Sample records for survival processing advantage
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Burns, Daniel J; Hart, Joshua; Griffith, Samantha E; Burns, Amy D
2013-01-01
Nairne, Thompson, and Pandeirada (2007) found that retention of words rated for their relevance to survival is superior to that of words encoded under numerous other deep processing conditions. They suggested that our memory systems might have evolved to confer an advantage for survival-relevant information. Burns, Burns, and Hwang (2011) suggested a two-process explanation of the proximate mechanisms responsible for the survival advantage. Whereas most control tasks encourage only one type of processing, the survival task encourages both item-specific and relational processing. They found that when control tasks encouraged both types of processing, the survival processing advantage was eliminated. However, none of their control conditions included non-survival scenarios (e.g., moving, vacation, etc.), so it is not clear how this two-process explanation would explain the survival advantage when scenarios are used as control conditions. The present experiments replicated the finding that the survival scenario improves recall relative to a moving scenario in both a between-lists and within-list design and also provided evidence that this difference was accompanied by an item-specific processing difference, not a difference in relational processing. The implications of these results for several existing accounts of the survival processing effect are discussed.
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The effects of healthy aging on the mnemonic benefit of survival processing
Stillman, Chelsea M.; Coane, Jennifer H.; Profaci, Caterina P.; Howard, James H.; Howard, Darlene V.
2013-01-01
A number of studies have shown that information is remembered better when it is processed for its survival relevance compared to when it is processed for relevance to other, non-survival-related contexts. Here we conducted three experiments to investigate whether the survival advantage also occurs for healthy older adults. In Experiment 1, older and younger adults rated words for their relevance to a grassland survival or moving scenario and then completed an unexpected free recall test on the words. We replicated the survival advantage in two separate groups of younger adults, one of which was placed under divided-attention conditions, but we did not find a survival advantage in the older adults. We then tested two additional samples of older adults using a between- (Experiment 2) or within-subjects (Experiment 3) design, but still found no evidence of the survival advantage in this age group. These results suggest that, although survival processing is an effective encoding strategy for younger adults, it does not provide the same mnemonic benefit to healthy elders. PMID:23896730
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Raymaekers, Linsey H C; Otgaar, Henry; Smeets, Tom
2014-01-01
Prior studies have convincingly demonstrated that survival-related processing of information enhances its subsequent retention. This phenomenon, known as the survival recall advantage, generalises to other stimuli, memory domains, and research populations, thereby underscoring its reliability. As previous studies used only short retention intervals between survival processing and the memory test, an important yet hitherto unanswered issue is whether this effect persists over time. The present experiment therefore examined whether survival processing also produces mnemonic benefits when retention is tested after longer delay periods. Participants (N =81) rated the relevance of words according to a survival and a moving scenario, and were then randomly assigned to the typical immediate (3-minute delay) retention test condition or conditions that included a 24- or 48-hour interval between survival processing and memory testing. In each of these conditions survival processing led to higher surprise free recall and recognition rates than processing words according to the moving scenario. Thus this study provides evidence that illustrates the longevity of survival processing advantages on memory performance.
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Bell, Raoul; Röer, Jan P; Buchner, Axel
2013-05-01
Recent research has highlighted the adaptive function of memory by showing that imagining being stranded in the grasslands without any survival material and rating words according to their survival value in this situation leads to exceptionally good memory for these words. Studies examining the role of emotions in causing the survival-processing memory advantage have been inconclusive, but some studies have suggested that the effect might be due to negativity or mortality salience. In Experiments 1 and 2, we compared the survival scenario to a control scenario that implied imagining a hopeless situation (floating in outer space with dwindling oxygen supplies) in which only suicide can avoid the agony of choking to death. Although this scenario was perceived as being more negative than the survival scenario, the survival-processing memory advantage persisted. In Experiment 3, thinking about the relevance of words for survival led to better memory for these words than did thinking about the relevance of words for death. This survival advantage was found for concrete, but not for abstract, words. The latter finding is consistent with the assumption that the survival instructions encourage participants to think about many different potential uses of items to aid survival, which may be a particularly efficient form of elaborate encoding. Together, the results suggest that thinking about death is much less effective in promoting recall than is thinking about survival. Therefore, the survival-processing memory advantage cannot be satisfactorily explained by negativity or mortality salience.
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Kostic, Bogdan; McFarlan, Chastity C; Cleary, Anne M
2012-07-01
Recent work (e.g., Nairne & Pandeirada, 2010) has shown that words are remembered better when they have been processed for their survival value in a grasslands context than when processed in other contexts. It has been suggested that this is because human memory systems were shaped by evolution specifically to help humans survive. Thus far, the survival processing advantage has mainly been shown with grasslands contexts, which are thought to be particularly relevant to human evolution. The present study demonstrated the survival processing advantage with other contexts (e.g., lost in a jungle), including with contexts that should not, in and of themselves, be relevant to human evolution (e.g., lost in outer space). We further examined whether implied social isolation plays a critical role in the survival advantage to memory by comparing scenarios in which the person is alone versus with other people present (e.g., lost at sea alone or with others), and whether the perceived source of danger is social isolation or other human attackers. A survival advantage was shown in both the isolation and the group settings, and whether the primary source of danger was isolation or other human attackers did not matter. These findings suggest that the survival advantage in memory is not dependent on evolutionarily relevant physical contexts (e.g., grasslands) or particular sources of perceived danger (social isolation vs. perceived attackers), showing the advantage to be robust and applicable to a variety of scenarios. 2012 APA, all rights reserved
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Burns, Daniel J; Burns, Sarah A; Hwang, Ana J
2011-01-01
J. S. Nairne, S. R. Thompson, and J. N. S. Pandeirada (2007) suggested that our memory systems may have evolved to help us remember fitness-relevant information and showed that retention of words rated for their relevance to survival is superior to that of words encoded under other deep processing conditions. The authors present 4 experiments that uncover the proximate mechanisms likely responsible. The authors obtained a recall advantage for survival processing compared with conditions that promoted only item-specific processing or only relational processing. This effect was eliminated when control conditions encouraged both item-specific and relational processing. Data from separate measures of item-specific and relational processing generally were consistent with the view that the memorial advantage for survival processing results from the encoding of both types of processing. Although the present study suggests the proximate mechanisms for the effect, the authors argue that survival processing may be fundamentally different from other memory phenomena for which item-specific and relational processing differences have been implicated. (PsycINFO Database Record (c) 2010 APA, all rights reserved).
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A Twin Protection Effect? Explaining Twin Survival Advantages with a Two-Process Mortality Model
2016-01-01
Twin studies that focus on the correlation in age-at-death between twin pairs have yielded important insights into the heritability and role of genetic factors in determining lifespan, but less attention is paid to the biological and social role of zygosity itself in determining survival across the entire life course. Using data from the Danish Twin Registry and the Human Mortality Database, we show that monozygotic twins have greater cumulative survival proportions at nearly every age compared to dizygotic twins and the Danish general population. We examine this survival advantage by fitting these data with a two-process mortality model that partitions survivorship patterns into extrinsic and intrinsic mortality processes roughly corresponding to acute, environmental and chronic, biological origins. We find intrinsic processes confer a survival advantage at older ages for males, while at younger ages, all monozygotic twins show a health protection effect against extrinsic death akin to a marriage protection effect. While existing research suggests an increasingly important role for genetic factors at very advanced ages, we conclude that the social closeness of monozygotic twins is a plausible driver of the survival advantage at ages <65. PMID:27192433
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Otgaar, Henry; Smeets, Tom; van Bergen, Saskia
2010-01-01
Recent studies have shown that processing words according to a survival scenario leads to superior retention relative to control conditions. Here, we examined whether a survival recall advantage could be elicited by using pictures. Furthermore, in Experiment 1, we were interested in whether survival processing also results in improved memory for details. Undergraduates rated the relevance of pictures in a survival, moving, or pleasantness scenario and were subsequently given a surprise free recall test. We found that survival processing yielded superior retention. We also found that distortions occurred more often in the survival condition than in the pleasantness condition. In Experiment 2, we directly compared the survival recall effect between pictures and words. A comparable survival recall advantage was found for pictures and words. The present findings support the idea that memory is enhanced by processing information in terms of fitness value, yet at the same time, the present results suggest that this may increase the risk for memory distortions.
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How can survival processing improve memory encoding?
Luo, Meng; Geng, Haiyan
2013-11-01
We investigated the psychological mechanism of survival processing advantage from the perspective of false memory in two experiments. Using a DRM paradigm in combination with analysis based on signal detection theory, we were able to separately examine participants' utilization of verbatim representation and gist representation. Specifically, in Experiment 1, participants rated semantically related words in a survival scenario for a survival condition but rated pleasantness of words in the same DRM lists for a non-survival control condition. The results showed that participants demonstrated more gist processing in the survival condition than in the pleasantness condition; however, the degree of item-specific processing in the two encoding conditions did not significantly differ. In Experiment 2, the control task was changed to a category rating task, in which participants were asked to make category ratings of words in the category lists. We found that the survival condition involved more item-specific processing than did the category condition, but we found no significant difference between the two encoding conditions at the level of gist processing. Overall, our study demonstrates that survival processing can simultaneously promote gist and item-specific representations. When the control tasks only promoted either item-specific representation or gist representation, memory advantages of survival processing occurred.
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On the Plasticity of the Survival Processing Effect
ERIC Educational Resources Information Center
Kroneisen, Meike; Erdfelder, Edgar
2011-01-01
Nairne, Thompson, and Pandeirada (2007) discovered a strong and rather general memory advantage for word material processed in a survival-related context. One possible explanation of this effect conceives survival processing as a special form of encoding: Nature specifically "tuned" our memory systems to process and remember…
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Is the Survival-Processing Memory Advantage Due to Richness of Encoding?
ERIC Educational Resources Information Center
Röer, Jan P.; Bell, Raoul; Buchner, Axel
2013-01-01
Memory for words rated according to their relevance in a grassland survival context is exceptionally good. According to Nairne, Thompson, and Pandeirada's (2007) evolutionary-based explanation, natural selection processes have tuned the human memory system to prioritize the processing of fitness-relevant information. The survival-processing memory…
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Developmental trends in adaptive memory.
Otgaar, Henry; Howe, Mark L; Smeets, Tom; Garner, Sarah R
2014-01-01
Recent studies have revealed that memory is enhanced when information is processed for fitness-related purposes. The main objective of the current experiments was to test developmental trends in the evolutionary foundation of memory using different types of stimuli and paradigms. In Experiment 1, 11-year-olds and adults were presented with neutral, negative, and survival-related DRM word lists. We found a memory benefit for the survival-related words and showed that false memories were more likely to be elicited for the survival-related word lists than for the other lists. Experiment 2 examined developmental trends in the survival processing paradigm using neutral, negative, and survival-related pictures. A survival processing advantage was found for survival-related pictures in adults, for negative pictures in 11/12-year-olds, and for neutral pictures in 7/8-year-olds. In Experiment 3, 11/12-year-olds and adults had to imagine the standard survival scenario or an adapted survival condition (or pleasantness condition) that was designed to reduce the possibilities for elaborative processing. We found superior memory retention for both survival scenarios in children and adults. Collectively, our results evidently show that the survival processing advantage is developmentally invariant and that certain proximate mechanisms (elaboration and distinctiveness) underlie these developmental trends.
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Adaptive Memory: Survival Processing Increases Both True and False Memory in Adults and Children
ERIC Educational Resources Information Center
Otgaar, Henry; Smeets, Tom
2010-01-01
Research has shown that processing information in a survival context can enhance the information's memorability. The current study examined whether survival processing can also decrease the susceptibility to false memories and whether the survival advantage can be found in children. In Experiment 1, adults rated semantically related words in a…
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Survival and Self-Descriptive Processing of Abstract and Concrete Nouns
ERIC Educational Resources Information Center
Caldwell, Jennifer
2010-01-01
Researchers have recently described a new processing task in which rating words on the basis of their survival or fitness relevance leads to better recall and recognition performance than several other well known deep processing tasks. The present study was designed to determine whether this survival processing advantage could be observed when…
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Is the survival-processing memory advantage due to richness of encoding?
Röer, Jan P; Bell, Raoul; Buchner, Axel
2013-07-01
Memory for words rated according to their relevance in a grassland survival context is exceptionally good. According to Nairne, Thompson, and Pandeirada's (2007) evolutionary-based explanation, natural selection processes have tuned the human memory system to prioritize the processing of fitness-relevant information. The survival-processing memory advantage has been replicated numerous times, but very little is known about the proximate mechanisms behind it. The richness-of-encoding hypothesis (Kroneisen & Erdfelder, 2011) implies that rating the usefulness of items in a survival context leads to the generation of a large number of ideas that may be used as retrieval cues at test to boost recall. In Experiment 1, the typical survival-processing recall advantage was obtained when words were rated according to their usefulness in 1 of 3 fictional contexts. In Experiment 2, participants were asked to write down any ideas that came to mind when thinking about the usefulness of the words. Consistent with the richness-of-encoding hypothesis, participants generated more ideas in the survival condition than in the fitness-irrelevant control conditions. In Experiment 3, participants generated more ideas for congruent than for incongruent words, demonstrating that the richness-of-encoding hypothesis can also account for the previously obtained congruency effect on recall (Butler, Kang, & Roediger, 2009). In both experiments the number of ideas written down predicted future recall performance well. Our results provide further evidence for the assumption that richness of encoding is an important proximate mechanism involved in memory performance in the survival-processing paradigm. PsycINFO Database Record (c) 2013 APA, all rights reserved.
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Adaptive Memory: Is There a Reproduction-Processing Effect?
Seitz, Benjamin M; Polack, Cody W; Miller, Ralph R
2017-12-14
Like all biological systems, human memory is likely to have been influenced by evolutionary processes, and its abilities have been subjected to selective mechanisms. Consequently, human memory should be primed to better remember information relevant to one's evolutionary fitness. Supporting this view, participants asked to rate words based on their relevance to an imaginary survival situation better recall those words (even the words rated low in relevancy) than the same words rated with respect to non-survival situations. This mnemonic advantage is called the "survival-processing effect," and presumably it was selected for because it contributed to evolutionary fitness. The same reasoning suggests that there should be an advantage for recall of information that has been rated for relevancy to reproduction and/or mate seeking, although little evidence has existed to assess this proposition. We used an experimental design similar to that in the original survival-processing effect study (Nairne, Thompson, & Pandeirada, 2007) and across 3 experiments tested several newly designed scenarios to determine whether a reproduction-processing effect could be found in an ancestral environment, a modern mating environment, and an ancestral environment in which the emphasis was on raising offspring as opposed to finding a mate. Our results replicated the survival-processing effect but provided no evidence of a reproduction-processing effect when the scenario emphasized finding a mate. However, when rating items on their relevancy to raising one's offspring in an ancestral environment, a mnemonic advantage comparable to that of the survival-processing effect was found. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Survival Processing Enhances Visual Search Efficiency.
Cho, Kit W
2018-05-01
Words rated for their survival relevance are remembered better than when rated using other well-known memory mnemonics. This finding, which is known as the survival advantage effect and has been replicated in many studies, suggests that our memory systems are molded by natural selection pressures. In two experiments, the present study used a visual search task to examine whether there is likewise a survival advantage for our visual systems. Participants rated words for their survival relevance or for their pleasantness before locating that object's picture in a search array with 8 or 16 objects. Although there was no difference in search times among the two rating scenarios when set size was 8, survival processing reduced visual search times when set size was 16. These findings reflect a search efficiency effect and suggest that similar to our memory systems, our visual systems are also tuned toward self-preservation.
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ERIC Educational Resources Information Center
Kostic, Bogdan; McFarlan, Chastity C.; Cleary, Anne M.
2012-01-01
Recent work (e.g., Nairne & Pandeirada, 2010) has shown that words are remembered better when they have been processed for their survival value in a grasslands context than when processed in other contexts. It has been suggested that this is because human memory systems were shaped by evolution specifically to help humans survive. Thus far,…
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Adaptive memory: the comparative value of survival processing.
Nairne, James S; Pandeirada, Josefa N S; Thompson, Sarah R
2008-02-01
We recently proposed that human memory systems are "tuned" to remember information that is processed for survival, perhaps as a result of fitness advantages accrued in the ancestral past. This proposal was supported by experiments in which participants showed superior memory when words were rated for survival relevance, at least relative to when words received other forms of deep processing. The current experiments tested the mettle of survival memory by pitting survival processing against conditions that are universally accepted as producing excellent retention, including conditions in which participants rated words for imagery, pleasantness, and self-reference; participants also generated words, studied words with the intention of learning them, or rated words for relevance to a contextually rich (but non-survival-related) scenario. Survival processing yielded the best retention, which suggests that it may be one of the best encoding procedures yet discovered in the memory field.
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ERIC Educational Resources Information Center
Burns, Daniel J.; Burns, Sarah A.; Hwang, Ana J.
2011-01-01
J. S. Nairne, S. R. Thompson, and J. N. S. Pandeirada (2007) suggested that our memory systems may have evolved to help us remember fitness-relevant information and showed that retention of words rated for their relevance to survival is superior to that of words encoded under other deep processing conditions. The authors present 4 experiments that…
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Adaptive memory: enhanced location memory after survival processing.
Nairne, James S; Vanarsdall, Joshua E; Pandeirada, Josefa N S; Blunt, Janell R
2012-03-01
Two experiments investigated whether survival processing enhances memory for location. From an adaptive perspective, remembering that food has been located in a particular area, or that potential predators are likely to be found in a given territory, should increase the chances of subsequent survival. Participants were shown pictures of food or animals located at various positions on a computer screen. The task was to rate the ease of collecting the food or capturing the animals relative to a central fixation point. Surprise retention tests revealed that people remembered the locations of the items better when the collection or capturing task was described as relevant to survival. These data extend the generality of survival processing advantages to a new domain (location memory) by means of a task that does not involve rating the relevance of words to a scenario. 2012 APA, all rights reserved
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False memories from survival processing make better primes for problem-solving.
Garner, Sarah R; Howe, Mark L
2014-01-01
Previous research has demonstrated that participants remember significantly more survival-related information and more information that is processed for its survival relevance. Recent research has also shown that survival materials and processing result in more false memories, ones that are adaptive inasmuch as they prime solutions to insight-based problems. Importantly, false memories for survival-related information facilitate problem solving more than false memories for other types of information. The present study explores this survival advantage using an incidental rather than intentional memory task. Here participants rated information either in the context of its importance to a survival-processing scenario or to moving to a new house. Following this, participants solved a number of compound remote associate tasks (CRATs), half of which had the solution primed by false memories that were generated during the processing task. Results showed that (a) CRATs were primed by false memories in this incidental task, with participants solving significantly more CRATs when primed than when unprimed, (b) this effect was greatest when participants rated items for survival than moving, and (c) processing items for a survival scenario improved overall problem-solving performance even when specific problems themselves were not primed. Results are discussed with regard to adaptive theories of memory.
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Stein, G; Meyer, C; Marlow, L; Christ, H; Müller, L P; Isenberg, J; Eysel, P; Schiffer, G; Faymonville, C
2017-02-01
Type II fractures of the odontoid process of the axis are the most common injury of the cervical spine in elderly patients. Only little evidence exists on whether elderly patients should be treated conservatively or surgically. The mortality and survival probability of 51 patients were determined in a retrospective study. The range of motion, pain and the neck disability index were clinically investigated. Of the 51 patients 37 were treated surgically and 14 conservatively. The conservatively treated group showed a higher mortality (64 % vs. 32 %). Kaplan-Meier analysis revealed a median survival of the conservatively treated group of 29 months, whereby during the first 3 months of treatment this group showed a higher survival probability and afterwards the surgically treated group showed a higher survival probability. The clinical examination of 20 patients revealed limited range of motion of the cervical spine. Additionally, moderate levels of pain and complaints were recorded using the neck disability index. Fractures of the odontoid process pose a far-reaching danger for elderly patients. A balanced assessment of the general condition should be carried out at the beginning of treatment of these patients. In the early phase following trauma no differences were found with respect to survival rates but for long-term survival the operatively treated group showed advantages; however, these advantages cannot be causally attributed to the choice of therapy.
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Complete hazard ranking to analyze right-censored data: An ALS survival study.
Huang, Zhengnan; Zhang, Hongjiu; Boss, Jonathan; Goutman, Stephen A; Mukherjee, Bhramar; Dinov, Ivo D; Guan, Yuanfang
2017-12-01
Survival analysis represents an important outcome measure in clinical research and clinical trials; further, survival ranking may offer additional advantages in clinical trials. In this study, we developed GuanRank, a non-parametric ranking-based technique to transform patients' survival data into a linear space of hazard ranks. The transformation enables the utilization of machine learning base-learners including Gaussian process regression, Lasso, and random forest on survival data. The method was submitted to the DREAM Amyotrophic Lateral Sclerosis (ALS) Stratification Challenge. Ranked first place, the model gave more accurate ranking predictions on the PRO-ACT ALS dataset in comparison to Cox proportional hazard model. By utilizing right-censored data in its training process, the method demonstrated its state-of-the-art predictive power in ALS survival ranking. Its feature selection identified multiple important factors, some of which conflicts with previous studies.
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Haploid deletion strains of Saccharomyces cerevisiae that determine survival during space flight
NASA Astrophysics Data System (ADS)
Johanson, Kelly; Allen, Patricia L.; Gonzalez-Villalobos, Romer A.; Nesbit, Jacqueline; Nickerson, Cheryl A.; Höner zu Bentrup, Kerstin; Wilson, James W.; Ramamurthy, Rajee; D'Elia, Riccardo; Muse, Kenneth E.; Hammond, Jeffrey; Freeman, Jake; Stodieck, Louis S.; Hammond, Timothy G.
2007-02-01
This study identifies genes that determine survival during a space flight, using the model eukaryotic organism, Saccharomyces cerevisiae. Select strains of a haploid yeast deletion series grew during storage in distilled water in space, but not in ground based static or clinorotation controls. The survival advantages in space in distilled water include a 133-fold advantage for the deletion of PEX19, a chaperone and import receptor for newly- synthesized class I peroxisomal membrane proteins, to 77-40 fold for deletion strains lacking elements of aerobic respiration, isocitrate metabolism, and mitochondrial electron transport. Following automated addition of rich growth media, the space flight was associated with a marked survival advantage of strains with deletions in catalytically active genes including hydrolases, oxidoreductases and transferases. When compared to static controls, space flight was associated with a marked survival disadvantage of deletion strains lacking transporter, antioxidant and catalytic activity. This study identifies yeast deletion strains with a survival advantage during storage in distilled water and space flight, and amplifies our understanding of the genes critical for survival in space.
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New Synthesis Of High-Performance Bismaleimides
NASA Technical Reports Server (NTRS)
Pater, Ruth H.; Lowther, Sharon; Cannon, Michelle; Smith, Janice; Whitely, Karen
1991-01-01
New general synthesis of tough and easy-to-process high-performance bismaleimides (BMI's) developed. Involves reaction of acetylene-terminated compounds with BMI's or biscitraconimides. Offers matrix resins and adhesives having combined advantages of toughness characteristic of thermoplastics and easy processability characteristic of thermosetting materials. Scheme has potential for providing high-performance matrix resins surviving well at high temperatures and absorb little moisture.
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Emotion Words, Regardless of Polarity, Have a Processing Advantage over Neutral Words
ERIC Educational Resources Information Center
Kousta, Stavroula-Thaleia; Vinson, David P.; Vigliocco, Gabriella
2009-01-01
Despite increasing interest in the interface between emotion and cognition, the role of emotion in cognitive tasks is unclear. According to one hypothesis, negative valence is more relevant for survival and is associated with a general slowdown of the processing of stimuli, due to a defense mechanism that freezes activity in the face of threat.…
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Nothing concentrates the mind: thoughts of death improve recall.
Hart, Joshua; Burns, Daniel J
2012-04-01
It seems likely that awareness of one's mortality is in some respects advantageous (e.g., because it helps individuals forestall death), but little research has explored the psychological mechanisms that might confer such an advantage. Recent research has shown that processing stimuli in terms of survival relevance enhances memory relative to a host of deep-processing conditions, so it is plausible that human memory has been selected to operate more efficiently when death thoughts (e.g., survival concerns) are activated. If so, then the mortality salience as a general psychological state should be sufficient to increase recall; the present experiments show this to be the case. The enhancing effect of mortality salience on recall occurred for both incidental and intentional learning tasks, relative to a variety of comparison conditions, and did not appear to be mediated by affect or arousal. Follow-up analyses revealed the effect to be mediated by the complexity of participants' elaborations about mortality. Potential theoretical implications are discussed.
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A chapter a day: Association of book reading with longevity.
Bavishi, Avni; Slade, Martin D; Levy, Becca R
2016-09-01
Although books can expose people to new people and places, whether books also have health benefits beyond other types of reading materials is not known. This study examined whether those who read books have a survival advantage over those who do not read books and over those who read other types of materials, and if so, whether cognition mediates this book reading effect. The cohort consisted of 3635 participants in the nationally representative Health and Retirement Study who provided information about their reading patterns at baseline. Cox proportional hazards models were based on survival information up to 12 years after baseline. A dose-response survival advantage was found for book reading by tertile (HRT2 = 0.83, p < 0.001, HRT3 = 0.77, p < 0.001), after adjusting for relevant covariates including age, sex, race, education, comorbidities, self-rated health, wealth, marital status, and depression. Book reading contributed to a survival advantage that was significantly greater than that observed for reading newspapers or magazines (tT2 = 90.6, p < 0.001; tT3 = 67.9, p < 0.001). Compared to non-book readers, book readers had a 23-month survival advantage at the point of 80% survival in the unadjusted model. A survival advantage persisted after adjustment for all covariates (HR = .80, p < .01), indicating book readers experienced a 20% reduction in risk of mortality over the 12 years of follow up compared to non-book readers. Cognition mediated the book reading-survival advantage (p = 0.04). These findings suggest that the benefits of reading books include a longer life in which to read them. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Takano, Sotaro; Pawlowska, Bogna J; Gudelj, Ivana; Yomo, Tetsuya; Tsuru, Saburo
2017-02-07
The amount of natural resources in the Earth's environment is in flux, which can trigger catastrophic collapses of ecosystems. How populations survive under nutrient-poor conditions is a central question in ecology. Curiously, some bacteria persist for a long time in nutrient-poor environments. Although this survival may be accomplished through cell death and the recycling of dead cells, the importance of these processes and the mechanisms underlying the survival of the populations have not been quantitated. Here, we use microbial laboratory experiments and mathematical models to demonstrate that death and recycling are essential activities for the maintenance of cell survival. We also show that the behavior of the survivors is governed by population density feedback, wherein growth is limited not only by the available resources but also by the population density. The numerical simulations suggest that population density-dependent recycling could be an advantageous behavior under starvation conditions. How organisms survive after exhaustion of resources is a central question in ecology. Starving Escherichia coli constitute a model system to understand survival mechanisms during long-term starvation. Although death and the recycling of dead cells might play a key role in the maintenance of long-term survival, their mechanisms and importance have not been quantitated. Here, we verified the significance of social recycling of dead cells for long-term survival. We also show that the survivors restrained their recycling and did not use all available nutrients released from dead cells, which may be advantageous under starvation conditions. These results indicate that not only the utilization of dead cells but also restrained recycling coordinate the effective utilization of limited resources for long-term survival under starvation. Copyright © 2017 Takano et al.
