latter case also some analyses were made to indicate conceivable mitigating measures for maintaining the integrity.The analyses were primarily concerned with the First Wall and Divertor heat transfer systems. Several enveloping transients were analysed with associated specific flow and heat load boundary conditions. The analyses were performed with the ATHENA and INTRA codes

ATHENA/INTRA analyses for ITER, NSSR-2

Energy Technology Data Exchange (ETDEWEB)

Shen, Kecheng; Eriksson, John; Sjoeberg, A

1999-02-01

The present report is a summary report including thermal-hydraulic analyses made at Studsvik Eco and Safety AB for the ITER NSSR-2 safety documentation. The objective of the analyses was to reveal the safety characteristics of various heat transfer systems at specified operating conditions and to indicate the conditions for which there were obvious risks of jeopardising the structural integrity of the coolant systems. In the latter case also some analyses were made to indicate conceivable mitigating measures for maintaining the integrity.The analyses were primarily concerned with the First Wall and Divertor heat transfer systems. Several enveloping transients were analysed with associated specific flow and heat load boundary conditions. The analyses were performed with the ATHENA and INTRA codes 8 refs, 14 figs, 15 tabs

Predictors of survival among HIV-positive children on ART in ...

African Journals Online (AJOL)

... 16(4): 335–343. Open Access article distributed in terms of the Creative Commons Attribution License ... and adjusted hazard ratios respectively. The results reveal ... Children who were initiated early on ART had higher survival probability over time (HR: 0.35 [95% ..... workers they will have desirable clinical outcomes.

Underestimation of species richness in neotropical frogs revealed by mtDNA analyses.

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Antoine Fouquet

2007-10-01

Full Text Available Amphibians are rapidly vanishing. At the same time, it is most likely that the number of amphibian species is highly underestimated. Recent DNA barcoding work has attempted to define a threshold between intra- and inter-specific genetic distances to help identify candidate species. In groups with high extinction rates and poorly known species boundaries, like amphibians, such tools may provide a way to rapidly evaluate species richness.Here we analyse published and new 16S rDNA sequences from 60 frog species of Amazonia-Guianas to obtain a minimum estimate of the number of undescribed species in this region. We combined isolation by distance, phylogenetic analyses, and comparison of molecular distances to evaluate threshold values for the identification of candidate species among these frogs.In most cases, geographically distant populations belong to genetically highly distinct lineages that could be considered as candidate new species. This was not universal among the taxa studied and thus widespread species of Neotropical frogs really do exist, contrary to previous assumptions. Moreover, the many instances of paraphyly and the wide overlap between distributions of inter- and intra-specific distances reinforce the hypothesis that many cryptic species remain to be described. In our data set, pairwise genetic distances below 0.02 are strongly correlated with geographical distances. This correlation remains statistically significant until genetic distance is 0.05, with no such relation thereafter. This suggests that for higher distances allopatric and sympatric cryptic species prevail. Based on our analyses, we propose a more inclusive pairwise genetic distance of 0.03 between taxa to target lineages that could correspond to candidate species.Using this approach, we identify 129 candidate species, two-fold greater than the 60 species included in the current study. This leads to estimates of around 170 to 460 frog taxa unrecognized in Amazonia

Metastatic breast cancer - age has a significant effect on survival ...

African Journals Online (AJOL)

The data on 217 elderly (aged ≥ 65 years) and 209 middleaged postmenopausal patients with metastatic breast cancer treated in the Department of Medical Oncology, University of Pretoria, from 1976 to 1985 were analysed to determine the effect of age on survival. When considered as a group, the elderly have a more ...

Incorporating movement patterns to improve survival estimates for juvenile bull trout

Science.gov (United States)

Bowerman, Tracy; Budy, Phaedra

2012-01-01

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

Disparities in survival after Hodgkin lymphoma: a population-based study

Science.gov (United States)

Keegan, Theresa H.M.; Clarke, Christina A.; Chang, Ellen T.; Shema, Sarah J.; Glaser, Sally L.

2009-01-01

Survival after Hodgkin lymphoma (HL) is generally favorable, but may vary by patient demographic characteristics. The authors examined HL survival according to race/ethnicity and neighborhood socioeconomic status (SES), determined from residential census block group at diagnosis. For 12,492 classical HL patients ≥15 years diagnosed in California during 1988-2006 and followed through 2007, we determined risk of overall and HL-specific death using Cox proportional hazards regression; analyses were stratified by age and Ann Arbor stage. Irrespective of disease stage, patients with lower neighborhood SES had worse overall and HL-specific survival than patients with higher SES. Patients with the lowest quintile of neighborhood SES had a 64% (patients aged 15-44 years) and 36% (≥45 years) increased risk of HL-death compared to patients with the highest quintile of SES; SES results were similar for overall survival. Even after adjustment for neighborhood SES, blacks and Hispanics had increased risks of HL-death 74% and 43% (15-44 years) and 40% and 17% (≥45 years), respectively, higher than white patients. The racial/ethnic differences in survival were evident for all stages of disease. These data provide evidence for substantial, and probably remediable, racial/ethnic and neighborhood SES disparities in HL outcomes. PMID:19557531

Survival After Palliative Radiotherapy in Patients with Breast Cancer and Bone-only Metastases.

Science.gov (United States)

Nieder, Carsten; Dalhaug, Astrid; Pawinski, Adam; Mannsåker, Bård; Haukland, Ellinor

Patients with bone-only metastases survive longer than patients with widespread visceral disease. We analyzed the prognostic impact of different baseline parameters, such as abnormal blood tests and receptor status in patients who received local radiotherapy, in addition to contemporary systemic treatment, according to national guidelines. Retrospective uni- and multivariate analyses of 57 consecutive female patients treated in the time period 2007-2014 (median follow-up=29 months). The median age was 59 years and the median time interval from the initial diagnosis of breast cancer was 57 months. The median survival was 23 months from radiotherapy and 32 months from initial diagnosis of metastatic disease. Five-year survival rates were 13 and 21%, respectively. Survival after radiotherapy was significantly longer in patients who were prescribed higher radiation doses; 29 months after ≥30 Gy and 10 months after radiotherapy improves survival in patients with bone-only disease suitable for local therapy. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Local survival of pied flycatcher males and females in a pollution gradient of a Cu smelter

International Nuclear Information System (INIS)

Eeva, T.; Hakkarainen, H.; Belskii, E.

2009-01-01

Survival is one of the most central population measures when the effects of the pollution are studied in natural bird populations. However, only few studies have actually measured rigorous survival estimates on adult birds. In recent years there has been a methodological advance in survival analyses by mark-recapture models. We modelled local survival (including mortality and emigration) with the program MARK in a population of a small insectivorous passerine bird, the pied flycatcher (Ficedula hypoleuca), around a point source of heavy metals. The local survival of females in the polluted area was about 50% lower than in the other areas. Males, however, survived relatively well in the heavily polluted area, but showed somewhat lower survival in the moderately polluted area. Different pollution effects between two sexes might be due to pollution-related differences in reproductive effort in females and males, and/or more intensive uptake of heavy metals by laying females. - Female pied flycatchers (Ficedula hypoleuca) show decreased local survival around a copper smelter.

Relation between delay and survival in 596 patients with breast cancer.

Science.gov (United States)

Machiavelli, M; Leone, B; Romero, A; Perez, J; Vallejo, C; Bianco, A; Rodriguez, R; Estevez, R; Chacon, R; Dansky, C

1989-01-01

To evaluate the influence of delay between first symptom and first treatment upon survival the medical records of 596 patients with breast cancer were reviewed. The following intervals were considered: less than 3 months; 3-6 months and greater than 6 months. Patients in the less than 3 months delay group had a better distribution by clinical stages and a 10-year survival rate higher than those in the longer delay groups (p = 0.034). However, within each stage no statistically significant difference in survival according to delay was observed. A Cox multivariate analysis revealed that performance status and stage of disease were independent predictors of survival, but not delay. Assuming the best prognosis for patients with clinical stages I and II and less than 3 months delay, the group with longer delay times had 15 deaths over what would have been predicted. This adverse effect was observed almost exclusively among patients over age 50 (14/15).

Association of MTHFR gene polymorphisms with breast cancer survival

International Nuclear Information System (INIS)

Martin, Damali N; Boersma, Brenda J; Howe, Tiffany M; Goodman, Julie E; Mechanic, Leah E; Chanock, Stephen J; Ambs, Stefan

2006-01-01

Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival. We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C) had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR) = 2.05; 95% confidence interval (CI), 1.05–4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31–1.35). The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17–6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12–1.04 for C/T or T/T versus C/C at codon 677). Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, p interaction = 0.088; C677T, p interaction = 0.026). We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival

Metabarcoding and metabolome analyses of copepod grazing reveal feeding preference and linkage to metabolite classes in dynamic microbial plankton communities.

Science.gov (United States)

Ray, Jessica L; Althammer, Julia; Skaar, Katrine S; Simonelli, Paolo; Larsen, Aud; Stoecker, Diane; Sazhin, Andrey; Ijaz, Umer Z; Quince, Christopher; Nejstgaard, Jens C; Frischer, Marc; Pohnert, Georg; Troedsson, Christofer

2016-11-01

In order to characterize copepod feeding in relation to microbial plankton community dynamics, we combined metabarcoding and metabolome analyses during a 22-day seawater mesocosm experiment. Nutrient amendment of mesocosms promoted the development of haptophyte (Phaeocystis pouchetii)- and diatom (Skeletonema marinoi)-dominated plankton communities in mesocosms, in which Calanus sp. copepods were incubated for 24 h in flow-through chambers to allow access to prey particles (<500 μm). Copepods and mesocosm water sampled six times spanning the experiment were analysed using metabarcoding, while intracellular metabolite profiles of mesocosm plankton communities were generated for all experimental days. Taxon-specific metabarcoding ratios (ratio of consumed prey to available prey in the surrounding seawater) revealed diverse and dynamic copepod feeding selection, with positive selection on large diatoms, heterotrophic nanoflagellates and fungi, while smaller phytoplankton, including P. pouchetii, were passively consumed or even negatively selected according to our indicator. Our analysis of the relationship between Calanus grazing ratios and intracellular metabolite profiles indicates the importance of carbohydrates and lipids in plankton succession and copepod-prey interactions. This molecular characterization of Calanus sp. grazing therefore provides new evidence for selective feeding in mixed plankton assemblages and corroborates previous findings that copepod grazing may be coupled to the developmental and metabolic stage of the entire prey community rather than to individual prey abundances. © 2016 John Wiley & Sons Ltd.

Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis

International Nuclear Information System (INIS)

Gunderson, Leonard L.; Sargent, Daniel J.; Tepper, Joel E.; O'Connell, Michael J.; Allmer, Cristine; Smalley, Steven R.; Martenson, James A.; Haller, Daniel G.; Mayer, Robert J.; Rich, Tyvin A.; Ajani, Jaffer A.; Macdonald, John S.; Goldberg, Richard M.

2002-01-01

Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n=200), NCCTG 86-47-51 (n=656), and INT 114 (n=1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned

Recognising out-of-hospital cardiac arrest during emergency calls increases bystander cardiopulmonary resuscitation and survival.

Science.gov (United States)

Viereck, Søren; Møller, Thea Palsgaard; Ersbøll, Annette Kjær; Bækgaard, Josefine Stokholm; Claesson, Andreas; Hollenberg, Jacob; Folke, Fredrik; Lippert, Freddy K

2017-06-01

Initiation of early bystander cardiopulmonary resuscitation (CPR) depends on bystanders' or medical dispatchers' recognition of out-of-hospital cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA recognition during the emergency call was associated with bystander CPR, return of spontaneous circulation (ROSC), and 30-day survival. Our secondary aim was to identify patient-, setting-, and dispatcher-related predictors of OHCA recognition. We performed an observational study of all OHCA patients' emergency calls in the Capital Region of Denmark from 01/01/2013-31/12/2013. OHCAs were collected from the Danish Cardiac Arrest Registry and the Mobile Critical Care Unit database. Emergency call recordings were identified and evaluated. Multivariable logistic regression analyses were applied to all OHCAs and witnessed OHCAs only to analyse the association between OHCA recognition and bystander CPR, ROSC, and 30-day survival. Univariable logistic regression analyses were applied to identify predictors of OHCA recognition. We included 779 emergency calls in the analyses. During the emergency calls, 70.1% (n=534) of OHCAs were recognised; OHCA recognition was positively associated with bystander CPR (odds ratio [OR]=7.84, 95% confidence interval [CI]: 5.10-12.05) in all OHCAs; and ROSC (OR=1.86, 95% CI: 1.13-3.06) and 30-day survival (OR=2.80, 95% CI: 1.58-4.96) in witnessed OHCA. Predictors of OHCA recognition were addressing breathing (OR=1.76, 95% CI: 1.17-2.66) and callers located by the patient's side (OR=2.16, 95% CI: 1.46-3.19). Recognition of OHCA during emergency calls was positively associated with the provision of bystander CPR, ROSC, and 30-day survival in witnessed OHCA. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Continuous and split-course radiotherapy in locally advanced carcinoma of the uterine cervix. Analyses of local control, distant metastases, crude survival, early and late morbidity and prognostic factors

International Nuclear Information System (INIS)

Pedersen, D.E.

1994-01-01

From 1974 to 1984, 442 consecutive patients with carcinoma of the uterine cervix were referred for combined intracavitary (IRT) and external radiotherapy (ERT). Dose prescriptions were performed based on the points A and B of the Manchester system. From 1978 the treatment strategy was changed from continuous (CRT) to split course radiotherapy (SCRT) with a higher total dose to point B, a lower dose to point A from the IRT, and a longer total treatment time (TTT). The purpose of the present thesis is: To evaluate local tumour control, distant metastases, survival and complications in the rectosigmoid and bladder in relation to treatment strategy (continuous and split course radiotherapy). To evaluate prognostic factors and importance of treatment strategy for local control, distant metastases, and survival by uni- and multivariate analyses. To develop a classification system (AADK, Aarhus, Denmark) for the recording of early and late radiation complications allowing and estimation of the importance of latency when reporting late radiotherapeutic morbidity and a rescoring of complication grade, and to compare results from AADK with those from the French-Italian glossary recording the maximal damage. To evaluate early and late radiotherapeutic morbidity and the importance of latency by comparing frequencies and actuarial estimates of late complications, to estimate the combined late organ morbidity and the probability of being alive, cured and without serious complications. (EG) (61 refs.)

Adult survival and population growth rate in Colorado big brown bats (Eptesicus fuscus)

Science.gov (United States)

O'Shea, T.J.; Ellison, L.E.; Stanley, T.R.

2011-01-01

We studied adult survival and population growth at multiple maternity colonies of big brown bats (Eptesicus fuscus) in Fort Collins, Colorado. We investigated hypotheses about survival using information-theoretic methods and mark-recapture analyses based on passive detection of adult females tagged with passive integrated transponders. We constructed a 3-stage life-history matrix model to estimate population growth rate (??) and assessed the relative importance of adult survival and other life-history parameters to population growth through elasticity and sensitivity analysis. Annual adult survival at 5 maternity colonies monitored from 2001 to 2005 was estimated at 0.79 (95% confidence interval [95% CI] = 0.77-0.82). Adult survival varied by year and roost, with low survival during an extreme drought year, a finding with negative implications for bat populations because of the likelihood of increasing drought in western North America due to global climate change. Adult survival during winter was higher than in summer, and mean life expectancies calculated from survival estimates were lower than maximum longevity records. We modeled adult survival with recruitment parameter estimates from the same population. The study population was growing (?? = 1.096; 95% CI = 1.057-1.135). Adult survival was the most important demographic parameter for population growth. Growth clearly had the highest elasticity to adult survival, followed by juvenile survival and adult fecundity (approximately equivalent in rank). Elasticity was lowest for fecundity of yearlings. The relative importances of the various life-history parameters for population growth rate are similar to those of large mammals. ?? 2011 American Society of Mammalogists.

Suppressing an anti-inflammatory cytokine reveals a strong age-dependent survival cost in mice.

Directory of Open Access Journals (Sweden)

Virginia Belloni

Full Text Available BACKGROUND: The central paradigm of ecological immunology postulates that selection acts on immunity as to minimize its cost/benefit ratio. Costs of immunity may arise because the energetic requirements of the immune response divert resources that are no longer available for other vital functions. In addition to these resource-based costs, mis-directed or over-reacting immune responses can be particularly harmful for the host. In spite of the potential importance of immunopathology, most studies dealing with the evolution of the immune response have neglected such non resource-based costs. To keep the immune response under control, hosts have evolved regulatory pathways that should be considered when studying the target of the selection pressures acting on immunity. Indeed, variation in regulation may strongly modulate the negative outcome of immune activation, with potentially important fitness consequences. METHODOLOGY/PRINCIPAL FINDINGS: Here, we experimentally assessed the survival costs of reduced immune regulation by inhibiting an anti-inflammatory cytokine (IL-10 with anti-IL-10 receptor antibodies (anti-IL-10R in mice that were either exposed to a mild inflammation or kept as control. The experiment was performed on young (3 months and old (15 months individuals, as to further assess the age-dependent cost of suppressing immune regulation. IL-10 inhibition induced high mortality in old mice exposed to the mild inflammatory insult, whereas no mortality was observed in young mice. However, young mice experienced a transitory lost in body mass when injected with the anti-IL-10R antibodies, showing that the treatment was to a lesser extent also costly for young individuals. CONCLUSIONS: These results suggest a major role of immune regulation that deserves attention when investigating the evolution of immunity, and indicate that the capacity to down-regulate the inflammatory response is crucial for late survival and longevity.

KMWin--a convenient tool for graphical presentation of results from Kaplan-Meier survival time analysis.

Science.gov (United States)

Gross, Arnd; Ziepert, Marita; Scholz, Markus

2012-01-01

Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.

KMWin--a convenient tool for graphical presentation of results from Kaplan-Meier survival time analysis.

Directory of Open Access Journals (Sweden)

Arnd Gross

Full Text Available BACKGROUND: Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav, SAS export (xpt or text file (dat, which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. RESULTS: On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. CONCLUSIONS: We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.

Colorectal cancers detected through screening are associated with lower stages and improved survival

DEFF Research Database (Denmark)

Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus Hedebo

2014-01-01

in the feasibility study cohort were reviewed with respect to the effect of screening participation on stages and survival. MATERIAL AND METHODS: All cases of CRC in a feasibility study cohort diagnosed from the beginning of the study until two years after the study ended were identified. Differences...... in the distribution of colon cancer stages and rectal cancer groups between the various screening categories were analysed through χ(2)-tests. Survival analysis with respect to screening groups was done by Kaplan-Meier and Cox-Mantel hazard ratios, and survival was corrected for lead time. RESULTS: Colon cancers...... detected through screening were diagnosed at significantly lower stages than among screening non-responders. There were relatively fewer locally advanced rectal cancers among patients diagnosed through positive FOBT than among non-responders. Survival among screening cancer patients was superior...

The Impact of Demographic and Socioeconomic Factors on Major Salivary Gland Cancer Survival.

Science.gov (United States)

Olarte, Lucia S; Megwalu, Uchechukwu C

2014-06-01

This study aimed to investigate the impact of demographic and socioeconomic factors on survival in patients with major salivary gland malignancies. Population-based study using the Surveillance, Epidemiology, and End Results (SEER) cancer database. The study cohort consisted of 10,735 men and women ages 20 and older who were diagnosed with major salivary gland carcinoma from 1973 to 2009. Kaplan-Meier analysis revealed that the overall and disease-specific survival was higher for women than for men (P impact on overall survival. Male sex (HR = 1.38; 95% CI, 1.27-1.49), increasing age, and single status (HR = 1.29; 95% CI, 1.19-1.39) had poor prognostic impact on disease-specific survival. For patients with salivary gland malignancies, there is a survival benefit for younger patients, female patients, and married patients. This highlights the significance of demographic factors on survival outcomes for patients with salivary gland malignancies and highlights areas for further research on health disparities. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Prognostic and survival analysis of 837 Chinese colorectal cancer patients.

Science.gov (United States)

Yuan, Ying; Li, Mo-Dan; Hu, Han-Guang; Dong, Cai-Xia; Chen, Jia-Qi; Li, Xiao-Fen; Li, Jing-Jing; Shen, Hong

2013-05-07

To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage III CRC patients.

Robust Public Key Cryptography — A New Cryptosystem Surviving Private Key Compromise

Science.gov (United States)

Shaik, Cheman

A weakness of the present-day public key cryptosystems is that these cryptosystems do not survive private-key compromise attacks resulting from an internal breach of trust. In a competitive business environment, private key compromise is a common incident that voids the strength of public key cryptosystems such as RSA and ECC. Bribing corporate employees to disclose their secret keys and inadvertently disclosing secret information are among a plethora of practical attacks that occur at the implementation level. Once a breach of trust takes place and subsequently the private key is revealed, any public key cryptosystem fails to secure electronic data in Internet communications. The revealed key may be used by an attacker to decipher the intercepted data at an intermediary router. This weakness of public key cryptography calls for an additional security measure that enables encryptions to survive private key compromise attacks.

Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial.

Science.gov (United States)

Klek, Stanislaw; Scislo, Lucyna; Walewska, Elzbieta; Choruz, Ryszard; Galas, Aleksander

2017-04-01

The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed. Analysis of the overall survival time did not reveal differences between groups (P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together. The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Candida albicans survival and biofilm formation under starvation conditions.

Science.gov (United States)

Ning, Y; Hu, X; Ling, J; Du, Y; Liu, J; Liu, H; Peng, Z

2013-01-01

To investigate the survival and biofilm formation capacity of Candida albicans in starvation and under anaerobic conditions. Candida albicans growth and survival were monitored in vitro for up to 8 months. Fungal suspensions from late exponential, stationary and starvation phases were incubated on human dentine, polystyrene and glass slides. Scanning electron microscopy (SEM) was used to observe the process of biofilm formation. 2,3-bis(2-Methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide inner salt (XTT) reduction assay was performed to quantify the biofilm formation capability, and confocal laser scanning microscopy (CLSM) was used to study and make semi-quantitative comparisons of the ultrastructure of biofilms formed on human dentine. 'XTT bioactivity' and 'COMSTAT results' were analysed by two-way analysis of variance (ANOVA) and one-way ANOVA, respectively. Candida albicans survived for over six months. SEM demonstrated that starving C. albicans produced mature biofilms on different substrata. C. albicans of the same growth phase incubated on human dentine displayed significantly higher biofilm formation capability than on polystyrene or glass slides (P roughness coefficient and surface/volume ratio (P < 0.05). Candida albicans cells can survive and form biofilms in anaerobic and nutrient-limited conditions and may pose a treatment challenge. © 2012 International Endodontic Journal.

survival of primary cemented total hip arthroplasties in east africa

African Journals Online (AJOL)

2017-09-11

Sep 11, 2017 ... In addition, patients who had not returned for follow-up in the last 12 months were contacted by phone and/or mail. A wide variety of cemented and non- cemented implants were used. End points of the implant were revision or removal for any reason. Survival was analysed by the use of Kaplan Meir tables.

A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

Directory of Open Access Journals (Sweden)

Roussos Charis

2009-12-01

Full Text Available Abstract Background Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level. Methods To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h. Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562. PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects. Results In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation and NOD1 (down-regulation indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar

Effect of bystander CPR initiation prior to the emergency call on ROSC and 30day survival

DEFF Research Database (Denmark)

Viereck, Søren; Palsgaard Møller, Thea; Kjær Ersbøll, Annette

2017-01-01

BACKGROUND: This study aimed at evaluating if time for initiation of bystander cardiopulmonary resuscitation (CPR) - prior to the emergency call (CPRprior) versus during the emergency call following dispatcher-assisted CPR (CPRduring) - was associated with return of spontaneous circulation (ROSC...... and corresponding emergency calls were evaluated. Multivariable logistic regression analyses were applied to evaluate the association between time for initiation of bystander CPR, ROSC, and 30-day survival. Univariable logistic regression analyses were applied to identify predictors of CPRprior. RESULTS: The study...... included 548 emergency calls for OHCA patients receiving bystander CPR, 34.9% (n=191) in the CPRpriorgroup and 65.1% (n=357) in the CPRduringgroup. Multivariable analyses showed no difference in ROSC (OR=0.88, 95% CI: 0.56-1.38) or 30-day survival (OR=1.14, 95% CI: 0.68-1.92) between CPRpriorand CPRduring...

Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

Science.gov (United States)

Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

2014-04-01

Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy.

Science.gov (United States)

Melucci, Elisa; Casini, Beatrice; Ronchetti, Livia; Pizzuti, Laura; Sperati, Francesca; Pallocca, Matteo; De Nicola, Francesca; Goeman, Frauke; Gallo, Enzo; Amoreo, Carla Azzurra; Sergi, Domenico; Terrenato, Irene; Vici, Patrizia; Di Lauro, Luigi; Diodoro, Maria Grazia; Pescarmona, Edoardo; Barba, Maddalena; Mazzotta, Marco; Mottolese, Marcella; Fanciulli, Maurizio; Ciliberto, Gennaro; De Maria, Ruggero; Buglioni, Simonetta; Maugeri-Saccà, Marcello

2018-02-05

An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice. Tissue samples were immunostained to evaluate the expression of YAP/TAZ. Mutational status of key Wnt pathway genes (CTNNB1, APC and FBXW7) was assessed by targeted DNA next-generation sequencing (NGS). Survival curves were estimated and compared by the Kaplan-Meier product-limit method and the log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) were verified in univariate Cox proportional hazard models. The final multivariate Cox models were obtained with variables testing significant at the univariate analysis, and by adjusting for all plausible predictors of the outcome of interest (PFS). We observed a significant association between TAZ expression and Wnt mutations (Chi-squared p = 0.008). Combined TAZ expression and Wnt mutations (TAZ pos /WNT mut ) was more frequently observed in patients with the shortest progression-free survival (negative outliers) (Fisher p = 0.021). Uni-and multivariate Cox regression analyses revealed that patients whose tumors harbored the TAZ pos /WNT mut signature had an increased risk of disease progression (univariate Cox: HR 2.27, 95% CI 1.27-4.05, p = 0.006; multivariate Cox: HR 2.73, 95% CI 1.41-5.29, p = 0.003). Finally, the TAZ pos /WNT mut signature negatively impacted overall survival. Collectively, our findings indicate that the oncogenic YAP/TAZ-Wnt crosstalk may be

Socioeconomic Status, Not Race, Is Associated With Reduced Survival in Esophagectomy Patients.

Science.gov (United States)

Erhunmwunsee, Loretta; Gulack, Brian C; Rushing, Christel; Niedzwiecki, Donna; Berry, Mark F; Hartwig, Matthew G

2017-07-01

Black patients with esophageal cancer have worse survival than white patients. This study examines this racial disparity in conjunction with socioeconomic status (SES) and explores whether race-based outcome differences exist using a national database. The associations between race and SES with overall survival of patients treated with esophagectomy for stages I to III esophageal cancer between 2003 and 2011 in the National Cancer Data Base were investigated using the Kaplan-Meier method and proportional hazards analyses. Median income by zip code and proportion of the zip code residents without a high school diploma were grouped into income and education quartiles, respectively and used as surrogates for SES. The association between race and overall survival stratified by SES is explored. Of 11,599 esophagectomy patients who met study criteria, 3,503 (30.2%) were in the highest income quartile, 2,847 (24.5%) were in the highest education quartile, and 610 patients (5%) were black. Before adjustment for SES, black patients had worse overall survival than white patients (median survival 23.0 versus 34.7 months, log rank p race was not. Prior studies have suggested that survival of esophageal cancer patients after esophagectomy is associated with race. Our study suggests that race is not significantly related to overall survival when adjusted for other prognostic variables. Socioeconomic status, however, remains significantly related to overall survival in our model. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Demographic origins of skewed operational and adult sex ratios: perturbation analyses of two-sex models.

Science.gov (United States)

Veran, Sophie; Beissinger, Steven R

2009-02-01

Skewed sex ratios - operational (OSR) and Adult (ASR) - arise from sexual differences in reproductive behaviours and adult survival rates due to the cost of reproduction. However, skewed sex-ratio at birth, sex-biased dispersal and immigration, and sexual differences in juvenile mortality may also contribute. We present a framework to decompose the roles of demographic traits on sex ratios using perturbation analyses of two-sex matrix population models. Metrics of sensitivity are derived from analyses of sensitivity, elasticity, life-table response experiments and life stage simulation analyses, and applied to the stable stage distribution instead of lambda. We use these approaches to examine causes of male-biased sex ratios in two populations of green-rumped parrotlets (Forpus passerinus) in Venezuela. Female local juvenile survival contributed the most to the unbalanced OSR and ASR due to a female-biased dispersal rate, suggesting sexual differences in philopatry can influence sex ratios more strongly than the cost of reproduction.

Ensemble survival tree models to reveal pairwise interactions of variables with time-to-events outcomes in low-dimensional setting

Science.gov (United States)

Dazard, Jean-Eudes; Ishwaran, Hemant; Mehlotra, Rajeev; Weinberg, Aaron; Zimmerman, Peter

2018-01-01

Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance. Using various linear and nonlinear time-to-events survival models in simulation studies, we first show the efficiency of our approach: true pairwise interaction-effects between variables are uncovered, while they may not be accompanied with their corresponding main-effects, and may not be detected by standard semi-parametric regression modeling and test statistics used in survival analysis. Moreover, using a RSF-based cross-validation scheme for generating prediction estimators, we show that informative predictors may be inferred. We applied our approach to an HIV cohort study recording key host gene polymorphisms and their association with HIV change of tropism or AIDS progression. Altogether, this shows how linear or nonlinear pairwise statistical interactions of variables may be efficiently detected with a predictive value in observational studies with time-to-event outcomes. PMID:29453930

The frontotemporal syndrome of ALS is associated with poor survival.

Science.gov (United States)

Govaarts, Rosanne; Beeldman, Emma; Kampelmacher, Mike J; van Tol, Marie-Jose; van den Berg, Leonard H; van der Kooi, Anneke J; Wijkstra, Peter J; Zijnen-Suyker, Marianne; Cobben, Nicolle A M; Schmand, Ben A; de Haan, Rob J; de Visser, Marianne; Raaphorst, Joost

2016-12-01

Thirty percent of ALS patients have a frontotemporal syndrome (FS), defined as behavioral changes or cognitive impairment. Despite previous studies, there are no firm conclusions on the effect of the FS on survival and the use of non-invasive ventilation (NIV) in ALS. We examined the effect of the FS on survival and the start and duration of NIV in ALS. Behavioral changes were defined as >22 points on the ALS-Frontotemporal-Dementia-Questionnaire or ≥3 points on ≥2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on ≥2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom onset and time from NIV initiation, respectively, to death. The impact of the explanatory variables on survival and NIV initiation were examined using Cox proportional hazards models. We included 110 ALS patients (76 men) with a mean age of 62 years. Median survival time was 4.3 years (95 % CI 3.53-5.13). Forty-seven patients (43 %) had an FS. Factors associated with shorter survival were FS, bulbar onset, older age at onset, short time to diagnosis and a C9orf72 repeat expansion. The adjusted hazard ratio (HR) for the FS was 2.29 (95 % CI 1.44-3.65, p NIV initiation (adjusted HR 2.70, 95 % CI 1.04-4.67, p = 0.04). In conclusion, there is an association between the frontotemporal syndrome and poor survival in ALS, which remains present after initiation of NIV.

The impact of adjuvant radiation therapy on survival in women with uterine carcinosarcoma

International Nuclear Information System (INIS)

Clayton Smith, D.; Kenneth Macdonald, O.; Gaffney, David K.

2008-01-01

Background and purpose: Uterine carcinosarcoma is an aggressive neoplasm and the benefit of adjuvant radiation therapy (RT) is unclear. This retrospective study analyzes the influence of RT on survival using a large population database. Materials and methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute. Women with uterine carcinosarcoma who underwent primary surgery were eligible. Survival rates and multivariate analyses were performed by standard methods. Results: Of the 2461 women in the analysis, 890 received adjuvant RT. Five-year rates of overall survival were 41.5% and 33.2% (P < 0.001) and uterine-specific survival were 56.0% and 50.8% (P = 0.005), for women receiving RT compared to those who did not. Women with stages I-III disease experienced a benefit in overall survival (HR 0.87, P = 0.03) while women with stage IV disease experienced benefits in overall (HR 0.63, P < 0.001) and uterine-specific survival (HR 0.63, P = 0.004) with RT. Conclusions: RT predicted for improved overall and disease specific survival in women with uterine carcinosarcoma within the SEER database. The benefit in disease specific survival was restricted to stage IV disease. These benefits may indicate a role for adjuvant RT in future prospective trials in the treatment of uterine carcinosarcoma

Sodium Iodide Symporter PET and BLI Noninvasively Reveal Mesoangioblast Survival in Dystrophic Mice

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Bryan Holvoet

2015-12-01

Full Text Available Muscular dystrophies are a heterogeneous group of myopathies, characterized by muscle weakness and degeneration, without curative treatment. Mesoangioblasts (MABs have been proposed as a potential regenerative therapy. To improve our understanding of the in vivo behavior of MABs and the effect of different immunosuppressive therapies, like cyclosporine A or co-stimulation-adhesion blockade therapy, on cell survival noninvasive cell monitoring is required. Therefore, cells were transduced with a lentiviral vector encoding firefly luciferase (Fluc and the human sodium iodide transporter (hNIS to allow cell monitoring via bioluminescence imaging (BLI and small-animal positron emission tomography (PET. Non-H2 matched mMABs were injected in the femoral artery of dystrophic mice and were clearly visible via small-animal PET and BLI. Based on noninvasive imaging data, we were able to show that co-stim was clearly superior to CsA in reducing cell rejection and this was mediated via a reduction in cytotoxic T cells and upregulation of regulatory T cells.

Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures.

Science.gov (United States)

Bohlen, Christopher J; Bennett, F Chris; Tucker, Andrew F; Collins, Hannah Y; Mulinyawe, Sara B; Barres, Ben A

2017-05-17

Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial DNA analyses revealed low genetic diversity in the endangered Indian wild ass Equus hemionus khur.

Science.gov (United States)

Khaire, Devendra; Atkulwar, Ashwin; Farah, Sameera; Baig, Mumtaz

2017-09-01

The Indian wild ass Equus hemionus khur, belonging to ass-like equid branch, inhabits the dry and arid desert of the Little Rann of Kutch, Gujarat. The E. h. khur is the sole survivor of Asiatic wild ass species/subspecies in South Asia. To provide first ever insights into the genetic diversity, phylogeny, and demography of the endangered Indian wild ass, we sampled 52 free-ranging individuals from the Little Rann of Kutch by using a non-invasive methodology. The sequencing of 230 bp in cytochrome b (Cyt b) and displacement loop (D-loop) region revealed that current ∼4000 extant population of Indian wild ass harbours low genetic diversity. Phylogenetic analyses confirmed that E. h. khur, E. h. onager, and E. h. kulan belong to a single strict monophyletic clade. Therefore, we suggest the delimitation of the five E. hemionus subspecies in vogue to a single species E. hemionus. The application of molecular clock confirmed that the Asiatic wild ass had undergone diversification 0.65 Million years ago. Demographic measurements assessed using a Bayesian skyline plot demonstrated decline in the maternal effective population size of the Indian wild ass during different periods; these periods coincided with the origin and rise of the Indus civilization in the northwest of the Indian subcontinent during the Neolithic. In conclusion, maintaining high genetic diversity in the existing isolated population of 4000 Indian wild asses inhabiting the wild ass sanctuary is important compared with subspecies preservation alone.

Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.

Science.gov (United States)

Ball, Robyn L; Fujiwara, Yasuhiro; Sun, Fengyun; Hu, Jianjun; Hibbs, Matthew A; Handel, Mary Ann; Carter, Gregory W

2016-08-12

The continuous and non-synchronous nature of postnatal male germ-cell development has impeded stage-specific resolution of molecular events of mammalian meiotic prophase in the testis. Here the juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis that allows decomposition of the transcriptional programs of spermatogonia and meiotic prophase substages. Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), prepared as surface-spread chromatin and immunolabeled for meiotic stage-specific protein markers (STRA8, SYCP3, phosphorylated H2AFX, and HISTH1T). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. Independent principal component analyses of cytological and transcriptomic data yielded similar patterns for both data types, providing strong evidence for substage-specific gene expression signatures. A novel permutation-based maximum covariance analysis (PMCA) was developed to map co-expressed transcripts to one or more of the eight meiotic prophase substages, thereby linking distinct molecular programs to cytologically defined cell states. Expression of meiosis-specific genes is not substage-limited, suggesting regulation of substage transitions at other levels. This integrated analysis provides a general method for resolving complex cell populations. Here it revealed not only features of meiotic substage-specific gene expression, but also a network of substage-specific transcription factors and relationships to potential target genes.

Propensity Score Matched Comparison of Intensity Modulated Radiation Therapy vs Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Survival Analysis from the National Cancer Database

Directory of Open Access Journals (Sweden)

Anthony Ricco

2017-08-01

Full Text Available PurposeNo direct comparisons between extreme hypofractionation and conventional fractionation have been reported in randomized trials for the treatment of localized prostate cancer. The goal of this study is to use a propensity score matched (PSM analysis with the National Cancer Database (NCDB for the comparison of stereotactic body radiation therapy (SBRT and intensity modulated radiation therapy (IMRT for organ confined prostate cancer.MethodsMen with localized prostate cancer treated with radiation dose ≥72 Gy for IMRT and ≥35 Gy for SBRT to the prostate only were abstracted from the NCDB. Men treated with previous surgery, brachytherapy, or proton therapy were excluded. Matching was performed to eliminate confounding variables via PSM. Simple 1–1 nearest neighbor matching resulted in a matched sample of 5,430 (2,715 in each group. Subset analyses of men with prostate-specific antigen (PSA > 10, GS = 7, and GS > 7 yielded matched samples of 1,020, 2,194, and 247, respectively.ResultsNo difference in survival was noted between IMRT and SBRT at 8 years (p = 0.65. Subset analyses of higher risk men with PSA > 10 or GS = 7 histology or GS > 7 histology revealed no difference in survival between IMRT and SBRT (p = 0.58, p = 0.68, and p = 0.62, respectively. Variables significant for survival for the matched group included: age (p < 0.0001, primary payor (p = 0.0001, Charlson/Deyo Score (p = 0.0002, PSA (p = 0.0013, Gleason score (p < 0.0001, and use of hormone therapy (p = 0.02.ConclusionUtilizing the NCDB, there is no difference in survival at 8 years comparing IMRT to SBRT in the treatment of localized prostate cancer. Subset analysis confirmed no difference in survival even for intermediate- and high-risk patients based on Gleason Score and PSA.

Effect of temperature on growth, survival and respiratory rate of larval allis shad Alosa alosa

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Hundt M.

2015-01-01

Full Text Available Prior species distribution models identified temperature as one of the most important environmental variables defining the present and future distribution of anadromous allis shad (Alosa alosa. The current study analysed effects of temperature on the recruitment-potential of allis shad by investigating growth and survival at 16, 20, 24 and 28 °C during a ten day rearing trial and by measuring mass-specific respiration. Highest growth in length was at 28 °C; growth at 16 °C was minimal. At the end of the rearing-period, no significant differences in survival between tested rearing-temperatures were found. Exposure to temperatures of 13 to 30 °C and subsequent measurement of mass-specific respiration revealed tolerance of temperatures up to 30 °C and a lower temperature limitation close to 16 °C. After acclimatization of larvae to temperatures ranging from 16−28 °C for 10 days, Q10-values of mass-specific respiration indicated a high adaptive capacity to increasing temperatures, but also the ability to adapt to temperatures as low as 16 °C. Our results indicate that the predicted temperature sensitivity of A. alosa cannot be explained by a direct physiological relationship. The obtained results can help to improve predictive modelling and the conservation of allis shad throughout its current distribution range.

KMWin – A Convenient Tool for Graphical Presentation of Results from Kaplan-Meier Survival Time Analysis

Science.gov (United States)

Gross, Arnd; Ziepert, Marita; Scholz, Markus

2012-01-01

Background Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. Results On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. Conclusions We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups. PMID:22723912

Reduced in-hospital survival rates of out-of-hospital cardiac arrest victims with obstructive pulmonary disease

DEFF Research Database (Denmark)

Blom, M T; Warnier, M J; Bardai, A

2013-01-01

) had comparable survival to ER (75% vs. 78%, OR 0.9 [95% CI: 0.6-1.3]) and to hospital admission (56% vs. 57%, OR 1.0 [0.7-1.4]). However, survival to hospital discharge was significantly lower among OPD patients (21% vs. 33%, OR 0.6 [0.4-0.9]). Multivariate regression analysis among patients who were...... with obstructive pulmonary disease (OPD) have a lower survival rate after OHCA than non-OPD patients. METHODS: We performed a community-based cohort study of 1172 patients with non-traumatic OHCA with ECG-documented VT/VF between 2005 and 2008. We compared survival to emergency room (ER), to hospital admission...... admitted to hospital (OPD: n=100, no OPD: n=561) revealed that OPD was an independent determinant of reduced 30-day survival rate (39% vs. 59%, adjusted OR 0.6 [0.4-1.0, p=0.035]). CONCLUSION: OPD-patients had lower survival rates after OHCA than non-OPD patients. Survival to ER and to hospital admission...

Games of lives in surviving childhood brain tumors.

Science.gov (United States)

Chen, Chin-Mi; Chen, Yueh-Chih; Haase, Joan E

2008-06-01

The purpose of this phenomenological study was to describe the commonality of the lived experience of adolescent and young adult survivors (AYAS) of brain tumors in Taiwan from a sociocultural perspective. Seven AYAS aged 13 to 22 years, who had survived 5 to 10 years from the time of diagnosis, participated in this study. In consideration of their emotional duress, each participant was interviewed only once. The data revealed an essential structure: the game of life. The essential structure included six themes as follows: (a) no longer playing well, (b) wandering on the outer edges of social life, (c) helplessly struggling with role obligations, (d) rationally regulating the meaning of surviving, (e) winning a new social face, and (f) mastering the game of life. The findings suggest how nurses might help AYAS to succeed in psychosocial adjustment.

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.

Science.gov (United States)

He, Sha-Sha; Chen, Yong; Shen, Xiao-Ming; Wang, Hong-Zhi; Sun, Peng; Dong, Jun; Guo, Gui-Fang; Chen, Ju-Gao; Xia, Liang-Ping; Hu, Pei-Li; Qiu, Hui-Juan; Liu, Shou-Sheng; Zhou, Yi-Xin; Wang, Wei; Hu, Wei-Han; Cai, Xiu-Yu

2017-01-01

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes ( P = 0.016) and distant metastasis ( P = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression ( P = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup ( P = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients ( P = 0.039 and 0.037, respectively). Conclusions : Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.

Modeling time-to-event (survival) data using classification tree analysis.

Science.gov (United States)

Linden, Ariel; Yarnold, Paul R

2017-12-01

Time to the occurrence of an event is often studied in health research. Survival analysis differs from other designs in that follow-up times for individuals who do not experience the event by the end of the study (called censored) are accounted for in the analysis. Cox regression is the standard method for analysing censored data, but the assumptions required of these models are easily violated. In this paper, we introduce classification tree analysis (CTA) as a flexible alternative for modelling censored data. Classification tree analysis is a "decision-tree"-like classification model that provides parsimonious, transparent (ie, easy to visually display and interpret) decision rules that maximize predictive accuracy, derives exact P values via permutation tests, and evaluates model cross-generalizability. Using empirical data, we identify all statistically valid, reproducible, longitudinally consistent, and cross-generalizable CTA survival models and then compare their predictive accuracy to estimates derived via Cox regression and an unadjusted naïve model. Model performance is assessed using integrated Brier scores and a comparison between estimated survival curves. The Cox regression model best predicts average incidence of the outcome over time, whereas CTA survival models best predict either relatively high, or low, incidence of the outcome over time. Classification tree analysis survival models offer many advantages over Cox regression, such as explicit maximization of predictive accuracy, parsimony, statistical robustness, and transparency. Therefore, researchers interested in accurate prognoses and clear decision rules should consider developing models using the CTA-survival framework. © 2017 John Wiley & Sons, Ltd.

Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer.

Directory of Open Access Journals (Sweden)

Jianfei Fu

Full Text Available The features related to the prognosis of patients with mucinous breast cancer (MBC remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes.The Surveillance, Epidemiology, and End Results (SEER database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC.There were 136569 (97.82% infiltrative ductal cancer (IDC patients and 3042 (2.18% MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively than patients with IDC (91.44 and 85.48%, respectively. Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816. Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789 than the traditional TNM system (C-index = 0.704, P< 0.001.Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in clinical practice. The competing risk

The role of innovation in the survival of the EU-15 entrepreneurs; El papel de la innovacion en la supevivencia de los emprendedores UE-15

Energy Technology Data Exchange (ETDEWEB)

Congregado, E.; Millan, J. M.; Roman, C.

2012-07-01

This work analyses the role of innovation at the country level in entrepreneur ship survival for the EU-15, considering entrepreneurs as those who hire employees (i.e., employers). We estimate survival models to analyse duration as an entrepreneur, using micro data drawn from the European Community Household Panel (ECHP). As measures of innovation, we use different aggregated indicators at the country level: technological effort; results of scientific technical activity, and education distribution of the population. Our results suggest that country innovation activities play a crucial role in entrepreneurial survival prospects. (Author)

Socioeconomic Impacts on Survival Differ by Race/Ethnicity among Adolescents and Young Adults with Non-Hodgkin's Lymphoma

International Nuclear Information System (INIS)

Kent, E. E.; Largent, J. A.; Ziogas, A.; Sender, J. A.; Culver, H. A.; Morris, R. A.; Sender, L. S.; Ziogas, A.; Culver, H. A.; Sender, L. S.; Culver, H. A.

2010-01-01

Shorter survival has been associated with low socioeconomic status (SES) among elderly non-Hodgkin's lymphoma (NHL) patients; however it remains unknown whether the same relationship holds for younger patients. We explored the California Cancer Registry (CCR), to investigate this relationship in adolescent and young adult (AYA) NHL patients diagnosed from 1996 to 2005. A case-only survival analysis was conducted to examine demographic and clinical variables hypothesized to be related to survival. Included in the final analysis were 3,489 incident NHL cases. In the multivariate analyses, all-cause mortality (ACM) was higher in individuals who had later stage at diagnosis (P<.05) or did not receive first-course chemotherapy (P<.05 ). There was also a significant gradient decrease in survival, with higher ACM at each decreasing quintile of SES (P<.001). Overall results were similar for lymphoma-specific mortality. In the race/ethnicity stratified analyses, only non-Hispanic Whites (NHWs) had a significant SES-ACM trend ( P<.001). Reduced overall and lymphoma-specific survival was associated with lower SES in AYAs with NHL, although a significant trend was only observed for NHWs

Modelling survival

DEFF Research Database (Denmark)

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

2016-01-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

Foreign acquisition, plant survival, and employment growth

DEFF Research Database (Denmark)

Bandick, Roger; Görg, Holger

This paper analyses the effect of foreign acquisition on survival probability and employment growth of target plant using data on Swedish manufacturing plants during the period 1993-2002.  An improvement over previous studies is that we take into account firm level heterogeneity by separating...... the lifetime of the acquired plants only if the plant was an exporter.  The effect differs depending on whether the acquisition is horizontal or vertical.  We also find robust positive employment growth effects only for exporters, and only if the takeover is vertical, not horizontal....

Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

Directory of Open Access Journals (Sweden)

Kristina Kirschner

2015-03-01

Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

Science.gov (United States)

Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

2017-06-01

We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Age of blood and survival after massive transfusion.

Science.gov (United States)

Sanz, C C; Pereira, A

2017-11-01

Massive transfusion is the clinical scenario where the presumed adverse effects of stored blood are expected to be more evident because the whole patient's blood volume is replaced by stored blood. To analyse the association between age of transfused red blood cells (RBC) and survival in massively transfused patients. In this retrospective study, clinical and transfusion data of all consecutive patients massively transfused between 2008 and 2014 in a large, tertiary-care hospital were electronically extracted from the Transfusion Service database and the patients' electronic medical records. Prognostic factors for in-hospital mortality were investigated by multivariate logistic regression. A total of 689 consecutive patients were analysed (median age: 61 years; 65% males) and 272 died in-hospital. Projected mortality at 2, 30, and 90 days was 21%, 35% and 45%, respectively. The odds ratio (OR) for in-hospital mortality among patients who survived after the 2nd day increased with patient age (OR: 1.037, 95% CI: 1.021-1.054; per year Ptransfused in the first 48hours (OR: 1.060; 95% CI: 1.038-1.020 per unit; Ptransfusion was associated with a higher proportion of old RBCs transfused in the first 48hours. Other factors associated with poor prognosis were older patient's age and larger volumes of transfused RBCs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Coding completeness and quality of relative survival-related variables in the National Program of Cancer Registries Cancer Surveillance System, 1995-2008.