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ERIC Educational Resources Information Center
White, Roderick E.; Thornhill, Stewart; Hampson, Elizabeth
2006-01-01
Biological evolutionary processes select for heritable behaviors providing a survival and reproductive advantage. Accordingly, how we behave is, at least in part, affected by the evolutionary history of our species. This research uses evolutionary psychology as the theoretical perspective for exploring the relationship between a heritable…
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The Competitive Advantage: Client Service.
ERIC Educational Resources Information Center
Leffel, Linda G.; DeBord, Karen B.
The adult education literature contains a considerable amount of research on and discussion of client service in the marketing process, management and staff roles in service- and product-oriented businesses, and the importance of client service and service quality to survival in the marketplace. By applying the principles of client-oriented…
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The survival advantage of olfaction in a competitive environment.
Asahina, Kenta; Pavlenkovich, Viktoryia; Vosshall, Leslie B
2008-08-05
Olfaction is generally assumed to be critical for survival because this sense allows animals to detect food and pheromonal cues. Although the ability to sense sex pheromones [1, 2, 3] is likely to be important for insects, the contribution of general odor detection to survival is unknown. We investigated the extent to which the olfactory system confers a survival advantage on Drosophila larvae foraging for food under conditions of limited resources and competition from other larvae.
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A Chapter a Day – Association of Book Reading with Longevity
Bavishi, Avni; Slade, Martin D.; Levy, Becca R.
2016-01-01
Although books can expose people to new people and places, whether books also have health benefits beyond other types of reading materials is not known. This study examined whether those who read books have a survival advantage over those who do not read books and over those who read other types of materials, and if so, whether cognition mediates this book reading effect. The cohort consisted of 3635 participants in the nationally representative Health and Retirement Study who provided information about their reading patterns at baseline. Cox proportional hazards models were based on survival information up to 12 years after baseline. A dose-response survival advantage was found for book reading by tertile (HRT2 = 0.83, p<.0001, HRT3 = 0.77, p<.0001), after adjusting for relevant covariates including age, sex, race, education, comorbidities, self-rated health, wealth, marital status, and depression. Book reading contributed to a survival advantage that was significantly greater than that observed for reading newspapers or magazines (tT2 = 90.6, p<.0001; tT3 = 67.9, p<.0001). Compared to non-book readers, book readers had a 4-month survival advantage at the point of 80% survival. Book readers also experienced a 20% reduction in risk of mortality over the 12 years of follow up compared to non-book readers. Cognitive score was a complete mediator of the book reading survival advantage (p=.04). These findings suggest that the benefits of reading books include a longer life in which to read them. PMID:27471129
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Sanguri, Sweta; Gupta, Damodar
2018-06-27
Low LET Ionizing radiation is known to alter intracellular redox balance by inducing free radical generation, which may cause oxidative modification of various cellular biomolecules. The extent of biomolecule-modifications/ damages and changes in vital processes (viz. cellular homeostasis, inter-/intra-cellular signaling, mitochondrial physiology/dynamics antioxidant defence systems) are crucial which in turn determine fate of cells. In the present study, we expended TLR expressing (normal/ transformed) and TLR null cells; and we have shown that mannan pretreatment in TLR expressing normal cells offers survival advantage against lethal doses of ionizing radiation. On the contrary, mannan pretreatment does not offer any protection against radiation to TLR null cells, NKE ρ° cells and transformed cells. In normal cells, abrupt decrease in mitochondrial membrane potential and endogenous ROS levels occurs following treatment with mannan. We intend to irradiate mannan-pretreated cells at a specific stage of perturbed mitochondrial functioning and ROS levels to comprehend if mannan pretreatment offers any survival advantage against radiation exposure to cells. Interestingly, pre-irradiation treatment of cells with mannan activates NFκB, p38 and JNK, alters mitochondrial physiology, increases expression of Cu/ZnSOD and MnSOD, minimizes oxidation of mitochondrial phospholipids and offers survival advantage in comparison to irradiated group, in TLR expressing normal cells. The study demonstrates that TLR and mitochondrial ETC functions are inevitable in radio-protective efficacy exhibited by mannan.
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Do Daughters Really Cause Divorce? Stress, Pregnancy, and Family Composition
Hamoudi, Amar; Nobles, Jenna
2014-01-01
Provocative studies have reported that in the United States, marriages producing firstborn daughters are more likely to divorce than those producing firstborn sons. The findings have been interpreted as contemporary evidence of fathers' son preference. Our study explores the potential role of another set of dynamics that may drive these patterns: namely, selection into live birth. Epidemiological evidence indicates that the characteristic female survival advantage may begin before birth. If stress accompanying unstable marriages has biological effects on fecundity, a female survival advantage could generate an association between stability and the sex composition of offspring. Combining regression and simulation techniques to analyze real-world data, we ask, How much of the observed association between sex of the firstborn child and risk of divorce could plausibly be accounted for by the joint effects of female survival advantage and reduced fecundity associated with unstable marriage? Using data from the National Longitudinal Survey of Youth (NLSY79), we find that relationship conflict predicts the sex of children born after conflict was measured; conflict also predicts subsequent divorce. Conservative specification of parameters linking pregnancy characteristics, selection into live birth, and divorce are sufficient to generate a selection-driven association between offspring sex and divorce, which is consequential in magnitude. Our findings illustrate the value of demographic accounting of processes which occur before birth—a period when many outcomes of central interest in the population sciences begin to take shape. PMID:25024115
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Do daughters really cause divorce? Stress, pregnancy, and family composition.
Hamoudi, Amar; Nobles, Jenna
2014-08-01
Provocative studies have reported that in the United States, marriages producing firstborn daughters are more likely to divorce than those producing firstborn sons. The findings have been interpreted as contemporary evidence of fathers' son preference. Our study explores the potential role of another set of dynamics that may drive these patterns: namely, selection into live birth. Epidemiological evidence indicates that the characteristic female survival advantage may begin before birth. If stress accompanying unstable marriages has biological effects on fecundity, a female survival advantage could generate an association between stability and the sex composition of offspring. Combining regression and simulation techniques to analyze real-world data, we ask, How much of the observed association between sex of the firstborn child and risk of divorce could plausibly be accounted for by the joint effects of female survival advantage and reduced fecundity associated with unstable marriage? Using data from the National Longitudinal Survey of Youth (NLSY79), we find that relationship conflict predicts the sex of children born after conflict was measured; conflict also predicts subsequent divorce. Conservative specification of parameters linking pregnancy characteristics, selection into live birth, and divorce are sufficient to generate a selection-driven association between offspring sex and divorce, which is consequential in magnitude. Our findings illustrate the value of demographic accounting of processes which occur before birth-a period when many outcomes of central interest in the population sciences begin to take shape.
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Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage.
Dodd, Antony N; Salathia, Neeraj; Hall, Anthony; Kévei, Eva; Tóth, Réka; Nagy, Ferenc; Hibberd, Julian M; Millar, Andrew J; Webb, Alex A R
2005-07-22
Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long- and short-circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.
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Zhang, Ju; Lou, Xiaomin; Zellmer, Lucas; Liu, Siqi; Xu, Ningzhi; Liao, D. Joshua
2014-01-01
Sporadic carcinogenesis starts from immortalization of a differentiated somatic cell or an organ-specific stem cell. The immortalized cell incepts a new or quasinew organism that lives like a parasite in the patient and usually proceeds to progressive simplification, constantly engendering intermediate organisms that are simpler than normal cells. Like organismal evolution in Mother Nature, this cellular simplification is a process of Darwinian selection of those mutations with growth- or survival-advantages, from numerous ones that occur randomly and stochastically. Therefore, functional gain of growth- or survival-sustaining oncogenes and functional loss of differentiation-sustaining tumor suppressor genes, which are hallmarks of cancer cells and contribute to phenotypes of greater malignancy, are not drivers of carcinogenesis but are results from natural selection of advantageous mutations. Besides this mutation-load dependent survival mechanism that is evolutionarily low and of an asexual nature, cancer cells may also use cell fusion for survival, which is an evolutionarily-higher mechanism and is of a sexual nature. Assigning oncogenes or tumor suppressor genes or their mutants as drivers to induce cancer in animals may somewhat coerce them to create man-made oncogenic pathways that may not really be a course of sporadic cancer formations in the human. PMID:25594068
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ERIC Educational Resources Information Center
Ecuyer-Dab, Isabelle; Robert, Michele
2004-01-01
Drawing on the theoretical and empirical foundations of two evolutionary models, we argue that, among humans and other mammals, a twofold selection process would parsimoniously account for sex-linked advantages in spatial contexts. In males, a superiority for both solving navigation-related spatial problems and understanding physical principles…
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Lefringhouse, Jason; Pavlik, Edward; Miller, Rachel; DeSimone, Christopher; Ueland, Frederick; Kryscio, Richard; van Nagell, J. R.
2014-01-01
Objective. The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer. Methods. Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions. Results. Cytoreduction to no visible disease (P < 0.0001) and complete response to platinum-based chemotherapy (P < 0.025) occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer (17 ± 1 months) than in those with Stage II1A disease (36 ± 8 months). Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup. Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy. PMID:25254047
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A novel mechanism for a survival advantage of vigilant individuals in groups.
van der Post, Daniel J; de Weerd, Harmen; Verbrugge, Rineke; Hemelrijk, Charlotte K
2013-11-01
In many animal species, vigilance is crucial for avoiding predation. In groups, however, nonvigilant individuals could benefit from the vigilance of others without any of the associated costs. In an evolutionary sense, such exploitation may be compensated if vigilant individuals have a survival advantage. The novelty in our model is that the probability to detect a predator is "distance dependent." We show that even if nonvigilant individuals benefit fully from information produced by vigilant individuals, vigilant individuals nevertheless enjoy a survival advantage. This happens because detection of predators is more likely when vigilant individuals happen to be targets of predation. We expect this distance-dependent mechanism to be compatible with previously reported mechanisms.
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Does the thought of death contribute to the memory benefit of encoding with a survival scenario?
Bugaiska, Aurélia; Mermillod, Martial; Bonin, Patrick
2015-01-01
Four studies tested whether the thought of death contributes to the survival processing advantage found in memory tests (i.e., the survival effect). In the first study, we replicated the "Dying To Remember" (DTR) effect identified by Burns and colleagues whereby activation of death thoughts led to better retention than an aversive control situation. In Study 2, we compared an ancestral survival scenario, a modern survival scenario and a "life-after-death" scenario. The modern survival scenario and the dying scenario led to higher levels of recall than the ancestral scenario. In Study 3, we used a more salient death-thought scenario in which people imagine themselves on death row. Results showed that the "death-row" scenario yielded a level of recall similar to that of the ancestral survival condition. We also collected ratings of death-related thoughts (Studies 3 and 4) and of survival-related and planning thoughts (Study 4). The ratings indicated that death-related thoughts were induced more by the dying scenarios than by the survival scenarios, whereas the reverse was observed for both survival-related and planning thoughts. The findings are discussed in the light of two contrasting views of the influence of mortality salience in the survival effect.
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Radial Domany-Kinzel models with mutation and selection
NASA Astrophysics Data System (ADS)
Lavrentovich, Maxim O.; Korolev, Kirill S.; Nelson, David R.
2013-01-01
We study the effect of spatial structure, genetic drift, mutation, and selective pressure on the evolutionary dynamics in a simplified model of asexual organisms colonizing a new territory. Under an appropriate coarse-graining, the evolutionary dynamics is related to the directed percolation processes that arise in voter models, the Domany-Kinzel (DK) model, contact process, and so on. We explore the differences between linear (flat front) expansions and the much less familiar radial (curved front) range expansions. For the radial expansion, we develop a generalized, off-lattice DK model that minimizes otherwise persistent lattice artifacts. With both simulations and analytical techniques, we study the survival probability of advantageous mutants, the spatial correlations between domains of neutral strains, and the dynamics of populations with deleterious mutations. “Inflation” at the frontier leads to striking differences between radial and linear expansions. For a colony with initial radius R0 expanding at velocity v, significant genetic demixing, caused by local genetic drift, occurs only up to a finite time t*=R0/v, after which portions of the colony become causally disconnected due to the inflating perimeter of the expanding front. As a result, the effect of a selective advantage is amplified relative to genetic drift, increasing the survival probability of advantageous mutants. Inflation also modifies the underlying directed percolation transition, introducing novel scaling functions and modifications similar to a finite-size effect. Finally, we consider radial range expansions with deflating perimeters, as might arise from colonization initiated along the shores of an island.
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Patterning and templating for nanoelectronics.
Galatsis, Kosmas; Wang, Kang L; Ozkan, Mihri; Ozkan, Cengiz S; Huang, Yu; Chang, Jane P; Monbouquette, Harold G; Chen, Yong; Nealey, Paul; Botros, Youssry
2010-02-09
The semiconductor industry will soon be launching 32 nm complementary metal oxide semiconductor (CMOS) technology node using 193 nm lithography patterning technology to fabricate microprocessors with more than 2 billion transistors. To ensure the survival of Moore's law, alternative patterning techniques that offer advantages beyond conventional top-down patterning are aggressively being explored. It is evident that most alternative patterning techniques may not offer compelling advantages to succeed conventional top-down lithography for silicon integrated circuits, but alternative approaches may well indeed offer functional advantages in realising next-generation information processing nanoarchitectures such as those based on cellular, bioinsipired, magnetic dot logic, and crossbar schemes. This paper highlights and evaluates some patterning methods from the Center on Functional Engineered Nano Architectonics in Los Angeles and discusses key benchmarking criteria with respect to CMOS scaling.
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Women live longer than men even during severe famines and epidemics
Zarulli, Virginia; Barthold Jones, Julia A.; Oksuzyan, Anna; Lindahl-Jacobsen, Rune; Christensen, Kaare; Vaupel, James W.
2018-01-01
Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors. PMID:29311321
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Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia.
Dretzke, J; Barton, P; Kaambwa, B; Connock, M; Uthman, O; Bayliss, S; Meads, C
2010-10-01
This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at 20,000 pounds/QALY (30,000 pounds/QALY) if a reduction in survival advantage relative to the manufacturer's base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.
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Recognition Without Words: Using Taste to Explore Survival Processing
Hallock, Henry L.; Garman, Heather D.; Cook, Shaun P.; Gallagher, Shawn P.
2017-01-01
Many educational demonstrations of memory and recall employ word lists and number strings; items that lend themselves to semantic organization and “chunking.” By applying taste recall to the adaptive memory paradigm, which evaluates memory from a survival-based evolutionary perspective, we have developed a simple, inexpensive exercise that defies mnemonic strategies. Most adaptive memory studies have evaluated recall of words encountered while imagining survival and non-survival scenarios. Here, we’ve left the lexical domain and hypothesized that taste memory, as measured by recognition, would be best when acquisition occurs under imagined threat of personal harm, namely poisoning. We tested participants individually while they evaluated eight teas in one of three conditions: in one, they evaluated the toxicity of the tea (survival condition), in a second, they considered the marketability of the tea and, in the third, they evaluated the bitterness of the tea. After a filler task, a surprise recognition task required the participants to taste and identify the eight original teas from a group of 16 that included eight novel teas. The survival condition led to better recognition than the bitterness condition but, surprisingly, it did not yield better recognition than the marketing condition. A second experiment employed a streamlined design more appropriate for classroom settings and failed to support the hypothesis that planning enhanced recognition in survival scenarios. This simple technique has, at least, revealed a robust levels-of-processing effect for taste recognition and invites students to consider the adaptive advantages of all forms of memory. PMID:28690433
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Women live longer than men even during severe famines and epidemics.
Zarulli, Virginia; Barthold Jones, Julia A; Oksuzyan, Anna; Lindahl-Jacobsen, Rune; Christensen, Kaare; Vaupel, James W
2018-01-23
Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors. Copyright © 2018 the Author(s). Published by PNAS.
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Gorey, Kevin M
2009-12-01
This study tested the hypothesis that relatively poor Canadian women with breast cancer have a survival advantage over their counterparts in the USA. Seventy-eight independent retrospective cohort (incidence between 1984 and 2000, followed until 2006) outcomes were synthesized. Fixed effects meta-regression models compared women with breast cancer in low-income areas of Canada and the USA. Low-income Canadian women were advantaged on survival [rate ratio (RR) = 1.14; 95% confidence interval (CI) 1.13-1.15] and their advantage was even larger among women <65 years of age who are not yet eligible for Medicare coverage in the USA (RR = 1.21, 95% CI 1.18-1.24). Canadian advantages were also larger for node positive breast cancer, which may present with greater clinical and managerial discretion (RR = 1.40, 95% CI 1.30-1.50), and smaller when Hawaii, the state providing the most Canadian-like access, was the US comparator (RR = 1.12, 95% CI 1.01-1.20). More inclusive health care insurance coverage in Canada vs the USA, particularly among each country's relatively poor people, seems the most plausible explanation for such Canadian advantages. Provision of health care for all Americans would likely prevent countless early deaths, particularly among the relatively poor.
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George, S; Primrose, J; Talbot, R; Smith, J; Mullee, M; Bailey, D; du Boulay, C; Jordan, H
2006-01-01
To investigate the relationship between survival in colorectal cancer patients and the number of lymph nodes examined by a pathologist, previously attributed to stage migration, we used data from a cohort of 5174 colorectal cancer patients recruited between September 1991 and August 1994, and followed-up for 5 years. We selected cases with data present on all prognostic variables, and stratified them into three groups by number of nodes examined. We made a multivariate survival comparison using a Cox regression model. In all, there were 3592 cases with data present on all prognostic variables. Patients who had >10 nodes identified had a significant survival advantage over those who had 5–10 identified, who had in turn a similar advantage over those with 0–4 identified (P<0.001). This effect was present in the whole group and at all Dukes' stages, although statistically significant only in stages B (P=0.004) and C (P=0.019). The effect remained after adjustment in a Cox regression model in which the mean number of nodes taken out by each surgical firm did not predict survival. In a sub-group with data on lymphocytic infiltration into the primary tumour a survival advantage was noted in those with prominent rather than mild infiltration (P<0.001): the former also tended to have more nodes found (P=0.015). Stage migration alone cannot explain these results, as survival advantages are noted across the whole population independent of stage. Lymphocytic infiltration into the primary tumour is prognostically important, and is associated with the number of nodes found. Reactive enlargement of lymph nodes in the mesentery may make them easier to find, reflect immune response to the tumour, and thus indirectly impact upon survival. PMID:16969342
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Rajeshkumar, N V; Yabuuchi, Shinichi; Pai, Shweta G; Tong, Zeen; Hou, Shihe; Bateman, Scott; Pierce, Daniel W; Heise, Carla; Von Hoff, Daniel D; Maitra, Anirban; Hidalgo, Manuel
2016-08-09
Albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) plus gemcitabine (GEM) combination has demonstrated efficient antitumour activity and statistically significant overall survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) compared with GEM monotherapy. This regimen is currently approved as a standard of care treatment option for patients with metastatic PDAC. It is unclear whether cremophor-based PTX combined with GEM provide a similar level of therapeutic efficacy in PDAC. We comprehensively explored the antitumour efficacy, effect on metastatic dissemination, tumour stroma and survival advantage following GEM, PTX and nab-PTX as monotherapy or in combination with GEM in a locally advanced, and a highly metastatic orthotopic model of human PDAC. Nab-PTX treatment resulted in significantly higher paclitaxel tumour plasma ratio (1.98-fold), robust stromal depletion, antitumour efficacy (3.79-fold) and survival benefit compared with PTX treatment. PTX plus GEM treatment showed no survival gain over GEM monotherapy. However, nab-PTX in combination with GEM decreased primary tumour burden, metastatic dissemination and significantly increased median survival of animals compared with either agents alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumour stroma and decreased proliferation of carcinoma cells. Notably, nab-PTX monotherapy was equivalent to nab-PTX plus GEM in providing survival advantage to mice in a highly aggressive metastatic PDAC model, indicating that nab-PTX could potentially stop the progression of late-stage pancreatic cancer. Our data confirmed that therapeutic efficacy of PTX and nab-PTX vary widely, and the contention that these agents elicit similar antitumour response was not supported. The addition of PTX to GEM showed no survival advantage, concluding that a clinical combination of PTX and GEM may unlikely to provide significant survival advantage over GEM monotherapy and may not be a viable alternative to the current standard-of-care nab-PTX plus GEM regimen for the treatment of PDAC patients.
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Bass, G A; Furlong, H; O'Sullivan, K E; Hennessy, T P J; Walsh, T N
2014-04-01
Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC (n=113) or SCC (n=98) were separately-randomised to identical protocols of MMT or surgical monotherapy. 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC (P=0.004), SCC (P=0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P<0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy (P=0.001); residual disease following MMT versus surgical monotherapy (P=0.008); SCC pCR versus surgical monotherapy (P=0.033). A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25-31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Surveillance and Radiation Therapy for Stage I Seminoma—Have We Learned From the Evidence?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Glaser, Scott M.; Vargo, John A.; Balasubramani, Goundappa K.
2016-01-01
Purpose: To analyze, in the setting of stage I seminoma, the factors affecting adjuvant treatment decisions and resulting survival outcomes, using a national dataset. Methods and Materials: We identified 33,094 stage I seminoma patients after orchiectomy from 1998 to 2012 from the National Cancer Data Base. Factors affecting treatment selection (active surveillance [AS] vs adjuvant treatment [AT]) were identified using a parsimonious multivariate logistic regression model. Propensity scores for treatment decision were generated and incorporated into a multivariate Cox regression analysis of overall survival. This process was then repeated within the AT cohort for factors predictive for chemotherapy [CT] versus radiationmore » therapy [RT]. Results: Only 33% of patients received AS, and 65% received AT (89% RT and 11% CT). From 1998 to 2012 the proportion receiving AS increased from 23% to 60%, whereas RT utilization decreased from 73% to 21%, and CT utilization increased from 2% to 17%. Utilization of low-dose RT increased from 1.5% in 1999 to 34% in 2012. There was a small absolute overall survival advantage to AT over AS at 10 years (95.0% vs 93.4%, propensity adjusted hazard ratio 0.58, P<.0005). Conclusions: There has been a significant increase in use of AS for stage I seminoma, influenced by both sociodemogrpahic and clinicopathologic factors. Between AT options, there has been significant increase in use of CT, mirrored by a decline in use of RT. Although overall survival remains high for all 3 treatment strategies, AT seems to be associated with a small absolute survival advantage over AS up to 10 years out from diagnosis.« less
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Smith, D G; Pearson, R A
2005-11-01
The large fluctuations seen in cattle populations during periods of drought in sub-Saharan Africa are not evident in the donkey population. Donkeys appear to have a survival advantage over cattle that is increasingly recognized by smallholder farmers in their selection of working animals. The donkey's survival advantages arise from both socioeconomic and biological factors. Socioeconomic factors include the maintenance of a low sustainable population of donkeys owing to their single-purpose role and their low social status. Also, because donkeys are not usually used as a meat animal and can provide a regular income as a working animal, they are not slaughtered in response to drought, as are cattle. Donkeys have a range of physiological and behavioural adaptations that individually provide small survival advantages over cattle but collectively may make a large difference to whether or not they survive drought. Donkeys have lower maintenance costs as a result of their size and spend less energy while foraging for food; lower energy costs result in a lower dry matter intake (DMI) requirement. In donkeys, low-quality diets are digested almost as efficiently as in ruminants and, because of a highly selective feeding strategy, the quality of diet obtained by donkeys in a given pasture is higher than that obtained by cattle. Lower energy costs of walking, longer foraging times per day and ability to tolerate thirst may allow donkeys to access more remote, under-utilized sources of forage that are inaccessible to cattle on rangeland. As donkeys become a more popular choice of working animal for farmers, specific management practices need to be devised that allow donkeys to fully maximize their natural survival advantages.
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Casey, Michael Jin; Wen, Xuerong; Rehman, Shehzad; Santos, Alfonso H; Andreoni, Kenneth A
2015-04-01
The OPTN/UNOS Kidney Paired Donation (KPD) Pilot Program allocates priority to zero-HLA mismatches. However, in unrelated living donor kidney transplants (LDKT)-the same donor source in KPD-no study has shown whether zero-HLA mismatches provide any advantage over >0 HLA mismatches. We hypothesize that zero-HLA mismatches among unrelated LDKT do not benefit graft survival. This retrospective SRTR database study analyzed LDKT recipients from 1987 to 2012. Among unrelated LDKT, subjects with zero-HLA mismatches were compared to a 1:1-5 matched (by donor age ±1 year and year of transplantation) control cohort with >0 HLA mismatches. The primary endpoint was death-censored graft survival. Among 32,654 unrelated LDKT recipients, 83 had zero-HLA mismatches and were matched to 407 controls with >0 HLA mismatches. Kaplan-Meier analyses for death-censored graft and patient survival showed no difference between study and control cohorts. In multivariate marginal Cox models, zero-HLA mismatches saw no benefit with death-censored graft survival (HR = 1.46, 95% CI 0.78-2.73) or patient survival (HR = 1.43, 95% CI 0.68-3.01). Our data suggest that in unrelated LDKT, zero-HLA mismatches may not offer any survival advantage. Therefore, particular study of zero-HLA mismatching is needed to validate its place in the OPTN/UNOS KPD Pilot Program allocation algorithm. © 2014 Steunstichting ESOT.
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Ehrlich, Joshua R.; Schwartz, Michael J.; Ng, Casey K.; Kauffman, Eric C.; Scherr, Douglas S.
2009-01-01
Purpose. To date, no study has examined a population-based registry to determine the impact of multiple malignancies on survival of bladder cancer patients. Our experience suggests that bladder cancer patients with multiple malignancies may have relatively positive outcomes. Materials & Methods. We utilized data from the Surveillance Epidemiology and End Results (SEERs) database to examine survival between patients with only bladder cancer (BO) and with bladder cancer and additional cancer(s) antecedent (AB), subsequent (BS), or antecedent and subsequent to bladder cancer (ABS). Results. Analyses demonstrated diminished survival among AB and ABS cohorts. However, when cohorts were substratified by stage, patients in the high-stage BS cohort appeared to have a survival advantage over high-stage BO patients. Conclusions. Bladder cancer patients with multiple malignancies have diminished survival. The survival advantage of high-stage BS patients is likely a statistical phenomenon. Such findings are important to shape future research and to improve our understanding of patients with multiple malignancies. PMID:20069054
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Chahin, Abdullah; Zorzopulos, Jorge; Jobes, David V.; Migdady, Yazan; Yamamoto, Michelle; Parejo, Nicholas; Palardy, John E.; Horn, David L.