Science.gov (United States)

Wilson, Reda J; O'Neil, M E; Ntekop, E; Zhang, Kevin; Ren, Y

2014-01-01

Calculating accurate estimates of cancer survival is important for various analyses of cancer patient care and prognosis. Current US survival rates are estimated based on data from the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End RESULTS (SEER) program, covering approximately 28 percent of the US population. The National Program of Cancer Registries (NPCR) covers about 96 percent of the US population. Using a population-based database with greater US population coverage to calculate survival rates at the national, state, and regional levels can further enhance the effective monitoring of cancer patient care and prognosis in the United States. The first step is to establish the coding completeness and coding quality of the NPCR data needed for calculating survival rates and conducting related validation analyses. Using data from the NPCR-Cancer Surveillance System (CSS) from 1995 through 2008, we assessed coding completeness and quality on 26 data elements that are needed to calculate cancer relative survival estimates and conduct related analyses. Data elements evaluated consisted of demographic, follow-up, prognostic, and cancer identification variables. Analyses were performed showing trends of these variables by diagnostic year, state of residence at diagnosis, and cancer site. Mean overall percent coding completeness by each NPCR central cancer registry averaged across all data elements and diagnosis years ranged from 92.3 percent to 100 percent. RESULTS showing the mean percent coding completeness for the relative survival-related variables in NPCR data are presented. All data elements but 1 have a mean coding completeness greater than 90 percent as was the mean completeness by data item group type. Statistically significant differences in coding completeness were found in the ICD revision number, cause of death, vital status, and date of last contact variables when comparing diagnosis years. The majority of data items had a coding

Pig slurry reduces the survival of Raltstonia solanacearum biovar 2 in soil

NARCIS (Netherlands)

Gorissen, A.; Overbeek, van L.S.; Elsas, van J.D.

2004-01-01

The effect of added pig slurry and solarization on the survival of Ralstonia solanacearum biovar 2 strain 1609 in soil was analysed in soil microcosms and field plots. In addition, the invasion of potato plants by R. solanacearum and the development of disease symptoms were determined, as measures

Big data analyses reveal patterns and drivers of the movements of southern elephant seals

KAUST Repository

Rodrí guez, J. P.; Ferná ndez-Gracia, Juan; Thums, Michele; Hindell, Mark A.; Sequeira, Ana M. M.; Meekan, Mark G.; Costa, Daniel P.; Guinet, Christophe; Harcourt, R.; McMahon, Clive R.; Muelbert, Monica; Duarte, Carlos M.; Eguí luz, V. M.

2017-01-01

The growing number of large databases of animal tracking provides an opportunity for analyses of movement patterns at the scales of populations and even species. We used analytical approaches, developed to cope with

Big data analyses reveal patterns and drivers of the movements of southern elephant seals

KAUST Repository

Rodríguez, Jorge P.

2017-03-02

The growing number of large databases of animal tracking provides an opportunity for analyses of movement patterns at the scales of populations and even species. We used analytical approaches, developed to cope with

Risk-adjusted survival after tissue versus mechanical aortic valve replacement: a 23-year assessment.

Science.gov (United States)

Gaca, Jeffrey G; Clare, Robert M; Rankin, J Scott; Daneshmand, Mani A; Milano, Carmelo A; Hughes, G Chad; Wolfe, Walter G; Glower, Donald D; Smith, Peter K

2013-11-01

Detailed analyses of risk-adjusted outcomes after mitral valve surgery have documented significant survival decrements with tissue valves at any age. Several recent studies of prosthetic aortic valve replacement (AVR) also have suggested a poorer performance of tissue valves, although analyses have been limited to small matched series. The study aim was to test the hypothesis that AVR with tissue valves is associated with a lower risk-adjusted survival, as compared to mechanical valves. Between 1986 and 2009, primary isolated AVR, with or without coronary artery bypass grafting (CABG), was performed with currently available valve types in 2148 patients (1108 tissue valves, 1040 mechanical). Patients were selected for tissue valves to be used primarily in the elderly. Baseline and operative characteristics were documented prospectively with a consistent variable set over the entire 23-year period. Follow up was obtained with mailed questionnaires, supplemented by National Death Index searches. The average time to death or follow up was seven years, and follow up for survival was 96.2% complete. Risk-adjusted survival characteristics for the two groups were evaluated using a Cox proportional hazards model with stepwise selection of candidate variables. Differences in baseline characteristics between groups were (tissue versus mechanical): median age 73 versus 61 years; non-elective surgery 32% versus 28%; CABG 45% versus 35%; median ejection fraction 55% versus 55%; renal failure 6% versus 1%; diabetes 18% versus 7% (pvalves; however, after risk adjustment for the adverse profiles of tissue valve patients, no significant difference was observed in survival after tissue or mechanical AVR. Thus, the hypothesis did not hold, and risk-adjusted survival was equivalent, of course qualified by the fact that selection bias was evident. With selection criteria that employed tissue AVR more frequently in elderly patients, tissue and mechanical valves achieved similar survival

MRE11-Deficiency Associated with Improved Long-Term Disease Free Survival and Overall Survival in a Subset of Stage III Colon Cancer Patients in Randomized CALGB 89803 Trial

Science.gov (United States)

Pavelitz, Thomas; Renfro, Lindsay; Foster, Nathan R.; Caracol, Amber; Welsch, Piri; Lao, Victoria Valinluck; Grady, William B.; Niedzwiecki, Donna; Saltz, Leonard B.; Bertagnolli, Monica M.; Goldberg, Richard M.; Rabinovitch, Peter S.; Emond, Mary; Monnat, Raymond J.; Maizels, Nancy

2014-01-01

Purpose Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. Patients and Methods Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. Results Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. Conclusions Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. Trial Registration ClinicalTrials.gov NCT00003835 PMID:25310185

MRE11-deficiency associated with improved long-term disease free survival and overall survival in a subset of stage III colon cancer patients in randomized CALGB 89803 trial.

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Thomas Pavelitz

Full Text Available Colon cancers deficient in mismatch repair (MMR may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer.Cancer and Leukemia Group B 89803 (Alliance randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV or irinotecan+FU/LV (IFL, with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS, and a secondary endpoint was disease-free survival (DFS. Non-proportional hazards were addressed using time-dependent covariates in Cox analyses.Of 625 tumor cases examined, 70 (11.2% exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11. In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed.Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples.ClinicalTrials.gov NCT00003835.

Survival outcomes for oligometastasis in resected non-small cell lung cancer.

Science.gov (United States)

Shimada, Yoshihisa; Saji, Hisashi; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2015-10-01

We investigated the factors associated with post-recurrence survival and the treatment for non-small-cell lung cancer patients with postoperative distant recurrence, especially oligometastasis. We reviewed the data of 272 patients with distant recurrence who underwent resection of non-small-cell lung cancer from January 2000 through December 2011. The type of distant recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n = 196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy (surgery 5, radiotherapy 9, sequential local and systemic therapy 28, chemoradiotherapy 5). Multivariate analysis revealed older age, non-adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver metastases, bone metastases, and polymetastasis had significant associations with unfavorable post-recurrence survival. Subgroup analysis of patients with oligometastasis showed histology and disease-free interval had a great impact on survival. Smoking history and histology were associated with survival in patients with lung oligometastasis, whereas systemic treatment and longer disease-free interval were related to increased post-recurrence survival in those with brain oligometastasis. This study showed that an oligometastatic state per se was a significant favorable factor. Optimization of personalized systemic treatment and adding local treatment are important in the management of patients with non-small-cell lung cancer and oligometastasis. © The Author(s) 2015.

Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex.

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Thomas Nebl

2011-09-01

Full Text Available Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca²⁺-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of ³²[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca²⁺-dependent phosphorylation patterns on three of its components--GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component.

Comparative physiological, metabolomic, and transcriptomic analyses reveal mechanisms of improved abiotic stress resistance in bermudagrass [Cynodon dactylon (L). Pers.] by exogenous melatonin

Science.gov (United States)

Shi, Haitao; Jiang, Chuan; Ye, Tiantian; Tan, Dun-xian; Reiter, Russel J.; Zhang, Heng; Liu, Renyi; Chan, Zhulong

2015-01-01

Melatonin (N-acetyl-5-methoxytryptamine), a well-known animal hormone, is also involved in plant development and abiotic stress responses. In this study, it is shown that exogenous application of melatonin conferred improved salt, drought, and cold stress resistances in bermudagrass. Moreover, exogenous melatonin treatment alleviated reactive oxygen species (ROS) burst and cell damage induced by abiotic stress; this involved activation of several antioxidants. Additionally, melatonin-pre-treated plants exhibited higher concentrations of 54 metabolites, including amino acids, organic acids, sugars, and sugar alcohols, than non-treated plants under abiotic stress conditions. Genome-wide transcriptomic profiling identified 3933 transcripts (2361 up-regulated and 1572 down-regulated) that were differentially expressed in melatonin-treated plants versus controls. Pathway and gene ontology (GO) term enrichment analyses revealed that genes involved in nitrogen metabolism, major carbohydrate metabolism, tricarboxylic acid (TCA)/org transformation, transport, hormone metabolism, metal handling, redox, and secondary metabolism were over-represented after melatonin pre-treatment. Taken together, this study provides the first evidence of the protective roles of exogenous melatonin in the bermudagrass response to abiotic stresses, partially via activation of antioxidants and modulation of metabolic homeostasis. Notably, metabolic and transcriptomic analyses showed that the underlying mechanisms of melatonin could involve major reorientation of photorespiratory and carbohydrate and nitrogen metabolism. PMID:25225478

Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.

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Ming He

2011-06-01

Full Text Available Cyclic dimeric GMP (c-di-GMP is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1, which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol. To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.

Survival after early-stage breast cancer of women previously treated for depression

DEFF Research Database (Denmark)

Suppli, Nis Frederik Palm; Johansen, Christoffer; Kessing, Lars Vedel

2017-01-01

treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer-specific survival, and risk of death by suicide of women who were and were not treated for depression before......Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material...... and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous...

Combined effects of extremely high frequency electromagnetic field and antibiotics on Enterococcus Hirae growth and survival

International Nuclear Information System (INIS)

Ohanyan, V.A.

2012-01-01

Combined effects of extremely high frequency electromagnetic field and antibiotics on Enterococcus hirae ATCC 9790 bacterial growth and survival were investigated using 51.8 GHz and 53 GHz frequencies in combination with two commonly used antibiotics: ampicillin and dalacin. Results revealed that, despite bacterial type and membrane structure and properties, the combined effect, especially with 53 GHz and dalacin, suppresses bacterial growth and decreases their survival

Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.

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Jason Abernathy

Full Text Available Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.

Transcatheter arterial chemoembolization combined with radiofrequency ablation can improve survival of patients with hepatocellular carcinoma with portal vein tumour thrombosis: Extending the indication for ablation?

International Nuclear Information System (INIS)

Zheng, J.-S.; Long, J.; Sun, B.; Lu, N.-N.; Fang, D.; Zhao, L.-Y.; Du, N.

2014-01-01

Aim: To retrospectively assess long-term survival benefit and safety of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombosis (PVTT), and to evaluate factors that significantly affect outcomes of these patients. Materials and methods: One hundred and thirty-four HCC patients (118 men and 16 women; mean age 54.8 years, range 26–79 years) with PVTT were retrospectively assessed. Patients were treated with TACE combined with RFA. Data analysed included patient demographics, liver volume, Child–Pugh score, and Cancer of the Liver Italian Programme (CLIP) score and imaging findings. Survival time (from occurrence of PVTT to last follow-up) was calculated using the Kaplan–Meier method, predictive factors and its correlation with survival was assessed using the multivariate Cox proportional hazards regression method. Results: The median overall survival (OS) time was 29.5 months (range 16.6–42.4 months), the 1, 3, and 5 year OS were 63%, 40%, and 23%. Cox hazards regression analysis revealed that functional remnant liver volume (FRLV), remnant liver volume (RLV)/total liver volume (TLV), radiation, tumour number, vascular endothelial growth factor (VEGF) distribution, and gross type were the only independent predictive factors of outcome (p = 0.039, 0.010, 0.009, 0.034, 0.031, and 0.000, respectively). Conclusion: TACE combined with RFA was found to be an effective therapy, FRLV and RLV/TLV have close correlation with survival for HCC patients with PVTT type I, II, or partial III and Child–Pugh A or B

RNA-seq analyses reveal insights into the function of respiratory nitrate reductase of the diazotroph Herbaspirillum seropedicae.

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Bonato, Paloma; Batista, Marcelo B; Camilios-Neto, Doumit; Pankievicz, Vânia C S; Tadra-Sfeir, Michelle Z; Monteiro, Rose Adele; Pedrosa, Fabio O; Souza, Emanuel M; Chubatsu, Leda S; Wassem, Roseli; Rigo, Liu Un

2016-09-01

Herbaspirillum seropedicae is a nitrogen-fixing β-proteobacterium that associates with roots of gramineous plants. In silico analyses revealed that H. seropedicae genome has genes encoding a putative respiratory (NAR) and an assimilatory nitrate reductase (NAS). To date, little is known about nitrate metabolism in H. seropedicae, and, as this bacterium cannot respire nitrate, the function of NAR remains unknown. This study aimed to investigate the function of NAR in H. seropedicae and how it metabolizes nitrate in a low aerated-condition. RNA-seq transcriptional profiling in the presence of nitrate allowed us to pinpoint genes important for nitrate metabolism in H. seropedicae, including nitrate transporters and regulatory proteins. Additionally, both RNA-seq data and physiological characterization of a mutant in the catalytic subunit of NAR (narG mutant) showed that NAR is not required for nitrate assimilation but is required for: (i) production of high levels of nitrite, (ii) production of NO and (iii) dissipation of redox power, which in turn lead to an increase in carbon consumption. In addition, wheat plants showed an increase in shoot dry weight only when inoculated with H. seropedicae wild type, but not with the narG mutant, suggesting that NAR is important to H. seropedicae-wheat interaction. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Mitogenome evolution in the last surviving woolly mammoth population reveals neutral and functional consequences of small population size

NARCIS (Netherlands)

Pecnerova, Patricia; Palkopoulou, E.; Wheat, Christopher W.; Skoglund, Pontus; Vartanyan, Sergey; Tikhonov, Alexei; Nikolskiy, Pavel; van der Plicht, Johannes; Diez-del-Molino, David; Dalen, Love

2017-01-01

The onset of the Holocene was associated with a global temperature increase, which led to a rise in sea levels and isolation of the last surviving population of woolly mammoths on Wrangel Island. Understanding what happened with the population’s genetic diversity at the time of the isolation and

Family members' experiences with intensive care unit diaries when the patient does not survive.

Science.gov (United States)

Johansson, Maria; Wåhlin, Ingrid; Magnusson, Lennart; Runeson, Ingrid; Hanson, Elizabeth

2018-03-01

The aim of the study was to explore how family members experienced the use of a diary when a relative does not survive the stay in the intensive care unit (ICU). A qualitative method with a hermeneutic approach was used. Nine participants who read/wrote eight diaries in total were interviewed. The collected data were analysed using a hermeneutic technique inspired by Geanellos. The analysis revealed an overall theme 'the diary was experienced as a bridge connecting the past with the future', which was a metaphor referring to the temporal aspect where there was the period with the diary up until the patient's death and then the postbereavement period. The diary contributed to both a rational and emotional understanding of the death of the patient and disclosed glimmers of light that still existed before the illness deteriorated. Further, the diary bridged the space between family members themselves and between family and nursing staff. It helped to maintain a feeling of togetherness and engagement in the care of the patient which family members found comforting. Family members of nonsurvivors had a need to have the ICU time explained and expressed. The diary might work as a form of 'survival kit' to gain coherence and understanding; to meet their needs during the hospital stay; and, finally, to act as a bereavement support by processing the death of the patient. © 2017 Nordic College of Caring Science.

PROGNOSTIC FACTORS FOR SURVIVAL IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH FIRST - LINE CHEMOTHERAPY

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Deyan Davidov

2017-05-01

Full Text Available Objective: The aim of this study was to investigate the prognostic significance for survival of certain clinical and pathological factors in patients with advanced or metastatic colorectal carcinoma (CRC treated with first- line chemotherapy. Methods: From 2002 to 2011 seventy- four consecutive patients with advanced or metastatic CRC, treated in UMHAT- Dr. G. Stranski, Department of Medical Oncology entered the study. Some patient’s characteristics, hematological and pathological parameters, were evaluated for their role as predictors of overall survival. The therapeutic regimens included FOLFOX or FOlFIRI. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment characteristics as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: In multivariate analysis a significant correlation was exhibited between survival, poor performance status and multiple sites of metastasis. Variables significantly associated with overall survival in univariate analysis were performance status>1, thrombocytosis, anemia and number of metastatic sites >1. Conclusion: These results indicated that poor performance status, anemia, thrombocytosis as well as multiple site of metastasis could be useful prognostic factors in patients with metastatic CRC.

Survival after out-of-hospital cardiac arrest in relation to sex: a nationwide registry-based study.

Science.gov (United States)

Wissenberg, Mads; Hansen, Carolina Malta; Folke, Fredrik; Lippert, Freddy K; Weeke, Peter; Karlsson, Lena; Rajan, Shahzleen; Søndergaard, Kathrine Bach; Kragholm, Kristian; Christensen, Erika Frischknecht; Nielsen, Søren L; Køber, Lars; Gislason, Gunnar H; Torp-Pedersen, Christian

2014-09-01

Crude survival has increased following an out-of-hospital cardiac arrest (OHCA). We aimed to study sex-related differences in patient characteristics and survival during a 10-year study period. Patients≥12 years old with OHCA of a presumed cardiac cause, and in whom resuscitation was attempted, were identified through the Danish Cardiac Arrest Registry 2001-2010. A total of 19,372 patients were included. One-third were female, with a median age of 75 years (IQR 65-83). Compared to females, males were five years younger; and less likely to have severe comorbidities, e.g., chronic obstructive pulmonary disease (12.8% vs. 16.5%); but more likely to have arrest outside of the home (29.4% vs. 18.7%), receive bystander CPR (32.9% vs. 25.9%), and have a shockable rhythm (32.6% vs. 17.2%), all p<0.001. Thirty-day crude survival increased in males (3.0% in 2001 to 12.9% in 2010); and in females (4.8% in 2001 to 6.7% in 2010), p<0.001. Multivariable logistic regression analyses adjusted for patient characteristics including comorbidities, showed no survival difference between sexes in patients with a non-shockable rhythm (OR 1.00; CI 0.72-1.40), while female sex was positively associated with survival in patients with a shockable rhythm (OR 1.31; CI 1.07-1.59). Analyses were rhythm-stratified due to interaction between sex and heart rhythm; there was no interaction between sex and calendar-year. Temporal increase in crude survival was more marked in males due to poorer prognostic characteristics in females with a lower proportion of shockable rhythm. In an adjusted model, female sex was positively associated with survival in patients with a shockable rhythm. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cross-validation and Peeling Strategies for Survival Bump Hunting using Recursive Peeling Methods

Science.gov (United States)

Dazard, Jean-Eudes; Choe, Michael; LeBlanc, Michael; Rao, J. Sunil

2015-01-01

We introduce a framework to build a survival/risk bump hunting model with a censored time-to-event response. Our Survival Bump Hunting (SBH) method is based on a recursive peeling procedure that uses a specific survival peeling criterion derived from non/semi-parametric statistics such as the hazards-ratio, the log-rank test or the Nelson--Aalen estimator. To optimize the tuning parameter of the model and validate it, we introduce an objective function based on survival or prediction-error statistics, such as the log-rank test and the concordance error rate. We also describe two alternative cross-validation techniques adapted to the joint task of decision-rule making by recursive peeling and survival estimation. Numerical analyses show the importance of replicated cross-validation and the differences between criteria and techniques in both low and high-dimensional settings. Although several non-parametric survival models exist, none addresses the problem of directly identifying local extrema. We show how SBH efficiently estimates extreme survival/risk subgroups unlike other models. This provides an insight into the behavior of commonly used models and suggests alternatives to be adopted in practice. Finally, our SBH framework was applied to a clinical dataset. In it, we identified subsets of patients characterized by clinical and demographic covariates with a distinct extreme survival outcome, for which tailored medical interventions could be made. An R package PRIMsrc (Patient Rule Induction Method in Survival, Regression and Classification settings) is available on CRAN (Comprehensive R Archive Network) and GitHub. PMID:27034730

Volunteering is associated with increased survival in able-bodied participants of the English Longitudinal Study of Ageing.

Science.gov (United States)

Rogers, Nina Trivedy; Demakakos, Panayotes; Taylor, Mark Steven; Steptoe, Andrew; Hamer, Mark; Shankar, Aparna

2016-06-01

Volunteering has been linked to reduced mortality in older adults, but the mechanisms explaining this effect remain unclear. This study investigated whether volunteering is associated with increased survival in participants of the English Longitudinal Study of Ageing and whether differences in survival are modified by functional disabilities. A multivariate Cox Proportional Hazards model was used to estimate the association of volunteering with survival over a period of 10.9 years in 10 324 participants, while controlling for selected confounders. To investigate effect modification by disability, the analyses were repeated in participants with and without self-reported functional disabilities. Volunteering was associated with a reduced probability of death from all causes in univariate analyses (HR=0.65, CI 0.58 to 0.73, pvolunteers had significantly increased survival compared with able-bodied non-volunteers (HR=0.81, 95% CI 0.69 to 0.95, p=0.009). There was no significant survival advantage among disabled volunteers, compared with disabled non-volunteers (HR=1.06, CI 0.88 to 1.29, p=0.53). Volunteering is associated with reduced mortality in older adults in England, but this effect appears to be limited to volunteers who report no disabilities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis

DEFF Research Database (Denmark)

Glintborg, Bente; Gudbjornsson, Bjorn; Krogh, Niels Steen

2014-01-01

Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P drug survival than...... Icelandic patients (1183 vs 483 days). In univariate analyses stratified by country, time until dose escalation, response rates, drug survival and 1-year's disease activity were independent of starting dose. Drug survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In clinical...... practice, > 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended in international guidelines. Lower starting doses did not affect drug survival or response....

DNA sequence analyses reveal abundant diversity, endemism and evidence for Asian origin of the porcini mushrooms.

Directory of Open Access Journals (Sweden)

Bang Feng

Full Text Available The wild gourmet mushroom Boletus edulis and its close allies are of significant ecological and economic importance. They are found throughout the Northern Hemisphere, but despite their ubiquity there are still many unresolved issues with regard to the taxonomy, systematics and biogeography of this group of mushrooms. Most phylogenetic studies of Boletus so far have characterized samples from North America and Europe and little information is available on samples from other areas, including the ecologically and geographically diverse regions of China. Here we analyzed DNA sequence variation in three gene markers from samples of these mushrooms from across China and compared our findings with those from other representative regions. Our results revealed fifteen novel phylogenetic species (about one-third of the known species and a newly identified lineage represented by Boletus sp. HKAS71346 from tropical Asia. The phylogenetic analyses support eastern Asia as the center of diversity for the porcini sensu stricto clade. Within this clade, B. edulis is the only known holarctic species. The majority of the other phylogenetic species are geographically restricted in their distributions. Furthermore, molecular dating and geological evidence suggest that this group of mushrooms originated during the Eocene in eastern Asia, followed by dispersal to and subsequent speciation in other parts of Asia, Europe, and the Americas from the middle Miocene through the early Pliocene. In contrast to the ancient dispersal of porcini in the strict sense in the Northern Hemisphere, the occurrence of B. reticulatus and B. edulis sensu lato in the Southern Hemisphere was probably due to recent human-mediated introductions.

DNA Sequence Analyses Reveal Abundant Diversity, Endemism and Evidence for Asian Origin of the Porcini Mushrooms

Science.gov (United States)

Feng, Bang; Xu, Jianping; Wu, Gang; Zeng, Nian-Kai; Li, Yan-Chun; Tolgor, Bau; Kost, Gerhard W.; Yang, Zhu L.

2012-01-01

The wild gourmet mushroom Boletus edulis and its close allies are of significant ecological and economic importance. They are found throughout the Northern Hemisphere, but despite their ubiquity there are still many unresolved issues with regard to the taxonomy, systematics and biogeography of this group of mushrooms. Most phylogenetic studies of Boletus so far have characterized samples from North America and Europe and little information is available on samples from other areas, including the ecologically and geographically diverse regions of China. Here we analyzed DNA sequence variation in three gene markers from samples of these mushrooms from across China and compared our findings with those from other representative regions. Our results revealed fifteen novel phylogenetic species (about one-third of the known species) and a newly identified lineage represented by Boletus sp. HKAS71346 from tropical Asia. The phylogenetic analyses support eastern Asia as the center of diversity for the porcini sensu stricto clade. Within this clade, B. edulis is the only known holarctic species. The majority of the other phylogenetic species are geographically restricted in their distributions. Furthermore, molecular dating and geological evidence suggest that this group of mushrooms originated during the Eocene in eastern Asia, followed by dispersal to and subsequent speciation in other parts of Asia, Europe, and the Americas from the middle Miocene through the early Pliocene. In contrast to the ancient dispersal of porcini in the strict sense in the Northern Hemisphere, the occurrence of B. reticulatus and B. edulis sensu lato in the Southern Hemisphere was probably due to recent human-mediated introductions. PMID:22629418

Recognising out-of-hospital cardiac arrest during emergency calls increases bystander cardiopulmonary resuscitation and survival

DEFF Research Database (Denmark)

Viereck, Søren; Møller, Thea Palsgaard; Ersbøll, Annette Kjær

2017-01-01

BACKGROUND: Initiation of early bystander cardiopulmonary resuscitation (CPR) depends on bystanders' or medical dispatchers' recognition of out-of-hospital cardiac arrest (OHCA). The primary aim of our study was to investigate if OHCA recognition during the emergency call was associated...... with bystander CPR, return of spontaneous circulation (ROSC), and 30-day survival. Our secondary aim was to identify patient-, setting-, and dispatcher-related predictors of OHCA recognition. METHODS: We performed an observational study of all OHCA patients' emergency calls in the Capital Region of Denmark from...... the association between OHCA recognition and bystander CPR, ROSC, and 30-day survival. Univariable logistic regression analyses were applied to identify predictors of OHCA recognition. RESULTS: We included 779 emergency calls in the analyses. During the emergency calls, 70.1% (n=534) of OHCAs were recognised...

Camouflage and Clutch Survival in Plovers and Terns

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Stoddard, Mary Caswell; Kupán, Krisztina; Eyster, Harold N.; Rojas-Abreu, Wendoly; Cruz-López, Medardo; Serrano-Meneses, Martín Alejandro; Küpper, Clemens

2016-09-01

Animals achieve camouflage through a variety of mechanisms, of which background matching and disruptive coloration are likely the most common. Although many studies have investigated camouflage mechanisms using artificial stimuli and in lab experiments, less work has addressed camouflage in the wild. Here we examine egg camouflage in clutches laid by ground-nesting Snowy Plovers Charadrius nivosus and Least Terns Sternula antillarum breeding in mixed aggregations at Bahía de Ceuta, Sinaloa, Mexico. We obtained digital images of clutches laid by both species. We then calibrated the images and used custom computer software and edge detection algorithms to quantify measures related to three potential camouflage mechanisms: pattern complexity matching, disruptive effects and background color matching. Based on our image analyses, Snowy Plover clutches, in general, appeared to be more camouflaged than Least Tern clutches. Snowy Plover clutches also survived better than Least Tern clutches. Unexpectedly, variation in clutch survival was not explained by any measure of egg camouflage in either species. We conclude that measures of egg camouflage are poor predictors of clutch survival in this population. The behavior of the incubating parents may also affect clutch predation. Determining the significance of egg camouflage requires further testing using visual models and behavioral experiments.

 Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

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Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

2016-01-01

 Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem

International Nuclear Information System (INIS)

Taktak, Azzam F G; Fisher, Anthony C; Damato, Bertil E

2004-01-01

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to >100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For <10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate

Modelling survival after treatment of intraocular melanoma using artificial neural networks and Bayes theorem

Energy Technology Data Exchange (ETDEWEB)

Taktak, Azzam F G [Department of Clinical Engineering, Duncan Building, Royal Liverpool University Hospital, Liverpool L7 8XP (United Kingdom); Fisher, Anthony C [Department of Clinical Engineering, Duncan Building, Royal Liverpool University Hospital, Liverpool L7 8XP (United Kingdom); Damato, Bertil E [Department of Ophthalmology, Royal Liverpool University Hospital, Liverpool L7 8XP (United Kingdom)

2004-01-07

This paper describes the development of an artificial intelligence (AI) system for survival prediction from intraocular melanoma. The system used artificial neural networks (ANNs) with five input parameters: coronal and sagittal tumour location, anterior tumour margin, largest basal tumour diameter and the cell type. After excluding records with missing data, 2331 patients were included in the study. These were split randomly into training and test sets. Date censorship was applied to the records to deal with patients who were lost to follow-up and patients who died from general causes. Bayes theorem was then applied to the ANN output to construct survival probability curves. A validation set with 34 patients unseen to both training and test sets was used to compare the AI system with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large differences in the mean 5 year survival probability figures when the number of records with matching characteristics was small. However, as the number of matches increased to >100 the system tended to agree with CR and KM. The validation set was also used to compare the system with a clinical expert in predicting time to metastatic death. The rms error was 3.7 years for the system and 4.3 years for the clinical expert for 15 years survival. For <10 years survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI system can match if not better the clinical expert's prediction. There were significant differences with CR and KM analyses when the number of records was small, but it was not known which model is more accurate.

Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma.

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Josep Puig

Full Text Available Intravoxel incoherent motion (IVIM is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma.Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D, pseudodiffusion coefficient (D*, and perfusion fraction (f were generated for contrast-enhancing regions (CER and non-enhancing regions (NCER. Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses.We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10-3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively. Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031; fCER combined with treatment predicted survival with 100% accuracy.The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

The 'revealed preferences' theory: Assumptions and conjectures

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Green, C.H.

1983-01-01

Being kind of intuitive psychology the 'Revealed-Preferences'- theory based approaches towards determining the acceptable risks are a useful method for the generation of hypotheses. In view of the fact that reliability engineering develops faster than methods for the determination of reliability aims the Revealed-Preferences approach is a necessary preliminary help. Some of the assumptions on which the 'Revealed-Preferences' theory is based will be identified and analysed and afterwards compared with experimentally obtained results. (orig./DG) [de

Survival in common cancers defined by risk and survival of family members

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Jianguang Ji

2011-10-01

Full Text Available Studies on survival between familial and sporadic cancers have been inconclusive and only recent data on a limited number of cancers are available on the concordance of survival between family members. In this review, we address these questions by evaluating the published and unpublished data from the nation-wide Swedish Family-Cancer Database and a total of 13 cancer sites were assessed. Using sporadic cancer as reference, HRs were close to 1.0 for most of the familial cancers in both the offspring and parental generations, which suggested that survival in patients with familial and sporadic cancers was equal, with an exception for ovarian cancer with a worse prognosis. Compared to offspring whose parents had a poor survival, those with a good parental survival had a decreased risk of death for most cancers and HR was significantly decreased for cancers in the breast, prostate, bladder, and kidney. For colorectal and nervous system cancers, favorable survival between the generations showed a borderline significance. These data are consistent in showing that both good and poor survival in certain cancers aggregate in families. Genetic factors are likely to contribute to the results. These observations call for intensified efforts to consider heritability in survival as one mechanism regulating prognosis in cancer patients.

Pre-transplant levels of ficolin-3 are associated with kidney graft survival

DEFF Research Database (Denmark)

Bay, Jakob T; Hein, Estrid; Sørensen, Søren S

2013-01-01

. 97 blood donors served as controls. Ficolin-3, C4 and C3 were measured in pre-transplant as well as in control serum samples. In controls, deposition of ficolin-3, C4, C3 and the terminal complement complex (TCC) was measured in an assay based on acetylated albumin as matrix. The ficolin-3 levels...... correlated with the serum levels of C4 and C3. The serum levels of ficolin-3 correlated with the deposition of ficolin-3, C4, C3 and TCC. Survival analyses showed that high pre-transplant serum levels of ficolin-3 were associated with decreased graft survival. These results suggest an important role...

[Medulloblastoma: improved survival in recent decades. Unicentric experience].

Science.gov (United States)

Igual Estellés, Lucía; Berlanga Charriel, Pablo; Cañete Nieto, Adela

2017-01-01

The aim of the study is to analyse variations in the treatment of medulloblastoma, the most common childhood brain tumour, and its impact on survival over the past two decades, as well as its clinical and pathological features. Survival analysis of all patients under 14 years old diagnosed with medulloblastoma between January 1990 and December 2013 in a Paediatric Oncology Unit. Sixty-three patients were diagnosed and treated for medulloblastoma, with a median follow-up of 5.1 years (range 0.65-21.7 years). The overall survival (OS) at 3 and 5 years was 66±13% and 55±14%, respectively. The OS at 5 years was 44%±25% in patients diagnosed in the 1990's, showing an increase to 70%±23% (p=0.032) since 2000. Clinical prognosis factors were included in the logistic regression model: age (p=0.008), presence of metastases and/or residual tumour (p=0.007), and receiving chemotherapy with radiotherapy after surgery (p=0.008). Statistically significant differences were observed for all of them. In our institution there has been a significant increase in medulloblastoma survival in the last decades. Multivariate analysis showed that this improvement was not related to the date of diagnosis, but with the introduction of chemotherapy in adjuvant treatment. This study confirmed that clinical factors significantly associated with worse outcome were age and presence of metastases at diagnosis. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

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Gonzalez Calzada, Nuria; Prats Soro, Enric; Mateu Gomez, Lluis; Giro Bulta, Esther; Cordoba Izquierdo, Ana; Povedano Panades, Monica; Dorca Sargatal, Jordi; Farrero Muñoz, Eva

2016-01-01

Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

Goseki grade and tumour location influence survival of patients with gastric cancer.

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Calik, Muhammet; Calik, Ilknur; Demirci, Elif; Altun, Eren; Gundogdu, Betul; Sipal, Sare; Gundogdu, Cemal

2014-01-01

Owing to the variability of histopathological features and biological behaviour in gastric carcinoma, a great number of categorisation methods such as classical histopathologic grading, Lauren classification, the TNM staging system and the newly presented Goseki grading method are used by pathologists and other scientists. In our study, we aimed to investigate whether Goseki grade and tumour location have an effects on survival of gastric cancer cases. Eighty-four patients with gastric adenocarcinoma were covered in the investigation. The importance of Goseki grading system and tumour location were analysed in addition to the TNM staging and other conventional prognostic parameters. The median survival time in our patients was 35 months (minimum: 5, maximum: 116). According to our findings, there was no relation between survival and tumour size (p=0.192) or classical histological type (p=0.270). In contrast, the Goseki grade and tumour location significantly correlated with survival (p=0.007 and p<0.001, respectively). Additionally, tumours of the intestinal type had a longer median survival time (60.0 months) than diffuse tumours (24.0 months). In addition to the TNM staging system, tumour location and the Goseki grading system may be used as significant prognostic parameters in patients with gastric cancer.

An approach to the drone fleet survivability assessment based on a stochastic continues-time model

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Kharchenko, Vyacheslav; Fesenko, Herman; Doukas, Nikos

2017-09-01

An approach and the algorithm to the drone fleet survivability assessment based on a stochastic continues-time model are proposed. The input data are the number of the drones, the drone fleet redundancy coefficient, the drone stability and restoration rate, the limit deviation from the norms of the drone fleet recovery, the drone fleet operational availability coefficient, the probability of the drone failure-free operation, time needed for performing the required tasks by the drone fleet. The ways for improving the recoverable drone fleet survivability taking into account amazing factors of system accident are suggested. Dependencies of the drone fleet survivability rate both on the drone stability and the number of the drones are analysed.

Immunological predictors of survival in HIV type 2-infected rural villagers in Guinea-Bissau

DEFF Research Database (Denmark)

Jaffar, Shabbar; Van der Loeff, Maarten Schim; Eugen-Olsen, Jesper

2005-01-01

We investigated the association between beta2-microglobulin, neopterin, serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), CD4 count, and plasma viremia with survival in 133 HIV-2-infected villagers and 160 controls living in rural Guinea-Bissau. Subjects were recruited......%, and plasma viral load were associated independently with survival in multivariate analyses. Neopterin and suPAR did not reach statistical significance. These findings suggest that immune activation is central to the pathogenesis of HIV. They also have important implications for resource-poor settings where...

Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

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Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

2015-01-01

Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

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Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

A Novel Inflammation-Based Stage (I Stage Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma

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Jian-Pei Li

2016-11-01

Full Text Available Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS, modified GPS (mGPS and C-reactive protein/Albumin (CRP/Alb ratio, platelet–lymphocyte ratio (PLR, and neutrophil–lymphocyte ratio (NLR, have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC. In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR. The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03 and PLR (>146.2 were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves analyzed by receiver operating characteristics (ROC curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR = 2.093; 95% Confidence interval (CI: 1.222–3.587; p = 0.007 and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010 were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001. The I stage had a higher area under the curve value (0.670 compared with other systemic inflammation

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients

DEFF Research Database (Denmark)

Møller, Henrik; Coupland, Victoria H; Tataru, Daniela

2018-01-01

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment...... and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following...... diagnosis. RESULTS: Survival improved over the period studied. The use of active treatment varied between geographical areas, with inter-quintile ranges of 9%-17% for surgical resection, 4%-13% for radical radiotherapy, and 22%-35% for chemotherapy. At 2 years, there were 188 potentially avoidable deaths...

Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

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Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

2017-01-01

Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

Intracellular contacts - effect of survival curve of mammal cells on the Dq value

International Nuclear Information System (INIS)

Durand, R.E.; Sutherland, R.M.

1980-01-01

Survival increase is observed in cells of the Chinese hamster of the V79-171 line which grow in the composition of multicell spheroids as compared with the survival after irradiation in a single state. The ratio of the Dsub(q) cell value in the composition of spheroids to Dsub(q) of separately growing cells increases as the mitotic cycle proceeds from the minimum value of 1.3 for cells in the Gi phase to the maximum value of 2.2 for cells in a late S-phase. The increase of survival during growth in the composition of spheroids is not characteristic for all cell types. Only a part of cultured MNNG-mutants of cells of the V79-171 Chinese hamster reveal radiomodifying effect of cell contact acting [ru

Social Relationships, Inflammation, and Cancer Survival.

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Boen, Courtney E; Barrow, David A; Bensen, Jeannette T; Farnan, Laura; Gerstel, Adrian; Hendrix, Laura H; Yang, Yang Claire

2018-05-01

Background: Social stressors, such as social relationship deficits, have been increasingly linked to chronic disease outcomes, including cancer. However, critical gaps exist in our understanding of the nature and strength of such links, as well as the underlying biological mechanisms relating social relationships to cancer progression and survival. Methods: Utilizing novel questionnaire and biomarker data from the UNC Health Registry/Cancer Survivorship Cohort, this study examines the associations between diverse measures of social support and mortality risk among individuals with cancer ( N = 1,004). We further assess the role of multiple serum markers of inflammation, including high-sensitivity C-reactive protein (CRP), IL6, TNFα, and VEGF, as potential mediators in the social relationship-cancer link. Results: The findings revealed that one's appraisal of their social support was associated with cancer mortality, such that individuals reporting higher levels of social support satisfaction had lower mortality risk than individuals reporting lower levels of satisfaction. The amount of support received, on the other hand, was not predictive of cancer survival. We further found evidence that inflammatory processes may undergird the link between social support satisfaction and mortality among individuals with cancer, with individuals reporting higher levels of social support satisfaction having lower levels of CRP, IL6, and TNFα. Conclusions: These results provide new knowledge of the biosocial processes producing population disparities in cancer outcomes. Impact: Our study offers new insights for intervention efforts aimed at promoting social connectedness as a means for improving cancer survival. Cancer Epidemiol Biomarkers Prev; 27(5); 541-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years

DEFF Research Database (Denmark)

Mendez, Ivar; Viñuela, Angel; Astradsson, Arnar

2008-01-01

Postmortem analysis of five subjects with Parkinson's disease 9-14 years after transplantation of fetal midbrain cell suspensions revealed surviving grafts that included dopamine and serotonin neurons without pathology. These findings are important for the understanding of the etiopathogenesis...

Water Properties in Cream Cheeses with Variations in pH, Fat, and Salt Content and Correlation to Microbial Survival

DEFF Research Database (Denmark)

Møller, Sandie M.; Hansen, Tina B.; Andersen, Simon Ulf

2012-01-01

and Staphylococcus aureus, and partial least-squares regression revealed that H-1 T-2 relaxation decay data were able to explain a large part of the variation in the survival of E. coli O157 (64-83%). However, the predictions of L. innocua and S. aureus survival were strongly dependent on the fat/water content...

Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

Science.gov (United States)

Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

2018-01-01

Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

Combined metabonomic and quantitative real-time PCR analyses reveal systems metabolic changes in Jurkat T-cells treated with HIV-1 Tat protein.

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Liao, Wenting; Tan, Guangguo; Zhu, Zhenyu; Chen, Qiuli; Lou, Ziyang; Dong, Xin; Zhang, Wei; Pan, Wei; Chai, Yifeng

2012-11-02

HIV-1 Tat protein is released by infected cells and can affect bystander uninfected T cells and induce numerous biological responses which contribute to its pathogenesis. To elucidate the complex pathogenic mechanism, we conducted a comprehensive investigation on Tat protein-related extracellular and intracellular metabolic changes in Jurkat T-cells using combined gas chromatography-mass spectrometry (GC-MS), reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and a hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS)-based metabonomics approach. Quantitative real-time PCR (qRT-PCR) analyses were further employed to measure expressions of several relevant enzymes together with perturbed metabolic pathways. Combined metabonomic and qRT-PCR analyses revealed that HIV-1 Tat caused significant and comprehensive metabolic changes, as represented by significant changes of 37 metabolites and 10 relevant enzymes in HIV-1 Tat-treated cells. Using MetaboAnalyst 2.0, it was found that 11 pathways (Impact-value >0.10) among the regulated pathways were acutely perturbed, including sphingolipid metabolism, glycine, serine and threonine metabolism, pyruvate metabolism, inositol phosphate metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism, pentose phosphate pathway, glycerophospholipid metabolism, glycolysis or gluconeogenesis. These results provide metabolic evidence of the complex pathogenic mechanism of HIV-1 Tat protein as a "viral toxin", and would help obligate Tat protein as "an important target" for therapeutic intervention and vaccine development.

Comparative physiological, metabolomic, and transcriptomic analyses reveal mechanisms of improved abiotic stress resistance in bermudagrass [Cynodon dactylon (L). Pers.] by exogenous melatonin.

Science.gov (United States)

Shi, Haitao; Jiang, Chuan; Ye, Tiantian; Tan, Dun-Xian; Reiter, Russel J; Zhang, Heng; Liu, Renyi; Chan, Zhulong

2015-02-01

Melatonin (N-acetyl-5-methoxytryptamine), a well-known animal hormone, is also involved in plant development and abiotic stress responses. In this study, it is shown that exogenous application of melatonin conferred improved salt, drought, and cold stress resistances in bermudagrass. Moreover, exogenous melatonin treatment alleviated reactive oxygen species (ROS) burst and cell damage induced by abiotic stress; this involved activation of several antioxidants. Additionally, melatonin-pre-treated plants exhibited higher concentrations of 54 metabolites, including amino acids, organic acids, sugars, and sugar alcohols, than non-treated plants under abiotic stress conditions. Genome-wide transcriptomic profiling identified 3933 transcripts (2361 up-regulated and 1572 down-regulated) that were differentially expressed in melatonin-treated plants versus controls. Pathway and gene ontology (GO) term enrichment analyses revealed that genes involved in nitrogen metabolism, major carbohydrate metabolism, tricarboxylic acid (TCA)/org transformation, transport, hormone metabolism, metal handling, redox, and secondary metabolism were over-represented after melatonin pre-treatment. Taken together, this study provides the first evidence of the protective roles of exogenous melatonin in the bermudagrass response to abiotic stresses, partially via activation of antioxidants and modulation of metabolic homeostasis. Notably, metabolic and transcriptomic analyses showed that the underlying mechanisms of melatonin could involve major reorientation of photorespiratory and carbohydrate and nitrogen metabolism. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

["That flesh, pink and perishable": analysis of disease-free survival analysis in breast cancer in Gipuzkoa (Spain) in the presence of competing risks].

Science.gov (United States)

Martínez-Camblor, Pablo; Larrañaga, Nerea; Sarasqueta, Cristina; Mitxelena, María José; Basterretxea, Mikel

2009-01-01

To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied. Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks

Science.gov (United States)

Glicksberg, Benjamin S.; Li, Li; Badgeley, Marcus A.; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D.; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L.; Hoffman, Gabriel E.; Dan Li, Shuyu; Schadt, Eric E.; Patel, Chirag J.; Chen, Rong; Dudley, Joel T.

2016-01-01

Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). Results: We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key ‘hub’ diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. Contacts: rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307606

Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

Directory of Open Access Journals (Sweden)

Jacqueline C Lieblein-Boff

Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

Comparative Genome Analyses of Serratia marcescens FS14 Reveals Its High Antagonistic Potential

Science.gov (United States)

Li, Pengpeng; Kwok, Amy H. Y.; Jiang, Jingwei; Ran, Tingting; Xu, Dongqing; Wang, Weiwu; Leung, Frederick C.

2015-01-01

S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens. PMID:25856195

Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

Science.gov (United States)

Li, Pengpeng; Kwok, Amy H Y; Jiang, Jingwei; Ran, Tingting; Xu, Dongqing; Wang, Weiwu; Leung, Frederick C

2015-01-01

S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs) in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

Survival and mortality rates among Danes with MS

DEFF Research Database (Denmark)

Brønnum-Hansen, H; Stenager, Egon; Hansen, Thomas

2006-01-01

Long-term survival and trends in overall and cause-specific excess mortality among people with MS have been studied using the Danish Multiple Sclerosis Registry, which contains information about all Danish MS patients since the mid-20th Century. A total of 4254 deaths among approximately 10......,000 people with MS, representing more than 200,000 person-years of observation, have been analysed. Overall, mortality was almost three times higher and life expectancy 10 years less among people with MS than for the general population. However, excess mortality has declined significantly since 1950....

Linear transform of the multi-target survival curve

Energy Technology Data Exchange (ETDEWEB)

Watson, J V [Cambridge Univ. (UK). Dept. of Clinical Oncology and Radiotherapeutics

1978-07-01

A completely linear transform of the multi-target survival curve is presented. This enables all data, including those on the shoulder region of the curve, to be analysed. The necessity to make a subjective assessment about which data points to exclude for conventional methods of analysis is, therefore, removed. The analysis has also been adapted to include a 'Pike-Alper' method of assessing dose modification factors. For the data cited this predicts compatibility with the hypothesis of a true oxygen 'dose-modification' whereas the conventional Pike-Alper analysis does not.

Witnessed arrest, but not delayed bystander cardiopulmonary resuscitation improves prehospital cardiac arrest survival.

Science.gov (United States)

Vukmir, R B

2004-05-01

This study correlated the effect of witnessing a cardiac arrest and instituting bystander CPR (ByCPR), as a secondary end point in a study evaluating the effect of bicarbonate on survival. This prospective, randomised, double blinded clinical intervention trial enrolled 874 prehospital cardiopulmonary arrest patients encountered in a prehospital urban, suburban, and rural regional emergency medical service (EMS) area. This group underwent conventional advanced cardiac life support intervention followed by empiric early administration of sodium bicarbonate (1 mEq/l), monitoring conventional resuscitation parameters. Survival was measured as presence of vital signs on emergency department (ED) arrival. Data were analysed using chi(2) with Pearson correlation and odds ratio where appropriate. The overall survival rate was 13.9% (110 of 792) of prehospital cardiac arrest patients. The mean (SD) time until provision of bystander cardiopulmonary resuscitation (ByCPR) by laymen was 2.08 (2.77) minutes, and basic life support (BLS) by emergency medical technicians was 6.62 (5.73) minutes. There was improved survival noted with witnessed cardiac arrest-a 2.2-fold increase in survival, 18.9% (76 of 402) versus 8.6% (27 of 315) compared with unwitnessed arrests (ptwo minutes (p = 0.3752). Survival after prehospital cardiac arrest is more likely when witnessed, but not necessarily when ByCPR was performed by laymen.

Bumblebee family lineage survival is enhanced in high-quality landscapes.