2014-01-01
IMT504 is a novel immunomodulatory oligonucleotide that has shown immunotherapeutic properties in early preclinical and clinical studies. IMT504 was tested in a neutropenic rat model of Pseudomonas aeruginosa bacteremia and sepsis. This animal system recapitulates many of the pathological processes found in neutropenic patients with Gram-negative, bacterial infections. The research was conducted in the setting of an academic research laboratory. The test subjects were Sprague-Dawley rats. Animals were rendered neutropenic by administration of cyclophosphamide, colonized with P. aeruginosa by oral feeding, and then randomized to receive IMT504 over a range of doses and treatment regimens representing early and late therapeutic interventions. IMT504 immunotherapy conferred a significant survival advantage over the 12-day study period compared with the results seen with placebo-treated animals when the therapy was administered at the onset of neutropenia and even in the absence of antibiotics and after the onset of fever and systemic infection. Notably, even late salvage IMT504 monotherapy was highly effective (13/14 surviving rats with IMT504 therapy versus 2/14 controls, P = <0.001). Moreover, late salvage IMT504 monotherapy was as effective as antibiotic therapy (13/14 surviving rats versus 21/21 rats, P = 0.88). In addition, no antagonism or loss of therapeutic efficacy was noted with combination therapy of IMT504 plus antibiotics. IMT504 immunotherapy provides a remarkable survival advantage in bacteremia and sepsis in neutropenic animals and deserves further study as a new treatment option in patients with, or at risk for, severe Gram-negative bacterial infections and sepsis. PMID:25512413
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Obesity and the gastrointestinal tract: you are what you eat.
Wolfe, M Michael; Boylan, Michael O
2014-01-01
Obesity represents a complex multifactorial syndrome that develops from interactions among genetic and environmental factors and is a leading cause of illness and death. The prevalence of obesity in the United States has increased dramatically since 1975. Although often ignored, the gastrointestinal tract, and the gastrointestinal regulatory peptides in particular, constitutes an ideal starting point for defining and investigating obesity as it represents the route by which all nutrients are ingested, processed, and absorbed. Another important factor to consider when evaluating the etiology of obesity is the capacity for all animals to store nutrients. Insulin is the most potent anabolic hormone, and it appears to have evolved from the need to maximize energy efficiency, obviating the requirement to continuously forage for food. Organisms expressing this important peptide possessed a distinct survival advantage and flourished. During the course of evolution, insulin biosynthesis translocated from the intestine to pancreatic islets, which necessitated a messenger from the intestine to complete the "enteroinsular axis." The eventual development of glucose-dependent insulinotropic polypeptide (GIP) and other incretins fulfilled this requirement. GIP appears to offer an additional survival benefit by not only stimulating intestinal glucose transport and maximally releasing insulin to facilitate nutrient storage but also by its insulin-mimetic properties, including enhanced uptake of glucose by adipocytes. This physiological redundancy offered by insulin and GIP ensured the survival of organisms during times when food was scarce. As food is no longer scarce, at least in the West, this survival advantage appears to have contributed to the current obesity epidemic.
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Letcher, B.H.; Dubreuil, T.; O'Donnell, M. J.; Obedzinski, M.; Griswold, K.; Nislow, K.H.
2004-01-01
We tested the influence of introduction time and the manner of introduction on growth, survival, and life-history expression of Atlantic salmon (Salmo salar). Introduction treatments included three fry stocking times and stream rearing of embryos. Despite poor growth conditions during the early stocking period, early-stocked fish were larger throughout the entire study period, likely the result of prior residence advantage. This interpretation was reinforced by the laboratory study, where early-stocked fish outgrew late-stocked fish when reared together, but not when they were reared separately. In contrast to growth, abundance of stocked fish was greatest for fish stocked during the middle period, and this stocking group produced the greatest number of smolts. Despite smaller size, survival of stream-incubated fish was generally greater than survival of stocked fish. Introduction timing had a pronounced effect on smolt age but a weak effect on extent of parr maturation. Overall, these observations indicate that small differences (???2 weeks) in introduction time can have long-term effects on size, survival, and life-history expression. Results suggest stabilizing selection on introduction times, mediated by the interaction between prior residence (advantage to fish introduced earlier) and habitat suitability (advantage to fish introduced later). ?? 2004 NRC Canada.
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Staying Alive: Problems of Survival.
ERIC Educational Resources Information Center
Stalheim, Bill
1990-01-01
Presented is an approach to the teaching of biological diversity using the theme of survival. Teaching methods for this approach and the advantages of its use are discussed. A suggested course outline is included. (CW)
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Roberts, Carla; Kean, Leslie; Archer, David; Balkan, Can; Hsu, Lewis L
2005-01-01
Stable mixed chimeric stem cell transplantation in hemoglobinopathies exploits shorter erythroid survival in hemolytic anemias, providing normal donor red blood cells with a competitive survival advantage. This study examined the level of stable mixed chimerism necessary for complete hematological cure of the thalassemic phenotype, using a nonmyeloablative busulfan chemotherapeutic preparation. Thalassemic mice transplanted from congenic wild-type donors developed partial mixed chimerism. Hematologic cure required >80% donor red blood cells and only >13% donor white blood cells. Murine and human transplant results were compared with a math model for survival advantage of donor peripheral blood cells produced by steady-state chimeric marrow.
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2011-01-01
Background Generalisability of longitudinal studies is threatened by issues such as choice of sampling frame, representativeness of the initial sample, and attrition. To determine representativeness, cohorts are often compared with the population of interest at baseline on demographic and health characteristics. This study illustrates the use of relative survival as a tool for assessing generalisability of results from a cohort of older people among whom death is a potential threat to generalisability. Methods The authors used data from the 1921-26 cohort (n = 12,416, aged 70-75 in 1996) of the Australian Longitudinal Study on Women's Health (ALSWH). Vital status was determined by linkage to the National Death Index, and expected deaths were derived using Australian life tables. Relative survival was estimated using observed survival in the cohort divided by expected survival among women of the same age and State or Territory. Results Overall, the ALSWH women showed relative survival 9.5% above the general population. Within States and Territories, the relative survival advantage varied from 6% to 23%. The interval-specific relative survival remained relatively constant over the 12 years (1996-2008) under review, indicating that the survival advantage of the cohort has not diminished over time. Conclusion This study demonstrates that relative survival can be a useful measure of generalisability in a longitudinal study of the health of the general population, particularly when participants are older. PMID:21294918
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Survival advantage in black versus white men with CKD: effect of estimated GFR and case mix.
Kovesdy, Csaba P; Quarles, L Darryl; Lott, Evan H; Lu, Jun Ling; Ma, Jennie Z; Molnar, Miklos Z; Kalantar-Zadeh, Kamyar
2013-08-01
Black dialysis patients have significantly lower mortality compared with white patients, in contradistinction to the higher mortality seen in blacks in the general population. It is unclear whether a similar paradox exists in patients with non-dialysis-dependent chronic kidney disease (CKD), and if it does, what its underlying reasons are. Historical cohort. 518,406 white and 52,402 black male US veterans with non-dialysis-dependent CKD stages 3-5. Black race. We examined overall and CKD stage-specific all-cause mortality using parametric survival models. The effect of sociodemographic characteristics, comorbid conditions, and laboratory characteristics on the observed differences was explored in multivariable models. During a median follow-up of 4.7 years, 172,093 patients died (mortality rate, 71.0 [95% CI, 70.6-71.3] per 1,000 patient-years). Black race was associated with significantly lower crude mortality (HR, 0.95; 95% CI, 0.94-0.97; P < 0.001). The survival advantage was attenuated after adjustment for age (HR, 1.14; 95% CI, 1.12-1.16), but was magnified after full multivariable adjustment (HR, 0.72; 95% CI, 0.70-0.73; P < 0.001). The unadjusted survival advantage of blacks was more prominent in those with more advanced stages of CKD, but CKD stage-specific differences were attenuated by multivariable adjustment. Exclusively male patients. Black patients with CKD have lower mortality compared with white patients. The survival advantage seen in blacks is accentuated in patients with more advanced stages of CKD, which may be explained by changes in case-mix and laboratory characteristics occurring during the course of kidney disease. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.
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Survival Advantage in Black Versus White Men With CKD: Effect of Estimated GFR and Case Mix
Kovesdy, Csaba P.; Quarles, L. Darryl; Lott, Evan H.; Lu, Jun Ling; Ma, Jennie Z.; Molnar, Miklos Z.; Kalantar-Zadeh, Kamyar
2013-01-01
Background Black dialysis patients have significantly lower mortality compared to white patients, in contradistinction to the higher mortality seen in blacks in the general population. It is unclear if a similar paradox exists in non–dialysis-dependent CKD, and if it does, what its underlying reasons are. Study Design Historical cohort. Setting & Participants 518,406 white and 52,402 black male US veterans with non-dialysis dependent CKD stages 3–5. Predictor Black race. Outcomes & Measurements We examined overall and CKD stage-specific all-cause mortality using parametric survival models. The effect of sociodemographic characteristics, comorbidities and laboratory characteristics on the observed differences was explored in multivariable models. Results Over a median follow-up of 4.7 years 172,093 patients died (mortality rate, 71.0 [95% CI, 70.6–71.3] per 1000 patient-years). Black race was associated with significantly lower crude mortality (HR, 0.95; 95% CI, 0.94–0.97; p<0.001). The survival advantage was attenuated after adjustment for age (HR, 1.14; 95% CI, 1.12–1.16), but was even magnified after full multivariable adjustment (HR, 0.72; 95% CI, 0.70–0.73; p<0.001). The unadjusted survival advantage of blacks was more prominent in those with more advanced stages of CKD, but CKD stage-specific differences were attenuated by multivariable adjustment. Limitations Exclusively male patients. Conclusions Black patients with CKD have lower mortality compared to white patients. The survival advantage seen in blacks is accentuated in patients with more advanced stages of CKD, which may be explained by changes in case mix and laboratory characteristics occurring during the course of kidney disease. PMID:23369826
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The obesity paradox and incident cardiovascular disease: A population-based study.
Chang, Virginia W; Langa, Kenneth M; Weir, David; Iwashyna, Theodore J
2017-01-01
Prior work suggests that obesity may confer a survival advantage among persons with cardiovascular disease (CVD). This obesity "paradox" is frequently studied in the context of prevalent disease, a stage in the disease process when confounding from illness-related weight loss and selective survival are especially problematic. Our objective was to examine the association of obesity with mortality among persons with incident CVD, where biases are potentially reduced, and to compare these findings with those based on prevalent disease. We used data from the Health and Retirement Study, an ongoing, nationally representative longitudinal survey of U.S. adults age 50 years and older initiated in 1992 and linked to Medicare claims. Cox proportional hazard models were used to estimate the association between weight status and mortality among persons with specific CVD diagnoses. CVD diagnoses were established by self-reported survey data as well as Medicare claims. Prevalent disease models used concurrent weight status, and incident disease models used pre-diagnosis weight status. We examined myocardial infarction, congestive heart failure, stroke, and ischemic heart disease. A strong and significant obesity paradox was consistently observed in prevalent disease models (hazard of death 18-36% lower for obese class I relative to normal weight), replicating prior findings. However, in incident disease models of the same conditions in the same dataset, there was no evidence of this survival benefit. Findings from models using survey- vs. claims-based diagnoses were largely consistent. We observed an obesity paradox in prevalent CVD, replicating prior findings in a population-based sample with longer-term follow-up. In incident CVD, however, we did not find evidence of a survival advantage for obesity. Our findings do not offer support for reevaluating clinical and public health guidelines in pursuit of a potential obesity paradox.
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Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M; Lipsitch, Marc; Malley, Richard
2007-09-01
The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H(2)O(2)), not LytA, and that the gene responsible for H(2)O(2) production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H(2)O(2) in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing DeltaspxB mutants that do not produce H(2)O(2). Likewise, addition of H(2)O(2) to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While DeltalytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H(2)O(2) has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the DeltaspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization.
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Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M.; Lipsitch, Marc; Malley, Richard
2007-01-01
The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H2O2), not LytA, and that the gene responsible for H2O2 production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H2O2 in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing ΔspxB mutants that do not produce H2O2. Likewise, addition of H2O2 to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While ΔlytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H2O2 has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the ΔspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization. PMID:17631628
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Directed evolution of bacteriorhodopsin for applications in bioelectronics
Wagner, Nicole L.; Greco, Jordan A.; Ranaghan, Matthew J.; Birge, Robert R.
2013-01-01
In nature, biological systems gradually evolve through complex, algorithmic processes involving mutation and differential selection. Evolution has optimized biological macromolecules for a variety of functions to provide a comparative advantage. However, nature does not optimize molecules for use in human-made devices, as it would gain no survival advantage in such cooperation. Recent advancements in genetic engineering, most notably directed evolution, have allowed for the stepwise manipulation of the properties of living organisms, promoting the expansion of protein-based devices in nanotechnology. In this review, we highlight the use of directed evolution to optimize photoactive proteins, with an emphasis on bacteriorhodopsin (BR), for device applications. BR, a highly stable light-activated proton pump, has shown great promise in three-dimensional optical memories, real-time holographic processors and artificial retinas. PMID:23676894
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Aravindan, Sheeja; Natarajan, Mohan; Awasthi, Vibhudutta; Herman, Terence S; Aravindan, Natarajan
2013-01-01
Recently, we demonstrated that radiation (IR) instigates the occurrence of a NFκB-TNFα feedback cycle which sustains persistent NFκB activation in neuroblastoma (NB) cells and favors survival advantage and clonal expansion. Further, we reported that curcumin targets IR-induced survival signaling and NFκB dependent hTERT mediated clonal expansion in human NB cells. Herein, we investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin analog in inhibiting persistent NFκB activation by disrupting the IR-induced NFκB-TNFα-NFκB feedback signaling in NB and subsequent mitigation of survival advantage and clonal expansion. EF24 profoundly suppressed the IR-induced NFκB-DNA binding activity/promoter activation and, maintained the NFκB repression by deterring NFκB-dependent TNFα transactivation/intercellular secretion in genetically varied human NB (SH-SY5Y, IMR-32, SK-PN-DW, MC-IXC and SK-N-MC) cell types. Further, EF24 completely suppressed IR-induced NFκB-TNFα cross-signaling dependent transactivation/translation of pro-survival IAP1, IAP2 and Survivin and subsequent cell survival. In corroboration, EF24 treatment maximally blocked IR-induced NFκB dependent hTERT transactivation/promoter activation, telomerase activation and consequent clonal expansion. EF24 displayed significant regulation of IR-induced feedback dependent NFκB and NFκB mediated survival signaling and complete regression of NB xenograft. Together, the results demonstrate for the first time that, novel synthetic monoketone EF24 potentiates radiotherapy and mitigates NB progression by selectively targeting IR-triggered NFκB-dependent TNFα-NFκB cross-signaling maintained NFκB mediated survival advantage and clonal expansion.
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Aravindan, Sheeja; Natarajan, Mohan; Awasthi, Vibhudutta; Herman, Terence S.; Aravindan, Natarajan
2013-01-01
Recently, we demonstrated that radiation (IR) instigates the occurrence of a NFκB-TNFα feedback cycle which sustains persistent NFκB activation in neuroblastoma (NB) cells and favors survival advantage and clonal expansion. Further, we reported that curcumin targets IR-induced survival signaling and NFκB dependent hTERT mediated clonal expansion in human NB cells. Herein, we investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin analog in inhibiting persistent NFκB activation by disrupting the IR-induced NFκB-TNFα-NFκB feedback signaling in NB and subsequent mitigation of survival advantage and clonal expansion. EF24 profoundly suppressed the IR-induced NFκB-DNA binding activity/promoter activation and, maintained the NFκB repression by deterring NFκB-dependent TNFα transactivation/intercellular secretion in genetically varied human NB (SH-SY5Y, IMR-32, SK–PN–DW, MC-IXC and SK–N-MC) cell types. Further, EF24 completely suppressed IR-induced NFκB-TNFα cross-signaling dependent transactivation/translation of pro-survival IAP1, IAP2 and Survivin and subsequent cell survival. In corroboration, EF24 treatment maximally blocked IR-induced NFκB dependent hTERT transactivation/promoter activation, telomerase activation and consequent clonal expansion. EF24 displayed significant regulation of IR-induced feedback dependent NFκB and NFκB mediated survival signaling and complete regression of NB xenograft. Together, the results demonstrate for the first time that, novel synthetic monoketone EF24 potentiates radiotherapy and mitigates NB progression by selectively targeting IR-triggered NFκB-dependent TNFα-NFκB cross-signaling maintained NFκB mediated survival advantage and clonal expansion. PMID:23967300
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Salamo, Oriana; Roghaee, Shiva; Schweitzer, Michael D; Mantero, Alejandro; Shafazand, Shirin; Campos, Michael; Mirsaeidi, Mehdi
2018-05-03
Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005-2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p < 0.001, Log-rank test). In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.
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Family-witnessed cardiopulmonary resuscitation.
Kidby, John
How nurses care for patients who have a cardiac arrest and for their family members who witness it has been identified as being paramount in determining relatives' acceptance of death and their ability to cope thereafter. In this article the author analyses the available literature, focuses on the advantages and disadvantages of families being present during cardiopulmonary resuscitation (CPR) in hospital and questions what effect this has on the grieving process (Kübler-Ross 1970). Nurses should take into account the views of relatives, although attempted resuscitation should never be compromised by family members being present. Evidence suggests that it can improve the grieving process for families and be helpful to patients who survive.
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The main factor affecting the competitiveness of Contractor Company
NASA Astrophysics Data System (ADS)
Nurisra; Malahayati, Nurul; Mahmuddin
2018-05-01
Contractor companies must have the competitive advantage to compete in maintaining the survival of the company. Problems arise because quite a lot of advantages can be used and these advantages must be used appropriately to produce competitiveness for the company to continue to compete and to win the competition. This study aims to determine the main factors affecting the competitiveness of medium-class contractors in Banda Aceh. Data collection was obtained through questionnaires distributed to 31 middle-class contractors in Banda Aceh. Data processing and analysis is done by using descriptive analysis. Based on the result of descriptive analysis, it can be concluded that the most important competitiveness factor with a mean score value 4.52 is the relationship, and the factor that has the highest mean score value is the relationship with the government of 4.97, while the result of the ranking analysis is obtained 25 factor that is critical to the competitiveness of medium-class contractors in Banda Aceh.
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Evanescent field refractometry in planar optical fiber.
Holmes, Christopher; Jantzen, Alexander; Gray, Alan C; Gow, Paul C; Carpenter, Lewis G; Bannerman, Rex H S; Gates, James C; Smith, Peter G R
2018-02-15
This Letter demonstrates a refractometer in integrated optical fiber, a new optical platform that planarizes fiber using flame hydrolysis deposition (FHD). The unique advantage of the technology is survivability in harsh environments. The platform is mechanically robust, and can survive elevated temperatures approaching 1000°C and exposure to common solvents, including acetone, gasoline, and methanol. For the demonstrated refractometer, fabrication was achieved through wet etching an SMF-28 fiber to a diameter of 8 μm before FHD planarization. An external refractive index was monitored using fiber Bragg gratings (FBGs), written into the core of the planarized fiber. A direct comparison to alternative FBG refractometers is made, for which the developed platform is shown to have comparable sensitivity, with the added advantage of survivability in harsh environments.
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Post-traumatic stress disorder: the neurobiological impact of psychological trauma
Sherin, Jonathan E.; Nemeroff, Charles B.
2011-01-01
The classic fight-or-flight response to perceived threat is a reflexive nervous phenomenon thai has obvious survival advantages in evolutionary terms. However, the systems that organize the constellation of reflexive survival behaviors following exposure to perceived threat can under some circumstances become dysregulated in the process. Chronic dysregulation of these systems can lead to functional impairment in certain individuals who become “psychologically traumatized” and suffer from post-traumatic stress disorder (PTSD), A body of data accumulated over several decades has demonstrated neurobiological abnormalities in PTSD patients. Some of these findings offer insight into the pathophysiology of PTSD as well as the biological vulnerability of certain populations to develop PTSD, Several pathological features found in PTSD patients overlap with features found in patients with traumatic brain injury paralleling the shared signs and symptoms of these clinical syndromes. PMID:22034143
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Patel, Manali I.; Schupp, Clayton W.; Gomez, Scarlett L.; Chang, Ellen T.; Wakelee, Heather A.
2013-01-01
Purpose Hispanics in the United States have lower age-adjusted mortality resulting from non–small-cell lung cancer (NSCLC) compared with non-Hispanic whites (NHWs). The purpose of this study was to evaluate individual, clinical, and neighborhood factors in survival among Hispanics with NSCLC. Patients and Methods We performed a retrospective analysis of NHWs and Hispanics with NSCLC between 1998 and 2007 in the California Cancer Registry (follow-up to December 2009). Kaplan-Meier curves depict survival by nativity for Hispanics with NSCLC. Cox proportional hazards models estimated hazard of mortality by race with adjustment for individual (age, sex, marital status), clinical (histologic grade, surgery, irradiation, chemotherapy), and neighborhood factors (neighborhood socioeconomic status, ethnic enclave). Results We included 14,280 Hispanic patients with NSCLC. Foreign-born Hispanics had 15% decreased risk of disease-specific mortality resulting from NSCLC compared with NHWs (hazard ratio [HR], 0.85; 95% CI, 0.83 to 0.88) after adjustment for individual, clinical, and neighborhood factors. After adjustment for individual factors, compared with US-born Hispanics, foreign-born Hispanics had 10% decreased risk of disease-specific mortality (HR, 0.90; 95% CI, 0.87 to 0.96). Clinical and neighborhood factors slightly moderated the survival benefit for foreign-born patients. A modestly more pronounced survival advantage was seen for foreign-born Hispanics living in low socioeconomic and high Hispanic enclave neighborhoods as compared with US-born Hispanics (HR, 0.86; 95% CI, 0.81 to 0.90). Conclusion Foreign-born Hispanics with NSCLC have a decreased risk of disease-specific mortality compared with NHWs and US-born Hispanics with NSCLC. Neighborhood factors slightly moderate this survival advantage. This survival advantage is slightly more pronounced in lower socioeconomic and higher Hispanic enclave neighborhoods. PMID:23960183
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Matrix metalloproteinase inhibitors as anticancer agents.
Konstantinopoulos, Panagiotis A; Karamouzis, Michalis V; Papatsoris, Athanasios G; Papavassiliou, Athanasios G
2008-01-01
The important role of matrix metalloproteinases (MMPs) in the process of carcinogenesis is well established. However, despite very promising activity in a plethora of preclinical models, MMP inhibitors (MMPIs) failed to demonstrate a statistically significant survival advantage in advanced stage clinical trials in most human malignancies. Herein, we review the implication of MMPs in carcinogenesis, outline the pharmacology and current status of various MMPIs as anticancer agents and discuss the etiologies for the discrepancy between their preclinical and clinical evaluation. Finally, strategies for effective incorporation of MMPIs in current anticancer therapies are proposed.
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Encounter with mesoscale eddies enhances survival to settlement in larval coral reef fishes
Shulzitski, Kathryn; Sponaugle, Su; Hauff, Martha; Walter, Kristen D.; Cowen, Robert K.
2016-01-01
Oceanographic features, such as eddies and fronts, enhance and concentrate productivity, generating high-quality patches that dispersive marine larvae may encounter in the plankton. Although broad-scale movement of larvae associated with these features can be captured in biophysical models, direct evidence of processes influencing survival within them, and subsequent effects on population replenishment, are unknown. We sequentially sampled cohorts of coral reef fishes in the plankton and nearshore juvenile habitats in the Straits of Florida and used otolith microstructure analysis to compare growth and size-at-age of larvae collected inside and outside of mesoscale eddies to those that survived to settlement. Larval habitat altered patterns of growth and selective mortality: Thalassoma bifasciatum and Cryptotomus roseus that encountered eddies in the plankton grew faster than larvae outside of eddies and likely experienced higher survival to settlement. During warm periods, T. bifasciatum residing outside of eddies in the oligotrophic Florida Current experienced high mortality and only the slowest growers survived early larval life. Such slow growth is advantageous in nutrient poor habitats when warm temperatures increase metabolic demands but is insufficient for survival beyond the larval stage because only fast-growing larvae successfully settled to reefs. Because larvae arriving to the Straits of Florida from distant sources must spend long periods of time outside of eddies, our results indicate that they have a survival disadvantage. High productivity features such as eddies not only enhance the survival of pelagic larvae, but also potentially increase the contribution of locally spawned larvae to reef populations. PMID:27274058
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Multipartite nonlocality distillation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hsu, Li-Yi; Wu, Keng-Shuo
2010-11-15
The stronger nonlocality than that allowed in quantum theory can provide an advantage in information processing and computation. Since quantum entanglement is distillable, can nonlocality be distilled in the nonsignalling condition? The answer is positive in the bipartite case. In this article the distillability of the multipartite nonlocality is investigated. We propose a distillation protocol solely exploiting xor operations on output bits. The probability-distribution vectors and matrix are introduced to tackle the correlators. It is shown that only the correlators with extreme values can survive the distillation process. As the main result, the amplified nonlocality cannot maximally violate any Bell-typemore » inequality. Accordingly, a distillability criterion in the postquantum region is proposed.« less
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Under multilevel selection: "when shall you be neither spiteful nor envious?".
Garay, József; Csiszár, Villő; Móri, Tamás F
2014-01-07
In this paper, we study the egalitarianism-game in multilevel selection situation. The individuals form reproductive groups. In each group, an egalitarianism-game determines the number of juveniles of different phenotypes (spiteful, envious, neutral and donator). Before the juveniles form the next reproductive group, they have to survive either predators' attacks or a fight between two groups. We adopt the ESS definition of Maynard Smith to multilevel selection. Based on the "group size advantage" assumption (which claims that each juvenile's survival rate depends on the size of his own group, supposing that either the survival rate under predators' attacks is higher in larger groups, or in inter-group aggression usually the larger group wins) we found that when the survival probability has a massive effect on the average fitness, then "group fitness maximizing behavior" (in our case, either neutral or donator) has evolutionary advantage over "competitive behavior" (in our case, either spiteful or envious). © 2013 Elsevier Ltd. All rights reserved.
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Chen, Yun-Lin; Lin, Tiao; Liu, An; Shi, Ming-Min; Hu, Bin; Shi, Zhong-Li; Yan, Shi-Gui
2015-01-28
There are some arguments between the use of hydroxyapatite and porous coating. Some studies have shown that there is no difference between these two coatings in total hip arthroplasty (THA), while several other studies have shown that hydroxyapatite has advantages over the porous one. We have collected the studies in Pubmed, MEDLINE, EMBASE, and the Cochrane library from the earliest possible years to present, with the search strategy of "(HA OR hydroxyapatite) AND ((total hip arthroplasty) OR (total hip replacement)) AND (RCT* OR randomiz* OR control* OR compar* OR trial*)". The randomized controlled trials and comparative observation trials that evaluated the clinical and radiographic effects between hydroxyapatite coating and porous coating were included. Our main outcome measurements were Harris hip score (HHS) and survival, while the secondary outcome measurements were osteolysis, radiolucent lines, and polyethylene wear. Twelve RCTs and 9 comparative observation trials were included. Hydroxyapatite coating could improve the HHS (p < 0.01), reduce the incidence of thigh pain (p = 0.01), and reduce the incidence of femoral osteolysis (p = 0.01), but hydroxyapatite coating had no advantages on survival (p = 0.32), polyethylene wear (p = 0.08), and radiolucent lines (p = 0.78). Hydroxyapatite coating has shown to have an advantage over porous coating. The HHS and survival was duration-dependent-if given the sufficient duration of follow-up, hydroxyapatite coating would be better than porous coating for the survival. The properties of hydroxyapatite and the implant design had influence on thigh pain incidence, femoral osteolysis, and polyethylene wear. Thickness of 50 to 80 μm and purity larger than 90% increased the thigh pain incidence. Anatomic design had less polyethylene wear.