Science.gov (United States)

Carvell, Claire; Bourke, Andrew F G; Dreier, Stephanie; Freeman, Stephen N; Hulmes, Sarah; Jordan, William C; Redhead, John W; Sumner, Seirian; Wang, Jinliang; Heard, Matthew S

2017-03-23

Insect pollinators such as bumblebees (Bombus spp.) are in global decline. A major cause of this decline is habitat loss due to agricultural intensification. A range of global and national initiatives aimed at restoring pollinator habitats and populations have been developed. However, the success of these initiatives depends critically upon understanding how landscape change affects key population-level parameters, such as survival between lifecycle stages, in target species. This knowledge is lacking for bumblebees, because of the difficulty of systematically finding and monitoring colonies in the wild. We used a combination of habitat manipulation, land-use and habitat surveys, molecular genetics and demographic and spatial modelling to analyse between-year survival of family lineages in field populations of three bumblebee species. Here we show that the survival of family lineages from the summer worker to the spring queen stage in the following year increases significantly with the proportion of high-value foraging habitat, including spring floral resources, within 250-1,000 m of the natal colony. This provides evidence for a positive impact of habitat quality on survival and persistence between successive colony cycle stages in bumblebee populations. These findings also support the idea that conservation interventions that increase floral resources at a landscape scale and throughout the season have positive effects on wild pollinators in agricultural landscapes.

Survival of Probiotic Lactobacilli in Acidic Environments Is Enhanced in the Presence of Metabolizable Sugars

OpenAIRE

Corcoran, B. M.; Stanton, C.; Fitzgerald, G. F.; Ross, R. P.

2005-01-01

Lactobacillus rhamnosus GG is an industrially significant probiotic strain with proven health benefits. In this study, the effect of glucose on L. rhamnosus GG survival was analyzed in simulated gastric juice at pH 2.0. It was found that the presence of 19.4 mM glucose resulted in up to 6-log10-enhanced survival following 90 min of exposure. Further work with dilute HCl confirmed that glucose was the sole component responsible. Comparative analysis with other Lactobacillus strains revealed th...

Cigarette smoking is associated with adverse survival among women with ovarian cancer

DEFF Research Database (Denmark)

Præstegaard, Camilla; Jensen, Allan; Jensen, Signe M

2017-01-01

,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses...

Environmental influences on Adelie penguin breeding schedules, endocrinology, and chick survival.

Science.gov (United States)

Ninnes, C E; Waas, J R; Ling, N; Nakagawa, S; Banks, J C; Bell, D G; Bright, A; Carey, P W; Chandler, J; Hudson, Q J; Ingram, J R; Lyall, K; Morgan, D K J; Stevens, M I; Wallace, J; Möstl, E

2011-08-01

To understand how the social and physical environment influences behaviour, reproduction and survival, studies of underlying hormonal processes are crucial; in particular, interactions between stress and reproductive responses may have critical influences on breeding schedules. Several authors have examined the timing of breeding in relation to environmental stimuli, while others have independently described endocrine profiles. However, few studies have simultaneously measured endocrine profiles, breeding behaviour, and offspring survival across seasons. We measured sex and stress hormone concentrations (oestrogens, testosterone, and corticosterone), timing of breeding, and chick survival, in Adelie penguins (Pygoscelis adeliae) at two colonies in two different years. Clutch initiation at Cape Bird South (CBS; year 1, ~14,000 pairs) occurred later than at Cape Crozier East (CCE; year 2, ~ 25,000 pairs); however, breeding was more synchronous at CBS. This pattern was probably generated by the persistence of extensive sea ice at CBS (year 1). Higher corticosterone metabolite and lower sex hormone concentrations at CBS correlated with later breeding and lower chick survival compared to at CCE - again, a likely consequence of sea ice conditions. Within colonies, sub-colony size (S, 50-100; M, 200-300; L, 500-600; XL, >1000 pairs) did not influence the onset or synchrony of breeding, chick survival, or hormone concentrations. We showed that the endocrine profiles of breeding Adelie penguins can differ markedly between years and/or colonies, and that combining measures of endocrinology, behaviour, and offspring survival can reveal the mechanisms and consequences that different environmental conditions can have on breeding ecology. Copyright © 2011 Elsevier Inc. All rights reserved.

Is there a difference in survival between men and women suffering in-hospital cardiac arrest?

Science.gov (United States)

Israelsson, Johan; Persson, Carina; Strömberg, Anna; Arestedt, Kristofer

2014-01-01

To describe in-hospital cardiac arrest (CA) events with regard to sex and to investigate if sex is associated with survival. Previous studies exploring differences between sexes are incongruent with regard to clinical outcomes. In order to provide equality and improve care, further investigations into these aspects are warranted. This registry study included 286 CAs. To investigate if sex was associated with survival, logistic regression analyses were performed. The proportion of CA with a resuscitation attempt compared to CA without resuscitation was higher among men. There were no associations between sex and survival when controlling for previously known predictors and interaction effects. Sex does not appear to be a predictor for survival among patients suffering CA where resuscitation is attempted. The difference regarding proportion of resuscitation attempts requires more attention. It is important to consider possible interaction effects when studying the sex perspective. Copyright © 2014 Elsevier Inc. All rights reserved.

Multinationals and plant survival

DEFF Research Database (Denmark)

Bandick, Roger

2010-01-01

The aim of this paper is twofold: first, to investigate how different ownership structures affect plant survival, and second, to analyze how the presence of foreign multinational enterprises (MNEs) affects domestic plants’ survival. Using a unique and detailed data set on the Swedish manufacturing...... sector, I am able to separate plants into those owned by foreign MNEs, domestic MNEs, exporting non-MNEs, and purely domestic firms. In line with previous findings, the result, when conditioned on other factors affecting survival, shows that foreign MNE plants have lower survival rates than non......-MNE plants. However, separating the non-MNEs into exporters and non-exporters, the result shows that foreign MNE plants have higher survival rates than non-exporting non-MNEs, while the survival rates of foreign MNE plants and exporting non-MNE plants do not seem to differ. Moreover, the simple non...

Important prognostic factors for the long-term survival of lung cancer subjects in Taiwan

International Nuclear Information System (INIS)

Chiang, Tai-An; Chen, Ping-Ho; Wu, Pei-Fen; Wang, Tsu-Nai; Chang, Po-Ya; Ko, Albert Min-Shan; Huang, Ming-Shyan; Ko, Ying-Chin

2008-01-01

This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan. Total of 24,910 subjects diagnosed with lung cancer was analysed. Survival estimates by Kaplan-Meier methods. Cox proportional-hazards model estimated the death risk (hazard ratio (HR)) for various prognostic factors. The prognostic indicators associated with a higher risk of lung cancer deaths are male gender (males versus females; HR = 1.07, 95% confidence intervals (CI): 1.03–1.11), males diagnosed in later periods (shown in 1991–1994 versus 1987–1990; HR = 1.13), older age at diagnosis, large cell carcinoma (LCC)/small cell carcinoma (SCC), and supportive care therapy over chemotherapy. The overall 5-year survival rate for lung cancer death was significantly poorer for males (21.3%) than females (23.6%). Subjects with squamous cell carcinoma (SQCC) and treatment by surgical resection alone had better prognosis. We find surgical resections to markedly increase 5-year survival rate from LCC, decreased risk of death from LCC, and no improved survival from SCC. Gender and clinical characteristics (i.e. diagnostic period, diagnostic age, histological type and treatment modality) play important roles in determining lung cancer survival

Pregnancy associated nasopharyngeal carcinoma: A retrospective case-control analysis of maternal survival outcomes

International Nuclear Information System (INIS)

Cheng, Yi-Kan; Zhang, Fan; Tang, Ling-Long; Chen, Lei; Zhou, Guan-Qun; Zeng, Mu-Sheng; Kang, Tie-Bang; Jia, Wei-Hua; Shao, Jian-Yong; Mai, Hai-Qiang; Guo, Ying; Ma, Jun

2015-01-01

Background: Pregnancy-associated nasopharyngeal carcinoma (PANPC) has been associated with poor survival. Recent advances in radiation technology and imaging techniques, and the introduction of chemotherapy have improved survival in nasopharyngeal carcinoma (NPC); however, it is not clear whether these changes have improved survival in PANPC. Therefore, the purpose of this study was to compare five-year maternal survival in patients with PANPC and non-pregnant patients with NPC. Methods: After adjusting for age, stage and chemotherapy mode, we conducted a retrospective case-control study among 36 non-metastatic PANPC patients and 36 non-pregnant NPC patients (control group) who were treated at our institution between 2000 and 2010. Results: The median age of both groups was 30 years (range, 23–35 years); median follow-up for all patients was 70 months. Locoregionally-advanced disease accounted for 83.3% of all patients with PANPC and 92.9% of patients who developed NPC during pregnancy. In both the PANPC and control groups, 31 patients (86.1%) received chemotherapy and all patients received definitive radiotherapy. The five-year rates for overall survival (70% vs. 78%, p = 0.72), distant metastasis-free survival (79% vs. 76%, p = 0.77), loco-regional relapse-free survival (97% vs. 91%, p = 0.69) and disease-free survival (69% vs. 74%, p = 0.98) were not significantly different between the PANPC and control groups. Multivariate analysis using a Cox proportional hazards model revealed that only N-classification was significantly associated with five-year OS. Conclusion: This study demonstrates that, in the modern treatment era, pregnancy itself may not negatively influence survival outcomes in patients with NPC; however, pregnancy may delay the diagnosis of NPC

Survivable architectures for time and wavelength division multiplexed passive optical networks

Science.gov (United States)

Wong, Elaine

2014-08-01

The increased network reach and customer base of next-generation time and wavelength division multiplexed PON (TWDM-PONs) have necessitated rapid fault detection and subsequent restoration of services to its users. However, direct application of existing solutions for conventional PONs to TWDM-PONs is unsuitable as these schemes rely on the loss of signal (LOS) of upstream transmissions to trigger protection switching. As TWDM-PONs are required to potentially use sleep/doze mode optical network units (ONU), the loss of upstream transmission from a sleeping or dozing ONU could erroneously trigger protection switching. Further, TWDM-PONs require its monitoring modules for fiber/device fault detection to be more sensitive than those typically deployed in conventional PONs. To address the above issues, three survivable architectures that are compliant with TWDM-PON specifications are presented in this work. These architectures combine rapid detection and protection switching against multipoint failure, and most importantly do not rely on upstream transmissions for LOS activation. Survivability analyses as well as evaluations of the additional costs incurred to achieve survivability are performed and compared to the unprotected TWDM-PON. Network parameters that impact the maximum achievable network reach, maximum split ratio, connection availability, fault impact, and the incremental reliability costs for each proposed survivable architecture are highlighted.

Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis

International Nuclear Information System (INIS)

Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young; Lee, Sang Min; Kim, Namkug; Kim, Tae Hoon; Song, Jin Woo

2018-01-01

To retrospectively investigate whether the baseline extent and 1-year change in regional disease patterns on CT can predict survival of patients with idiopathic pulmonary fibrosis (IPF). A total of 144 IPF patients with CT scans at the time of diagnosis and 1 year later were included. The extents of five regional disease patterns were quantified using an in-house texture-based automated system. The fibrosis score was defined as the sum of the extent of honeycombing and reticular opacity. The Cox proportional hazard model was used to determine the independent predictors of survival. A total of 106 patients (73.6%) died during the follow-up period. Univariate analysis revealed that age, baseline forced vital capacity, total lung capacity, diffusing capacity of the lung for carbon monoxide, six-minute walk distance, desaturation , honeycombing, reticular opacity, fibrosis score, and interval changes in honeycombing and fibrosis score were significantly associated with survival. Multivariate analysis revealed that age, desaturation, fibrosis score and interval change in fibrosis score were significant independent predictors of survival (p = 0.003, <0.001, 0.001 and <0.001). The C-index for the developed model was 0.768. Texture-based, automated CT quantification of fibrosis can be used as an independent predictor of survival in IPF patients. (orig.)

Prediction of survival by texture-based automated quantitative assessment of regional disease patterns on CT in idiopathic pulmonary fibrosis

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young; Lee, Sang Min; Kim, Namkug [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Kim, Tae Hoon; Song, Jin Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Pulmonary and Critical Care Medicine, Seoul (Korea, Republic of)

2018-03-15

To retrospectively investigate whether the baseline extent and 1-year change in regional disease patterns on CT can predict survival of patients with idiopathic pulmonary fibrosis (IPF). A total of 144 IPF patients with CT scans at the time of diagnosis and 1 year later were included. The extents of five regional disease patterns were quantified using an in-house texture-based automated system. The fibrosis score was defined as the sum of the extent of honeycombing and reticular opacity. The Cox proportional hazard model was used to determine the independent predictors of survival. A total of 106 patients (73.6%) died during the follow-up period. Univariate analysis revealed that age, baseline forced vital capacity, total lung capacity, diffusing capacity of the lung for carbon monoxide, six-minute walk distance, desaturation{sub ,} honeycombing, reticular opacity, fibrosis score, and interval changes in honeycombing and fibrosis score were significantly associated with survival. Multivariate analysis revealed that age, desaturation, fibrosis score and interval change in fibrosis score were significant independent predictors of survival (p = 0.003, <0.001, 0.001 and <0.001). The C-index for the developed model was 0.768. Texture-based, automated CT quantification of fibrosis can be used as an independent predictor of survival in IPF patients. (orig.)

Spatial genetic analyses reveal cryptic population structure and migration patterns in a continuously harvested grey wolf (Canis lupus population in north-eastern Europe.

Directory of Open Access Journals (Sweden)

Maris Hindrikson

Full Text Available Spatial genetics is a relatively new field in wildlife and conservation biology that is becoming an essential tool for unravelling the complexities of animal population processes, and for designing effective strategies for conservation and management. Conceptual and methodological developments in this field are therefore critical. Here we present two novel methodological approaches that further the analytical possibilities of STRUCTURE and DResD. Using these approaches we analyse structure and migrations in a grey wolf (Canislupus population in north-eastern Europe. We genotyped 16 microsatellite loci in 166 individuals sampled from the wolf population in Estonia and Latvia that has been under strong and continuous hunting pressure for decades. Our analysis demonstrated that this relatively small wolf population is represented by four genetic groups. We also used a novel methodological approach that uses linear interpolation to statistically test the spatial separation of genetic groups. The new method, which is capable of using program STRUCTURE output, can be applied widely in population genetics to reveal both core areas and areas of low significance for genetic groups. We also used a recently developed spatially explicit individual-based method DResD, and applied it for the first time to microsatellite data, revealing a migration corridor and barriers, and several contact zones.

Stereotactic Radiosurgery in the Management of Brain Metastases: An Institutional Retrospective Analysis of Survival

International Nuclear Information System (INIS)

Frazier, James L.; Batra, Sachin; Kapor, Sumit; Vellimana, Ananth; Gandhi, Rahul; Carson, Kathryn A.; Shokek, Ori; Lim, Michael; Kleinberg, Lawrence; Rigamonti, Daniele

2010-01-01

Purpose: The objective of this study was to report our experience with stereotactic radiosurgery performed with the Gamma Knife (GK) in the treatment of patients with brain metastases and to compare survival for those treated with radiosurgery alone with survival for those treated with radiosurgery and whole-brain radiotherapy. Methods and Materials: Prospectively collected demographic and clinical characteristics and treatment and survival data on 237 patients with intracranial metastases who underwent radiosurgery with the GK between 2003 and 2007 were reviewed. Kaplan-Meier and Cox proportional hazards regression analyses were used to compare survival by demographic and clinical characteristics and treatment. Results: The mean age of the patient population was 56 years. The most common tumor histologies were non-small-cell lung carcinoma (34.2%) and breast cancer (13.9%). The median overall survival time was 8.5 months from the time of treatment. The median survival times for patients with one, two/three, and four or more brain metastases were 8.5, 9.4, and 6.7 months, respectively. Patients aged 65 years or greater and those aged less than 65 years had median survival times of 7.8 and 9 months, respectively (p = 0.008). The Karnofsky Performance Score (KPS) at the time of treatment was a significant predictor of survival: those patients with a KPS of 70 or less had a median survival of 2.9 months compared with 10.3 months (p = 0.034) for those with a KPS of 80 or greater. There was no statistically significant difference in survival between patients treated with radiosurgery alone and those treated with radiosurgery plus whole-brain radiotherapy. Conclusions: Radiosurgery with the GK is an efficacious treatment modality for brain metastases. A KPS greater than 70, histology of breast cancer, smaller tumor volume, and age less than 65 years were associated with a longer median survival in our study.

Survival analysis models and applications

CERN Document Server

Liu, Xian

2012-01-01

Survival analysis concerns sequential occurrences of events governed by probabilistic laws.  Recent decades have witnessed many applications of survival analysis in various disciplines. This book introduces both classic survival models and theories along with newly developed techniques. Readers will learn how to perform analysis of survival data by following numerous empirical illustrations in SAS. Survival Analysis: Models and Applications: Presents basic techniques before leading onto some of the most advanced topics in survival analysis.Assumes only a minimal knowledge of SAS whilst enablin

The Poor Survival among Pulmonary Tuberculosis Patients in Chiapas, Mexico: The Case of Los Altos Region

OpenAIRE

Nájera-Ortiz, J. C.; Sánchez-Pérez, H. J.; Ochoa-Díaz-López, H.; Leal-Fernández, G.; Navarro-Giné, A.

2012-01-01

Objective. To analyse survival in patients with pulmonary tuberculosis (PTB) and factors associated with such survival. Design. Study of a cohort of patients aged over 14 years diagnosed with PTB from January 1, 1998 to July 31, 2005. During 2004–2006 a home visit was made to each patient and, during 2008-2009, they were visited again. During these visits a follow-up interview was administered; when the patient had died, a verbal autopsy was conducted with family members. Statistical analysis...

Prognostic and survival analysis of presbyopia: The healthy twin study

Science.gov (United States)

Lira, Adiyani; Sung, Joohon

2015-12-01

Presbyopia, a vision condition in which the eye loses its flexibility to focus on near objects, is part of ageing process which mostly perceptible in the early or mid 40s. It is well known that age is its major risk factor, while sex, alcohol, poor nutrition, ocular and systemic diseases are known as common risk factors. However, many other variables might influence the prognosis. Therefore in this paper we developed a prognostic model to estimate survival from presbyopia. 1645 participants which part of the Healthy Twin Study, a prospective cohort study that has recruited Korean adult twins and their family members based on a nation-wide registry at public health agencies since 2005, were collected and analyzed by univariate analysis as well as Cox proportional hazard model to reveal the prognostic factors for presbyopia while survival curves were calculated by Kaplan-Meier method. Besides age, sex, diabetes, and myopia; the proposed model shows that education level (especially engineering program) also contribute to the occurrence of presbyopia as well. Generally, at 47 years old, the chance of getting presbyopia becomes higher with the survival probability is less than 50%. Furthermore, our study shows that by stratifying the survival curve, MZ has shorter survival with average onset time about 45.8 compare to DZ and siblings with 47.5 years old. By providing factors that have more effects and mainly associate with presbyopia, we expect that we could help to design an intervention to control or delay its onset time.

Interglacial insects and their possible survival in Greenland during the last glacial stage

DEFF Research Database (Denmark)

Bøcher, Jens Jensenius

2012-01-01

Sediments from the last interglacial (Eemian) in Jameson Land, East Greenland, and the Thule area, NW Greenland, have revealed a number of insect fragments of both arctic and more or less warmth-demanding species. Altogether, the interglacial fauna of Coleoptera (beetles) indicates boreal...... beetle species such as Amara alpina and Isochnus arcticus did not survive the last glacial stage in Greenland. Two factors that have not been sufficiently considered when discussing survival contra extinction are the importance of microclimate and the number of sun-hours during the Arctic summer. Even...... among the Coleoptera, which as a group fares quite badly in the Arctic, there might be survivors, at least among those found both during the interglacial and as fossils during the early Holocene. First of all, glacial survival applies to the seed bug Nysius groenlandicus, which was widespread during...

Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

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Couturier Marie

2012-02-01

Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

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Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

2017-08-21

Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study

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Colleoni, Marco; Giobbie-Hurder, Anita; Regan, Meredith M

2011-01-01

Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged ov...

Transcriptomic analyses reveal novel genes with sexually dimorphic expression in the zebrafish gonad and brain.

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Rajini Sreenivasan

Full Text Available BACKGROUND: Our knowledge on zebrafish reproduction is very limited. We generated a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale gene expression profiles in adult gonads and other organs. METHODOLOGY/PRINCIPAL FINDINGS: We have identified 116638 gonad-derived zebrafish expressed sequence tags (ESTs, 21% of which were isolated in our lab. Following in silico normalization, we constructed a gonad-derived microarray comprising 6370 unique, full-length cDNAs from differentiating and adult gonads. Labeled targets from adult gonad, brain, kidney and 'rest-of-body' from both sexes were hybridized onto the microarray. Our analyses revealed 1366, 881 and 656 differentially expressed transcripts (34.7% novel that showed highest expression in ovary, testis and both gonads respectively. Hierarchical clustering showed correlation of the two gonadal transcriptomes and their similarities to those of the brains. In addition, we have identified 276 genes showing sexually dimorphic expression both between the brains and between the gonads. By in situ hybridization, we showed that the gonadal transcripts with the strongest array signal intensities were germline-expressed. We found that five members of the GTP-binding septin gene family, from which only one member (septin 4 has previously been implicated in reproduction in mice, were all strongly expressed in the gonads. CONCLUSIONS/SIGNIFICANCE: We have generated a gonad-derived zebrafish cDNA microarray and demonstrated its usefulness in identifying genes with sexually dimorphic co-expression in both the gonads and the brains. We have also provided the first evidence of large-scale differential gene expression between female and male brains of a teleost. Our microarray would be useful for studying gonad development, differentiation and function not only in zebrafish but also in related teleosts via cross-species hybridizations. Since several genes have been shown to play similar

Review of epidemiological and clinical characteristics and overall survival in patients with colorectal cancer

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Michelle Eisenhardt

2013-10-01

Full Text Available Backgound and Objectives: Colorectal cancer (CRC has high incidence, is often treatable and curable if diagnosed early. This study aimed to identify the epidemiological characteristic and assess overall survival in patients with CRC treated at a center specializing in oncology. Methods: Medical records of 127 patients with CRC were retrospectively evaluated. Clinical and epidemiological characteristics, in addition to treatment protocols and adverse reactions presented by patients were reviewed. The association of significance was assessed by chi-square and Fisher exact tests. The survival analyses were performed using the Kaplan-Meier method. The confidence interval was of 95% (p

Investigating Rates of Hunting and Survival in Declining European Lapwing Populations.

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Guillaume Souchay

Full Text Available Understanding effects of harvest on population dynamics is of major interest, especially for declining species. European lapwing Vanellus vanellus populations increased from the 1960s until the 1980s and declined strongly thereafter. About 400,000 lapwings are harvested annually and it is thus of high conservation relevance to assess whether hunting was a main cause for the observed changes in lapwing population trends. We developed a multi-event cause-specific mortality model which we applied to a long-term ring-recovery data set (1960-2010 of > 360,000 records to estimate survival and cause-specific mortalities. We found no temporal change in survival over the last 50 years for first-year (FY and older birds (after first-year; AFY originating from different ringing areas. Mean survival was high, around 0.60 and 0.80 for FY and AFY individuals, respectively. The proportion of total mortality due to hunting was <0.10 over the study period and the estimated proportion of harvested individuals (kill rate was <0.05 in each year. Our result of constant survival indicates that demographic processes other than survival were responsible for the pronounced change in lapwing population trends in the 1980s. Our findings lend support to the hypothesis that hunting was not a significant contributor to the large-scale decline of lapwing populations. To halt the ongoing decline of European lapwing populations management should focus on life history stages other than survival (e.g. productivity. Further analyses are required to investigate the contribution of other demographic rates to the decline of lapwings and to identify the most efficient conservation actions.

Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

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Pengpeng Li

Full Text Available S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein

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Buschow, Sonja I; Ramazzotti, Matteo; Reinieren-Beeren, Inge M J

2017-01-01

-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large....... Intriguingly, this was only the case for expression of PEBP1 after, but not prior to, DC vaccination. Moreover, the change in PEBP1 expression upon vaccination correlated well with survival. Further analyses revealed that PEBP1 expression positively correlated with genes involved in T cell responses...... but inversely correlated with genes associated with myeloid cells and aberrant inflammation including STAT3, NOTCH1, and MAPK1. Concordantly, PEBP1 inversely correlated with the myeloid/lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease....

Nitrogen reserves, spring regrowth and winter survival of field-grown alfalfa (Medicago sativa) defoliated in the autumn.

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Dhont, Catherine; Castonguay, Yves; Nadeau, Paul; Bélanger, Gilles; Drapeau, Raynald; Laberge, Serge; Avice, Jean-Christophe; Chalifour, François-P

2006-01-01

The objective of the study was to characterize variations in proline, arginine, histidine, vegetative storage proteins, and cold-inducible gene expression in overwintering roots of field-grown alfalfa, in response to autumn defoliation, and in relation to spring regrowth and winter survival. Field trials, established in 1996 in eastern Canada, consisted of two alfalfa cultivars ('AC Caribou' and 'WL 225') defoliated in 1997 and 1998 either only twice during the summer or three times with the third defoliation taken 400, 500 or 600 growing degree days (basis 5 degrees C) after the second summer defoliation. The root accumulation of proline, arginine, histidine and soluble proteins of 32, 19 and 15 kDa, characterized as alfalfa vegetative storage proteins, was reduced the following spring by an early autumn defoliation at 400 or 500 growing degree days in both cultivars; the 600-growing-degree-days defoliation treatment had less or no effect. Transcript levels of the cold-inducible gene msaCIA, encoding a glycine-rich protein, were markedly reduced by autumn defoliation in 'WL 225', but remained unaffected in the more winter-hardy cultivar 'AC Caribou'. The expression of another cold-inducible gene, the dehydrin homologue msaCIG, was not consistently affected by autumn defoliation. Principal component analyses, including components of root organic reserves at the onset of winter, along with yield and plant density in the following spring, revealed that (a) amino acids and soluble proteins are positively related to the vigour of spring regrowth but poorly related to winter survival and (b) winter survival, as indicated by plant density in the spring, is associated with higher concentrations of cryoprotective sugars in alfalfa roots the previous autumn. An untimely autumn defoliation of alfalfa reduces root accumulation of specific N reserves such as proline, arginine, histidine and vegetative storage proteins that are positively related to the vigour of spring

Immunotherapy for recurrent malignant glioma: an interim report on survival.

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Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

1990-12-01

We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Time dependent ethnic convergence in colorectal cancer survival in hawaii

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Hundahl Scott A

2003-02-01

Full Text Available Abstract Background Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. Methods Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese. The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. Results Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. Conclusion Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated.

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

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Landon L. Waldner

2012-10-01

Full Text Available 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.

Applied survival analysis using R

CERN Document Server

Moore, Dirk F

2016-01-01

Applied Survival Analysis Using R covers the main principles of survival analysis, gives examples of how it is applied, and teaches how to put those principles to use to analyze data using R as a vehicle. Survival data, where the primary outcome is time to a specific event, arise in many areas of biomedical research, including clinical trials, epidemiological studies, and studies of animals. Many survival methods are extensions of techniques used in linear regression and categorical data, while other aspects of this field are unique to survival data. This text employs numerous actual examples to illustrate survival curve estimation, comparison of survivals of different groups, proper accounting for censoring and truncation, model variable selection, and residual analysis. Because explaining survival analysis requires more advanced mathematics than many other statistical topics, this book is organized with basic concepts and most frequently used procedures covered in earlier chapters, with more advanced topics...

Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

DEFF Research Database (Denmark)

Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

2015-01-01

BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non......-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised...... disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised...

Long-term Survival of Straumann Dental Implants with TPS Surfaces: A Retrospective Study with a Follow-up of 12 to 23 Years.

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Becker, Stephan T; Beck-Broichsitter, Benedicta E; Rossmann, Christian M; Behrens, Eleonore; Jochens, Arne; Wiltfang, Jörg

2016-06-01

The aim of this study was to evaluate the long-term dental implant survival rates of Straumann dental implants in a university hospital environment over 12 to 23 years. A total of 388 Straumann dental implants with titanium-sprayed surfaces (TPS) were inserted in 92 patients between 1988 and 1999 in the Department of Oral and Maxillofacial Surgery of the University Hospital Schleswig-Holstein in Kiel, and they were reevaluated with standardized clinical and radiological exams. Kaplan-Meier analyses were performed for individual factors. Cox proportional hazard regression analysis was used to detect the factors influencing long-term implant failure. The long-term implant survival rate was 88.03% after an observation time of 12.2 to 23.5 years. Cox regression revealed statistically significant influences of the International Team for Implantology (ITI) implantation type (p = .00354) and tobacco smoking (p = .01264) on implant failure. A proportion 82.8% of the patients with implant losses had a medical history of periodontitis. Peri-implantitis was diagnosed in 9.7% of the remaining implants in the long-term survey. This study emphasized the long-term rehabilitation capabilities of Straumann dental implants in complex cases. The survival rates after several years constitute important information for patients, as well as for clinicians, in deciding about different concepts of tooth replacement. Patient-related and technical factors - determined before implant placement - could help to predict the risk of implant loss. © 2015 Wiley Periodicals, Inc.

Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli.

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Shan Goh

Full Text Available BACKGROUND: Genes essential for bacterial growth are of particular scientific interest. Many putative essential genes have been identified or predicted in several species, however, little is known about gene expression requirement stringency, which may be an important aspect of bacterial physiology and likely a determining factor in drug target development. METHODOLOGY/PRINCIPAL FINDINGS: Working from the premise that essential genes differ in absolute requirement for growth, we describe silencing of putative essential genes in E. coli to obtain a titration of declining growth rates and transcript levels by using antisense peptide nucleic acids (PNA and expressed antisense RNA. The relationship between mRNA decline and growth rate decline reflects the degree of essentiality, or stringency, of an essential gene, which is here defined by the minimum transcript level for a 50% reduction in growth rate (MTL(50. When applied to four growth essential genes, both RNA silencing methods resulted in MTL(50 values that reveal acpP as the most stringently required of the four genes examined, with ftsZ the next most stringently required. The established antibacterial targets murA and fabI were less stringently required. CONCLUSIONS: RNA silencing can reveal stringent requirements for gene expression with respect to growth. This method may be used to validate existing essential genes and to quantify drug target requirement.

Survival probabilities of loggerhead sea turtles (Caretta caretta estimated from capture-mark-recapture data in the Mediterranean Sea

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Paolo Casale

2007-06-01

Full Text Available Survival probabilities of loggerhead sea turtles (Caretta caretta are estimated for the first time in the Mediterranean by analysing 3254 tagging and 134 re-encounter data from this region. Most of these turtles were juveniles found at sea. Re-encounters were live resightings and dead recoveries and data were analysed with Barker’s model, a modified version of the Cormack-Jolly-Seber model which can combine recapture, live resighting and dead recovery data. An annual survival probability of 0.73 (CI 95% = 0.67-0.78; n=3254 was obtained, and should be considered as a conservative estimate due to an unknown, though not negligible, tag loss rate. This study makes a preliminary estimate of the survival probabilities of in-water developmental stages for the Mediterranean population of endangered loggerhead sea turtles and provides the first insights into the magnitude of the suspected human-induced mortality in the region. The model used here for the first time on sea turtles could be used to obtain survival estimates from other data sets with few or no true recaptures but with other types of re-encounter data, which are a common output of tagging programmes involving these wide-ranging animals.

Prognostic model for long-term survival of locally advanced non-small-cell lung cancer patients after neoadjuvant radiochemotherapy and resection integrating clinical and histopathologic factors

International Nuclear Information System (INIS)

Pöttgen, Christoph; Stuschke, Martin; Graupner, Britta; Theegarten, Dirk; Gauler, Thomas; Jendrossek, Verena; Freitag, Lutz; Jawad, Jehad Abu; Gkika, Eleni; Wohlschlaeger, Jeremias; Welter, Stefan; Hoiczyk, Matthias; Schuler, Martin; Stamatis, Georgios; Eberhardt, Wilfried

2015-01-01

Outcome of consecutive patients with locally advanced non-small cell lung cancer and histopathologically proven mediastional lymph node metastases treated with induction chemotherapy, neoadjuvant radiochemotherapy and thoracotomy at the West German Cancer Center between 08/2000 and 06/2012 was analysed. A clinico-pathological prognostic model for survival was built including partial or complete response according to computed tomography imaging (CT) as clinical parameters as well as pathologic complete remission (pCR) and mediastinal nodal clearance (MNC) as histopathologic factors. Proportional hazard analysis (PHA) and recursive partitioning analysis (RPA) were used to identify prognostic factors for survival. Long-term survival was defined as survival ≥ 36 months. A total of 157 patients were treated, median follow-up was 97 months. Among these patients, pCR and MNC were observed in 41 and 85 patients, respectively. Overall survival was 56 ± 4% and 36 ± 4% at 24 and 60 months, respectively. Sensitivities of pCR and MNC to detect long-term survivors were 38% and 61%, specificities were 84% and 52%, respectively. Multivariable survival analysis revealed pCR, cN3 category, and gender, as prognostic factors at a level of α < 0.05. Considering only preoperative available parameters, CT response became significant. Classifying patients with a predicted hazard above the median as high risk group and the remaining as low risk patients yielded better separation of the survival curves by the inclusion of histopathologic factors than by preoperative factors alone (p < 0.0001, log rank test). Using RPA, pCR was identified as the top prognostic factor above clinical factors (p = 0.0006). No long term survivors were observed in patients with cT3-4 cN3 tumors without pCR. pCR is the dominant histopathologic response parameter and improves prognostic classifiers, based on clinical parameters. The validated prognostic model can be used to estimate individual prognosis and

Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks.

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Glicksberg, Benjamin S; Li, Li; Badgeley, Marcus A; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L; Hoffman, Gabriel E; Dan Li, Shuyu; Schadt, Eric E; Patel, Chirag J; Chen, Rong; Dudley, Joel T

2016-06-15

Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key 'hub' diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Human papilloma virus and survival of oropharyngeal cancer patients treated with surgery and adjuvant radiotherapy.

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Broglie, Martina A; Soltermann, Alex; Haile, Sarah R; Huber, Gerhard F; Stoeckli, Sandro J

2015-07-01

Impact of p16 protein, a surrogate marker for human papilloma virus induced cancer, p53 and EGFR as well as clinical factors on survival in a patient cohort with oropharyngeal squamous cell carcinoma (OPSCC) treated by surgical resection and adjuvant radiotherapy (RT) ± concomitant chemotherapy (CT). This is a retrospective analysis of patient's charts and tumor tissue. 57 patients were consecutively included and their tumor tissue assembled on a tissue microarray following immunohistochemical analysis. Survival times were estimated by means of Kaplan-Meier analysis. The importance of clinical and immunohistochemical factors for outcome was estimated by cox proportional hazard models. With 88% 5-year overall survival, 91% 5-year disease-specific survival and 91% 5-year disease-free survival, respectively, we found excellent survival rates in this surgically treated patient cohort of mainly advanced OPSCC (93% AJCC stage III or IV). The only factors positively influencing survival were p16 overexpression as well as p53 negativity and even more pronounced the combination of those biomarkers. Survival analysis of patients classified into three risk categories according to an algorithm based on p16, smoking, T- and N-category revealed a low, intermediate and high-risk group with significant survival differences between the low and the high-risk group. Patients with OPSCC can be successfully treated by surgery and adjuvant RT ± CT with a clear survival benefit of p16 positive, p53 negative patients. We recommend considering a combination of immunohistochemical (p16, p53) and clinical factors (smoking, T- and N-category) for risk stratification.

Density-dependent intraspecific aggression regulates survival in northern Yellowstone wolves (Canis lupus).

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Cubaynes, Sarah; MacNulty, Daniel R; Stahler, Daniel R; Quimby, Kira A; Smith, Douglas W; Coulson, Tim

2014-11-01

Understanding the population dynamics of top-predators is essential to assess their impact on ecosystems and to guide their management. Key to this understanding is identifying the mechanisms regulating vital rates. Determining the influence of density on survival is necessary to understand the extent to which human-caused mortality is compensatory or additive. In wolves (Canis lupus), empirical evidence for density-dependent survival is lacking. Dispersal is considered the principal way in which wolves adjust their numbers to prey supply or compensate for human exploitation. However, studies to date have primarily focused on exploited wolf populations, in which density-dependent mechanisms are likely weak due to artificially low wolf densities. Using 13 years of data on 280 collared wolves in Yellowstone National Park, we assessed the effect of wolf density, prey abundance and population structure, as well as winter severity, on age-specific survival in two areas (prey-rich vs. prey-poor) of the national park. We further analysed cause-specific mortality and explored the factors driving intraspecific aggression in the prey-rich northern area of the park. Overall, survival rates decreased during the study. In northern Yellowstone, density dependence regulated adult survival through an increase in intraspecific aggression, independent of prey availability. In the interior of the park, adult survival was less variable and density-independent, despite reduced prey availability. There was no effect of prey population structure in northern Yellowstone, or of winter severity in either area. Survival was similar among yearlings and adults, but lower for adults older than 6 years. Our results indicate that density-dependent intraspecific aggression is a major driver of adult wolf survival in northern Yellowstone, suggesting intrinsic density-dependent mechanisms have the potential to regulate wolf populations at high ungulate densities. When low prey availability or high

Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis.

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van der Burgh, Hannelore K; Schmidt, Ruben; Westeneng, Henk-Jan; de Reus, Marcel A; van den Berg, Leonard H; van den Heuvel, Martijn P

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data to predict survival of ALS patients using deep learning, a machine learning technique highly effective in a broad range of big-data analyses. A group of 135 ALS patients was included from whom high-resolution diffusion-weighted and T1-weighted images were acquired at the first visit to the outpatient clinic. Next, each of the patients was monitored carefully and survival time to death was recorded. Patients were labeled as short, medium or long survivors, based on their recorded time to death as measured from the time of disease onset. In the deep learning procedure, the total group of 135 patients was split into a training set for deep learning (n = 83 patients), a validation set (n = 20) and an independent evaluation set (n = 32) to evaluate the performance of the obtained deep learning networks. Deep learning based on clinical characteristics predicted survival category correctly in 68.8% of the cases. Deep learning based on MRI predicted 62.5% correctly using structural connectivity and 62.5% using brain morphology data. Notably, when we combined the three sources of information, deep learning prediction accuracy increased to 84.4%. Taken together, our findings show the added value of MRI with respect to predicting survival in ALS, demonstrating the advantage of deep learning in disease prognostication.

Influence of beta blockers on survival in dogs with severe subaortic stenosis.

Science.gov (United States)

Eason, B D; Fine, D M; Leeder, D; Stauthammer, C; Lamb, K; Tobias, A H

2014-01-01

Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical. To determine the influence of beta blocker treatment on survival time in dogs with severe SAS. Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011. Fifty dogs met the inclusion criteria. Twenty-seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all-cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all-cause (P = .93) or cardiac-cause (P = .97) mortality analyses. Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Disentangling the effects of tocilizumab on neutrophil survival and function.

Science.gov (United States)

Gaber, Timo; Hahne, Martin; Strehl, Cindy; Hoff, Paula; Dörffel, Yvonne; Feist, Eugen; Burmester, Gerd-Rüdiger; Buttgereit, Frank

2016-06-01

The synovial tissue in rheumatoid arthritis (RA) represents a hypoxic environment with up-regulated pro-inflammatory cytokines and cellular infiltrates including neutrophils. Although inhibition of the interleukin (IL)6 receptor pathway by tocilizumab is a potent treatment option for RA, it may also cause adverse effects such as an occasionally high-grade neutropenia. We analysed the impact of tocilizumab on survival, mediator secretion, oxidative burst, phagocytosis and energy availability of high-dose toll-like receptor (TLR)2/4-stimulated neutrophils (to mimic an arthritis flare) under normoxic versus hypoxic conditions. Human neutrophils were purified, pre-treated with varying doses of tocilizumab, dexamethasone or human IgG1 and high-dose-stimulated with lipopolysaccharide (LPS) alone-triggering TLR2/4-, LPS plus IL6, or left unstimulated. Cells were then incubated under normoxic (18 % O2) or hypoxic (1 % O2) conditions and subsequently analysed. Neutrophil survival and energy availability were significantly decreased by tocilizumab in a dose-dependent manner in high-dose TLR2/4-stimulated cells, but to a greater extent under normoxia as compared to hypoxia. We also found high-dose LPS-stimulated oxidative burst and phagocytosis of neutrophils to be higher under hypoxic versus normoxic conditions, but this difference was reduced by tocilizumab. Finally, we observed that tocilizumab affected neutrophil mediator secretion as a function of oxygen availability. Tocilizumab is known for both beneficial effects and a higher incidence of neutropenia when treating RA patients. Our results suggest that both effects can at least in part be explained by a reduction in neutrophil survival, a dose-dependent inhibition of hypoxia-induced NADPH oxidase-mediated oxidative burst and phagocytosis of infiltrating hypoxic neutrophils and an alteration of mediator secretion.

Combined Metabonomic and Quantitative RT-PCR Analyses Revealed Metabolic Reprogramming Associated with Fusarium graminearum Resistance in Transgenic Arabidopsis thaliana

Directory of Open Access Journals (Sweden)

Fangfang Chen

2018-01-01

Full Text Available Fusarium head blight disease resulting from Fusarium graminearum (FG infection causes huge losses in global production of cereals and development of FG-resistant plants is urgently needed. To understand biochemistry mechanisms for FG resistance, here, we have systematically investigated the plant metabolomic phenotypes associated with FG resistance for transgenic Arabidopsis thaliana expressing a class-I chitinase (Chi, a Fusarium-specific recombinant antibody gene (CWP2 and fused Chi-CWP2. Plant disease indices, mycotoxin levels, metabonomic characteristics, and expression levels of several key genes were measured together with their correlations. We found that A. thaliana expressing Chi-CWP2 showed higher FG resistance with much lower disease indices and mycotoxin levels than the wild-type and the plants expressing Chi or CWP2 alone. The combined metabonomic and quantitative RT-PCR analyses revealed that such FG-resistance was closely associated with the promoted biosynthesis of secondary metabolites (phenylpropanoids, alkanoids and organic osmolytes (proline, betaine, glucose, myo-inositol together with enhanced TCA cycle and GABA shunt. These suggest that the concurrently enhanced biosyntheses of the shikimate-mediated secondary metabolites and organic osmolytes be an important strategy for A. thaliana to develop and improve FG resistance. These findings provide essential biochemical information related to FG resistance which is important for developing FG-resistant cereals.

Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

DEFF Research Database (Denmark)

Horwich, A.; Specht, L.; Ashley, S.

1997-01-01

relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial......To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

Multi-objective optimisation for spacecraft design for demise and survivability

OpenAIRE

Trisolini, Mirko; Colombo, Camilla; Lewis, Hugh

2017-01-01

The paper presents the development of a multi-objective optimisation framework to study the effects that preliminary design choices have on the demisability and the survivability of a spacecraft. Building a spacecraft such that most of it will demise during the re-entry through design-for-demise strategies may lead to design that are more vulnerable to space debris impacts, thus compromising the reliability of the mission. The two models developed to analyse the demisability and the survivabi...

Explorative data analysis of MCL reveals gene expression networks implicated in survival and prognosis supported by explorative CGH analysis

International Nuclear Information System (INIS)

Blenk, Steffen; Engelmann, Julia C; Pinkert, Stefan; Weniger, Markus; Schultz, Jörg; Rosenwald, Andreas; Müller-Hermelink, Hans K; Müller, Tobias; Dandekar, Thomas

2008-01-01

Mantle cell lymphoma (MCL) is an incurable B cell lymphoma and accounts for 6% of all non-Hodgkin's lymphomas. On the genetic level, MCL is characterized by the hallmark translocation t(11;14) that is present in most cases with few exceptions. Both gene expression and comparative genomic hybridization (CGH) data vary considerably between patients with implications for their prognosis. We compare patients over and below the median of survival. Exploratory principal component analysis of gene expression data showed that the second principal component correlates well with patient survival. Explorative analysis of CGH data shows the same correlation. On chromosome 7 and 9 specific genes and bands are delineated which improve prognosis prediction independent of the previously described proliferation signature. We identify a compact survival predictor of seven genes for MCL patients. After extensive re-annotation using GEPAT, we established protein networks correlating with prognosis. Well known genes (CDC2, CCND1) and further proliferation markers (WEE1, CDC25, aurora kinases, BUB1, PCNA, E2F1) form a tight interaction network, but also non-proliferative genes (SOCS1, TUBA1B CEBPB) are shown to be associated with prognosis. Furthermore we show that aggressive MCL implicates a gene network shift to higher expressed genes in late cell cycle states and refine the set of non-proliferative genes implicated with bad prognosis in MCL. The results from explorative data analysis of gene expression and CGH data are complementary to each other. Including further tests such as Wilcoxon rank test we point both to proliferative and non-proliferative gene networks implicated in inferior prognosis of MCL and identify suitable markers both in gene expression and CGH data

Germination, survival and growth of three vascular plants on biological soil crusts from a Mexican tropical desert.

Science.gov (United States)

Godínez-Alvarez, H; Morín, C; Rivera-Aguilar, V

2012-01-01

Information about the effects of biological soil crusts (BSC) on germination, seedling survival and growth of vascular plants is controversial because they can have positive, neutral or negative effects. This controversy may be because most studies conducted until now have just analysed one or two recruitment stages independently. To understand the BSC effects on vascular plants, it is necessary to consider each stage of the recruitment process and synthesise all this information. The goal of this study was twofold. First, we analyse germination, seedling survival and growth of three vascular plants (Agave marmorata, Prosopis laevigata and Neobuxbaumia tetetzo) on BSC (cyanobacteria and mixed crust) from a tropical desert region of south-central México. Second, we synthesise the information to determine the total effect of BSC on plant species performance. We conducted experiments under controlled conditions to evaluate the proportion of germinated seeds, proportion of surviving seedlings and seedling dry weight in BSC and bare soil. Results showed that BSC have different effects on germination, seedling survival and growth of plant species. Plant species performance was qualitatively higher on BSC than bare soil. The highest performance of A. marmorata and P. laevigata was observed on cyanobacteria and mixed crusts, respectively. The highest performance of N. tetetzo was on both crust types. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Racial disparities in the survival of American children, adolescents, and young adults with acute lymphoblastic leukemia, acute myelogenous leukemia, and Hodgkin lymphoma.

Science.gov (United States)

Kahn, Justine M; Keegan, Theresa H M; Tao, Li; Abrahão, Renata; Bleyer, Archie; Viny, Aaron D

2016-09-01

Race-based survival in children and adolescents with hematologic malignancies has been a national challenge for decades. Large-scale investigations of age- and race-based survival trends over time in these patients have not previously been reported. The objective of this study was to investigate whether race- and age-related differences in pediatric and adolescent and young adult (AYA) leukemia and lymphoma survival persist and to what extent these differences have changed over time. Using the Surveillance, Epidemiology, and End Results program, this study investigated the outcomes of black and white (1975-2012; n = 27,369) and white and Hispanic (1992-2012; n = 20,574) children (0-14 years old) and AYAs (15-39 years old) with acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and Hodgkin lymphoma (HL). Estimates of 5- and 10-year relative survival were compared over time. Trends showed a convergence of survival for white and black children with ALL but a divergence in survival for AYA patients. Hispanic children and AYAs both suffered inferior outcomes. Trends for AML revealed persistent survival differences between black and white children and suggested worsening disparities for AYAs. Survival trends in HL revealed sustained survival differences between black and white AYA patients, whereas no differences were found in Hispanic and white patient outcomes for AML or HL. Although survival for children and AYAs with ALL, AML, and HL has improved over the past 4 decades, differences persist between black, white, and Hispanic children and AYAs; survival disparities between black and white children with ALL have been nearly eliminated. Strategies aimed at identifying causality and reducing disparities are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2723-2730. © 2016 American Cancer Society. © 2016 American Cancer Society.

Benefits of marriage on relative and conditional relative cancer survival differ between males and females in the USA.

Science.gov (United States)

Merrill, Ray M; Johnson, Erin

2017-10-01

The purpose of the paper is to assess the influence of marital status on conditional relative survival of cancer according to sex. Analyses involved 779,978 males and 1,032,868 females diagnosed with 1 of 13 cancer types between 2000 and 2008, and followed through 2013. Data are from the Surveillance, Epidemiology, and End Results (SEER) Program. Regression models were adjusted for age, sex, race, and tumor stage. Five-year relative survival conditional on years already survived is higher among married patients with less lethal cancers (oral cavity and pharynx, colon and rectum, breast, urinary bladder, kidney and renal pelvis, melanoma of the skin, thyroid, lymphoma). For more lethal cancers, married patients have similar (liver, lung and bronchus, pancreas, leukemia) or poorer (brain and other nervous system) cancer survival. Separated/divorced or widowed patients have the lowest conditional relative survival rates. For most cancers, 5-year cancer relative survival rates conditional on time already survived through 5 years approach 70 to 90% of that for the general population. The beneficial effect of marriage on survival decreases with years already survived. Superior conditional relative survival rates in females decrease with time already survived and are less pronounced in married patients. Five-year relative survival rates improve with time already survived. The benefits of marriage on conditional relative survival are greater for less lethal cancers. Greater 5-year conditional relative survival rates in females narrow with time already survived and are less pronounced in married patients. Conditional relative survival rates of cancer can lead to more informed decisions and understanding regarding treatment and prognosis.