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The time course of attentional modulation on emotional conflict processing.
Zhou, Pingyan; Yang, Guochun; Nan, Weizhi; Liu, Xun
2016-01-01
Cognitive conflict resolution is critical to human survival in a rapidly changing environment. However, emotional conflict processing seems to be particularly important for human interactions. This study examined whether the time course of attentional modulation on emotional conflict processing was different from cognitive conflict processing during a flanker task. Results showed that emotional N200 and P300 effects, similar to colour conflict processing, appeared only during the relevant task. However, the emotional N200 effect preceded the colour N200 effect, indicating that emotional conflict can be identified earlier than cognitive conflict. Additionally, a significant emotional N100 effect revealed that emotional valence differences could be perceived during early processing based on rough aspects of input. The present data suggest that emotional conflict processing is modulated by top-down attention, similar to cognitive conflict processing (reflected by N200 and P300 effects). However, emotional conflict processing seems to have more time advantages during two different processing stages.
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Survival of female Lesser Scaup: Effects of body size, age, and reproductive effort
Rotella, J.J.; Clark, R.G.; Afton, A.D.
2003-01-01
In birds, larger females generally have greater breeding propensity, reproductive investment, and success than do smaller females. However, optimal female body size also depends on how natural selection acts during other parts of the life cycle. Larger female Lesser Scaup (Aythya affinis) produce larger eggs than do smaller females, and ducklings from larger eggs survive better than those hatching from smaller eggs. Accordingly, we examined patterns of apparent annual survival for female scaup and tested whether natural selection on female body size primarily was stabilizing, a frequent assumption in studies of sexually dimorphic species in which males are the larger sex, or was directional, counter-acting reproductive advantages of large size. We estimated survival using mark-recapture methods for individually marked females from two study sites in Canada (Erickson, Manitoba; St. Denis, Saskatchewan). Structurally larger (adults) and heavier (ducklings) females had lower survival than did smaller individuals in Manitoba; no relationship was detected in adults from Saskatchewan. Survival of adult females declined with indices of increasing reproductive effort at both sites; consequently, the cost of reproduction could explain age-related patterns of breeding propensity in scaup. Furthermore, if larger females are more likely to breed than are smaller females, then cost of reproduction also may help explain why survival was lower for larger females. Overall, we found that advantages of large body size of female scaup during breeding or as young ducklings apparently were counteracted by natural selection favoring lightweight juveniles and structurally smaller adult females through higher annual survival.
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Nanotechnology for the detection and kill of circulating tumor cells
NASA Astrophysics Data System (ADS)
Gao, Yang; Yuan, Zhou
2014-09-01
Circulating tumor cells (CTCs) represent a surrogate biomarker of hematogenous metastases and thus could be considered as a `liquid biopsy' which reveals metastasis in action. But it is absolutely a challenge to detect CTCs due to their extreme rarity. At present, the most common principle is to take advantage of the epithelial surface markers of CTCs which attach to a specific antibody. Antibody-magnetic nanobeads combine with the epithelial surface markers, and then the compound is processed by washing, separation, and detection. However, a proportion of CTC antigen expressions are down-regulated or lost in the process of epithelial-mesenchymal transition (EMT), and thus, this part of CTCs cannot be detected by classical detection methods such as CellSearch. To resolve this problem, some multiple-marker CTC detections have been developed rapidly. Additionally, nanotechnology is a promising approach to kill CTCs with high efficiency. Implantable nanotubes coated with apoptosis-promoting molecules improve the disease-free survival and overall survival. The review introduces some novel CTC detection techniques and therapeutic methods by virtue of nanotechnology to provide a better knowledge of the progress about CTC study.
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Longevity of outstanding sporting achievers: Mind versus muscle
Smerdon, David C.; Clarke, Philip M.
2018-01-01
Background While there is strong evidence showing the survival advantage of elite athletes, much less is known about those engaged in mind sports such as chess. This study aimed to examine the overall as well as regional survival of International Chess Grandmasters (GMs) with a reference to the general population, and compare relative survival (RS) of GMs with that of Olympic medallists (OMs). Methods Information on 1,208 GMs and 15,157 OMs, respectively, from 28 countries were extracted from the publicly available data sources. The Kaplan-Meier method was used to estimate the survival rates of the GMs. A Cox proportional hazards model was used to adjust the survival for region, year at risk, age at risk and sex, and to estimate the life expectancy of the GMs. The RS rate was computed by matching each GM or OM by year at risk, age at risk and sex to the life table of the country the individual represented. Results The survival rates of GMs at 30 and 60 years since GM title achievement were 87% and 15%, respectively. The life expectancy of GMs at the age of 30 years (which is near the average age when they attained a GM title) was 53.6 ([95% CI]: 47.7–58.5) years, which is significantly greater than the overall weighted mean life expectancy of 45.9 years for the general population. Compared to Eastern Europe, GMs in North America (HR [95% CI]: 0.51 [0.29–0.88]) and Western Europe (HR [95% CI]: 0.53 [0.34–0.83]) had a longer lifespan. The RS analysis showed that both GMs and OMs had a significant survival advantage over the general population, and there was no statistically significant difference in the RS of GMs (RS [95% CI]: 1.14 [1.08–1.20]) compared to OMs: (RS [95% CI]: 1.09 [1.07–1.11]) at 30 years. Conclusion Elite chess players live longer than the general population and have a similar survival advantage to elite competitors in physical sports. PMID:29723296
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McNeely, Christian A; Vassileva, Christina M
2015-01-01
The short-term advantage of mitral valve repair versus replacement for degenerative disease has been extensively documented. These advantages include lower operative mortality, improved survival, better preservation of left-ventricular function, shorter post-operative hospital stay, lower total costs, and fewer valve-related complications, including thromboembolism, anticoagulation-related bleeding events and late prosthetic dysfunction. More recent written data are available indicating the long-term advantage of repair versus replacement. While at some institutions, the repair rate for degenerative disease may exceed 90%, the national average in 2007 was only 69%. Making direct comparisons between mitral valve repair and replacement using the available studies does present some challenges however, as there are often differences in baseline characteristics between patient groups as well as other dissimilarities between studies. The purpose of this review is to systematically summarize the long-term survival and reoperation data of mitral valve repair versus replacement for degenerative disease. A PubMed search was done and resulted in 12 studies that met our study criteria for comparing mitral valve repair versus replacement for degenerative disease. A systematic review was then conducted abstracting survival and reoperation data. PMID:25158683
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Powell, J T; Sweeting, M J; Ulug, P; Blankensteijn, J D; Lederle, F A; Becquemin, J-P; Greenhalgh, R M
2017-02-01
The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575. © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.
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The obesity paradox and incident cardiovascular disease: A population-based study
Langa, Kenneth M.; Weir, David; Iwashyna, Theodore J.
2017-01-01
Background Prior work suggests that obesity may confer a survival advantage among persons with cardiovascular disease (CVD). This obesity “paradox” is frequently studied in the context of prevalent disease, a stage in the disease process when confounding from illness-related weight loss and selective survival are especially problematic. Our objective was to examine the association of obesity with mortality among persons with incident CVD, where biases are potentially reduced, and to compare these findings with those based on prevalent disease. Methods We used data from the Health and Retirement Study, an ongoing, nationally representative longitudinal survey of U.S. adults age 50 years and older initiated in 1992 and linked to Medicare claims. Cox proportional hazard models were used to estimate the association between weight status and mortality among persons with specific CVD diagnoses. CVD diagnoses were established by self-reported survey data as well as Medicare claims. Prevalent disease models used concurrent weight status, and incident disease models used pre-diagnosis weight status. Results We examined myocardial infarction, congestive heart failure, stroke, and ischemic heart disease. A strong and significant obesity paradox was consistently observed in prevalent disease models (hazard of death 18–36% lower for obese class I relative to normal weight), replicating prior findings. However, in incident disease models of the same conditions in the same dataset, there was no evidence of this survival benefit. Findings from models using survey- vs. claims-based diagnoses were largely consistent. Conclusion We observed an obesity paradox in prevalent CVD, replicating prior findings in a population-based sample with longer-term follow-up. In incident CVD, however, we did not find evidence of a survival advantage for obesity. Our findings do not offer support for reevaluating clinical and public health guidelines in pursuit of a potential obesity paradox. PMID:29216243
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2012-01-01
Background We examined the mediating effects of health insurance on poverty-colon cancer care and survival relationships and the moderating effects of poverty on health insurance-colon cancer care and survival relationships among women and men in California. Methods We analyzed registry data for 3,291 women and 3,009 men diagnosed with colon cancer between 1996 and 2000 and followed until 2011 on lymph node investigation, stage at diagnosis, surgery, chemotherapy, wait times and survival. We obtained socioeconomic data for individual residences from the 2000 census to categorize the following neighborhoods: high poverty (30% or more poor), middle poverty (5-29% poor) and low poverty (less than 5% poor). Primary health insurers were Medicaid, Medicare, private or none. Results Evidence of mediation was observed for women, but not for men. For women, the apparent effect of poverty disappeared in the presence of payer, and the effects of all forms of health insurance seemed strengthened. All were advantaged on 6-year survival compared to the uninsured: Medicaid (RR = 1.83), Medicare (RR = 1.92) and private (RR = 1.83). Evidence of moderation was also only observed for women. The effects of all forms of health insurance were stronger for women in low poverty neighborhoods: Medicaid (RR = 2.90), Medicare (RR = 2.91) and private (RR = 2.60). For men, only main effects of poverty and payers were observed, the advantaging effect of private insurance being largest. Across colon cancer care processes, Medicare seemed most instrumental for women, private payers for men. Conclusions Health insurance substantially mediates the quality of colon cancer care and poverty seems to make the effects of being uninsured or underinsured even worse, especially among women in the United States. These findings are consistent with the theory that more facilitative social and economic capital is available in more affluent neighborhoods, where women with colon cancer may be better able to absorb the indirect and direct, but uncovered, costs of care. PMID:23092403
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A general model for the scaling of offspring size and adult size.
Falster, Daniel S; Moles, Angela T; Westoby, Mark
2008-09-01
Understanding evolutionary coordination among different life-history traits is a key challenge for ecology and evolution. Here we develop a general quantitative model predicting how offspring size should scale with adult size by combining a simple model for life-history evolution with a frequency-dependent survivorship model. The key innovation is that larger offspring are afforded three different advantages during ontogeny: higher survivorship per time, a shortened juvenile phase, and advantage during size-competitive growth. In this model, it turns out that size-asymmetric advantage during competition is the factor driving evolution toward larger offspring sizes. For simplified and limiting cases, the model is shown to produce the same predictions as the previously existing theory on which it is founded. The explicit treatment of different survival advantages has biologically important new effects, mainly through an interaction between total maternal investment in reproduction and the duration of competitive growth. This goes on to explain alternative allometries between log offspring size and log adult size, as observed in mammals (slope = 0.95) and plants (slope = 0.54). Further, it suggests how these differences relate quantitatively to specific biological processes during recruitment. In these ways, the model generalizes across previous theory and provides explanations for some differences between major taxa.
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Moulder, David E; Hatoum, Diana; Tay, Enoch; Lin, Yiguang; McGowan, Eileen M
2018-06-08
Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance. The tumor suppressor protein p53 is emerging as a key regulator of metabolic processes and metabolic reprogramming in cancer cells—balancing the pendulum between cell death and survival. This review provides an overview of the classical and emerging non-classical tumor suppressor roles of p53 in regulating mitochondrial dynamics: mitochondrial engagement in cell death processes in the prevention of cancer. On the other hand, we discuss p53 as a key metabolic switch in cellular function and survival. The focus is then on the conceivable roles of p53 in breast cancer metabolism. Understanding the metabolic functions of p53 within breast cancer metabolism will, in due course, reveal critical metabolic hotspots that cancers advantageously re-engineer for sustenance. Illustration of these events will pave the way for finding novel therapeutics that target cancer metabolism and serve to overcome the breast cancer burden.
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NASA Astrophysics Data System (ADS)
Calleri, Daniel V.; Rosengaus, Rebeca B.; Traniello, James F. A.
2005-06-01
To determine the impact of inbreeding and outbreeding on disease resistance and survival during colony foundation, nestmate (NM) and non-nestmate (NON) primary reproductives of the dampwood termite Zootermopsis angusticollis were exposed to a single or double dose of conidia of the entomopathogenic fungus Metarhizium anisopliae. Male and female primary reproductive pairs originating from the same parent colony had higher survivorship than NON pairs in control and conidia-exposure treatments. The survival advantage of NM primary reproductives increased with the intensity of pathogen challenge and was significantly greater in the single- and double-dose treatments than in the controls. Although NM pairs had significantly lower mortality than NON pairs, the survivorship of colonies stabilized as they matured and inbred and outbred colonies did not differ in offspring production. These results demonstrate that colony foundation by NON male and female reproductives may have a disease-related survival cost during this critical phase of their life cycle. There may also be a cost associated with lower offspring heterozygosity, but in the first generation this does not appear to significantly impact colony growth.
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Schupp, Clayton W; Press, David J; Gomez, Scarlett Lin
2014-05-01
Hispanics are more likely than other racial/ethnic groups in the United States to be diagnosed with later stage of prostate cancer, yet they have lower prostate cancer mortality rates. The authors evaluated the impact of nativity and neighborhood-level Hispanic ethnic enclave on prostate cancer survival among Hispanics. A total of 35,427 Hispanic men diagnosed with invasive prostate cancer from 1995 through 2008 in the California Cancer Registry were studied; vital status data were available through 2010. Block group-level neighborhood measures were developed from US Census data. Stage-stratified Cox proportional hazards models were used to assess the effect of nativity and ethnic enclave on prostate cancer survival. In models adjusted for neighborhood socioeconomic status and other individual factors, foreign-born Hispanics were found to have a significantly lower risk of prostate cancer survival (hazards ratio [HR], 0.81; 95% confidence interval [95% CI], 0.75-0.87). Living in an ethnic enclave appeared to modify this effect, with the survival advantage slightly more pronounced in the high ethnic enclave neighborhoods (HR, 0.78; 95% CI, 0.71-0.86) compared with low ethnic enclave neighborhoods (HR, 0.86; 95% CI, 0.76-0.98). Despite lower socioeconomic status, Hispanic immigrants have better survival after prostate cancer than US-born Hispanics and this pattern was more striking among those living in ethnic enclaves. Identifying the modifiable individual and neighborhood-level factors that facilitate this survival advantage in Hispanic immigrants may help to inform specific interventions to improve survival among all patients. © 2014 American Cancer Society.
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Immigration Factors and Prostate Cancer Survival Among Hispanic Men in California
Schupp, Clayton W.; Press, David J.; Gomez, Scarlett Lin
2017-01-01
BACKGROUND Hispanics are more likely than other racial/ethnic groups in the United States to be diagnosed with later stage of prostate cancer, yet they have lower prostate cancer mortality rates. The authors evaluated the impact of nativity and neighborhood-level Hispanic ethnic enclave on prostate cancer survival among Hispanics. METHODS A total of 35,427 Hispanic men diagnosed with invasive prostate cancer from 1995 through 2008 in the California Cancer Registry were studied; vital status data were available through 2010. Block group-level neighborhood measures were developed from US Census data. Stage-stratified Cox proportional hazards models were used to assess the effect of nativity and ethnic enclave on prostate cancer survival. RESULTS In models adjusted for neighborhood socioeconomic status and other individual factors, foreign-born Hispanics were found to have a significantly lower risk of prostate cancer survival (hazards ratio [HR], 0.81; 95% confidence interval [95% CI], 0.75–0.87). Living in an ethnic enclave appeared to modify this effect, with the survival advantage slightly more pronounced in the high ethnic enclave neighborhoods (HR, 0.78; 95% CI, 0.71–0.86) compared with low ethnic enclave neighborhoods (HR, 0.86; 95% CI, 0.76–0.98). CONCLUSIONS Despite lower socioeconomic status, Hispanic immigrants have better survival after prostate cancer than US-born Hispanics and this pattern was more striking among those living in ethnic enclaves. Identifying the modifiable individual and neighborhood-level factors that facilitate this survival advantage in Hispanic immigrants may help to inform specific interventions to improve survival among all patients. PMID:24477988
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Loss of DNA mismatch repair imparts a selective advantage in planarian adult stem cells.
Hollenbach, Jessica P; Resch, Alissa M; Palakodeti, Dasaradhi; Graveley, Brenton R; Heinen, Christopher D
2011-01-01
Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.
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Loss of DNA Mismatch Repair Imparts a Selective Advantage in Planarian Adult Stem Cells
Hollenbach, Jessica P.; Resch, Alissa M.; Palakodeti, Dasaradhi; Graveley, Brenton R.; Heinen, Christopher D.
2011-01-01
Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis. PMID:21747960
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Stephenson, Anne L; Sykes, Jenna; Stanojevic, Sanja; Quon, Bradley S; Marshall, Bruce C; Petren, Kristofer; Ostrenga, Josh; Fink, Aliza K; Elbert, Alexander; Goss, Christopher H
2017-04-18
In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States. Population-based study. 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers. Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013. Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival. Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status. Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results. Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage. U.S. Cystic Fibrosis Foundation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ando, Seiichiro, E-mail: andosei78102@biscuit.ocn.ne.jp; Amano, Hirofumi; Amano, Eri
2010-04-09
FTY720 is a novel investigational agent targeting the sphingosine 1-phosphate (S1P) receptors with an ability to cause immunosuppression by inducing lymphocyte sequestration in lymphoid organs. Systemic lupus erythematosus (SLE) is refractory autoimmune disease characterized by the production of a wide variety of autoantibodies and immune complex (IC)-mediated lupus nephritis. Among several SLE-prone strains of mice, BXSB is unique in terms of the disease-associated monocytosis in periphery and the reduced frequency of marginal zone B (MZ B) cells in spleen. In the present study, we examined the effect of FTY720 on lupus nephritis of BXSB mice. FTY720 treatment resulted in amore » marked decrease in lymphocytes, but not monocytes, in peripheral blood, and caused relocalization of marginal zone B (MZ B) cells into the follicle in the spleen. These changes did not affect the production of autoantibodies, thus IgG and C3 were deposited in glomeruli in FTY720-treated mice. Despite these IC depositions, FTY720-treated mice showed survival advantage with the improved proteinuria. Histological analysis revealed that FTY720 suppressed mesangial cell proliferation and inflammatory cell infiltration. These results suggest that FTY720 ameliorates lupus nephritis by inhibiting the end-stage inflammatory process following IC deposition in glomeruli.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sperduto, Paul W., E-mail: psperduto@mropa.com; Shanley, Ryan; Luo, Xianghua
2014-11-01
Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPAmore » are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less
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Sperduto, Paul W.; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh
2015-01-01
Purpose Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. Results The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P = .05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. PMID:25304947
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Sperduto, Paul W; Shanley, Ryan; Luo, Xianghua; Andrews, David; Werner-Wasik, Maria; Valicenti, Richard; Bahary, Jean-Paul; Souhami, Luis; Won, Minhee; Mehta, Minesh
2014-11-01
Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool (brainmetgpa.com) simplified GPA use. The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the number of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
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Bacteria survival probability in bactericidal filter paper.
Mansur-Azzam, Nura; Hosseinidoust, Zeinab; Woo, Su Gyeong; Vyhnalkova, Renata; Eisenberg, Adi; van de Ven, Theo G M
2014-05-01
Bactericidal filter papers offer the simplicity of gravity filtration to simultaneously eradicate microbial contaminants and particulates. We previously detailed the development of biocidal block copolymer micelles that could be immobilized on a filter paper to actively eradicate bacteria. Despite the many advantages offered by this system, its widespread use is hindered by its unknown mechanism of action which can result in non-reproducible outcomes. In this work, we sought to investigate the mechanism by which a certain percentage of Escherichia coli cells survived when passing through the bactericidal filter paper. Through the process of elimination, the possibility that the bacterial survival probability was controlled by the initial bacterial load or the existence of resistant sub-populations of E. coli was dismissed. It was observed that increasing the thickness or the number of layers of the filter significantly decreased bacterial survival probability for the biocidal filter paper but did not affect the efficiency of the blank filter paper (no biocide). The survival probability of bacteria passing through the antibacterial filter paper appeared to depend strongly on the number of collision between each bacterium and the biocide-loaded micelles. It was thus hypothesized that during each collision a certain number of biocide molecules were directly transferred from the hydrophobic core of the micelle to the bacterial lipid bilayer membrane. Therefore, each bacterium must encounter a certain number of collisions to take up enough biocide to kill the cell and cells that do not undergo the threshold number of collisions are expected to survive. Copyright © 2014 Elsevier B.V. All rights reserved.
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2008-01-01
required soldiers to traverse knee to neck deep 14°C water. Recently, the proliferation of wilderness activities such as mountain climbing, backcountry...Red Cross Cold Water Survival Curves (Figure 2). While useful as a “ rule of thumb” estimate of hypothermia survival, models such as Molnar’s [8] are...low body fat (e.g. body builders) are an exception to this rule . The advantage of having a little more mass can be demonstrated by CESM by
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Lowery, William J; Stany, Michael P; Phippen, Neil T; Bunch, Kristen P; Oliver, Kate E; Tian, Chunqiao; Maxwell, G Larry; Darcy, Kathleen M; Hamilton, Chad A
2015-02-01
Marriage confers a survival advantage for many cancers but has yet to be evaluated in uterine cancer patients. We sought to determine whether uterine cancer survival varied by self-reported relationship status. Data were downloaded from the Surveillance, Epidemiology, and End Results program for women diagnosed with uterine cancer (between 1991 and 2010 in nine geographic regions). Patients with complete clinical data for analysis were categorized as married, single, widowed or other (divorced or separated). Differences in distributions were evaluated using Chi-square, exact and/or Mantel-Haenszel test. Uterine cancer survival was analyzed by Kaplan-Meier method with log-rank test and multivariate Cox regression analysis. Of 47,420 eligible patients, 56% were married, 15% were single and 19% were widows. Married vs. non-married women had a higher likelihood of having low risk (grade 1/2 endometrioid) endometrial cancer and local disease (p<0.0001), and a reduced risk of cancer death (HR=0.8, 95% CI=0.77-0.84). Multivariate evaluation of uterine cancer survival by relationship type indicated that widows consistently had significantly worse uterine cancer survival than single, married and other women in all patients and subset analyses (p<0.0001). While marital status is associated with differential uterine cancer survival, evaluation of self-reported relationship by type indicated that the poor outcome observed in widows explained most of the benefit attributed to marriage. This report identifies widows as a new high-risk subpopulation with significantly inferior outcomes potentially benefiting from personalized care and social support. Published by Elsevier Inc.
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SCEW: a Microsoft Excel add-in for easy creation of survival curves.
Khan, Haseeb Ahmad
2006-07-01
Survival curves are frequently used for reporting survival or mortality outcomes of experimental pharmacological/toxicological studies and of clinical trials. Microsoft Excel is a simple and widely used tool for creation of numerous types of graphic presentations however it is difficult to create step-wise survival curves in Excel. Considering the familiarity of clinicians and biomedical scientists with Excel, an algorithm survival curves in Excel worksheet (SCEW) has been developed for easy creation of survival curves directly in Excel worksheets. The algorithm has been integrated in the form of Excel add-in for easy installation and usage. The program is based on modification of frequency data for binary break-up using the spreadsheet formula functions whereas a macro subroutine automates the creation of survival curves. The advantages of this program are simple data input, minimal procedural steps and the creation of survival curves in the familiar confines of Excel.
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Condón, Santiago; Mañas, Pilar
2017-01-01
Heat has been used extensively in the food industry as a preservation method, especially due to its ability to inactivate microorganisms present in foods. However, many aspects regarding the mechanisms of bacterial inactivation by heat and the factors affecting this process are still not fully understood. The purpose of this review is to offer a general overview of the most important aspects of the physiology of the inactivation or survival of microorganisms, particularly vegetative bacteria, submitted to heat treatments. This could help improve the design of current heat processes methods in order to apply milder and/or more effective treatments that could fulfill consumer requirements for fresh-like foods while maintaining the advantages of traditional heat treatments. PMID:29189748
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The Nuclear Barcode: a New Taggant for Identifying Explosives
NASA Astrophysics Data System (ADS)
Seman, James; Johnson, Catherine; Castaño, Carlos
2017-06-01
Creating an effective taggant system for explosives is a challenging problem since the taggant used must be designed to endure the detonation process. A new taggant for use in explosives has been recently developed and named the `nuclear barcode'. The nuclear barcode tags explosives by adding low concentrations of eight different elements to the explosive, and then reads the tag from the post-blast residue using neutron activation analysis (NAA) to identify the elements and their concentrations. The nuclear barcode can be used to identify explosives after detonation by sampling the post-blast residue that is deposited due to incomplete reaction of the explosives. This method of tagging explosives creates an identifying taggant that survives detonation as NAA detects atomic nuclei as opposed to using any chemical or physical properties of the taggant that don't always survive the detonation process. Additional advantages this taggant method offers is ease of recovery of the taggant after detonation, and a total of 25.6 billion possible taggants as currently conceived, which enables the nuclear barcode to be used to tag individual batches of explosives. This paper describes the development of the nuclear barcode taggant system and its potential use in the explosives industry.
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Roberts, Jess C.; Li, Guojun; Reitzel, Lorraine R.; Wei, Qingyi; Sturgis, Erich M.
2010-01-01
Purpose It is unknown whether there are survival disparities between men and women with squamous cell carcinoma of the head and neck (SCCHN), though some data suggest that men have worse outcomes. We conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a survival advantage exists for female compared with male SCCHN patients receiving similar care. Experimental Design We selected 286 female patients and 286 matched male patients from within a prospective epidemiologic study of 1654 patients with incident SCCHN evaluated and treated at a single large multidisciplinary cancer center. Matching variables included age (± 10 years), race/ethnicity, smoking status (never versus ever), tumor site (oral cavity versus oropharynx versus larynx versus hypopharynx), tumor classification (T1–2 versus T3–4), nodal status (negative versus positive), and treatment (surgery, radiation therapy, surgery and radiation therapy, surgery and chemotherapy, chemoradiotherapy, or surgery and chemoradiotherapy). Results Matched-pair and log-rank analyses showed no significant differences between women and men in recurrence-free, disease-specific, or overall survival. When the analysis was restricted to individual sites (oral cavity, oropharynx, or larynx/hypopharynx), there was also no evidence of a disparity in survival associated with sex. Conclusions We conclude that there is no evidence to suggest that a survival advantage exists for women as compared to men with SCCHN receiving similar multidisciplinary directed care at a tertiary cancer center. PMID:20943762
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Surviving helicopter crashes at sea: a review of studies of underwater egress from helicopters.
Ryack, B L; Luria, S M; Smith, P F
1986-06-01
The problem of escaping from a submerged helicopter is discussed. The effectiveness of illuminated escape hatches in facilitating escape has been demonstrated. The relative advantages of different types of lights are compared. Escape training, illuminating the emergency exits, and providing breathing devices should greatly enhance the chances of survival in a helicopter crash at sea.
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Retirement as Meaningful: Positive Retirement Stereotypes Associated with Longevity
Ng, Reuben; Allore, Heather G.; Monin, Joan K.; Levy, Becca R.
2016-01-01
Studies examining the association between retirement and health have produced mixed results. This may be due to previous studies treating retirement as merely a change in job status rather than a transition associated with stereotypes or societal beliefs (e.g., retirement is a time of mental decline or retirement is a time of growth). To examine whether these stereotypes are associated with health, we studied retirement stereotypes and survival over a 23-year period among 1,011 older adults. As predicted by stereotype embodiment theory, it was found that positive stereotypes about physical health during retirement showed a survival advantage of 4.5 years (hazard ratio = 0.88, p = .022) and positive stereotypes about mental health during retirement tended to show a survival advantage of 2.5 years (hazard ratio = 0.87, p = .034). Models adjusted for relevant covariates such as age, gender, race, employment status, functional health, and self-rated health. These results suggest that retirement preparation could benefit from considering retirement stereotypes. PMID:27346893
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Airborne ladar man-in-the-loop operations in tactical environments
NASA Astrophysics Data System (ADS)
Grobmyer, Joseph E., Jr.; Lum, Tommy; Morris, Robert E.; Hard, Sarah J.; Pratt, H. L.; Florence, Tom; Peddycoart, Ed
2004-09-01
The U.S. Army Research, Development and Engineering Command (RDECOM) is developing approaches and processes that will exploit the characteristics of current and future Laser Radar (LADAR) sensor systems for critical man-in-the-loop tactical processes. The importance of timely and accurate target detection, classification, identification, and engagement for future combat systems has been documented and is viewed as a critical enabling factor for FCS survivability and lethality. Recent work has demonstrated the feasibility of using low cost but relatively capable personal computer class systems to exploit the information available in Ladar sensor frames to present the war fighter or analyst with compelling and usable imagery for use in the target identification and engagement processes in near real time. The advantages of LADAR imagery are significant in environments presenting cover for targets and the associated difficulty for automated target recognition (ATR) technologies.
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Valsecchi, M G; Silvestri, D; Sasieni, P
1996-12-30
We consider methodological problems in evaluating long-term survival in clinical trials. In particular we examine the use of several methods that extend the basic Cox regression analysis. In the presence of a long term observation, the proportional hazard (PH) assumption may easily be violated and a few long term survivors may have a large effect on parameter estimates. We consider both model selection and robust estimation in a data set of 474 ovarian cancer patients enrolled in a clinical trial and followed for between 7 and 12 years after randomization. Two diagnostic plots for assessing goodness-of-fit are introduced. One shows the variation in time of parameter estimates and is an alternative to PH checking based on time-dependent covariates. The other takes advantage of the martingale residual process in time to represent the lack of fit with a metric of the type 'observed minus expected' number of events. Robust estimation is carried out by maximizing a weighted partial likelihood which downweights the contribution to estimation of influential observations. This type of complementary analysis of long-term results of clinical studies is useful in assessing the soundness of the conclusions on treatment effect. In the example analysed here, the difference in survival between treatments was mostly confined to those individuals who survived at least two years beyond randomization.
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Smith-Greenaway, Emily
2013-11-01
Mothers' literacy skills are emerging as a key determinant of children's health and survival in low-income contexts, with emphasis on the cognitive and psychological agency that literacy skills provide. This work has clearly established a strong association between mothers' reading skills--a key subcomponent of broader literacy and language skills--and child mortality. However, this relatively nascent literature has not yet considered how broader social structures condition the process. In Nigeria and in sub-Saharan Africa more broadly, gender-based social inequality constrains many mothers' decision-making power over children's health matters; this structural feature may condition the association between mothers' reading skills and child mortality. This paper uses data from the 2003 Nigerian Demographic and Health Survey (N = 12,076) to test the conditionality of the relationship between mothers' reading skills and child survival on mothers' decision-making power, highlighting how structural realities should factor more heavily into this individual-action-oriented literature. Among Nigerian children whose mothers have decision-making power, mothers' reading skills convey a 27 percent lower risk of child mortality; however, for children whose mothers lack decision-making power, mothers' reading skills do not yield a significant survival advantage. Overall, these findings support the need for future work to further analyze how broader social structures condition the benefits of mothers' reading skills for children's health. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Smith-Greenaway, Emily
2013-01-01
Mothers’ literacy skills are emerging as a key determinant of children’s health and survival in low-income contexts, with emphasis on the cognitive and psychological agency that literacy skills provide. This work has clearly established a strong association between mothers’ reading skills—a key subcomponent of broader literacy and language skills—and child mortality. However, this relatively nascent literature has not yet considered how broader social structures condition the process. In Nigeria and in sub-Saharan Africa more broadly, gender-based social inequality constrains many mothers’ decision-making power over children’s health matters; this structural feature may condition the association between mothers’ reading skills and child mortality. This paper uses data from the 2003 Nigerian Demographic and Health Survey (N = 12,076) to test the conditionality of the relationship between mothers’ reading skills and child survival on mothers’ decision-making power, highlighting how structural realities should factor more heavily into this individual-action-oriented literature. Among Nigerian children whose mothers have decision-making power, mothers’ reading skills convey a 27 percent lower risk of child mortality; however, for children whose mothers lack decision-making power, mothers’ reading skills do not yield a significant survival advantage. Overall, these findings support the need for future work to further analyze how broader social structures condition the benefits of mothers’ reading skills for children’s health. PMID:24161100
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Yung, Mimi C.
2014-01-01
Caulobacter crescentus is known to tolerate high levels of uranium [U(VI)], but its detoxification mechanism is poorly understood. Here we show that C. crescentus is able to facilitate U(VI) biomineralization through the formation of U-Pi precipitates via its native alkaline phosphatase activity. The U-Pi precipitates, deposited on the cell surface in the form of meta-autunite structures, have a lower U/Pi ratio than do chemically produced precipitates. The enzyme that is responsible for the phosphatase activity and thus the biomineralization process is identified as PhoY, a periplasmic alkaline phosphatase with broad substrate specificity. Furthermore, PhoY is shown to confer a survival advantage on C. crescentus toward U(VI) under both growth and nongrowth conditions. Results obtained in this study thus highlight U(VI) biomineralization as a resistance mechanism in microbes, which not only improves our understanding of bacterium-mineral interactions but also aids in defining potential ecological niches for metal-resistant bacteria. PMID:24878600
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Duongthingoc, Diep; George, Paul; Katopo, Lita; Gorczyca, Elizabeth; Kasapis, Stefan
2013-12-01
This work investigates the effect of whey protein agglomeration on the survivability of Saccharomyces boulardii within spray dried microcapsules. It attempts to go beyond phenomenological observations by establishing a relationship between physicochemical characteristics of the polymeric matrix and its effect on probiotic endurance upon spray drying. It is well known that this type of thermal shock has lethal consequences on the yeast cells. To avoid such undesirable outcome, we take advantage of the early agglomeration phenomenon observed for whey protein by adjusting the pH value of preparations close to isoelectric point (pH 4-5). During the subsequent process of spray drying, development of whey protein agglomerates induces formation of an early crust, and the protein in this molten globular state creates a cohesive network encapsulating the yeast cells. It appears that the early crust formation at a given sample pH and temperature regime during spray drying benefits the survivability of S. boulardii within microcapsules. Copyright © 2013. Published by Elsevier Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yung, M C; Jiao, Y
2014-07-22
Caulobacter crescentus is known to tolerate high levels of uranium [U(VI)], but its detoxification mechanism is poorly understood. Here we show that C. crescentus is able to facilitate U(VI) biomineralization through the formation of U-P i precipitates via its native alkaline phosphatase activity. The U-P i precipitates, deposited on the cell surface in the form of meta-autunite structures, have a lower U/P i ratio than do chemically produced precipitates. The enzyme that is responsible for the phosphatase activity and thus the biomineralization process is identified as PhoY, a periplasmic alkaline phosphatase with broad substrate specificity. Furthermore, PhoY is shown tomore » confer a survival advantage on C. crescentus toward U(VI) under both growth and nongrowth conditions. Results obtained in this study thus highlight U(VI) biomineralization as a resistance mechanism in microbes, which not only improves our understanding of bacterium-mineral interactions but also aids in defining potential ecological niches for metal-resistant bacteria.« less
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Evolutionary Dynamics of Spore Killers
Nauta, M. J.; Hoekstra, R. F.
1993-01-01
Spore killing in ascomycetes is a special form of segregation distortion. When a strain with the Killer genotype is crossed to a Sensitive type, spore killing is expressed by asci with only half the number of ascospores as usual, all surviving ascospores being of the Killer type. Using population genetic modeling, this paper explores conditions for invasion of Spore killers and for polymorphism of Killers, Sensitives and Resistants (which neither kill, nor get killed), as found in natural populations. The models show that a population with only Killers and Sensitives can never be stable. The invasion of Killers and stable polymorphism only occur if Killers have some additional advantage during the process of spore killing. This may be due to the effects of local sib competition or some kind of ``heterozygous'' advantage in the stage of ascospore formation or in the short diploid stage of the life cycle. This form of segregation distortion appears to be essentially different from other, well-investigated forms, and more field data are needed for a better understanding of spore killing. PMID:8293989
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Kuprewicz, Erin K.
2015-01-01
Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate) enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis) and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although tradeoffs in seed survival do exist. PMID:25970832
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Spataro, Rossella; Bono, Valeria; Marchese, Santino; La Bella, Vincenzo
2012-12-15
Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic lateral sclerosis (ALS) patients with a respiratory failure or when the non-invasive ventilation (NIV) is no longer effective. We evaluated the clinical characteristics and survival of a cohort of tracheostomized ALS patients, followed in a single ALS Clinical Center. Between 2001 and 2010, 87 out of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in 25. After tracheostomy, most patients were followed up through telephone interviews to caregivers. A complete survival analysis could be performed in fifty-two TMV patients. 31.3% ALS patients underwent tracheostomy, with a male prevalence (M/F=1.69) and a median age of 61 years (interquartile range=47-66). After tracheostomy, nearly all patients were under home care. TMV ALS patients were more likely than non-tracheostomized (NT) patients to be implanted with a PEG device, although the bulbar-/spinal-onset ratio did not differ between the two groups. Kaplan-Meyer analysis showed that tracheostomy increases median survival (TMV, 47 months vs NT, 31 months, p=0.008), with the greatest effect in patients younger than 60 at onset (TMV ≤ 60 years, 57.5 months vs NT ≤ 60 years, 38.5 months, p=0.002). TMV is increasingly performed in ALS patients. Nearly all TMV patients live at home and most of them are fed through a PEG device. Survival after tracheostomy is generally increased, with the stronger effect in patients younger than 60. This survival advantage is apparently lost when TMV is performed in patients older than 60. The results of this study might be useful for the decision-making process of patients and their families about this advanced palliative care. Copyright © 2012. Published by Elsevier B.V.
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Brundage, Michael D.; Feldman‐Stewart, Deb; Dixon, Peter; Gregg, Richard; Youssef, Youssef; Davies, Diane; Mackillop, William J.
2008-01-01
Purpose To describe the structure and use of a decision aid for patients with locally advanced non‐small cell lung cancer (LA‐NSCLC) who are eligible for combined‐modality treatment (CMT) or for radiotherapy alone (RT). Methods The aid included a structured description of the treatment options and trade‐off exercises designed to help clarify the patient’s values for the relevant outcomes by determining the patient’s survival advantage threshold (the increase in survival conferred by CMT over RT that the patient deemed necessary for choosing CMT). Additional outcome measures included each patient’s strength of treatment preference, decisional conflict, objective understanding of survival information, decisional role preference, and evaluation of the aid itself. Results Twenty‐five patients met the eligibility criteria for study. Of these, seven declined the decision aid because they had a clear treatment preference (four chose CMT and three chose RT). The remaining 18 participants completed the decision aid; 16 chose CMT and two chose RT. All 18 patients wished to participate in the decision to some extent. All patients reported that using the decision support was useful to them and recommended its use for others. No patient or physician reported that the aid interfered with the physician‐patient relationship. Patients’ 3‐year survival advantage thresholds, and their median survival advantage thresholds, were each strongly correlated with their strengths of treatment preference (ρ=0.80, P < 0.001 and ρ=0.77, P < 0.001, respectively). For all but one patient, either their 3‐year or median survival threshold was consistent with their final treatment choice. Eight patients reported a stronger treatment preference after using the decision aid. Conclusions We conclude that a treatment trade‐off based decision aid for patients with locally advanced non‐small cell lung cancer is feasible, that it demonstrates internal consistency and convergent validity, and that it is favourably evaluated by patients and their physicians. The aid seems to help patients understand the benefits and risks of treatment and to choose the treatment that is most consistent with their values. PMID:11281912
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Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S
2018-05-01
To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption. Cancer 2018;124:1921-8. © 2018 American Cancer Society. © 2018 American Cancer Society.
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Pasquali, Sandro; Yim, Guang; Vohra, Ravinder S; Mocellin, Simone; Nyanhongo, Donald; Marriott, Paul; Geh, Ju Ian; Griffiths, Ewen A
2017-03-01
This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. The optimal treatment for resectable esophageal cancer is unknown. A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.
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Esmerino, E A; Paixão, J A; Cruz, A G; Garitta, L; Hough, G; Bolini, H M A
2015-11-01
For years, just-about-right (JAR) scales have been among the most used techniques to obtain sensory information about consumer perception, but recently, some researchers have harshly criticized the technique. The present study aimed to apply survival analysis to estimate the optimum sucrose concentration in probiotic petit suisse cheese and compare the survival analysis to JAR scales to verify which technique more accurately predicted the optimum sucrose concentration according to consumer acceptability. Two panels of consumers (total=170) performed affective tests to determine the optimal concentration of sucrose in probiotic petit suisse using 2 different methods of analysis: JAR scales (n=85) and survival analysis (n=85). Then an acceptance test was conducted using naïve consumers (n=100) between 18 and 60 yr old, with 2 samples of petit suisse, one with the ideal sucrose determined by JAR scales and the other with the ideal sucrose content determined by survival analysis, to determine which formulation was in accordance with consumer acceptability. The results indicate that the 2 sensory methods were equally effective in predicting the optimum sucrose level in probiotic petit suisse cheese, and no significant differences were detected in any of the characteristics related to liking evaluated. However, survival analysis has important advantages over the JAR scales. Survival analysis has shown the potential to be an advantageous tool for dairy companies because it was able to accurately predict the optimum sucrose content in a consumer-friendly way and was also practical for researchers because experimental sensory work is simpler and has been shown to be more cost effective than JAR scales without losses of consumer acceptability. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
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Working memory load eliminates the survival processing effect.
Kroneisen, Meike; Rummel, Jan; Erdfelder, Edgar
2014-01-01
In a series of experiments, Nairne, Thompson, and Pandeirada (2007) demonstrated that words judged for their relevance to a survival scenario are remembered better than words judged for a scenario not relevant on a survival dimension. They explained this survival-processing effect by arguing that nature "tuned" our memory systems to process and remember fitness-relevant information. Kroneisen and Erdfelder (2011) proposed that it may not be survival processing per se that facilitates recall but the richness and distinctiveness with which information is encoded. To further test this account, we investigated how the survival processing effect is affected by cognitive load. If the survival processing effect is due to automatic processes or, alternatively, if survival processing is routinely prioritized in dual-task contexts, we would expect this effect to persist under cognitive load conditions. If the effect relies on cognitively demanding processes like richness and distinctiveness of encoding, however, the survival processing benefit should be hampered by increased cognitive load during encoding. Results were in line with the latter prediction, that is, the survival processing effect vanished under dual-task conditions.
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2013-01-01
Background We examined the mediating effect of health insurance on poverty-breast cancer care and survival relationships and the moderating effect of poverty on health insurance-breast cancer care and survival relationships in California. Methods Registry data for 6,300 women with breast cancer diagnosed between 1996 and 2000 and followed until 2011 on stage at diagnosis, surgeries, adjuvant treatments and survival were analyzed. Socioeconomic data were obtained for residences from the 2000 census to categorize neighborhoods: high poverty (30% or more poor), middle poverty (5%-29% poor) and low poverty (less than 5% poor). Primary payers or health insurers were Medicaid, Medicare, private or uninsured. Results Evidence of survival mediation was observed for women with node negative breast cancer. The apparent effect of poverty disappeared in the presence of Medicare or private health insurance. Women who were so insured were advantaged on 8-year survival compared to the uninsured or those insured by Medicaid (OR = 1.89). Evidence of payer moderation by poverty was also observed for women with node negative breast cancer. The survival advantaging effect of Medicare or private insurance was stronger in low poverty (OR = 1.81) than it was in middle poverty (OR = 1.57) or in high poverty neighborhoods (OR = 1.16). This same pattern of mediated and moderated effects was also observed for early stage at diagnosis, shorter waits for adjuvant radiation therapy and for the receipt of sentinel lymph node biopsies. These findings are consistent with the theory that more facilitative social and economic capital is available in low poverty neighborhoods, where women with breast cancer may be better able to absorb the indirect and direct, but uncovered, costs of care. As for treatments, main protective effects as well as moderator effects indicative of protection, particularly in high poverty neighborhoods were observed for women with private health insurance. Conclusions America’s multi-tiered health insurance system mediates the quality of breast cancer care. The system is inequitable and unjust as it advantages the well insured and the well to do. Recent health care reforms ought to be enacted in ways that are consistent with their federal legislative intent, that high quality health care be truly available to all. PMID:23311824
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Phase separation like dynamics during Myxococcus xanthus fruiting body formation
NASA Astrophysics Data System (ADS)
Liu, Guannan; Thutupalli, Shashi; Wigbers, Manon; Shaevitz, Joshua
2015-03-01
Collective motion exists in many living organisms as an advantageous strategy to help the entire group with predation, forage, and survival. However, the principles of self-organization underlying such collective motions remain unclear. During various developmental stages of the soil-dwelling bacterium, Myxococcus xanthus, different types of collective motions are observed. In particular, when starved, M. xanthus cells eventually aggregate together to form 3-dimensional structures (fruiting bodies), inside which cells sporulate in response to the stress. We study the fruiting body formation process as an out of equilibrium phase separation process. As local cell density increases, the dynamics of the aggregation M. xanthus cells switch from a spatio-temporally random process, resembling nucleation and growth, to an emergent pattern formation process similar to a spinodal decomposition. By employing high-resolution microscopy and a video analysis system, we are able to track the motion of single cells within motile collective groups, while separately tuning local cell density, cell velocity and reversal frequency, probing the multi-dimensional phase space of M. xanthus development.
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Barbizan, Roberta; Seabra Ferreira, Rui
2016-01-01
Axonal injuries at the interface between central and peripheral nervous system, such as ventral root avulsion (VRA), induce important degenerative processes, mostly resulting in neuronal and motor function loss. In the present work, we have compared two different fibrin sealants, one derived from human blood and another derived from animal blood and Crotalus durissus terrificus venom, as a promising treatment for this type of injury. Lewis rats were submitted to VRA (L4–L6) and had the avulsed roots reimplanted to the surface of the spinal cord, with the aid of fibrin sealant. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity, 4 and 12 weeks after lesion. Sciatic nerves were processed to investigate Schwann cell activity by p75NTR expression (4 weeks after surgery) and to count myelinated axons and morphometric evaluation (12 weeks after surgery). Walking track test was used to evaluate gait recovery, up to 12 weeks. The results indicate that both fibrin sealants are similarly efficient. However, the snake-derived fibrin glue is a potentially safer alternative for being a biological and biodegradable product which does not contain human blood derivatives. Therefore, the venom glue can be a useful tool for the scientific community due to its advantages and variety of applications. PMID:27642524
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NASA Astrophysics Data System (ADS)
Wavering, Thomas A.; Greene, Jonathan A.; Meller, Scott A.; Bailey, Timothy A.; Kozikowski, Carrie L.; Lenahan, Shannon M.; Murphy, Kent A.; Camden, Michael P.; Simmons, Larry W.
1999-01-01
Optical fiber sensors have numerous advantages over conventional sensing technologies. One such advantage is that optical fiber sensors can operate in high temperature environments. While most conventional electrical-based sensors do not operate reliably over 300 degrees C, fused silica based optical fiber sensors can survive up to 900 degrees C, and sapphire based optical fiber sensors can survive up to 2000 degrees C. Using both fused silica and sapphire technologies, we present result for high temperature strain, pressure, and temperature sensors using Extrinsic Fabry-Perot INterferometric-based and Bragg grating sensors. High temperature strain and temperature sensors were used to conduct fatigue testing of composite coupons at 600 degrees C. The results from these specific high temperature applications are presented along with future applications and directions for these sensors.
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p53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, Flore; Labuschagne, Christiaan F; Vousden, Karen H
2015-07-01
The function of p53 as a tumour suppressor has been attributed to its ability to promote cell death or permanently inhibit cell proliferation. However, in recent years, it has become clear that p53 can also contribute to cell survival. p53 regulates various metabolic pathways, helping to balance glycolysis and oxidative phosphorylation, limiting the production of reactive oxygen species, and contributing to the ability of cells to adapt to and survive mild metabolic stresses. Although these activities may be integrated into the tumour suppressive functions of p53, deregulation of some elements of the p53-induced response might also provide tumours with a survival advantage.
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The Dauer Mutation of the Caenorhabditis Elegans, Simulated with the Penna and the Stauffer Models
NASA Astrophysics Data System (ADS)
Colonius, Kerstin
Two aging models were analyzed on whether they can confirm the dauer mutation of the nematode helps to preserve the species. As a result the Penna model shows that populations with dauer larvae survive bad environmental conditions, whereas populations without it die out. In the Stauffer model, the advantage of the dauer mutation for the survival is only given under certain conditions.
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Gender differentials and old age survival in the Nairobi slums, Kenya.
Bennett, Rachel; Chepngeno-Langat, Gloria; Evandrou, Maria; Falkingham, Jane
2016-08-01
This paper examines gender differentials in survival amongst older people (50+ years) in the Nairobi slums and to the best of our knowledge is the first study of its kind in an urban African setting. The results provide evidence contrary to the expected paradox of poorer self-rated health yet better survival amongst older women. Older women in the Nairobi slums have poorer self-rated health and poorer circumstances across other factors, including disability and socio-economic status. Further, older women in the slums do not have better survival. The conventional female advantage in mortality only becomes apparent after accounting for the cumulative influence of individual characteristics, social networks, health and socio-economic status, suggesting the female advantage in unadjusted old-age mortality does not apply to contexts where women experience significant disadvantage across multiple life domains. This highlights the urgent need to redress the support, status and opportunities available for women across the life course in contexts such as the Nairobi slums. In addition, a greater number of factors differentiate mortality risk amongst men than amongst women, suggesting inequality amongst slum dwelling older men and highlighting the need for gender sensitive interventions which account for the particular needs of both genders in old age. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Racial and ethnic disparities in end-stage kidney failure-survival paradoxes in African-Americans.
Agodoa, Lawrence; Eggers, Paul
2007-01-01
The risk of death is nearly 45% lower in African-Americans than Caucasians undergoing chronic hemodialysis. In light of the higher mortality rate in African-Americans in the general US population, this paradox requires explanation and further investigation. Factors that may contribute to this survival advantage include a younger age at which African-Americans arrive at end-stage renal disease (ESRD) and the slightly higher body mass index. On the other hand, factors, such as lower residual renal function, lower mean hemoglobin and hematocrit, increased prevalence of hypertension, a higher prevalence of catheter use for initial dialysis, and generally lower dose of dialysis should put African-Americans on dialysis at a higher risk of death. This survival advantage seems to be completely annulled with a successful renal transplant. Finally, it should be noted that ESRD carries with it a very high mortality rate in all racial and ethnic groups. A successful renal transplant improves but does not restore the expected remaining life times. Therefore, aggressive approach is required in investigating the factors that confer such high mortality risk on ESRD patients.
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Progression-free survival as a primary endpoint in clinical trials of metastatic colorectal cancer
Gill, S.; Berry, S.; Biagi, J.; Butts, C.; Buyse, M.; Chen, E.; Jonker, D.; Mărginean, C.; Samson, B.; Stewart, J.; Thirlwell, M.; Wong, R.; Maroun, J.A.
2011-01-01
In recent years, significant advances have been made in the management of metastatic colorectal cancer. Traditionally, an improvement in overall survival has been considered the “gold standard”—the most convincing measure of efficacy. However, overall survival requires larger patient numbers and longer follow-up and may often be confounded by other factors, including subsequent therapies and crossover. Given the number of active therapies for potential investigation, demand for rapid evaluation and early availability of new therapies is growing. Progression-free survival is regarded as an important measure of treatment benefit and, compared with overall survival, can be evaluated earlier, with fewer patients and no confounding by subsequent lines of therapy. The present paper reviews the advantages, limitations, and relevance of progression-free survival as a primary endpoint in randomized trials of metastatic colorectal cancer. PMID:21969810
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Facing danger: how do people behave in times of need? The case of adult attachment styles.
Ein-Dor, Tsachi
2014-01-01
Bowlby's (1982) attachment theory has generated an enormous body of research and conceptual elaborations. Although attachment theory and research propose that attachment security provides a person with many adaptive advantages, during all phases of the life cycle, numerous studies indicate that almost half of the human species can be classified as insecurely attached or insecure with respect to attachment. It seems odd that evolution left humans in this vulnerable position, unless there are some advantages to individuals or groups, under at least some conditions, of anxious and avoidant attachment styles. I argue that a social group containing members with different attachment patterns may be more conducive to survival than a homogeneous group of securely attached individuals because each attachment disposition has specific adaptive advantages that promote the survival of the individual and people around him or her when facing threats and perils. In making this argument, I extend the scope of attachment theory and research by considering a broader range of adaptive functions of insecure attachment strategies, and present data to support my argument.
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Competing risks models and time-dependent covariates
Barnett, Adrian; Graves, Nick
2008-01-01
New statistical models for analysing survival data in an intensive care unit context have recently been developed. Two models that offer significant advantages over standard survival analyses are competing risks models and multistate models. Wolkewitz and colleagues used a competing risks model to examine survival times for nosocomial pneumonia and mortality. Their model was able to incorporate time-dependent covariates and so examine how risk factors that changed with time affected the chances of infection or death. We briefly explain how an alternative modelling technique (using logistic regression) can more fully exploit time-dependent covariates for this type of data. PMID:18423067
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Survival probabilities at spherical frontiers.
Lavrentovich, Maxim O; Nelson, David R
2015-06-01
Motivated by tumor growth and spatial population genetics, we study the interplay between evolutionary and spatial dynamics at the surfaces of three-dimensional, spherical range expansions. We consider range expansion radii that grow with an arbitrary power-law in time: R(t) = R0(1 + t/t(∗))Θ, where Θ is a growth exponent, R0 is the initial radius, and t(∗) is a characteristic time for the growth, to be affected by the inflating geometry. We vary the parameters t(∗) and Θ to capture a variety of possible growth regimes. Guided by recent results for two-dimensional inflating range expansions, we identify key dimensionless parameters that describe the survival probability of a mutant cell with a small selective advantage arising at the population frontier. Using analytical techniques, we calculate this probability for arbitrary Θ. We compare our results to simulations of linearly inflating expansions (Θ = 1 spherical Fisher-Kolmogorov-Petrovsky-Piscunov waves) and treadmilling populations (Θ = 0, with cells in the interior removed by apoptosis or a similar process). We find that mutations at linearly inflating fronts have survival probabilities enhanced by factors of 100 or more relative to mutations at treadmilling population frontiers. We also discuss the special properties of "marginally inflating" (Θ = 1/2) expansions. Copyright © 2015 Elsevier Inc. All rights reserved.