Gender-Dependent Survival of Allogeneic Trophoblast Stem Cells in Liver

Science.gov (United States)

Epple-Farmer, Jessica; Debeb, Bisrat G.; Smithies, Oliver; Binas, Bert

2012-01-01

In view of the well-known phenomenon of trophoblast immune privilege, trophoblast stem cells (TSCs) might be expected to be immune privileged, which could be of interest for cell or gene therapies. Yet in the ectopic sites tested so far, TSC transplants fail to show noticeable immune privilege and seem to lack physiological support. However, we show here that after portal venous injection, green fluorescent protein (GFP)-labeled TSCs survive for several months in the livers of allogeneic female but not male mice. Gonadectomy experiments revealed that this survival does not require the presence of ovarian hormones but does require the absence of testicular factors. By contrast, GFP-labeled allogeneic embryonic stem cells (ESCs) are reliably rejected; however, these same ESCs survive when mixed with unlabeled TSCs. The protective effect does not require immunological compatibility between ESCs and TSCs. Tumors were not observed in animals with either successfully engrafted TSCs or coinjected ESCs. We conclude that in a suitable hormonal context and location, ectopic TSCs can exhibit and confer immune privilege. These findings suggest applications in cell and gene therapy as well as a new model for studying trophoblast immunology and physiology. PMID:19523327

Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Lewandowski, Robert J.; Memon, Khairuddin; Hickey, Ryan; Gates, Vanessa L.; Atassi, Bassel; Vouche, Michael; Atassi, Rohi; Desai, Kush; Hohlastos, Elias; Sato, Kent; Habib, Ali [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Mulcahy, Mary F.; Kircher, Sheetal; Newman, Steven B.; Nimeiri, Halla; Benson, Al B. [Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States); Marshall, Karen; Williams, Melissa; Salzig, Krystina; Salem, Riad [Robert H. Lurie Comprehensive Cancer Center, Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Chicago, IL (United States); Northwestern University, Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL (United States)

2014-10-15

The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n = 104) than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2) who received no biologic agents (n = 52) compared with those that did (n = 162) (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC. (orig.)

The outcome and survival of palliative surgery in thoraco-lumbar spinal metastases: contemporary retrospective cohort study

NARCIS (Netherlands)

Nemelc, R.M.; Stadhouder, A.; van Royen, B.J.; Jiya, T.U.

2014-01-01

Purpose To evaluate outcome and survival and to identify prognostic variables for patients surgically treated for spinal metastases. Methods A retrospective study was performed on 86 patients, surgically treated for spinal metastases. Preoperative analyses of the ASIA and spinal instability

Dying to remember, remembering to survive: mortality salience and survival processing.

Science.gov (United States)

Burns, Daniel J; Hart, Joshua; Kramer, Melanie E; Burns, Amy D

2014-01-01

Processing items for their relevance to survival improves recall for those items relative to numerous other deep processing encoding techniques. Perhaps related, placing individuals in a mortality salient state has also been shown to enhance retention of items encoded after the morality salience manipulation (e.g., in a pleasantness rating task), a phenomenon we dubbed the "dying-to-remember" (DTR) effect. The experiments reported here further explored the effect and tested the possibility that the DTR effect is related to survival processing. Experiment 1 replicated the effect using different encoding tasks, demonstrating that the effect is not dependent on the pleasantness task. In Experiment 2 the DTR effect was associated with increases in item-specific processing, not relational processing, according to several indices. Experiment 3 replicated the main results of Experiment 2, and tested the effects of mortality salience and survival processing within the same experiment. The DTR effect and its associated difference in item-specific processing were completely eliminated when the encoding task required survival processing. These results are consistent with the interpretation that the mechanisms responsible for survival processing and DTR effects are overlapping.

Cannabinoid receptor-2 immunoreactivity is associated with survival in squamous cell carcinoma of the head and neck.

Science.gov (United States)

Klein Nulent, Thomas J W; Van Diest, Paul J; van der Groep, Petra; Leusink, Frank K J; Kruitwagen, Cas L J J; Koole, Ronald; Van Cann, Ellen M

2013-10-01

The prediction of progression of individual tumours, prognosis, and survival in squamous cell carcinoma (SCC) of the head and neck is difficult. Cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptor expression is related to survival in several types of cancer, and the aim of this study was to find out whether the expression of CB1 and CB2 receptors is associated with survival in primary SCC of the head and neck. We made immunohistochemical analyses of the cannabinoid receptors on tissue arrays from 240 patients with the disease. Receptor immunoreactivity was classified as none, weak, moderate, or strong staining. Overall survival and disease-specific survival were plotted using Kaplan-Meier survival curves. A multivariate Cox proportional hazard model was created with all the relevant clinical and pathological features. Strong immunoreactivity of the CB2 receptor was significantly associated with reduced disease-specific survival (p=0.007). Cox-proportional hazard ratio (HR) showed that CB2 receptor immunoreactivity contributed to the prediction of survival (HR 3.6, 95% CI 1.5-8.7, p=0.004). Depth of invasion (HR 2.2, 95% CI 1.2-4.2, p=0.01) and vascular invasion (HR 2.5, 95% CI 1.4-4.5, p=0.001) were also associated with survival. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Isopropanolic black cohosh extract and recurrence-free survival after breast cancer.

Science.gov (United States)

Henneicke-von Zepelin, H H; Meden, H; Kostev, K; Schröder-Bernhardi, D; Stammwitz, U; Becher, H

2007-03-01

To investigate the influence of an isopropanolic Cimicifuga racemosa extract (iCR) on recurrence-free survival after breast cancer, including estrogen-dependent tumors. This pharmacoepidemiologic observational retrospective cohort study examined breast cancer patients treated at general, gynecological and internal facilities linked to a medical database in Germany. The main endpoint was disease-free survival following a diagnosis of breast cancer. The impact of treatment with iCR following diagnosis was analyzed by Cox-proportional hazards models, controlling for age and other confounders. Of 18,861 patients, a total of 1,102 had received an iCR therapy. The mean overall observation time was 3.6 years. Results showed that iCR was not associated with an increase in the risk of recurrence but associated with prolonged disease-free survival. After 2 years following initial diagnosis, 14% of the control group had developed a recurrence, while the iCR group reached this proportion after 6.5 years. The primary Cox regression model controlling for age, tamoxifen use and other confounders demonstrated a protractive effect of iCR on the rate of recurrence (hazard ratio 0.83, 95% confidence interval 0.69 0.99). This effect remained consistent throughout all variations of the statistical model, including subgroup analyses. TNM status was unknown but did not bias the iCR treatment decision as investigated separately. Hence, it was assumed to be equally distributed between treatment groups. Correlation analyses showed good internal and external validity of the database. An increase in the risk of breast cancer recurrence for women having had iCR treatment, compared to women not treated with iCR is unlikely.

Re-evaluating neonatal-age models for ungulates: does model choice affect survival estimates?

Directory of Open Access Journals (Sweden)

Troy W Grovenburg

Full Text Available 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

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

KAUST Repository

Ferreira, Ari J S

2014-06-12

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

KAUST Repository

Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

2014-01-01

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

Directory of Open Access Journals (Sweden)

Ari J S Ferreira

Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

The experience of fatherhood following childhood cancer survival.

Science.gov (United States)

Agnew, Francis; Higgins, Aiveen; Casey, Maureen; McCarthy, Anthony

2017-07-01

This study explored the experience of becoming a father following childhood cancer survival. Semi-structured interviews were conducted with five fathers and analysed using interpretative phenomenological analysis. Three superordinate themes emerged: 'moving away from and revisiting the experience of cancer', 'making sense of fortune and loss following a life-threatening illness' and 'valuing the opportunity to be a father'. The transition to fatherhood brought unique and specific challenges to fathers. Nevertheless, all appeared to have positively adjusted to this transition. Findings recommended providing information and support to childhood survivors who wish to or who are about to become fathers.

Influence of membrane fatty acid composition and fluidity on airborne survival of Escherichia coli.

Science.gov (United States)

Ng, Tsz Wai; Chan, Wing Lam; Lai, Ka Man

2018-04-01

Finding ways to predict and control the survival of bacterial aerosols can contribute to the development of ways to alleviate a number of crucial microbiological problems. Significant damage in the membrane integrity of Escherichia coli during aerosolization and airborne suspension has been revealed which has prompted the question of how the membrane fatty acid composition and fluidity influence the survival of airborne bacteria. Two approaches of using isogenic mutants and different growth temperatures were selected to manipulate the membrane fatty acid composition of E. coli before challenging the bacteria with different relative humidity (RH) levels in an aerosol chamber. Among the mutants (fabR - , cfa. fadA - ), fabR - had the lowest membrane fluidity index (FI) and generally showed a higher survival than the parental strain. Surprisingly, its resistance to airborne stress was so strong that its viability was fully maintained even after airborne suspension at 40% RH, a harsh RH level to bacterial survival. Moreover, E. coli cultured at 20 °C with a higher FI than that at 30 and 37 °C generally had a lower survival after aerosolization and airborne suspension. Unlike FI, individual fatty acid and cyclopropane fatty acid composition did not relate to the bacterial survival. Lipid peroxidation of the membrane was undetected in all the bacteria. Membrane fluidity plays a stronger role in determining the bacteria survival during airborne suspension than during aerosolization. Certain relationships between FI and bacteria survival were identified, which could help predict the transmission of bacteria under different conditions.

IR-induced autophagy plays a role in survival of HeLa cells

International Nuclear Information System (INIS)

Kang, Mi Young; Jang, Eun Yeong; Ryu, Tae Ho; Chung, Dong Min; Kim, Jin Hong; Kim, Jin Kyu

2014-01-01

Cells respond to stress with repair, or are diverted into irreversible cell cycle exit (senescence) or are eliminated through programmed cell death. There are two major morphologically distinctive forms of programmed cell death, apoptosis and autophagic cell death. Apoptosis contribute to cell death, whereas autophagy can play a dual role in mediating either cell survival or death in response to various stress stimuli. Here we analysed cellular responses induced by IR. The understanding of an appropriate cellular stress response is of crucial importance in foreseeing the cell fate. Apoptotic feagures were not detected in HeLa under our experimental irradiation condition. Autophagic cell death in HeLa may play an important role in cell protection and can result in cell survival

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients

DEFF Research Database (Denmark)

Møller, Henrik; Coupland, Victoria H; Tataru, Daniela

2018-01-01

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment...... and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following...... to statistical adjustments for age, sex, socio-economic status, performance status and co-morbidity. CONCLUSION: The extent of use of different treatment modalities varies between geographical areas in England. These variations are not attributable to measurable patient and tumour characteristics, and more...

Mesothelin-specific Immune Responses Predict Survival of Patients With Brain Metastasis

DEFF Research Database (Denmark)

Zhenjiang, Liu; Rao, Martin; Luo, Xiaohua

2017-01-01

BACKGROUND: Patients with advanced malignancies, e.g. lung cancer, ovarian cancer or melanoma, frequently present with brain metastases. Clinical presentation and disease progression of cancer is in part shaped by the interaction of the immune system with malignant cells. Antigen-targeted immune ...... of the primary tumor origin. Analyses of immunological markers could potentially serve as prognostic markers in patients with brain metastases and help to select patients in need for adjunct, immunological, treatment strategies....... were tested for interferon gamma (IFN-γ) production, after which univariate and multivariate analyses (Cox stepwise regression model) were performed to identify independent clinical and immunological factors associated with patient survival. Patients were followed-up for at least 500days after surgery...

The emergence, growth and decline of political priority for newborn survival in Bolivia.

Science.gov (United States)

Smith, Stephanie L

2014-12-01

Bolivia is expected to achieve United Nations Millennium Development Goal Four, reducing under-five child mortality by two-thirds between 2021 and 2025. However, progress on child mortality reduction masks a disproportionately slow decline in newborn deaths during the 2000s. Bolivia's neonatal mortality problem emerged on the policy agenda in the mid-1990s and grew through 2004 in relationship to political commitments to international development goals and the support of a strong policy network. Network status declined later in the decade. This study draws upon a framework for analysing determinants of political priority for global health initiatives to understand the trajectory of newborn survival policy in Bolivia from the early 1990s. A process-tracing case study methodology is used, informed by interviews with 26 individuals with close knowledge of newborn survival policy in the country and extensive document analysis. The case of newborn survival in Bolivia highlights the significance of political commitments to international development goals, health policy network characteristics (cohesion, composition, status and key actor support) and political transitions and instability in shaping agenda status, especially decline-an understudied phenomenon considering the transitory nature of policy priorities. The study suggests that the sustainability of issue attention therefore become a focal point for health policy networks and analyses. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.

Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis.

Science.gov (United States)

Kang, Young Ae; Kim, Song Yee; Jo, Kyung-Wook; Kim, Hee Jin; Park, Seung-Kyu; Kim, Tae-Hyung; Kim, Eun Kyung; Lee, Ki Man; Lee, Sung Soon; Park, Jae Seuk; Koh, Won-Jung; Kim, Dae Yun; Shim, Tae Sun

2013-01-01

Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death. Copyright © 2013 S. Karger AG, Basel.

[Association between socioeconomic status and survival after a first episode of myocardial infarction].

Science.gov (United States)

Nazzal, Carolina; Alonso, Faustino; Cerecera, Francisco; Ojeda, José Miguel

2017-07-01

A low socioeconomic status is associated with higher overall mortality rates. To assess the effect of socioeconomic inequalities on survival of patients hospitalized with a first myocardial infarction. Analysis of hospital discharge and mortality databases of the Ministry of Health. Patients aged over 15 years discharged between 2002 and 2011 with a first myocardial infarction (code I-21, ICD-10) were identified. Their survival was verified with the mortality registry. Survival from 0 to 28 and from 29 to 365 days was analyzed. Socioeconomic status was determined using the type of health insurance, stratified as public insurance (low and medium status) and private insurance (high status). Prais-Winsten trend (P-W) and Cox survival analyses were done. We analyzed 59,557 patients (69% males). Sixty three percent were of low socioeconomic status, 19% medium and 18% high. Between 2002 and 2011 the increase in survival was higher among patients of low socioeconomic status, mainly in women (P-W coefficients 0.58:0.31-0.86 in men and 1.12:0.84-1.41 in women for 0-28 days survival and 0.24:0.09-0.39 in men and 0.48:0.37-0.60 in women for 29-365 days survival, respectively). However, age and year of hospitalization adjusted analysis showed a higher mortality risk among patients of low socioeconomic status at 0-28 days (HR 1.67:1.53-1.83 for men and 1.49:1.34-1.66 for women) and at 29-365 days (HR 2.30:1.75-2.71 for men and 1.90:1.56-1.85 for women). Survival after a myocardial infarction improved in the last decade especially in patients of low socioeconomic status. However, subjects of this stratum continue to have a higher mortality.

Volume of high-risk intratumoral subregions at multi-parametric MR imaging predicts overall survival and complements molecular analysis of glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Cui, Yi; Li, Ruijiang [Stanford University, Department of Radiation Oncology, Palo Alto, CA (United States); Hokkaido University, Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido (Japan); Ren, Shangjie [Tianjin University, School of Electrical Engineering and Automation, Tianjin Shi (China); Tha, Khin Khin; Shirato, Hiroki [Hokkaido University, Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Hokkaido (Japan); Hokkaido University, Department of Radiology and Nuclear Medicine, Hokkaido (Japan); Wu, Jia [Stanford University, Department of Radiation Oncology, Palo Alto, CA (United States)

2017-09-15

To develop and validate a volume-based, quantitative imaging marker by integrating multi-parametric MR images for predicting glioblastoma survival, and to investigate its relationship and synergy with molecular characteristics. We retrospectively analysed 108 patients with primary glioblastoma. The discovery cohort consisted of 62 patients from the cancer genome atlas (TCGA). Another 46 patients comprising 30 from TCGA and 16 internally were used for independent validation. Based on integrated analyses of T1-weighted contrast-enhanced (T1-c) and diffusion-weighted MR images, we identified an intratumoral subregion with both high T1-c and low ADC, and accordingly defined a high-risk volume (HRV). We evaluated its prognostic value and biological significance with genomic data. On both discovery and validation cohorts, HRV predicted overall survival (OS) (concordance index: 0.642 and 0.653, P < 0.001 and P = 0.038, respectively). HRV stratified patients within the proneural molecular subtype (log-rank P = 0.040, hazard ratio = 2.787). We observed different OS among patients depending on their MGMT methylation status and HRV (log-rank P = 0.011). Patients with unmethylated MGMT and high HRV had significantly shorter survival (median survival: 9.3 vs. 18.4 months, log-rank P = 0.002). Volume of the high-risk intratumoral subregion identified on multi-parametric MRI predicts glioblastoma survival, and may provide complementary value to genomic information. (orig.)

Survival of alpha particle irradiated cells as a function of the shape and size of the sensitive volume (nucleus)

International Nuclear Information System (INIS)

Stinchcomb, T.G.; Roeske, J.C.

1995-01-01

Microdosimetry is the study of the stochastic variation of energy deposited within sub-cellular targets. As such, the size and shape of the critical target (i.e. cell nucleus) are essential when considering microdosimetric quantities. In this work, a microdosimetric analysis examines the expected cell survival as a function of the size and shape of the cell nucleus under conditions of irradiation emitting alpha particles. The results indicate that, in general, cell survival is relatively insensitive to changes in the shape of the cell nucleus when the volume is held constant. However, cell survival is a strong function of the variation in the size of the target. These results are useful when analysing the results of cell survival experiments for alpha particle emitters. (Author)

Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

Science.gov (United States)

Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

2013-01-01

The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

Intrapair Comparison of Life-Course Appetite and Physical Activity in Elderly Danish Twins

DEFF Research Database (Denmark)

Løkkegaard, Laura Ekstrøm; Larsen, Lisbeth A; Christensen, Kaare

2016-01-01

. They were asked to compare their appetite and physical activity to that of their co-twins in different stages of life. On an individual level, we found a positive association between current self-reported physical activity and late-life survival for elderly twins. This was supported by the intrapair...... analyses, which revealed a positive association between midlife and current physical activity and late-life survival. A positive association between lower appetite and late-life survival was found generally over the life course in the individual level analyses but not in the intrapair analyses. Kappa...

Comparison of survival of adolescents and young adults with hematologic malignancies in Osaka, Japan.

Science.gov (United States)

Nakata-Yamada, Kayo; Inoue, Masami; Ioka, Akiko; Ito, Yuri; Tabuchi, Takahiro; Miyashiro, Isao; Masaie, Hiroaki; Ishikawa, Jun; Hino, Masayuki; Tsukuma, Hideaki

2016-01-01

The survival gap between adolescents and young adults (AYAs) with hematological malignancies persists in many countries. To determine to what extent it does in Japan, we investigated survival and treatment regimens in 211 Japanese AYAs (15-29 years) in the Osaka Cancer Registry diagnosed during 2001-2005 with hematological malignancies, and compared adolescents (15-19 years) with young adults (20-29 years). AYAs with acute lymphoblastic leukemia (ALL) had a poor 5-year survival (44%), particularly young adults (29% vs. 64% in adolescents, p = 0.01). Additional investigation for patients with ALL revealed that only 19% of young adults were treated with pediatric treatment regimens compared with 45% of adolescents (p = 0.05). Our data indicate that we need to focus on young adults with ALL and to consider establishing appropriate cancer care system and guidelines for them in Japan.

Evolutionary genetic analyses of MEF2C gene: implications for learning and memory in Homo sapiens.

Science.gov (United States)

Kalmady, Sunil V; Venkatasubramanian, Ganesan; Arasappa, Rashmi; Rao, Naren P

2013-02-01

MEF2C facilitates context-dependent fear conditioning (CFC) which is a salient aspect of hippocampus-dependent learning and memory. CFC might have played a crucial role in human evolution because of its advantageous influence on survival of species. In this study, we analyzed 23 orthologous mammalian gene sequences of MEF2C gene to examine the evidence for positive selection on this gene in Homo sapiens using Phylogenetic Analysis by Maximum Likelihood (PAML) and HyPhy software. Both PAML Bayes Empirical Bayes (BEB) and HyPhy Fixed Effects Likelihood (FEL) analyses supported significant positive selection on 4 codon sites in H. sapiens. Also, haplotter analysis revealed significant ongoing positive selection on this gene in Central European population. The study findings suggest that adaptive selective pressure on this gene might have influenced human evolution. Further research on this gene might unravel the potential role of this gene in learning and memory as well as its pathogenetic effect in certain hippocampal disorders with evolutionary basis like schizophrenia. Copyright © 2012 Elsevier B.V. All rights reserved.

Diet and stable isotope analyses reveal the feeding ecology of the orangeback squid Sthenoteuthis pteropus (Steenstrup 1855 (Mollusca, Ommastrephidae in the eastern tropical Atlantic.

Directory of Open Access Journals (Sweden)

Véronique Merten

Full Text Available In the eastern tropical Atlantic, the orangeback flying squid Sthenoteuthis pteropus (Steenstrup 1855 (Cephalopoda, Ommastrephidae is a dominant species of the epipelagic nekton community. This carnivore squid has a short lifespan and is one of the fastest-growing squids. In this study, we characterise the role of S. pteropus in the pelagic food web of the eastern tropical Atlantic by investigating its diet and the dynamics of its feeding habits throughout its ontogeny and migration. During three expeditions in the eastern tropical Atlantic in 2015, 129 specimens were caught by hand jigging. Stomach content analyses (via visual identification and DNA barcoding were combined with stable isotope data (∂15N and ∂13C of muscle tissue to describe diet, feeding habits and trophic ecology of S. pteropus. Additionally, stable isotope analyses of incremental samples along the squid's gladius-the chitinous spiniform structure supporting the muscles and organs-were carried out to explore possible diet shifts through ontogeny and migration. Our results show that S. pteropus preys mainly on myctophid fishes (e.g. Myctophum asperum, Myctophum nitidulum, Vinciguerria spp., but also on other teleost species, cephalopods (e.g. Enoploteuthidae, Bolitinidae, Ommastrephidae, crustaceans and possibly on gelatinous zooplankton as well. The squid shows a highly opportunistic feeding behaviour that includes cannibalism. Our study indicates that the trophic position of S. pteropus may increase by approximately one trophic level from a mantle length of 15 cm to 47 cm. The reconstructed isotope-based feeding chronologies of the gladii revealed high intra- and inter-individual variability in the squid's trophic position and foraging area. These findings are not revealed by diet or muscle tissue stable isotope analysis. This suggests a variable and complex life history involving individual variation and migration. The role of S. pteropus in transferring energy and

Diet and stable isotope analyses reveal the feeding ecology of the orangeback squid Sthenoteuthis pteropus (Steenstrup 1855) (Mollusca, Ommastrephidae) in the eastern tropical Atlantic.