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Chen, Yaning; Li, Weihong; Zhou, Honghua; Chen, Yapeng; XinmingHao; Fu, Aihong; Ma, Jianxin
2017-06-01
Studying the water use processes of desert riparian vegetation in arid regions and analyzing the response and adaptation strategies of plants to drought stress are of great significance for developing ecological restoration measures. Based on field monitoring and test analyses of physiological ecological indicators of dominant species (Populus euphratica and Tamarix chinensis) in the desert riparian forest in the lower reaches of the Tarim River, the water relations of P. euphratica and T. chinensis under drought stress are discussed and some water use strategies put forward. The results show that (1) concerning plant water uptake, desert riparian forests depend mainly on groundwater to survive under long-term water stress. (2) Concerning plant water distribution, the survival of P. euphratica and nearby shallow root plants is mainly due to the hydraulic lift and water redistribution of P. euphratica under drought stress. (3) Concerning plant water transport, P. euphratica sustains the survival of competitive and advantageous branches by improving their ability to acquire water while restraining the growth of inferior branches. (4) Concerning plant transpiration, the sap flow curves of daily variations of P. euphratica and T. chinensis were wide-peak sin and narrower-peak respectively. T. chinensis has better environmental adaptability.
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Total quality in acute care hospitals: guidelines for hospital managers.
Holthof, B
1991-08-01
Quality improvement can not focus exclusively on peer review and the scientific evaluation of medical care processes. These essential elements have to be complemented with a focus on individual patient needs and preferences. Only then will hospitals create the competitive advantage needed to survive in an increasingly market-driven hospital industry. Hospital managers can identify these patients' needs by 'living the patient experience' and should then set the hospital's quality objectives according to its target patients and their needs. Excellent quality program design, however, is not sufficient. Successful implementation of a quality improvement program further requires fundamental changes in pivotal jobholders' behavior and mindset and in the supporting organizational design elements.
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Faries, Mark B; Han, Dale; Reintgen, Michael; Kerivan, Lauren; Reintgen, Douglas; Caracò, Corrado
2018-05-18
While there is no doubt that regional lymph node metastases are an enormously important factor in melanoma staging and treatment, the biology behind this significance and its precise implications for treatment planning have been a leading controversy in melanoma and other solid tumors for over a century. Recent clinical data, including data from prospective randomized clinical trials have refined our understanding of the process of nodal metastases and the advantages and disadvantages of different clinical management strategies. This review presents two points of view in this debate and discusses the results of new data analyses as well as pivotal clinical trials informing the discussion.
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Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne
2013-10-01
There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate <20 mL/min (p < 0.0001), <15 mL/min (p < 0.0001) and <12 mL/min (p = 0.002). When factors influencing survival were stratified for both groups independently, renal replacement therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p < 0.05; 95% confidence interval = 1.14-2.13). A total of 47% of conservative management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.
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Connock, Martin; Hyde, Chris; Moore, David
2011-10-01
The UK National Institute for Health and Clinical Excellence (NICE) has used its Single Technology Appraisal (STA) programme to assess several drugs for cancer. Typically, the evidence submitted by the manufacturer comes from one short-term randomized controlled trial (RCT) demonstrating improvement in overall survival and/or in delay of disease progression, and these are the pre-eminent drivers of cost effectiveness. We draw attention to key issues encountered in assessing the quality and rigour of the manufacturers' modelling of overall survival and disease progression. Our examples are two recent STAs: sorafenib (Nexavar®) for advanced hepatocellular carcinoma, and azacitidine (Vidaza®) for higher-risk myelodysplastic syndromes (MDS). The choice of parametric model had a large effect on the predicted treatment-dependent survival gain. Logarithmic models (log-Normal and log-logistic) delivered double the survival advantage that was derived from Weibull models. Both submissions selected the logarithmic fits for their base-case economic analyses and justified selection solely on Akaike Information Criterion (AIC) scores. AIC scores in the azacitidine submission failed to match the choice of the log-logistic over Weibull or exponential models, and the modelled survival in the intervention arm lacked face validity. AIC scores for sorafenib models favoured log-Normal fits; however, since there is no statistical method for comparing AIC scores, and differences may be trivial, it is generally advised that the plausibility of competing models should be tested against external data and explored in diagnostic plots. Function fitting to observed data should not be a mechanical process validated by a single crude indicator (AIC). Projective models should show clear plausibility for the patients concerned and should be consistent with other published information. Multiple rather than single parametric functions should be explored and tested with diagnostic plots. When trials have survival curves with long tails exhibiting few events then the robustness of extrapolations using information in such tails should be tested.
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Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy
2013-09-01
10]. However, the level of IFP has been shown to predict disease free survival for cervix cancer (34% disease free survival (DFS) if IFP > 19 mmHg...in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res, 2001. 61(17): p. 6400-5. 12... cancer (LABC). Monitoring tumor response is advantageous for patients. This project aims to using the subharmonic signals from ultrasound contrast agents
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ERIC Educational Resources Information Center
Bosch, Van Den Robert
1979-01-01
Contains a discussion of insects' ability to survive, of the development of pesticides and the introduction of DDT, of the problems of pesticide use and resistance to insecticides, and of the advantages of integrated pest control. (BB)
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The adaptive value of tool-aided defense against wild animal attacks.
Crabb, Peter B; Elizaga, Andrew
2008-01-01
Throughout history humans have faced the persistent threat of attacks by wild animals, and how humans respond to this problem can make the difference between survival and death. In theory, the use of tools to fend off animal attacks would be more effective than resisting bare-handed, yet evidence for the advantage of tool-aided defense is scarce and equivocal. Two studies of news accounts of wild animal attacks against humans were conducted to test the hypothesis that tool-aided defense is indeed associated with reductions in injuries and deaths. Results of both Study 1 (N=172) and Study 2 (N=370) supported the hypothesis. The observed survival advantage of tool-aided defense for modern humans suggests that this tactic also would have worked for human ancestors who lived more closely to dangerous wild animals. 2008 Wiley-Liss, Inc.
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Extensive variation, but not local adaptation in an Australian alpine daisy.
Hirst, Megan J; Sexton, Jason P; Hoffmann, Ary A
2016-08-01
Alpine plants often occupy diverse habitats within a similar elevation range, but most research on local adaptation in these plants has focused on elevation gradients. In testing for habitat-related local adaptation, local effects on seed quality and initial plant growth should be considered in designs that encompass multiple populations and habitats. We tested for local adaptation across alpine habitats in a morphologically variable daisy species, Brachyscome decipiens, in the Bogong High Plains in Victoria, Australia. We collected seed from different habitats, controlled for maternal effects through initial seed size estimates, and characterized seedling survival and growth in a field transplant experiment. We found little evidence for local adaptation for survival or plant size, based on three adaptation measures: Home versus Away, Local versus Foreign, and Sympatric versus Allopatric (SA). The SA measure controlled for planting site and population (site-of-origin) effects. There were significant differences due to site-of-origin and planting site effects. An important confounding factor was the size of plants directly after transplantation of seedlings, which had a large impact on subsequent seedling survival and growth. Initial differences in plant width and height influenced subsequent survival across the growing season but in opposing directions: wide plants had higher survival, but tall plants had lower survival. In an additional controlled garden experiment at Cranbourne Royal Botanic Gardens, site-of-origin effects detected in the field experiments disappeared under more benign homogeneous conditions. Although B. decipiens from different source areas varied significantly when grown across a range of alpine habitats, these differences did not translate into a local or habitat-related fitness advantage. This lack of local advantage may signal weak past selection, and/or weak adaptive transgeneration (plasticity) effects.
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Kim, Kwang Min; Kim, Jiyu; Sinn, Dong Hyun; Kim, Hye Seung; Kim, Kyunga; Kang, Wonseok; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon
2018-04-03
In order to claim a benefit of screen-based diagnosis for asymptomatic individuals, treatment of occult disease needs to offer survival advantages compared to the treatment of symptomatic disease, yet information on this issue is scarce with regard to hepatocellular carcinoma (HCC) screening. A total of 3353 treatment-naïve, consecutive, newly diagnosed HCC patients [age: 57.9 ± 10.3, male: 2,689 (80.2%), hepatitis B virus: 2555 (76.2%)], diagnosed between 2010 and 2013 were analyzed. Data on the mode of detection was prospectively collected at the time of HCC diagnosis and was used to group patients into occult or symptomatic cases. Overall, 643 (19.2%) patients were symptomatic cases. The proportion of patients undergoing resection, radiofrequency ablation or transplantation were lower in symptomatic cases than occult cases (20.8 vs. 56.2%, p < .001). Survival was better in occult cases than symptomatic cases (71.2 vs. 30.4% at three-years, p < .001), with a multivariable-adjusted hazard ratio of 1.40 (95% confidence interval (CI), 1.24-1.58). When stratified by tumor stage, a survival benefit was not observed for patients diagnosed at modified International Union Against Cancer (mUICC) stage I, but presenting symptoms were diverse and nonspecific. In a statistical model adjusting for potential lead-time bias, the association between overall survival and the mode of detection was markedly attenuated and was no longer significant when the treatment modality was included in the model (hazard ratio, 0.94; 95% CI, 0.82-1.07). Treatment of occult disease offered a survival benefit to patients over symptomatic cases. These data support screening practices for asymptomatic individuals to diagnose occult HCC.
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Outcomes of HPV-related nasal squamous cell carcinoma.
Chowdhury, Naweed; Alvi, Sameer; Kimura, Kyle; Tawfik, Ossama; Manna, Pradip; Beahm, David; Robinson, Ann; Kerley, Spencer; Hoover, Larry
2017-07-01
Human papilloma virus (HPV) infection has been shown to play an integral role in the development and prognosis of various head and neck cancers. Generational changes in sexual behavior may have led to an increased incidence of positivity in recent years. HPV positivity in both benign and malignant lesions of the sinonasal cavities has been shown in previous studies (estimates range from 20%-30% for malignancy). We intend to investigate if HPV positivity affected survival outcomes in our patient cohort. Twenty-six patients diagnosed pathologically for sinonasal squamous cell carcinoma (SCC) with available archived biopsy specimens were retrospectively analyzed to obtain HPV status using a real-time, multiplex polymerase chain reaction assay that detects and quantifies 15 known high-risk HPV types. Demographic information was collected, and survival analyses were performed using the Kaplan-Meier estimation. Sixteen of 26 (62%) SCC tumors in the patient cohort were positive for HPV DNA. HPV types 16 and 18 were the most common (n = 8 and 2, respectively), although a wide range of HPV types across the 15 tested were positive. Survival analyses showed a statistically significant survival advantage (median survival of 12 vs. 54 months) when accounting for HPV positivity using log-rank testing (P < 0.003). HPV positivity appears to be present in a significant proportion of squamous cell carcinoma cases of the nasal cavity. In our limited patient population there does appear to be a survival advantage to HPV positivity. Further prospective, multi-institutional trials with standardized treatment protocols are needed to elucidate the true impact of HPV positivity in this subset of head and neck cancers. 4. Laryngoscope, 127:1600-1603, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.
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HLA AND CROSS·REACTIVE ANTIGEN GROUP MATCHING FOR CADAVER KIDNEY ALLOCATION1
Starzl, Thomas E.; Eliasziw, Michael; Gjertson, David; Terasaki, Paul I.; Fung, John J.; Trucco, Massimo; Martell, Joan; McMichael, John; Scantlebury, Velma; Shapiro, Ron; Donner, Allan
2010-01-01
Background Allocation of cadaver kidneys by graded human leukocyte antigen (HLA) compatibility scoring arguably has had little effect on overall survival while prejudicing the transplant candidacy of African-American and other hard to match populations. Consequently, matching has been proposed of deduced amino acid residues of the individual HLA molecules shared by cross-reactive antigen groups (CREGs). We have examined the circumstances under which compatibility with either method impacted graft survival. Methods Using Cox proportional hazards regression modeling, we studied the relationship between levels of conventional HLA mismatch and other donor and recipient factors on primary cadaver kidney survival between 1981 and 1995 at the University of Pittsburgh (n=1,780) and in the United Network for Organ Sharing (UNOS) Scientific Registry during 1991–1995 (n=31,291). The results were compared with those obtained by the matching of amino acid residues that identified CREG-compatible cases with as many as four (but not five and six) HLA mismatches. Results With more than one HLA mismatch (>85% of patients in both series), most of the survival advantage of a zero mismatch was lost. None of the HLA loci were “weak.” In the UNOS (but not Pittsburgh) category of one-HLA mismatch (n=1334), a subgroup of CREG-matched recipients (35.3%) had better graft survival than the remaining 64.7%, who were CREG-mismatched. There was no advantage of a CREG match in the two- to four-HLA incompatibility tiers. Better graft survival with tacrolimus was observed in both the Pittsburgh and UNOS series. Conclusions Obligatory national sharing of cadaver kidneys is justifiable only for zero-HLA-mismatched kidneys. The potential value of CREG matching observed in the one-HLA-mismatched recipients of the UNOS (but not the Pittsburgh) experience deserves further study. PMID:9381546
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Chromium genotoxicity: a double-edged sword
Nickens, Kristen P.; Patierno, Steven R.; Ceryak, Susan
2010-01-01
Certain forms of hexavalent chromium [Cr(VI)] are known respiratory carcinogens that induce a broad spectrum of DNA damage. Cr(VI)-carcinogenesis may be initiated or promoted through several mechanistic processes including, the intracellular metabolic reduction of Cr(VI) producing chromium species capable of interacting with DNA to yield genotoxic and mutagenic effects, Cr(VI)-induced inflammatory/immunological responses, and alteration of survival signaling pathways. Cr(VI) enters the cell through nonspecific anion channels, and is metabolically reduced by agents including ascorbate, glutathione, and cysteine to Cr(V), Cr(IV), and Cr(III). Cr(III) has a weak membrane permeability capacity and is unable to cross the cell membrane, thereby trapping it within the cell where it can bind to DNA and produce genetic damage leading to genomic instability. Structural genetic lesions produced by the intracellular reduction of Cr(VI) include DNA adducts, DNA strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites, and DNA inter- and intrastrand crosslinks. The damage induced by Cr(VI) can lead to dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints, dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and the disruption of key regulatory gene networks responsible for the balance of cell survival and cell death, which may all play an important role in Cr(VI) carcinogenesis. Several lines of evidence have indicated that neoplastic progression is a result of consecutive genetic/epigenetic changes that provide cellular survival advantages, and ultimately lead to the conversion of normal human cells to malignant cancer cells. This review is based on studies that provide a glimpse into Cr(VI) carcinogenicity via mechanisms including Cr(VI)-induced death-resistance, the involvement of DNA repair mechanisms in survival after chromium exposure, and the activation of survival signaling cascades in response to Cr(VI) genotoxicity. PMID:20430016
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Naturalizing aesthetics: brain areas for aesthetic appraisal across sensory modalities.
Brown, Steven; Gao, Xiaoqing; Tisdelle, Loren; Eickhoff, Simon B; Liotti, Mario
2011-09-01
We present here the most comprehensive analysis to date of neuroaesthetic processing by reporting the results of voxel-based meta-analyses of 93 neuroimaging studies of positive-valence aesthetic appraisal across four sensory modalities. The results demonstrate that the most concordant area of activation across all four modalities is the right anterior insula, an area typically associated with visceral perception, especially of negative valence (disgust, pain, etc.). We argue that aesthetic processing is, at its core, the appraisal of the valence of perceived objects. This appraisal is in no way limited to artworks but is instead applicable to all types of perceived objects. Therefore, one way to naturalize aesthetics is to argue that such a system evolved first for the appraisal of objects of survival advantage, such as food sources, and was later co-opted in humans for the experience of artworks for the satisfaction of social needs. Copyright © 2011 Elsevier Inc. All rights reserved.
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When anticipation beats accuracy: Threat alters memory for dynamic scenes.
Greenstein, Michael; Franklin, Nancy; Martins, Mariana; Sewack, Christine; Meier, Markus A
2016-05-01
Threat frequently leads to the prioritization of survival-relevant processes. Much of the work examining threat-related processing advantages has focused on the detection of static threats or long-term memory for details. In the present study, we examined immediate memory for dynamic threatening situations. We presented participants with visually neutral, dynamic stimuli using a representational momentum (RM) paradigm, and manipulated threat conceptually. Although the participants in both the threatening and nonthreatening conditions produced classic RM effects, RM was stronger for scenarios involving threat (Exps. 1 and 2). Experiments 2 and 3 showed that this effect does not generalize to the nonthreatening objects within a threatening scene, and that it does not extend to arousing happy situations. Although the increased RM effect for threatening objects by definition reflects reduced accuracy, we argue that this reduced accuracy may be offset by a superior ability to predict, and thereby evade, a moving threat.
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Embryonic background risk promotes the survival of tadpoles facing surface predators
Chivers, Douglas P.; Ferrari, Maud C. O.
2018-01-01
Exposure to intense predation risk can induce morphological and behavioural phenotypes that prepare prey, often at young ages, for surviving attacks from unknown predators. However, previous studies revealed that this survival advantage depended on the predator species. Here, we used alarm cues from injured conspecifics to simulate a period of high predation risk for embryonic wood frogs, Lithobates sylvaticus. Two weeks post-hatching, we tested whether the embryonic risk exposure influenced survival in encounters with two novel predators: (1) a spider (Dolomedes sp.) that ambushes prey exclusively on the surface of the water, and (2) the adult predacious diving beetle (Dytiscus sp.) which displays underwater sit-and-wait posture and pursuit tactics. Tadpoles exposed to embryonic high-risk survived longer when encountering spiders, whereas background risk had no influence on survival with adult beetles. These findings, coupled with survival studies involving other predator types, indicate that a high-risk environment promotes tadpole survival in future encounters with unknown sit-and-wait predators, but at the cost of increased vulnerability to novel predators capable of active pursuit. PMID:29561913
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Diversity and natural functions of antibiotics produced by beneficial and plant pathogenic bacteria.
Raaijmakers, Jos M; Mazzola, Mark
2012-01-01
Soil- and plant-associated environments harbor numerous bacteria that produce antibiotic metabolites with specific or broad-spectrum activities against coexisting microorganisms. The function and ecological importance of antibiotics have long been assumed to yield a survival advantage to the producing bacteria in the highly competitive but resource-limited soil environments through direct suppression. Although specific antibiotics may enhance producer persistence when challenged by competitors or predators in soil habitats, at subinhibitory concentrations antibiotics exhibit a diversity of other roles in the life history of the producing bacteria. Many processes modulated by antibiotics may be inherently critical to the producing bacterium, such as the acquisition of substrates or initiation of developmental changes that will ensure survival under stressful conditions. Antibiotics may also have roles in more complex interactions, including in virulence on host plants or in shaping the outcomes of multitrophic interactions. The innate functions of antibiotics to producing bacteria in their native ecosystem are just beginning to emerge, but current knowledge already reveals a breadth of activities well beyond the historical perspective of antibiotics as weaponry in microbial conflicts.
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Muñoz, David J.; Miller, David A.W.; Sutherland, Chris; Grant, Evan H. Campbell
2016-01-01
The cryptic behavior and ecology of herpetofauna make estimating the impacts of environmental change on demography difficult; yet, the ability to measure demographic relationships is essential for elucidating mechanisms leading to the population declines reported for herpetofauna worldwide. Recently developed spatial capture–recapture (SCR) methods are well suited to standard herpetofauna monitoring approaches. Individually identifying animals and their locations allows accurate estimates of population densities and survival. Spatial capture–recapture methods also allow estimation of parameters describing space-use and movement, which generally are expensive or difficult to obtain using other methods. In this paper, we discuss the basic components of SCR models, the available software for conducting analyses, and the experimental designs based on common herpetological survey methods. We then apply SCR models to Red-backed Salamander (Plethodon cinereus), to determine differences in density, survival, dispersal, and space-use between adult male and female salamanders. By highlighting the capabilities of SCR, and its advantages compared to traditional methods, we hope to give herpetologists the resource they need to apply SCR in their own systems.
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Wound healing and longevity: Lessons from long-lived αMUPA mice
Yanai, Hagai; Toren, Dimitri; Vierlinger, Klemens; Hofner, Manuela; Nöhammer, Christa; Chilosi, Marco; Budovsky, Arie; Fraifeld, Vadim E.
2015-01-01
Does the longevity phenotype offer an advantage in wound healing (WH)? In an attempt to answer this question, we explored skin wound healing in the long-lived transgenic αMUPA mice, a unique model of genetically extended life span. These mice spontaneously eat less, preserve their body mass, are more resistant to spontaneous and induced tumorigenesis and live longer, thus greatly mimicking the effects of caloric restriction (CR). We found that αMUPA mice showed a much slower age-related decline in the rate of WH than their wild-type counterparts (FVB/N). After full closure of the wound, gene expression in the skin of old αMUPA mice returned close to basal levels. In contrast, old FVB/N mice still exhibited significant upregulation of genes associated with growth-promoting pathways, apoptosis and cell-cell/cell-extra cellular matrix interaction, indicating an ongoing tissue remodeling or an inability to properly shut down the repair process. It appears that the CR-like longevity phenotype is associated with more balanced and efficient WH mechanisms in old age, which could ensure a long-term survival advantage. PMID:25960543
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Advances in Monitoring Cell-Based Therapies with Magnetic Resonance Imaging: Future Perspectives
Ngen, Ethel J.; Artemov, Dmitri
2017-01-01
Cell-based therapies are currently being developed for applications in both regenerative medicine and in oncology. Preclinical, translational, and clinical research on cell-based therapies will benefit tremendously from novel imaging approaches that enable the effective monitoring of the delivery, survival, migration, biodistribution, and integration of transplanted cells. Magnetic resonance imaging (MRI) offers several advantages over other imaging modalities for elucidating the fate of transplanted cells both preclinically and clinically. These advantages include the ability to image transplanted cells longitudinally at high spatial resolution without exposure to ionizing radiation, and the possibility to co-register anatomical structures with molecular processes and functional changes. However, since cellular MRI is still in its infancy, it currently faces a number of challenges, which provide avenues for future research and development. In this review, we describe the basic principle of cell-tracking with MRI; explain the different approaches currently used to monitor cell-based therapies; describe currently available MRI contrast generation mechanisms and strategies for monitoring transplanted cells; discuss some of the challenges in tracking transplanted cells; and suggest future research directions. PMID:28106829
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Plumage polymorphism and fitness in Swainson's hawks.
Briggs, C W; Collopy, M W; Woodbridge, B
2011-10-01
We examine the maintenance of a plumage polymorphism, variation in plumages among the same age and sex class within a population, in a population of Swainson's Hawks. We take advantage of 32 years of data to examine two prevalent hypotheses used to explain the persistence of morphs: apostatic selection and heterozygous advantage. We investigate differences in fitness among three morph classes of a melanistic trait in Swainson's Hawks: light (7% of the local breeding population), intermediate (57%) and dark (36%). Specifically, we examined morph differences in adult apparent survival, breeding success, annual number of fledglings produced, probability of offspring recruitment into the breeding population and lifetime reproductive success (LRS). If apostatic selection were a factor in maintaining morphs, we would expect that individuals with the least frequent morph would perform best in one or more of these fitness categories. Alternatively, if heterozygous advantage played a role in the maintenance of this polymorphism, we would expect heterozygotes (i.e. intermediate morphs) to have one or more increased rates in these categories. We found no difference in adult apparent survival between morph classes. Similarly, there were no differences in breeding success, nest productivity, LRS or probability of recruitment of offspring between parental morph. We conclude that neither apostatic selection nor heterozygous advantage appear to play a role in maintaining morphs in this population. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.
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Rational use of intensity-modulated radiation therapy: the importance of clinical outcome.
De Neve, Wilfried; De Gersem, Werner; Madani, Indira
2012-01-01
During the last 2 decades, intensity-modulated radiation therapy (IMRT) became a standard technique despite its drawbacks of volume delineation, planning, robustness of delivery, challenging quality assurance, and cost as compared with non-IMRT. The theoretic advantages of IMRT dose distributions are generally accepted, but the clinical advantages remain debatable because of the lack of clinical assessment of the effort that is required to overshadow the disadvantages. Rational IMRT use requires a positive advantage/drawback balance. Only 5 randomized clinical trials (RCTs), 3 in the breast and 2 in the head and neck, which compare IMRT with non-IMRT (2-dimensional technique in four fifths of the trials), have been published (as of March 2011), and all had toxicity as the primary endpoint. More than 50 clinical trials compared results of IMRT-treated patients with a non-IMRT group, mostly historical controls. RCTs systematically showed a lower toxicity in IMRT-treated patients, and the non-RCTs confirmed these findings. Toxicity reduction, counterbalancing the drawbacks of IMRT, was convincing for breast and head and neck IMRT. For other tumor sites, the arguments favoring IMRT are weaker because of the inability to control bias outside the randomized setting. For anticancer efficacy endpoints, like survival, disease-specific survival, or locoregional control, the balance between advantages and drawbacks is fraught with uncertainties because of the absence of robust clinical data. Copyright © 2012 Elsevier Inc. All rights reserved.
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On the susceptibility of adaptive memory to false memory illusions.
Howe, Mark L; Derbish, Mary H
2010-05-01
Previous research has shown that survival-related processing of word lists enhances retention for that material. However, the claim that survival-related memories are more accurate has only been examined when true recall and recognition of neutral material has been measured. In the current experiments, we examined the adaptive memory superiority effect for different types of processing and material, measuring accuracy more directly by comparing true and false recollection rates. Survival-related information and processing was examined using word lists containing backward associates of neutral, negative, and survival-related critical lures and type of processing (pleasantness, moving, survival) was varied using an incidental memory paradigm. Across four experiments, results showed that survival-related words were more susceptible than negative and neutral words to the false memory illusion and that processing information in terms of its relevance to survival independently increased this susceptibility to the false memory illusion. Overall, although survival-related processing and survival-related information resulted in poorer, not more accurate, memory, such inaccuracies may have adaptive significance. These findings are discussed in the context of false memory research and recent theories concerning the importance of survival processing and the nature of adaptive memory. Copyright 2009 Elsevier B.V. All rights reserved.
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2012-01-01
Introduction Conventional monophasic defibrillators for out-of-hospital cardiac-arrest patients have been replaced with biphasic defibrillators. However, the advantage of biphasic over monophasic defibrillation for pediatric out-of-hospital cardiac-arrest patients remains unknown. This study aimed to compare the survival outcomes of pediatric out-of-hospital cardiac-arrest patients who underwent monophasic defibrillation with those who underwent biphasic defibrillation. Methods This prospective, nationwide, population-based observational study included pediatric out-of-hospital cardiac-arrest patients from January 1, 2005, to December 31, 2009. The primary outcome measure was survival at 1 month with minimal neurologic impairment. The secondary outcome measures were survival at 1 month and the return of spontaneous circulation before hospital arrival. Multivariable logistic regression analysis was performed to identify the independent association between defibrillator type (monophasic or biphasic) and outcomes. Results Among 5,628 pediatric out-of-hospital cardiac-arrest patients (1 through 17 years old), 430 who received defibrillation shock with monophasic or biphasic defibrillator were analyzed. The number of patients who received defibrillation shock with monophasic defibrillator was 127 (30%), and 303 (70%) received defibrillation shock with biphasic defibrillator. The survival rates at 1 month with minimal neurologic impairment were 17.5% and 24.4%, the survival rates at 1 month were 32.3% and 35.6%, and the rates of return of spontaneous circulation before hospital arrival were 24.4% and 27.4% in the monophasic and biphasic defibrillator groups, respectively. Hierarchic logistic regression analyses by using generalized estimation equations found no significant difference between the two groups in terms of 1-month survival with minimal neurologic impairment (odds ratio (OR), 1.57; 95% confidence interval (CI), 0.87 to 2.83; P = 0.14) and 1-month survival (OR, 1.38; 95% CI, 0.87 to 2.18; P = 0.17). Conclusions The present nationwide population-based observational study could not confirm an advantage of biphasic over monophasic defibrillators for pediatric OHCA patients. PMID:23148767
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Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence
Liu, Chun-Jen; Chang, Juliana; Lee, Po-Huang; Lin, Deng-Yn; Wu, Cheng-Chung; Jeng, Long-Bin; Lin, Yih-Jyh; Mok, King-Tong; Lee, Wei-Chen; Yeh, Hong-Zen; Ho, Ming-Chih; Yang, Sheng-Shun; Yang, Mei-Due; Yu, Ming-Chin; Hu, Rey-Heng; Peng, Cheng-Yuan; Lai, Kuan-Lang; Chang, Stanley Shi-Chung; Chen, Pei-Jer
2014-01-01
AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection. METHODS: A total of 143 patients (83.1% of the 172 participants in the phase II study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase II trial. Safety parameters and the following efficacy endpoints were investigated: (1) time to recurrence; (2) disease-free survival; and (3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group: (1) the recurrence-free rate increased from 50% to 63%, and (2) time to recurrence at the 36th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate (11 out of 54 patients). Additionally, subgroup analyses of patients with (1) multiple tumors or a single tumor ≥ 2 cm; and (2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage (56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC. PMID:25170226
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Yu, Zi-Chao; Chen, Xiu-Lan; Shen, Qing-Tao; Zhao, Dian-Li; Tang, Bai-Lu; Su, Hai-Nan; Wu, Zhao-Yu; Qin, Qi-Long; Xie, Bin-Bin; Zhang, Xi-Ying; Yu, Yong; Zhou, Bai-Cheng; Chen, Bo; Zhang, Yu-Zhong
2015-01-01
Sea ice is one of the most frigid environments for marine microbes. In contrast to other ocean ecosystems, microbes in permanent sea ice are space confined and subject to many extreme conditions, which change on a seasonal basis. How these microbial communities are regulated to survive the extreme sea ice environment is largely unknown. Here, we show that filamentous phages regulate the host bacterial community to improve survival of the host in permanent Arctic sea ice. We isolated a filamentous phage, f327, from an Arctic sea ice Pseudoalteromonas strain, and we demonstrated that this type of phage is widely distributed in Arctic sea ice. Growth experiments and transcriptome analysis indicated that this phage decreases the host growth rate, cell density and tolerance to NaCl and H2O2, but enhances its motility and chemotaxis. Our results suggest that the presence of the filamentous phage may be beneficial for survival of the host community in sea ice in winter, which is characterized by polar night, nutrient deficiency and high salinity, and that the filamentous phage may help avoid over blooming of the host in sea ice in summer, which is characterized by polar day, rich nutrient availability, intense radiation and high concentration of H2O2. Thus, while they cannot kill the host cells by lysing them, filamentous phages confer properties advantageous to host survival in the Arctic sea ice environment. Our study provides a foremost insight into the ecological role of filamentous phages in the Arctic sea ice ecosystem. PMID:25303713
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Evolutionary history and distance dependence control survival of dipterocarp seedlings.
Bagchi, Robert; Press, Malcolm C; Scholes, Julie D
2010-01-01
One important hypothesis to explain tree-species coexistence in tropical forests suggests that increased attack by natural enemies near conspecific trees gives locally rare species a competitive advantage. Host ranges of natural enemies generally encompass several closely related plant taxa suggesting that seedlings should also do poorly around adults of closely related species. We investigated the effects of adult Parashorea malaanonan on seedling survival in a Bornean rain forest. Survival of P. malaanonan seedlings was highest at intermediate distances from parent trees while heterospecific seedlings were unaffected by distance. Leaf herbivores did not drive this relationship. Survival of seedlings was lowest for P. malaanonan, and increased with phylogenetic dissimilarity from this species, suggesting that survival of close relatives of common species is reduced. This study suggests that distance dependence contributes to species coexistence and highlights the need for further investigation into the role of shared plant enemies in community dynamics.
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Strategic focus. A game plan for collaboration in a competitive marketplace.
Tweed, S C
1993-10-01
How can home care agencies brace for the coming changes and not only survive health care reform, but thrive in it? Collaboration is an effective tool for gaining competitive advantage in the marketplace.
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Robert-Richard, Elodie; Moreau-Gaudry, François; Lalanne, Magalie; Lamrissi-Garcia, Isabelle; Cario-André, Muriel; Guyonnet-Dupérat, Véronique; Taine, Laurence; Ged, Cécile; de Verneuil, Hubert
2008-01-01
Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. We used a recently obtained murine model to check the feasibility of gene therapy in this disease. Lentivirus-mediated transfer of the human UROS cDNA into hematopoietic stem cells (HSCs) from Urosmut248 mice resulted in a complete and long-term enzymatic, metabolic, and phenotypic correction of the disease, favored by a survival advantage of corrected red blood cells. These results demonstrate that the cure of this mouse model of CEP at a moderate transduction level supports the proof of concept of a gene therapy in this disease by transplantation of genetically modified hematopoietic stem cells. PMID:18179890
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The puzzle of Muslim advantage in child survival in India.
Bhalotra, Sonia; Valente, Christine; van Soest, Arthur
2010-03-01
The socioeconomic status of Indian Muslims is, on average, considerably lower than that of upper-caste Hindus. Muslims nevertheless exhibit substantially higher child survival rates, and have done for decades. This paper analyses this seeming puzzle. A decomposition of the survival differential confirms that some compositional effects favour Muslims but that, overall, differences in characteristics and especially the Muslim deficit in parental education predict a Muslim disadvantage. The results of this study contribute to a recent literature that debates the importance of socioeconomic status (SES) in determining health and survival. They augment a growing literature on the role of religion or culture as encapsulating important unobservable behaviours or endowments that influence health, indeed, enough to reverse the SES gradient that is commonly observed. Copyright 2009 Elsevier B.V. All rights reserved.
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Combination of palbociclib and radiotherapy for glioblastoma
Whittaker, Shane; Madani, Daniel; Joshi, Swapna; Chung, Sylvia A; Johns, Terrance; Day, Bryan; Khasraw, Mustafa; McDonald, Kerrie L
2017-01-01
The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic. PMID:28690875
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Longo, Ana V; Zamudio, Kelly R
2017-02-01
Fluctuating environments can modulate host-pathogen interactions by providing a temporary advantage to one of the interacting organisms. However, we know very little about how environmental conditions facilitate beneficial interactions between hosts and their microbial communities, resulting in individual persistence with a particular pathogen. Here, we experimentally infected Eleutherodactylus coqui frogs with the fungal pathogen Batrachochytrium dendrobatidis (Bd) under environmental conditions known to confer the survival advantage to the host during the warm-wet season, or alternatively to the pathogen during the cool-dry season. We used 16S rRNA amplicon sequencing to quantify changes in bacterial richness and phylogenetic diversity, and identified operational taxonomic units (OTUs) that became overrepresented or suppressed as a consequence of Bd infection. During the warm-wet season, frogs limited Bd infections, recruited putatively beneficial bacteria and returned to pre-infection levels of richness and phylogenetic diversity. In contrast, during the cool-dry season, Bd infections kept increasing through time, and bacterial diversity remained constant. Our findings confirm that infection outcome not only depends on abiotic factors, but also on biotic interactions between hosts and their associated bacterial communities.
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Stanton, Margaret A; Lonsdorf, Elizabeth V; Pusey, Anne E; Goodall, Jane; Murray, Carson M
2014-08-01
Parental investment theory predicts that maternal resources are finite and allocated among offspring based on factors including maternal age and condition, and offspring sex and parity. Among humans, firstborn children are often considered to have an advantage and receive greater investment than their younger siblings. However, conflicting evidence for this "firstborn advantage" between modern and hunter-gatherer societies raises questions about the evolutionary history of differential parental investment and birth order. In contrast to humans, most non-human primate firstborns belong to young, inexperienced mothers and exhibit higher mortality than laterborns. In this study, we investigated differences in maternal investment and offspring outcomes based on birth order (firstborn vs. later-born) among wild chimpanzees ( Pan troglodyte schweinfurthii ). During the critical first year of life, primiparous mothers nursed, groomed, and played with their infants more than did multiparous mothers. Furthermore, this pattern of increased investment in firstborns appeared to be compensatory, as probability of survival did not differ by birth order. Our study did not find evidence for a firstborn advantage as observed in modern humans but does suggest that unlike many other primates, differences in maternal behavior help afford chimpanzee first-borns an equal chance of survival.
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Autonomous intelligent military robots: Army ants, killer bees, and cybernetic soldiers
NASA Astrophysics Data System (ADS)
Finkelstein, Robert
The rationale for developing autonomous intelligent robots in the military is to render conventional warfare systems ineffective and indefensible. The Desert Storm operation demonstrated the effectiveness of such systems as unmanned air and ground vehicles and indicated the future possibilities of robotic technology. Robotic military vehicles would have the advantages of expendability, low cost, lower complexity compared to manned systems, survivability, maneuverability, and a capability to share in instantaneous communication and distributed processing of combat information. Basic characteristics of intelligent systems and hierarchical control systems with sensor inputs are described. Genetic algorithms are seen as a means of achieving appropriate levels of intelligence in a robotic system. Potential impacts of robotic technology in the military are outlined.
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Fu, Huihui; Yuan, Jie; Gao, Haichun
2015-10-15
Facultative bacteria can grow under either oxic or anoxic conditions. While oxygen provides substantial advantages in energy yield by respiration, it can become life-threatening because of reactive oxygen species that derive from the molecule naturally. Thus, to survive and thrive in a given niche, these bacteria have to constantly regulate physiological processes to make maximum benefits from oxygen respiration while restraining oxidative stress. Molecular mechanisms and physiological consequences of oxidative stress have been under extensive investigation for decades, mostly on research model Escherichia coli, from which our understanding of bacterial oxidative stress response is largely derived. Nevertheless, given that bacteria live in enormously diverse environments, to cope with oxidative stress different strategies are conceivably developed. Copyright © 2015 Elsevier Inc. All rights reserved.
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The harm of petroleum-polluted soil and its remediation research
NASA Astrophysics Data System (ADS)
Wang, Shuguang; Xu, Yan; Lin, Zhaofeng; Zhang, Jishi; Norbu, Namkha; Liu, Wei
2017-08-01
Land resources are the foundation of human's survival and development, and it's one of the most valuable natural resources of each country. In view of the serious problems of petroleum pollution to soil caused during the exploration and development processes, this article based on a large number of literature researches, firstly discussed the compositions and properties of petroleum contaminants, secondly investigated some restoration methods for the current situation of petroleum polluted soil, compared and analyzed the advantages and disadvantages of three kinds of bioremediation technologies. Finally, according to the deficiencies of previous research and existing problems, made an outlook of the physical and chemical remediation, bioremediation, and microbe-plant remediation, to provide some enlightenments for petroleum-contaminated soil remediation.
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Milbrath, Meghan O; van Tran, Toan; Huang, Wei-Fong; Solter, Leellen F; Tarpy, David R; Lawrence, Frank; Huang, Zachary Y
2015-02-01
Honey bees (Apis mellifera) are infected by two species of microsporidia: Nosema apis and Nosemaceranae. Epidemiological evidence indicates that N. ceranae may be replacing N. apis globally in A. mellifera populations, suggesting a potential competitive advantage of N. ceranae. Mixed infections of the two species occur, and little is known about the interactions among the host and the two pathogens that have allowed N. ceranae to become dominant in most geographical areas. We demonstrated that mixed Nosema species infections negatively affected honey bee survival (median survival=15-17days) more than single species infections (median survival=21days and 20days for N. apis and N. ceranae, respectively), with median survival of control bees of 27days. We found similar rates of infection (percentage of bees with active infections after inoculation) for both species in mixed infections, with N. apis having a slightly higher rate (91% compared to 86% for N. ceranae). We observed slightly higher spore counts in bees infected with N. ceranae than in bees infected with N. apis in single microsporidia infections, especially at the midpoint of infection (day 10). Bees with mixed infections of both species had higher spore counts than bees with single infections, but spore counts in mixed infections were highly variable. We did not see a competitive advantage for N. ceranae in mixed infections; N. apis spore counts were either higher or counts were similar for both species and more N. apis spores were produced in 62% of bees inoculated with equal dosages of the two microsporidian species. N. ceranae does not, therefore, appear to have a strong within-host advantage for either infectivity or spore growth, suggesting that direct competition in these worker bee mid-guts is not responsible for its apparent replacement of N. apis. Copyright © 2014 Elsevier Inc. All rights reserved.
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Huang, Bin-Tao; Tan, Yan; Zhao, Wei-Hong; Zeng, Qing-Chun; Li, Bing-Sheng; Chen, Rui-Lin
2014-02-01
This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM). Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65-89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52). Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P < 0.05). The overall safety profiles showed that 26 of 128 (20.3 %) patients died in the PAD arm, while 13 of 175 patients died (7.4 %) in the CBd group (P < 0.01). Similarly, the PAD arm had a higher serious infection rate than that of the CBd arm (39.2 vs. 13.1 %, P < 0.01). Bortezomib benefits elderly patients with newly diagnosed MM; they achieve satisfactory treatment responses and survival advantages. Further, patients treated with CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.
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Dying to remember, remembering to survive: mortality salience and survival processing.
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.
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Vanli, Güliz; Sempoux, Christine; Widmann, Christian
2017-06-01
Activation of oncogenes is the initial step in cellular transformation. Oncogenes favor aberrant proliferation, which, at least initially, induces cellular stress. This oncogenic stress can act as a safeguard mechanism against further transformation by inducing senescence or apoptosis. Yet, the few premalignant cells that tolerate and escape these senescent or apoptotic responses are those that will ultimately generate tumors. The caspase-3/p120 RasGAP module is a stress-sensing device that promotes survival under mild stress conditions. A point mutation in RasGAP that prevents its cleavage by caspase-3 inactivates the pro-survival capacity of the device. When the mice homozygous for this mutation (D455A knock-in mice) are patho-physiologically challenged, they experience much stronger cellular damage than their wild-type counterparts and the affected organs rapidly lose their functionality. We reasoned that the caspase-3/p120 RasGAP module could help premalignant cells to cope with oncogenic stress and hence favor the development of tumors. Using gamma-irradiation and N-ethyl-N-nitrosourea (ENU) as tumor initiators, we assessed the survival advantage that the caspase-3/p120 RasGAP module could provide to premalignant cells. No difference in overall mortality between wild-type and D455A knock-in mice were observed. However, the number of ENU-induced liver tumors in the knock-in mice was higher than in control mice. These results indicate that the caspase-3/p120 RasGAP stress-sensing module impacts on carcinogen-induced liver cancer incidence but not sufficiently so as to affect overall survival. Hence, gamma irradiation and ENU-induced tumorigenesis processes do not critically rely on a survival mechanism that contributes to the maintenance of organ homeostasis in stressed healthy tissues. © 2017 Wiley Periodicals, Inc.
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Value-based contracting innovated Medicare advantage healthcare delivery and improved survival.
Mandal, Aloke K; Tagomori, Gene K; Felix, Randell V; Howell, Scott C
2017-02-01
In Medicare Advantage (MA) with its CMS Hierarchical Condition Categories (CMS-HCC) payment model, CMS reimburses private plans (Medicare Advantage Organizations [MAOs]) with prospective, monthly, health-based or risk-adjusted, capitated payments. The effect of this payment methodology on healthcare delivery remains debatable. How value-based contracting generates cost efficiencies and improves clinical outcomes in MA is studied. A difference in contracting arrangements between an MAO and 2 provider groups facilitated an intervention-control, preintervention-postintervention, difference-in-differences approach among statistically similar, elderly, community-dwelling MA enrollees within one metropolitan statistical area. Starting in 2009, for intervention-group MA enrollees, the MAO and a provider group agreed to full-risk capitation combined with a revenue gainshare. The gainshare was based on increases in the Risk Adjustment Factor (RAF), which modified the CMS-HCC payments. For the control group, the MAO continued to reimburse another provider group through fee-for-service. RAF, utilization, and survival were followed until December 31, 2012. The intervention group's mean RAF increased significantly (P <.001), estimating $2,519,544 per 1000 members of additional revenue. The intervention increased office-based visits (P <.001). Emergency department visits (P <.001) and inpatient hospital admissions (P = .002) decreased. This change in utilization saved $2,071,293 per 1000 enrollees. By intensifying office-based care for these MA enrollees with multiple comorbidities, a 6% survival benefit with a 32.8% lower hazard of death (P <.001) was achieved. Value-based contracting can drive utilization patterns and improve clinical outcomes among chronically ill, elderly MA members.
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Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M
2017-04-25
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82-0.98)). Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted.
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NASA Astrophysics Data System (ADS)
Lukman, Iing; Ibrahim, Noor A.; Daud, Isa B.; Maarof, Fauziah; Hassan, Mohd N.
2002-03-01
Survival analysis algorithm is often applied in the data mining process. Cox regression is one of the survival analysis tools that has been used in many areas, and it can be used to analyze the failure times of aircraft crashed. Another survival analysis tool is the competing risks where we have more than one cause of failure acting simultaneously. Lunn-McNeil analyzed the competing risks in the survival model using Cox regression with censored data. The modified Lunn-McNeil technique is a simplify of the Lunn-McNeil technique. The Kalbfleisch-Prentice technique is involving fitting models separately from each type of failure, treating other failure types as censored. To compare the two techniques, (the modified Lunn-McNeil and Kalbfleisch-Prentice) a simulation study was performed. Samples with various sizes and censoring percentages were generated and fitted using both techniques. The study was conducted by comparing the inference of models, using Root Mean Square Error (RMSE), the power tests, and the Schoenfeld residual analysis. The power tests in this study were likelihood ratio test, Rao-score test, and Wald statistics. The Schoenfeld residual analysis was conducted to check the proportionality of the model through its covariates. The estimated parameters were computed for the cause-specific hazard situation. Results showed that the modified Lunn-McNeil technique was better than the Kalbfleisch-Prentice technique based on the RMSE measurement and Schoenfeld residual analysis. However, the Kalbfleisch-Prentice technique was better than the modified Lunn-McNeil technique based on power tests measurement.
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Dey, Mahua; Chang, Alan L; Miska, Jason; Wainwright, Derek A; Ahmed, Atique U; Balyasnikova, Irina V; Pytel, Peter; Han, Yu; Tobias, Alex; Zhang, Lingjiao; Qiao, Jian; Lesniak, Maciej S
2015-07-01
Dendritic cells (DCs) are professional APCs that are traditionally divided into two distinct subsets, myeloid DC (mDCs) and plasmacytoid DC (pDCs). pDCs are known for their ability to secrete large amounts of IFN-α. Apart from IFN-α production, pDCs can also process Ag and induce T cell immunity or tolerance. In several solid tumors, pDCs have been shown to play a critical role in promoting tumor immunosuppression. We investigated the role of pDCs in the process of glioma progression in the syngeneic murine model of glioma. We show that glioma-infiltrating pDCs are the major APC in glioma and are deficient in IFN-α secretion (p < 0.05). pDC depletion leads to increased survival of the mice bearing intracranial tumor by decreasing the number of regulatory T cells (Tregs) and by decreasing the suppressive capabilities of Tregs. We subsequently compared the ability of mDCs and pDCs to generate effective antiglioma immunity in a GL261-OVA mouse model of glioma. Our data suggest that mature pDCs and mDCs isolated from naive mice can be effectively activated and loaded with SIINFEKL Ag in vitro. Upon intradermal injection in the hindleg, a fraction of both types of DCs migrate to the brain and lymph nodes. Compared to mice vaccinated with pDC or control mice, mice vaccinated with mDCs generate a robust Th1 type immune response, characterized by high frequency of CD4(+)T-bet(+) T cells and CD8(+)SIINFEKEL(+) T cells. This robust antitumor T cell response results in tumor eradication and long-term survival in 60% of the animals (p < 0.001). Copyright © 2015 by The American Association of Immunologists, Inc.
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Russell, Robyn J; Scott, Colin; Jackson, Colin J; Pandey, Rinku; Pandey, Gunjan; Taylor, Matthew C; Coppin, Christopher W; Liu, Jian-Wei; Oakeshott, John G
2011-01-01
Here, we compare the evolutionary routes by which bacteria and insects have evolved enzymatic processes for the degradation of four classes of synthetic chemical insecticide. For insects, the selective advantage of such degradative activities is survival on exposure to the insecticide, whereas for the bacteria the advantage is simply a matter of access to additional sources of nutrients. Nevertheless, bacteria have evolved highly efficient enzymes from a wide variety of enzyme families, whereas insects have relied upon generalist esterase-, cytochrome P450- and glutathione-S-transferase-dependent detoxification systems. Moreover, the mutant insect enzymes are less efficient kinetically and less diverged in sequence from their putative ancestors than their bacterial counterparts. This presumably reflects several advantages that bacteria have over insects in the acquisition of new enzymatic functions, such as a broad biochemical repertoire from which new functions can be evolved, large population sizes, high effective mutation rates, very short generation times and access to genetic diversity through horizontal gene transfer. Both the insect and bacterial systems support recent theory proposing that new biochemical functions often evolve from ‘promiscuous’ activities in existing enzymes, with subsequent mutations then enhancing those activities. Study of the insect enzymes will help in resistance management, while the bacterial enzymes are potential bioremediants of insecticide residues in a range of contaminated environments. PMID:25567970
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Meyer, D M; Bennett, L E; Novick, R J; Hosenpud, J D
2001-09-01
The appropriate age to perform bilateral, sequential lung transplants (BSLT) in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Although single lung transplant (SLT) offers an advantage in terms of organ availability, the long-term survival may not warrant this strategy in all age groups. We analyzed 2,260 lung transplant recipients (1835 SLT, 425 BSLT) with COPD recorded in the International Society for Heart and Lung Transplantation/United Network for Organ Sharing thoracic registry between January 1991 and December 1997. To assess mortality, we performed univariate (Kaplan-Meier method and the chi-square statistic) and multivariate analyses (proportional hazards method). Because of incomplete morbidity data in the international registry, only data from U.S. centers (n = 1778, 1467 SLT, 311 BSLT) were used in the morbidity analysis. Survival rates (%) computed using the Kaplan-Meier method at 30 days, 1 year, and 5 years for the patients aged < 50 years were 93.6, 80.2, and 43.6, respectively, for the SLT patients, and 94.9, 84.7, and 68.2, respectively, for the BSLT patients. For patients aged 50 to 60 years, survival rates (%) were 93.5, 79.4, and 39.8 for the SLT patients compared with 93.0, 79.7, and 60.5 for the BSLT patients. For those aged > 60 years, SLT survival (%) was 93.0, 72.9, and 36.4, compared with 77.8 and 66.0 for the BSLT group (a 5-year rate could not be completed in this group). The multivariate model showed a higher risk ratio for mortality in patients aged 40 to 57 years who received SLT vs BSLT. Recipient age and procedure type did not appear to affect the development of rejection, bronchiolitis obliterans, bronchial stricture, or lung infection. Single lung transplant may offer acceptable early survival for patients with end-stage respiratory failure. However, long-term survival data favors BSLT in recipients until approximately age 60 years. These data suggest that a BSLT approach offers a significant survival advantage to recipients younger than 60 years of age.
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Automating Microbial Directed Evolution For Bioengineering Applications
NASA Astrophysics Data System (ADS)
Lee, A.; Demachkie, I. S.; Sardesh, N.; Arismendi, D.; Ouandji, C.; Wang, J.; Blaich, J.; Gentry, D.
2016-12-01
From a micro-biology perspective, directed evolution is a technique that uses controlled environmental pressures to select for a desired phenotype. Directed evolution has the distinct advantage over rational design of not needing extensive knowledge of the genome or pathways associated with a microorganism to induce phenotypes. However, there are currently limitations to the applicability of this technique including being time-consuming, error-prone, and dependent on existing assays that may lack selectivity for the given phenotype. The AADEC (Autonomous Adaptive Directed Evolution Chamber) system is a proof-of-concept instrument to automate and improve the technique such that directed evolution can be used more effectively as a general bioengineering tool. A series of tests using the automated system and comparable by-hand survival assay measurements have been carried out using UV-C radiation and Escherichia coli cultures in order to demonstrate the advantages of the AADEC versus traditional implementations of directed evolution such as random mutagenesis. AADEC uses UV-C exposure as both a source of environmental stress and mutagenesis, so in order to evaluate the UV-C tolerance obtained from the cultures, a manual UV-C exposure survival assay was developed alongside the device to compare the survival fractions at a fixed dosage. This survival assay involves exposing E.coli to UV-C radiation using a custom-designed exposure hood to control the flux and dose. Surviving cells are counted then transferred to the next iteration and so on for several iterations to calculate the survival fractions for each exposure iteration. This survival assay primarily serves as a baseline for the AADEC device, allowing quantification of the differences between the AADEC system over the manual approach. The primary data of comparison is survival fractions; this is obtained by optical density and plate counts in the manual assay and by optical density growth curve fits pre- and post-exposure in the automated case. This data can then be compiled to calculate trends over the iterations to characterize increasing UV-C resistance of the E.coli strains. The observed trends are statistically indistinguishable through several iterations from both sources.
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Cancer survival in Eastern and Western Germany after the fall of the iron curtain.
Jansen, Lina; Gondos, Adam; Eberle, Andrea; Emrich, Katharina; Holleczek, Bernd; Katalinic, Alexander; Brenner, Hermann
2012-09-01
Prior to the German reunification, cancer survival was much lower in East than in West Germany. We compare cancer survival between Eastern and Western Germany in the early twenty-first century, i.e. the second decade after the German reunification. Using data from 11 population-based cancer registries covering a population of 33 million people, 5-year age-standardized relative survival for the time period 2002-2006 was estimated for the 25 most common cancers using model-based period analysis. In 2002-2006, 5-year relative survival was very similar for most cancers, with differences below 3% units for 20 of 25 cancer sites. Larger, statistically significant survival advantages were seen for oral cavity, oesophagus, and gallbladder cancer and skin melanoma in the West and for leukemia in the East. Our study shows that within two decades after the assimilation of political and health care systems, the former major survival gap of cancer patients in Eastern Germany has been essentially overcome. This result is encouraging as it suggests that, even though economic conditions have remained difficult in Eastern Germany, comparable health care provision may nevertheless enable comparable levels of cancer survival within a relatively short period of time.
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Textbooks: Prospects for the Technological Era.