Science.gov (United States)

Merten, Véronique; Christiansen, Bernd; Javidpour, Jamileh; Piatkowski, Uwe; Puebla, Oscar; Gasca, Rebeca; Hoving, Henk-Jan T

2017-01-01

In the eastern tropical Atlantic, the orangeback flying squid Sthenoteuthis pteropus (Steenstrup 1855) (Cephalopoda, Ommastrephidae) is a dominant species of the epipelagic nekton community. This carnivore squid has a short lifespan and is one of the fastest-growing squids. In this study, we characterise the role of S. pteropus in the pelagic food web of the eastern tropical Atlantic by investigating its diet and the dynamics of its feeding habits throughout its ontogeny and migration. During three expeditions in the eastern tropical Atlantic in 2015, 129 specimens were caught by hand jigging. Stomach content analyses (via visual identification and DNA barcoding) were combined with stable isotope data (∂15N and ∂13C) of muscle tissue to describe diet, feeding habits and trophic ecology of S. pteropus. Additionally, stable isotope analyses of incremental samples along the squid's gladius-the chitinous spiniform structure supporting the muscles and organs-were carried out to explore possible diet shifts through ontogeny and migration. Our results show that S. pteropus preys mainly on myctophid fishes (e.g. Myctophum asperum, Myctophum nitidulum, Vinciguerria spp.), but also on other teleost species, cephalopods (e.g. Enoploteuthidae, Bolitinidae, Ommastrephidae), crustaceans and possibly on gelatinous zooplankton as well. The squid shows a highly opportunistic feeding behaviour that includes cannibalism. Our study indicates that the trophic position of S. pteropus may increase by approximately one trophic level from a mantle length of 15 cm to 47 cm. The reconstructed isotope-based feeding chronologies of the gladii revealed high intra- and inter-individual variability in the squid's trophic position and foraging area. These findings are not revealed by diet or muscle tissue stable isotope analysis. This suggests a variable and complex life history involving individual variation and migration. The role of S. pteropus in transferring energy and nutrients from

Repair models of cell survival and corresponding computer program for survival curve fitting

International Nuclear Information System (INIS)

Shen Xun; Hu Yiwei

1992-01-01

Some basic concepts and formulations of two repair models of survival, the incomplete repair (IR) model and the lethal-potentially lethal (LPL) model, are introduced. An IBM-PC computer program for survival curve fitting with these models was developed and applied to fit the survivals of human melanoma cells HX118 irradiated at different dose rates. Comparison was made between the repair models and two non-repair models, the multitar get-single hit model and the linear-quadratic model, in the fitting and analysis of the survival-dose curves. It was shown that either IR model or LPL model can fit a set of survival curves of different dose rates with same parameters and provide information on the repair capacity of cells. These two mathematical models could be very useful in quantitative study on the radiosensitivity and repair capacity of cells

Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension.

Science.gov (United States)

Hasler, Elisabeth D; Müller-Mottet, Séverine; Furian, Michael; Saxer, Stéphanie; Huber, Lars C; Maggiorini, Marco; Speich, Rudolf; Bloch, Konrad E; Ulrich, Silvia

2016-07-01

Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m(2)) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66-0.95; P = .004). In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival in Patients Diagnosed with Hepatocellular Carcinoma (HCC).

Science.gov (United States)

Lamarca, Angela; Mendiola, Marta; Bernal, Elsa; Heredia, Victoria; Díaz, Esther; Miguel, María; Pastrian, Laura G; Burgos, Emilio; Feliu, Jaime; Barriuso, Jorge

2015-01-01

Hepatocellular carcinoma (HCC) tends to develop in the liver when there is a high level of background inflammation (cirrhosis). Treatment options are limited and mainly based on systemic therapies such as anti-angiogenic drugs (e.g. sorafenib). Connective tissue growth factor (CTGF) is a matricellular protein involved in inflammation, tumour growth and angiogenesis. The aim of this study is to determine the expression of CTGF and hypoxia inducible factors (HIF) in HCC and to clarify its impact on relapse and survival. Eligibility criteria for the study consisted of patients with a diagnosis of HCC, formalin-fixed and paraffin-embedded (FFPE) biopsy tissue, as well as relapse and available survival data. A tissue microarray was constructed from ≥ 70% tumoural sections. The expressions of CTGF, HIF1α and HIF2α were analysed by immunohistochemistry. The relationship between expression of CTGF/HIF1α and CTGF/HIF2α were analysed. Univariate and multivariate analyses were performed. Fifty-three patients were screened; 39 patients were eligible for this study. Patients were treated with radical intent. At the end of follow up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and 7.7% distant metastases). Estimated median disease-free survival (DFS) and overall survival (OS) were 23.4 (95%CI 7.18-39.66) and 38.6 months (95%CI 30.7-46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and diffuse 23.1%. A non-statistically significant relationship between expression of CTGF and HIF was shown supporting an alternative pathway for CTGF expression in HCC. In multivariate analysis CTGF expression was an independent factor related to OS, with shorter survival in those patients with focal/diffuse CTGF expression (HR 2.46; 95%CI 1.18-5.15). Our results support that expression of CTGF is an independent factor associated with shorter OS in HCC. Further analysis of CTGF expression in a larger series of HCC patients is required to confirm

Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

International Nuclear Information System (INIS)

Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Agarwal, Chapla; Agarwal, Rajesh

2014-01-01

Highlights: • Silibinin inhibits fibronectin-induce motile morphology in PC3 cells. • Silibinin inhibits fibronectin-induced migration and invasion in PC3 cells. • Silibinin targets fibronectin-induced integrins and downstream signaling molecule. - Abstract: Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell–cell interaction with integrins-based cell–matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells’ interaction with extracellular matrix component fibronectin. Silibinin (50–200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and

Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

Energy Technology Data Exchange (ETDEWEB)

Deep, Gagan [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Kumar, Rahul; Jain, Anil K. [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Agarwal, Rajesh, E-mail: Rajesh.agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States)

2014-10-15

Highlights: • Silibinin inhibits fibronectin-induce motile morphology in PC3 cells. • Silibinin inhibits fibronectin-induced migration and invasion in PC3 cells. • Silibinin targets fibronectin-induced integrins and downstream signaling molecule. - Abstract: Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell–cell interaction with integrins-based cell–matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells’ interaction with extracellular matrix component fibronectin. Silibinin (50–200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and

The outcome and survival of palliative surgery in thoraco-lumbar spinal metastases: contemporary retrospective cohort study.

Science.gov (United States)

Nemelc, R M; Stadhouder, A; van Royen, B J; Jiya, T U

2014-11-01

Purpose: To evaluate outcome and survival and to identify prognostic variables for patients surgically treated for spinal metastases. Methods: A retrospective study was performed on 86 patients, surgically treated for spinal metastases. Preoperative analyses of the ASIA and spinal instability neoplastic scores (SINS) were performed. Survival curves of different prognostic variables were made by Kaplan–Meier analysis and the variables entered in a Cox proportional hazards model to determine their significance on survival. The correlation between preoperative radiotherapy and postoperative wound infections was also evaluated. Results: Survival analysis was performed on 81 patients,37 women and 44 men. Five patients were excluded due to missing data. Median overall survival was 38 weeks [95 % confidence interval (CI) 27.5–48.5 weeks], with a 3-month survival rate of 81.5 %. Breast tumor had the best median survival of 127 weeks and lung tumor the worst survival of 18 weeks. Univariate analysis showed tumor type, preoperative ASIA score (p = 0.01) and visceral metastases(p = 0.18) were significant prognostic variables for survival.Colon tumors had 5.53 times hazard ratio compared to patients with breast tumor. ASIA-C score had more than 13.03 times the hazard ratio compared to patients with an ASIA-E score. Retrospective analysis of the SINS scores showed 34 patients with a score of 13–18 points, 44 patients with a score of 7–12 points, and 1 patient with a score of 6 points. Preoperative radiotherapy had no influence on the postoperative incidence of deep surgical wound infections (p = 0.37). Patients with spinal metastases had a median survival of 38 weeks postoperative. The primary tumor type and ASIA score were significant prognostic factors for survival. Preoperative radiotherapy neither had influence on survival nor did it constitute a risk for postoperative surgical wound infections.

Associations between advanced cancer patients' survival and family caregiver presence and burden.

Science.gov (United States)

Dionne-Odom, J Nicholas; Hull, Jay G; Martin, Michelle Y; Lyons, Kathleen Doyle; Prescott, Anna T; Tosteson, Tor; Li, Zhongze; Akyar, Imatullah; Raju, Dheeraj; Bakitas, Marie A

2016-05-01

We conducted a randomized controlled trial (RCT) of an early palliative care intervention (ENABLE: Educate, Nurture, Advise, Before Life Ends) for persons with advanced cancer and their family caregivers. Not all patient participants had a caregiver coparticipant; hence, we explored whether there were relationships between patient survival, having an enrolled caregiver, and caregiver outcomes prior to death. One hundred and twenty-three patient-caregiver dyads and 84 patients without a caregiver coparticipant participated in the ENABLE early versus delayed (12 weeks later) RCT. We collected caregiver quality-of-life (QOL), depression, and burden (objective, stress, and demand) measures every 6 weeks for 24 weeks and every 3 months thereafter until the patient's death or study completion. We conducted survival analyses using log-rank and Cox proportional hazards models. Patients with a caregiver coparticipant had significantly shorter survival (Wald = 4.31, HR = 1.52, CI: 1.02-2.25, P = 0.04). After including caregiver status, marital status (married/unmarried), their interaction, and relevant covariates, caregiver status (Wald = 6.25, HR = 2.62, CI: 1.23-5.59, P = 0.01), being married (Wald = 8.79, HR = 2.92, CI: 1.44-5.91, P = 0.003), and their interaction (Wald = 5.18, HR = 0.35, CI: 0.14-0.87, P = 0.02) were significant predictors of lower patient survival. Lower survival in patients with a caregiver was significantly related to higher caregiver demand burden (Wald = 4.87, CI: 1.01-1.20, P = 0.03) but not caregiver QOL, depression, and objective and stress burden. Advanced cancer patients with caregivers enrolled in a clinical trial had lower survival than patients without caregivers; however, this mortality risk was mostly attributable to higher survival by unmarried patients without caregivers. Higher caregiver demand burden was also associated with decreased patient survival. © 2016 The Authors. Cancer Medicine published by

Revealed social preference for potable groundwater: An Eastern Iowa case study

Science.gov (United States)

Raunikar, R. P.; Bernknopf, R. L.; Forney, W.; Mishra, S.

2011-12-01

The spatially explicit land use and land cover information provided by Landsat moderate-resolution land imagery (MRLI) is needed to more efficiently balance the production of goods and services over landscapes. For example, economic trade-offs are needed to provide both clean groundwater resources and other non-environmental goods and services produced by activities that affect the vadose zone and thus contribute to contamination of groundwater. These trade-off choices are made by numerous economic agents and are constrained by many social institutions including governmental regulations at many levels, contractual obligations and traditions. In effect, on a social level, society acts as if it values groundwater by foregoing other goods to protect these resources. The result of the protection afforded to groundwater resources is observable by measuring contamination in well samples. This observed level of groundwater contamination risk is the revealed preference of society as a whole for clean groundwater. We observed the risk of groundwater contamination in a sampling of well data from our study area (35 counties of Eastern Iowa.) We used a proportional hazard model to quantify the nitrate contamination survival implied by the panel of 19,873 well data, where remaining below a 10 mg/ml maximum contamination level (MCL) is defined as survival. We tested the data for evidence that the levels of protection provided to these resources is correlated with aquifer and vadose zone characteristics and geographic location and whether it changed over time and with economic and other conditions. We demonstrate the use of a nitrate conditioned hazard function for projecting the survival of wells based on nitrate exposure information over the 1940 to 2010 time period. We discuss results of simulations of the survival process that demonstrate the economic significance of this approach. We find that aquifer survival has been significantly improving over time. The principle of

Differential survival among sSOD-1* genotypes in Chinook Salmon

Science.gov (United States)

Hayes, Michael C.; Reisenbichler, Reginald R.; Rubin, Stephen P.; Wetzel, Lisa A.; Marshall , Anne R.

2011-01-01

Differential survival and growth were tested in Chinook salmon Oncorhynchus tshawytscha expressing two common alleles, *–100 and *–260, at the superoxide dismutase locus (sSOD-1*). These tests were necessary to support separate studies in which the two alleles were used as genetic marks under the assumption of mark neutrality. Heterozygous adults were used to produce progeny with –100/–100, –100/–260, and –260/–260 genotypes that were reared in two natural streams and two hatcheries in the states of Washington and Oregon. The latter also were evaluated as returning adults. In general, the genotype ratios of juveniles reared at hatcheries were consistent with high survival and little or no differential survival in the hatchery. Adult returns at one hatchery were significantly different from the expected proportions, and the survival of the –260/–260 genotype was 0.56–0.89 times that of the –100/–100 genotype over four year-classes. Adult returns at a second hatchery (one year-class) were similar but not statistically significant: survival of the –260/–260genotype relative to the –100/–100 genotype was 0.76. The performance of the heterozygote group was intermediate at both hatcheries. Significant differences in growth were rarely observed among hatchery fish (one year-class of juveniles and one age-class of adult males) but were consistent with greater performance for the –100/–100 genotype. Results from two groups of juveniles reared in streams (one year-class from each stream) suggested few differences in growth, but the observed genotype ratios were significantly different from the expected ratios in one stream. Those differences were consistent with the adult data; survival for the –260/–260 genotype was 76% of that of the –100/–100 genotype. These results, which indicate nonneutrality among sSOD-1* genotypes, caused us to modify our related studies and suggest caution in the interpretation of results and analyses in

Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

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Borges, Ana; Sousa, Inês; Castro, Luis

2017-06-01

This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

Factors driving inequality in prostate cancer survival: a population based study.

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Richéal M Burns

Full Text Available PURPOSE: As cancer control strategies have become more successful, issues around survival have become increasingly important to researchers and policy makers. The aim of this study was to examine the role of a range of clinical and socio-demographic variables in explaining variations in survival after a prostate cancer diagnosis, paying particular attention to the role of healthcare provider(s i.e. private versus public status. METHODS: Data were extracted from the National Cancer Registry Ireland, for patients diagnosed with prostate cancer from 1998-2009 (N = 26,183. A series of multivariate Cox and logistic regression models were used to examine the role of healthcare provider and socio-economic status (area-based deprivation on survival, controlling for age, stage, Gleason grade, marital status and region of residence. Survival was based on all-cause mortality. RESULTS: Older individuals who were treated in a private care setting were more likely to have survived than those who had not, when other factors were controlled for. Differences were evident with respect to marital status, region of residence, clinical stage and Gleason grade. The effect of socio-economic status was modified by healthcare provider, such that risk of death was higher in those men of lower socio-economic status treated by public, but not private providers in the Cox models. The logistic models revealed a socio-economic gradient in risk of death overall; the gradient was larger for those treated by public providers compared to those treated by private providers when controlling for a range of other confounding factors. CONCLUSION: The role of healthcare provider and socio-economic status in survival of men with prostate cancer may give rise to concerns that warrant further investigation.

Statin use and survival following glioblastoma multiforme

DEFF Research Database (Denmark)

Gaist, David; Hallas, Jesper; Friis, Søren

2014-01-01

with glioblastoma multiforme (GBM). METHODS: We identified 1562 patients diagnosed with GBM during 2000-2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥2......-cause death associated with prediagnostic statin use. RESULTS: A total of 339 GBM patients were included in the analyses. Of these, 325 died during median follow-up of 6.9 months (interquartile range: 3.8-13.4 months). Prediagnostic statin use was associated with a reduced HR of death (0.79; 95% CI: 0......: 0.63-1.01). CONCLUSION: Long-term prediagnostic statin use may improve survival following GBM....

Antioxidant defenses predict long-term survival in a passerine bird.

Directory of Open Access Journals (Sweden)

Nicola Saino

2011-05-01

Full Text Available Normal and pathological processes entail the production of oxidative substances that can damage biological molecules and harm physiological functions. Organisms have evolved complex mechanisms of antioxidant defense, and any imbalance between oxidative challenge and antioxidant protection can depress fitness components and accelerate senescence. While the role of oxidative stress in pathogenesis and aging has been studied intensively in humans and model animal species under laboratory conditions, there is a dearth of knowledge on its role in shaping life-histories of animals under natural selection regimes. Yet, given the pervasive nature and likely fitness consequences of oxidative damage, it can be expected that the need to secure efficient antioxidant protection is powerful in molding the evolutionary ecology of animals. Here, we test whether overall antioxidant defense varies with age and predicts long-term survival, using a wild population of a migratory passerine bird, the barn swallow (Hirundo rustica, as a model.Plasma antioxidant capacity (AOC of breeding individuals was measured using standard protocols and annual survival was monitored over five years (2006-2010 on a large sample of selection episodes. AOC did not covary with age in longitudinal analyses after discounting the effect of selection. AOC positively predicted annual survival independently of sex. Individuals were highly consistent in their relative levels of AOC, implying the existence of additive genetic variance and/or environmental (including early maternal components consistently acting through their lives.Using longitudinal data we showed that high levels of antioxidant protection positively predict long-term survival in a wild animal population. Present results are therefore novel in disclosing a role for antioxidant protection in determining survival under natural conditions, strongly demanding for more longitudinal eco-physiological studies of life-histories in

The Ross procedure offers excellent survival compared with mechanical aortic valve replacement in a real-world setting.

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Andreas, Martin; Wiedemann, Dominik; Seebacher, Gernot; Rath, Claus; Aref, Tandis; Rosenhek, Raphael; Heinze, Georg; Eigenbauer, Ernst; Simon, Paul; Ruetzler, Kurt; Hiesmayr, Joerg-Michael; Moritz, Anton; Laufer, Guenther; Kocher, Alfred

2014-09-01

The ideal prosthesis for young patients requiring aortic valve replacement has not been defined to date. Although the Ross procedure provides excellent survival, its application is still limited. We compared the long-term survival after the Ross procedure with mechanical aortic valve replacement. All consecutive Ross procedures and mechanical aortic valve replacements performed between 1991 and 2008 at a single centre were analysed. Only adult patients between 18 and 50 years of age were included in the study. Survival and valve-related complications were evaluated. Furthermore, survival was compared with the age- and sex-matched Austrian population. A total of 159 Ross patients and 173 mechanical valve patients were included. The cumulative survival for the Ross procedure was significantly better, with survival rates of 96, 94 and 93% at 5, 10 and 15 years, respectively, in comparison to 90, 84 and 75% (P Ross group but was significantly reduced in the mechanical valve group. In a real-world setting, the Ross procedure is associated with a long-term survival benefit in young adults in comparison to mechanical aortic valve replacement. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

Directory of Open Access Journals (Sweden)

Nelson S. Yee

2015-10-01

Full Text Available The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8 in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca²⁺ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.

Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Chen, Helen H.W. [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Chou, Cheng-Yang [Department of Obstetrics and Gynecology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Wu, Yuan-Hua; Hsueh, Wei-Ting; Hsu, Chiung-Hui [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Guo, How-Ran [Department of Environmental and Occupational Health, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Lee, Wen-Ying, E-mail: 7707@so-net.net.tw [Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan (China) and Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Wu-Chou, E-mail: sunnysu@mail.ncku.edu.tw [Department of Internal Medicine, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China)

2012-02-01

Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

DEFF Research Database (Denmark)

Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even

2016-01-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein....../sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our...... findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue...

Survival prediction of non-small cell lung cancer patients using radiomics analyses of cone-beam CT images

DEFF Research Database (Denmark)

van Timmeren, Janna E; Leijenaar, Ralph T H; van Elmpt, Wouter

2017-01-01

was validated. MATERIAL AND METHODS: One training dataset of 132 and two validation datasets of 62 and 94stage I-IV NSCLC patients were included. Interchangeability was assessed by performing a linear regression on CT and CBCT extracted features. A two-step correction was applied prior to model validation...... different between groups with high and low prognostic value for both modalities. Harrell's concordance index was 0.69 for CT and 0.66 for CBCT models for dataset 1. Conclusions The results show that a subset of radiomic features extracted from CT and CBCT images are interchangeable using simple linear...... regression. Moreover, a previously developed radiomics signature has prognostic value for overall survival in three CBCT cohorts, showing the potential of CBCT radiomics to be used as prognostic imaging biomarker....

Poor horse traders: large mammals trade survival for reproduction during the process of feralization

Science.gov (United States)

Grange, Sophie; Duncan, Patrick; Gaillard, Jean-Michel

2009-01-01

We investigated density dependence on the demographic parameters of a population of Camargue horses (Equus caballus), individually monitored and unmanaged for eight years. We also analysed the contributions of individual demographic parameters to changes in the population growth rates. The decrease in resources caused a loss of body condition. Adult male survival was not affected, but the survival of foals and adult females decreased with increasing density. Prime-aged females maintained high reproductive performance at high density, and their survival decreased. The higher survival of adult males compared with females at high density presumably results from higher investment in reproduction by mares. The high fecundity in prime-aged females, even when at high density, may result from artificial selection for high reproductive performance, which is known to have occurred in all the major domestic ungulates. Other studies suggest that feral ungulates including cattle and sheep, as these horses, respond differently from wild ungulates to increases in density, by trading adult survival for reproduction. As a consequence, populations of feral animals should oscillate more strongly than their wild counterparts, since they should be both more invasive (as they breed faster), and more sensitive to harsh environmental conditions (as the population growth rate of long-lived species is consistently more sensitive to a given proportional change in adult survival than to the same change in any other vital rate). If this principle proves to be general, it has important implications for management of populations of feral ungulates. PMID:19324787

Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

Science.gov (United States)

Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

2013-11-01

Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

International Nuclear Information System (INIS)

Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

2010-01-01

Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

Parameter resolution in two models for cell survival after radiation

International Nuclear Information System (INIS)

Di Cera, E.; Andreasi Bassi, F.; Arcovito, G.

1989-01-01

The resolvability of model parameters for the linear-quadratic and the repair-misrepair models for cell survival after radiation has been studied by Monte Carlo simulations as a function of the number of experimental data points collected in a given dose range and the experimental error. Statistical analysis of the results reveals the range of experimental conditions under which the model parameters can be resolved with sufficient accuracy, and points out some differences in the operational aspects of the two models. (orig.)

Impact of Nitrate Use on Survival in Acute Heart Failure: A Propensity-Matched Analysis.

Science.gov (United States)

Ho, Edwin C; Parker, John D; Austin, Peter C; Tu, Jack V; Wang, Xuesong; Lee, Douglas S

2016-02-12

There is limited evidence that the use of nitrates in acute decompensated heart failure early after presentation to a hospital can improve clinical outcomes. We aimed to determine whether early nitrate exposure is associated with improved survival in a large retrospective cohort study. We examined 11 078 acute decompensated heart failure patients who presented to emergency departments in Ontario, Canada, between 2004 and 2007, in the Enhanced Feedback For Effective Cardiac Treatment and the Emergency Heart failure Mortality Risk Grade studies. In propensity-matched analyses, we examined the effect of nitrate administration in the acute emergency department setting for its impact on death at 7, 30, and 365 days. In propensity-matched analyses, we found no difference in survival between those who received nitrates in the emergency department and the non-nitrate comparator group. Hazard ratios for mortality were 0.76 (95% CI; 0.51, 1.12) over 7 days, 0.97 (95% CI; 0.77, 1.21) over 30 days, and 0.91 (95% CI; 0.82, 1.02) over 1 year of follow-up. There was no significant difference in survival or hospital length of stay between nitrate and non-nitrate controls in extended follow-up. There was also no significant effect of nitrates in subgroups stratified by presence of chest pain, troponin elevation, chronic nitrate use, and known coronary artery disease. In acute decompensated heart failure, use of nitrates acutely in the emergency department setting was not associated with improvement in short-term or near-term survival. Our study does not support generalized use of nitrates when the primary goal of therapy is to reduce mortality. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Proteomic analyses of male contributions to honey bee sperm storage and mating

OpenAIRE

Collins, A M; Caperna, T J; Williams, V; Garrett, W M; Evans, J D

2006-01-01

Honey bee (Apis mellifera L.) queens mate early in life and store sperm for years. Male bees likely contribute significantly to sperm survival. Proteins were extracted from seminal vesicles and semen of mature drones, separated by electrophoresis, and analysed by peptide mass fingerprinting. Computer searches against three databases, general species, honey bees and fruit flies, were performed. Spectra were used to query the recently generated honey bee genome protein list as well as general s...

Effects of marital status on survival of hepatocellular carcinoma by race/ethnicity and gender.

Science.gov (United States)

Wu, Wenrui; Fang, Daiqiong; Shi, Ding; Bian, Xiaoyuan; Li, Lanjuan

2018-01-01

It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship. We identified eligible patients from Surveillance, Epidemiology and End Results (SEER) database during 2004-2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan-Meier curves. We also estimated crude hazard ratios (CHRs) and adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models. A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married) was highest for Hispanic (AHR =1.25, 95% CI, 1.13-1.39; P married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality.

Diversification patterns and survival as firms mature

DEFF Research Database (Denmark)

Coad, Alexander Jean-Luc; Guenther, C.

2013-01-01

We focus on the relationship between age and diversification patterns of German machine tool manufacturers in the post-war era. We distinguish between 'minor diversification' (adding a new product variation within a familiar submarket) and 'major diversification' (expanding the product portfolio...... lines). Second, we find that product portfolios of larger firms tend to be more diversified. Third, with respect to consecutive diversification activities, quantile autoregression plots show that firms experiencing diversification in one period are unlikely to repeat this behavior in the following year....... Fourth, survival estimations reveal that diversification activities reduce the risk of exit in general and to a varying degree at different ages. These results are interpreted using Penrosean growth theory....

Survival curves for irradiated cells

International Nuclear Information System (INIS)

Gibson, D.K.