ERIC Educational Resources Information Center
Bettex, Maurice
1995-01-01
Examines why textbooks will survive despite competition from new technological inventions. Discusses opposition to textbooks through the development of audiovisual aids, multimedia, and interactivity; advantages of textbooks over other educational media; development of print media; five principles for developing textbook content; and future…
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Re-analysis of survival data of cancer patients utilizing additive homeopathy.
Gleiss, Andreas; Frass, Michael; Gaertner, Katharina
2016-08-01
In this short communication we present a re-analysis of homeopathic patient data in comparison to control patient data from the same Outpatient´s Unit "Homeopathy in malignant diseases" of the Medical University of Vienna. In this analysis we took account of a probable immortal time bias. For patients suffering from advanced stages of cancer and surviving the first 6 or 12 months after diagnosis, respectively, the results show that utilizing homeopathy gives a statistically significant (p<0.001) advantage over control patients regarding survival time. In conclusion, bearing in mind all limitations, the results of this retrospective study suggest that patients with advanced stages of cancer might benefit from additional homeopathic treatment until a survival time of up to 12 months after diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Did 20 years of technological innovations in hemodialysis contribute to better patient outcomes?
Lameire, Norbert; Van Biesen, Wim; Vanholder, Raymond
2009-12-01
During the past two decades, impressive technological innovations have been introduced in the field of hemodialysis. This review analyzes whether these have been translated into better patient survival. The potential impacts of an increase in dialysis dosage, the preference of high-flux versus low-flux membranes, the choice between convection and diffusion as dialysis strategy, the chemical composition and biologic purity of dialysate, the effect of sodium, potassium, volume profiling, and the intradialytic volume monitoring aiming at improving hemodynamic stability are explored. Studies in which the dialysis dosage was increased were not associated with increased patient survival, whereas the superiority of high-flux over low-flux membranes is not convincingly demonstrated. Although strict evidence is lacking, observational data suggest an advantage of convective over pure diffusive strategies. Longer duration of the dialysis sessions and/or higher frequency of dialysis is probably beneficial, but the results of powerful randomized, controlled trials should be awaited. Sodium profiling has more disadvantages than advantages, whereas potassium profiling mainly in arrhythmia-prone patients with ventricular hypertrophy should be considered. Intradialytic blood volume monitoring has reduced intradialytic hypotension episodes, but hard evidence for improving patient survival is lacking. Overall, the major technological advances in dialysis have not yet been translated into longer patient survival. Optimal predialysis care in preventing the cardiovascular damage that accumulates before the start of dialysis and timely creation of an arteriovenous fistula as vascular access is a more effective and more economic strategy in the long-term outcome of the dialysis patient.
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Davenport, Andrew; Peters, Sanne A E; Bots, Michiel L; Canaud, Bernard; Grooteman, Muriel P C; Asci, Gulay; Locatelli, Francesco; Maduell, Francisco; Morena, Marion; Nubé, Menso J; Ok, Ercan; Torres, Ferran; Woodward, Mark; Blankestijn, Peter J
2016-01-01
Mortality remains high for hemodialysis patients. Online hemodiafiltration (OL-HDF) removes more middle-sized uremic toxins but outcomes of individual trials comparing OL-HDF with hemodialysis have been discrepant. Secondary analyses reported higher convective volumes, easier to achieve in larger patients, and improved survival. Here we tested different methods to standardize OL-HDF convection volume on all-cause and cardiovascular mortality compared with hemodialysis. Pooled individual patient analysis of four prospective trials compared thirds of delivered convection volume with hemodialysis. Convection volumes were either not standardized or standardized to weight, body mass index, body surface area, and total body water. Data were analyzed by multivariable Cox proportional hazards modeling from 2793 patients. All-cause mortality was reduced when the convective dose was unstandardized or standardized to body surface area and total body water; hazard ratio (95% confidence intervals) of 0.65 (0.51-0.82), 0.74 (0.58-0.93), and 0.71 (0.56-0.93) for those receiving higher convective doses. Standardization by body weight or body mass index gave no significant survival advantage. Higher convection volumes were generally associated with greater survival benefit with OL-HDF, but results varied across different ways of standardization for body size. Thus, further studies should take body size into account when evaluating the impact of delivered convection volume on mortality end points. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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Intraguild Competition of Three Noctuid Maize Pests.
Bentivenha, J P F; Baldin, E L L; Hunt, T E; Paula-Moraes, S V; Blankenship, E E
2016-08-01
The western bean cutworm Striacosta albicosta (Smith), the fall armyworm Spodoptera frugiperda (J. E. Smith), and the corn earworm Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) are among the major lepidopteran pests of maize in the United States, belonging to the same guild and injuring the reproductive tissues of this crop. Here, intraguild competition of these lepidopterans on non-Bt maize was evaluated through survival analysis of each species under laboratory and field conditions. Competition scenarios were carried out in arenas containing maize silk or ear tissue, using larvae on different stadium of development. Fitness cost competition studies were conducted to examine the influence of intraguild competition and cannibalism and predation rates on larval development. The survival of S. albicosta competing with the other species was significantly lower than in intraspecific competition, even when the larvae were more developed than the competitor. For S. frugiperda, survival remained high in the different competition scenarios, except when competing in a smaller stadium with H. zea Larvae of H. zea had a high rate of cannibalism, higher survival when competing against S. albicosta than S. frugiperda, and reduced survival when the H. zea larvae were at the same development stadium or smaller than the competitors. Based on fitness cost results, the absence of a competitor for the feeding source may confer an advantage to the larval development of S. frugiperda and H. zea Our data suggest that S. frugiperda has a competitive advantage against the other species, while S. albicosta has the disadvantage in the intraguild competition on non-Bt maize. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Fitness of artemisinin-resistant Plasmodium falciparum in vitro
Hott, Amanda; Tucker, Matthew S.; Casandra, Debora; Sparks, Kansas; Kyle, Dennis E.
2015-01-01
Objectives Drug resistance confers a fitness advantage to parasites exposed to frequent drug pressure, yet these mutations also may incur a fitness cost. We assessed fitness advantages and costs of artemisinin resistance in Plasmodium falciparum in vitro to understand how drug resistance will spread and evolve in a competitive environment. Methods Genotyping of SNPs, drug susceptibility assays and copy number determination were used to assess the impact of artemisinin resistance on parasite fitness. An artemisinin-resistant clone (C9) selected in vitro from an isogenic parental clone (D6) was used to conduct competitive growth studies to assess fitness of artemisinin resistance. The resistant and susceptible clones were mixed or grown alone in the presence and absence of drug pressure (dihydroartemisinin or pyrimethamine) to quantify the rate at which artemisinin resistance was gained or lost. Results We experimentally demonstrate for the first time that artemisinin resistance provides a fitness advantage that is selected for with infrequent exposure to drug, but is lost in the absence of exposure to artemisinin drugs. The best correlations with artemisinin resistance were decreased in vitro drug susceptibility to artemisinin derivatives, increased copy number of Pf3D7_1030100 and an SNP in Pf3D7_0307600. An SNP conferring an E208K mutation in the kelch gene (Pf3D7_1343700) was not associated with resistance. Furthermore, we observed second-cycle ring-stage dormancy induced by pyrimethamine, suggesting that dormancy is a fitness trait that provides an advantage for survival from antimalarial drug stress. Conclusions Artemisinin-resistant P. falciparum have a fitness advantage to survive and predominate in the population even in the face of infrequent exposure to artemisinin drugs. PMID:26203183
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Evolutionary game dynamics of controlled and automatic decision-making
NASA Astrophysics Data System (ADS)
Toupo, Danielle F. P.; Strogatz, Steven H.; Cohen, Jonathan D.; Rand, David G.
2015-07-01
We integrate dual-process theories of human cognition with evolutionary game theory to study the evolution of automatic and controlled decision-making processes. We introduce a model in which agents who make decisions using either automatic or controlled processing compete with each other for survival. Agents using automatic processing act quickly and so are more likely to acquire resources, but agents using controlled processing are better planners and so make more effective use of the resources they have. Using the replicator equation, we characterize the conditions under which automatic or controlled agents dominate, when coexistence is possible and when bistability occurs. We then extend the replicator equation to consider feedback between the state of the population and the environment. Under conditions in which having a greater proportion of controlled agents either enriches the environment or enhances the competitive advantage of automatic agents, we find that limit cycles can occur, leading to persistent oscillations in the population dynamics. Critically, however, these limit cycles only emerge when feedback occurs on a sufficiently long time scale. Our results shed light on the connection between evolution and human cognition and suggest necessary conditions for the rise and fall of rationality.
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Evolutionary game dynamics of controlled and automatic decision-making.
Toupo, Danielle F P; Strogatz, Steven H; Cohen, Jonathan D; Rand, David G
2015-07-01
We integrate dual-process theories of human cognition with evolutionary game theory to study the evolution of automatic and controlled decision-making processes. We introduce a model in which agents who make decisions using either automatic or controlled processing compete with each other for survival. Agents using automatic processing act quickly and so are more likely to acquire resources, but agents using controlled processing are better planners and so make more effective use of the resources they have. Using the replicator equation, we characterize the conditions under which automatic or controlled agents dominate, when coexistence is possible and when bistability occurs. We then extend the replicator equation to consider feedback between the state of the population and the environment. Under conditions in which having a greater proportion of controlled agents either enriches the environment or enhances the competitive advantage of automatic agents, we find that limit cycles can occur, leading to persistent oscillations in the population dynamics. Critically, however, these limit cycles only emerge when feedback occurs on a sufficiently long time scale. Our results shed light on the connection between evolution and human cognition and suggest necessary conditions for the rise and fall of rationality.
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Evans, W K
1997-04-01
Statistics Canada (Ottawa, Ontario, Canada) is in the process of developing the Population Health Model to simulate the health and common illnesses of Canadians. The Population Health Model incorporates a lung cancer module that is based on contemporary Canadian practice. This microsimulation model can be used to estimate the total direct care costs of treating all lung cancer cases diagnosed in Canada and to evaluate the cost and cost-effectiveness of new therapeutic interventions as they are introduced into practice. Gemcitabine, a new nucleoside analogue with a broad spectrum of antitumor activity, is about to be introduced on the Canadian market. The Population Health Model has been used to estimate the cost-effectiveness of gemcitabine in the management of lung cancer over a range of drug doses per treatment cycle starting at 1,000 mg/m2 weekly x 3, as well as potential survival benefits. The survival of stage IV non-small cell lung cancer (NSCLC) patients treated on an international trial of gemcitabine (EO-18) was used to estimate the potential survival gain relative to the survival of stage IV NSCLC patients managed with best supportive care on a randomized trial conducted by the National Cancer Institute of Canada (BR 5). Sensitivity analyses were performed assuming that the survival gain was 25% or 50% less than that reported in the EO-18 trial. The perspective of the economic analysis is that of the government as payer in a universal health care system, and all costs are expressed in 1993 Canadian dollars. Based on the apparent survival advantage of the EO-18 trial in comparison to best supportive care, the cost per life-year gained ranged from $632 to $9,285, depending on the dose per treatment cycle. At the highest dose per cycle (2,000 mg/m2) and with survival reduced by 50% as compared with the EO-18 result, the cost per life-year gained was estimated to be $17,390. From these estimates of direct care costs in the Canadian health care system, gemcitabine appears to be a cost-effective intervention for advanced NSCLC.
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Somashekhar, S P
2015-08-01
Lymph-node-positive gynaecological cancers remain a pharmacotherapeutic challenge, and patients with lymph-node-positive gynaecological cancers have poor survival. The purpose of this review is to determine whether a survival advantage arises from surgical debulking of enlarged positive lymph nodes in different types of gynaecological cancers. Information from studies published on the survival benefits from debulking lymph nodes in gynaecological cancers was investigated. Pertaining to therapeutic lymphadenectomy, survival benefit can be analysed in two ways, direct survival benefit following therapeutic lymphadenectomy of bulky positive metastatic lymph nodes and indirect survival benefit, which results after a sequela of systematic lymphadenectomy, proper, accurate staging of disease and stage migration and tailor-made adjuvant treatment. The direct hypothesis of therapeutic lymphadenectomy and survival benefit has been prospected in cervical cancers and vulval cancers and in post-chemotherapy residual paraarotic nodal mass in germ cell ovarian cancer. The indirect survival benefit of therapeutic paraarotic lymphadenectomy in high-risk endometrial cancers and advanced epithelial ovarian cancers needs to be tested in randomized controlled trials. More randomized controlled trials are required to investigate this research question. Further, indirect benefit due to tailor-made adjuvant treatment, secondary to accurate staging achieved as a sequela of systematic lymphadenectomy, needs to be analysed in future trials. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.
Koskivuo, I; Vihinen, P; Mäki, M; Talve, L; Vahlberg, T; Suominen, E
2017-03-01
Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.
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Social Networks as a Source of Competitive Advantage for the Firm.
ERIC Educational Resources Information Center
Van Laere, Kristien; Heene, Aime
2003-01-01
Proposes a conceptual framework for managing relationships of small and medium-sized enterprises, based on the necessity of cooperation for survival. Describes characteristics of embedded relationship in stakeholder interactions, including trust, durability, information transfer, and collaboration. (Contains 72 references.) (SK)
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Patient's Guide to Living with Atrial Fibrillation
... study showed that there was no advantage of one approach over the other in terms of survival. Patients ... series of different treatments before the best management approach is found for them. ... of AF, particularly if one is taking warfarin. There are many types of ...
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Brusletto, Birgit; Torp, Steffen; Ihlebæk, Camilla Martha; Vinje, Hege Forbech
2018-06-01
We investigated persons who survived cancer (PSC) and their experiences in returning to sustainable work. Videotaped, qualitative, in-depth interviews with previous cancer patients were analyzed directly using "Interpretative Phenomenological Analysis" (IPA). Four men and four women aged 42-59 years participated. Mean time since last treatment was nine years. All participants had worked for more than 3 years when interviewed. An advisory team of seven members with diverse cancer experiences contributed as co-researchers. The entire trajectory from cancer diagnosis until achievement of sustainable work was analog to a journey, and a process model comprising five phases was developed, including personal situations, treatments, and work issues. The theme "return-to-work" (RTW) turned out to be difficult to separate from the entire journey that started at the time of diagnosis. PSCs were mainly concerned about fighting for life in phases 1 and 2. In phase 3 and 4, some participants had to adjust and make changes at work more than once over a period of 1-10 years before reaching sustainable work in phase 5. Overall, the ability to adapt to new circumstances, take advantage of emerging opportunities, and finding meaningful occupational activities were crucial. Our process model may be useful as a tool when discussing the future working life of PSCs. Every individual's journey towards sustainable work was unique, and contained distinct and long-lasting efforts and difficulties. The first attempt to RTW after cancer may not be persistent. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Bowles, K; DeSandre-Robinson, D; Kubicek, L; Lurie, D; Milner, R; Boston, S E
2016-12-01
Local control is a major challenge in treating canine nasal tumours. Surgical cytoreduction prior to radiation therapy has not been shown to offer a survival advantage. Only one study has previously evaluated the outcome when surgery is performed after radiation, which demonstrated an improved survival time compared with radiation alone. The purpose of this study was to investigate the outcome of surgery after definitive radiation on survival times in dogs with sinonasal tumours. Medical records were retrospectively reviewed for dogs with nasal tumours that received definitive radiation followed by surgery. Information obtained from medical record review included signalment, diagnosis, treatment and outcome. The median survival time was 457 days. No long-term side effects were observed. These findings suggest that exenteration of the nasal cavity following definitive radiation for treatment of dogs with nasal tumours is well-tolerated and provides a similar survival duration to previous reports of radiation alone. © 2014 John Wiley & Sons Ltd.
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Shepherd, Robert K.; Coco, Anne; Epp, Stephanie B.; Crook, Jeremy M.
2007-01-01
The development and maintenance of spiral ganglion neurons (SGNs) appears to be supported by both neural activity and neurotrophins. Removal of this support leads to their gradual degeneration. Here, we examine whether the exogenous delivery of the neurotrophin brain-derived neurotrophic factor (BDNF) in concert with electrical stimulation (ES) provides a greater protective effect than delivery of BDNF alone in vivo. The left cochlea of profoundly deafened guinea pigs was implanted with an electrode array and drug delivery system. BDNF or artificial perilymph (AP) was delivered continuously for 28 days. ES induced neural activity in two cohorts (BDNF/ES and AP/ES) while control animals received BDNF or AP without ES (BDNF/- and AP/-). The right cochleae of each animal served as deafened untreated controls. Electrically-evoked auditory brainstem responses (EABRs) were recorded immediately following surgery and at completion of the drug delivery period. AP/ES and AP/- cohorts showed an increase in EABR threshold over the implantation period while both BDNF cohorts exhibited a reduction in threshold (P < 0.001, t-test). Changes in neural sensitivity were complemented by significant differences in both SGN survival and soma area. BDNF cohorts demonstrated a significant trophic or survival advantage and larger soma area compared with AP-treated and deafened control cochleae; this advantage was greatest in the base of the cochlea. Importantly, ES significantly enhanced the survival effects of BDNF throughout the majority of the cochlea (P < 0.05, Bonferroni's test), while there was no evidence of trophic support provided by ES alone. Co-treatment of SGNs with BDNF and ES provide a substantial functional and trophic advantage; this treatment may have important implications for neural prostheses. PMID:15844207
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Design of a radio telescope surface segment actuator based on a form-closed eccentric cam
NASA Astrophysics Data System (ADS)
Smith, David R.
2014-07-01
As radio telescopes have reached larger diameters and higher frequencies, it is typically not possible to meet their surface accuracy specifications using passive homology-based designs. The most common solution to this problem in the current generation of large, high-frequency radio telescopes is to employ a system of linear actuators to correct the surface shape of the primary reflector. The exact specifications of active surface actuators vary with the telescope. However, they have many common features, some of which drive their design. In general, these actuators must provide precise and repeatable positioning under significant loads during operation and they must withstand even higher loads for survival conditions. For general safety, they typically must hold position in the event of a power failure and must incorporate position limits, whether electrical, mechanical, or both. Because the number of actuators is generally high for large active surfaces (hundreds or even thousands of actuators), they must also be reliable and of reasonable individual cost. Finally, for maximum flexibility in their installation, they must be compact. This paper presents a concept for an active surface actuator based on a form-closed eccentric cam (kinematically, a Scotch Yoke mechanism). Such a design is limited in stroke, but offers potential advantages in terms of manufacture, compactness, measurement, and survival loading. The paper demonstrates that some of the expected advantages cannot be practically realized, due to dimensions that are driven by survival loading conditions. As a result, this concept is likely to offer an advantage over conventional screw-type actuators only for cases where actuator runaway and stall are the driving considerations.
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Yanhua, Wang; Hao, Hang; Li, Yan; Zhang, Shengmin
2016-04-01
Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Novel selenium-substituted hydroxyapatite nanoparticles (SeHAN) were designed to serve as anticancer agent. The authors examined the nanoparticles by physicochemical techniques. The in vivo efficacy and toxicity of these nanoparticles were also investigated on a nude mice model of human hepatocellular carcinoma. The results showed that the selenite ions can be incorporated into the hydroxyapatite lattice facilely. They exhibited bundles of needles shape with a size of 160-200 nm. In the in vivo study, they showed better survival advantage. The overall survival rate of nude mice in the control, pure hydroxyapatite and SeHAN group were 50.00%, 76.92%, and 100.00% respectively. Blood biochemical studies showed that SeHAN group had significantly lower toxicities on the liver and kidney functions. Histopathological studies confirmed that massive tumor necrosis and calcium deposition were evident after SeHAN treatment. Moreover, immunohistochemistry and Western blot assay showed significantly reduced expression of the Ki-67, VEGF and MMP-9 protein in the SeHAN group. Taken together, these results suggest that the selenium-substituted hydroxyapatite nanoparticles could be a new type of promising anticancer agent to provide both survival advantage and lower toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.
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Fluctuating survival selection explains variation in avian group size
Brown, Charles R.; Brown, Mary Bomberger; Roche, Erin A.; O’Brien, Valerie A.; Page, Catherine E.
2016-01-01
Most animal groups vary extensively in size. Because individuals in certain sizes of groups often have higher apparent fitness than those in other groups, why wide group size variation persists in most populations remains unexplained. We used a 30-y mark–recapture study of colonially breeding cliff swallows (Petrochelidon pyrrhonota) to show that the survival advantages of different colony sizes fluctuated among years. Colony size was under both stabilizing and directional selection in different years, and reversals in the sign of directional selection regularly occurred. Directional selection was predicted in part by drought conditions: birds in larger colonies tended to be favored in cooler and wetter years, and birds in smaller colonies in hotter and drier years. Oscillating selection on colony size likely reflected annual differences in food availability and the consequent importance of information transfer, and/or the level of ectoparasitism, with the net benefit of sociality varying under these different conditions. Averaged across years, there was no net directional change in selection on colony size. The wide range in cliff swallow group size is probably maintained by fluctuating survival selection and represents the first case, to our knowledge, in which fitness advantages of different group sizes regularly oscillate over time in a natural vertebrate population. PMID:27091998
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Fluctuating survival selection explains variation in avian group size.
Brown, Charles R; Brown, Mary Bomberger; Roche, Erin A; O'Brien, Valerie A; Page, Catherine E
2016-05-03
Most animal groups vary extensively in size. Because individuals in certain sizes of groups often have higher apparent fitness than those in other groups, why wide group size variation persists in most populations remains unexplained. We used a 30-y mark-recapture study of colonially breeding cliff swallows (Petrochelidon pyrrhonota) to show that the survival advantages of different colony sizes fluctuated among years. Colony size was under both stabilizing and directional selection in different years, and reversals in the sign of directional selection regularly occurred. Directional selection was predicted in part by drought conditions: birds in larger colonies tended to be favored in cooler and wetter years, and birds in smaller colonies in hotter and drier years. Oscillating selection on colony size likely reflected annual differences in food availability and the consequent importance of information transfer, and/or the level of ectoparasitism, with the net benefit of sociality varying under these different conditions. Averaged across years, there was no net directional change in selection on colony size. The wide range in cliff swallow group size is probably maintained by fluctuating survival selection and represents the first case, to our knowledge, in which fitness advantages of different group sizes regularly oscillate over time in a natural vertebrate population.
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Fluctuating survival selection explains variation in avian group size
Brown, Charles B.; Brown, Mary Bomberger; Roche, Erin A.; O'brien, Valerie A; Page, Catherine E.
2016-01-01
Most animal groups vary extensively in size. Because individuals in certain sizes of groups often have higher apparent fitness than those in other groups, why wide group size variation persists in most populations remains unexplained. We used a 30-y mark–recapture study of colonially breeding cliff swallows (Petrochelidon pyrrhonota) to show that the survival advantages of different colony sizes fluctuated among years. Colony size was under both stabilizing and directional selection in different years, and reversals in the sign of directional selection regularly occurred. Directional selection was predicted in part by drought conditions: birds in larger colonies tended to be favored in cooler and wetter years, and birds in smaller colonies in hotter and drier years. Oscillating selection on colony size likely reflected annual differences in food availability and the consequent importance of information transfer, and/or the level of ectoparasitism, with the net benefit of sociality varying under these different conditions. Averaged across years, there was no net directional change in selection on colony size. The wide range in cliff swallow group size is probably maintained by fluctuating survival selection and represents the first case, to our knowledge, in which fitness advantages of different group sizes regularly oscillate over time in a natural vertebrate population.
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Efficacy outcome selection in the therapeutic hypothermia after pediatric cardiac arrest trials.
Holubkov, Richard; Clark, Amy E; Moler, Frank W; Slomine, Beth S; Christensen, James R; Silverstein, Faye S; Meert, Kathleen L; Pollack, Murray M; Dean, J Michael
2015-01-01
The Therapeutic Hypothermia After Pediatric Cardiac Arrest trials will determine whether therapeutic hypothermia improves survival with good neurobehavioral outcome, as assessed by the Vineland Adaptive Behavior Scales Second Edition, in children resuscitated after cardiac arrest in the in-hospital and out-of-hospital settings. We describe the innovative efficacy outcome selection process during Therapeutic Hypothermia After Pediatric Cardiac Arrest protocol development. Consensus assessment of potential outcomes and evaluation timepoints. None. We evaluated practical and technical advantages of several follow-up timepoints and continuous/categorical outcome variants. Simulations estimated power assuming varying hypothermia benefit on mortality and on neurobehavioral function among survivors. Twelve months after arrest was selected as the optimal assessment timepoint for pragmatic and clinical reasons. Change in Vineland Adaptive Behavior Scales Second Edition from prearrest level, measured as quasicontinuous with death and vegetative status being worst-possible levels, yielded optimal statistical power. However, clinicians preferred simpler multicategorical or binary outcomes because of easier interpretability and favored outcomes based solely on postarrest status because of concerns about accurate parental assessment of prearrest status and differing clinical impact of a given Vineland Adaptive Behavior Scales Second Edition change depending on prearrest status. Simulations found only modest power loss from categorizing or dichotomizing quasicontinuous outcomes because of high expected mortality. The primary outcome selected was survival with 12-month Vineland Adaptive Behavior Scales Second Edition no less than two SD below a reference population mean (70 points), necessarily evaluated only among children with prearrest Vineland Adaptive Behavior Scales Second Edition greater than or equal to 70. Two secondary efficacy outcomes, 12-month survival and quasicontinuous Vineland Adaptive Behavior Scales Second Edition change from prearrest level, will be evaluated among all randomized children, including those with compromised function prearrest. Extensive discussion of optimal efficacy assessment timing, and of the advantages versus drawbacks of incorporating prearrest status and using quasicontinuous versus simpler outcomes, was highly beneficial to the final Therapeutic Hypothermia After Pediatric Cardiac Arrest design. A relatively simple, binary primary outcome evaluated at 12 months was selected, with two secondary outcomes that address the potential disadvantages of primary outcome.
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NASA Astrophysics Data System (ADS)
Burghardt, Gordon M.
2017-03-01
Nobuo Masataka [1] has provided a novel and ambitious approach to understanding variations in mental and neural functioning in humans by embedding them in the concept of neurodiversity. He is particularly interested in Autism Spectrum Disorder (ASD) and views it as on a continuum falling within normal human behavioral variation. If this is true and ASD has been maintained in a population by selection, then, he argues, ASD individuals may have had survival advantages during the EEA (environment of evolutionary adaptiveness), before the advent of large and complex societies. After this point, properly interpreting and responding to social and global cues gained importance at the expense of detailed feature based processing of nonsocial features of the environment.
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Jeong, Seung Hee; Hjort, Klas; Wu, Zhigang
2015-02-12
Stretchable electronics offers unsurpassed mechanical compliance on complex or soft surfaces like the human skin and organs. To fully exploit this great advantage, an autonomous system with a self-powered energy source has been sought for. Here, we present a new technology to pattern liquid alloys on soft substrates, targeting at fabrication of a hybrid-integrated power source in microfluidic stretchable electronics. By atomized spraying of a liquid alloy onto a soft surface with a tape transferred adhesive mask, a universal fabrication process is provided for high quality patterns of liquid conductors in a meter scale. With the developed multilayer fabrication technique, a microfluidic stretchable wireless power transfer device with an integrated LED was demonstrated, which could survive cycling between 0% and 25% strain over 1,000 times.
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Jeong, Seung Hee; Hjort, Klas; Wu, Zhigang
2015-01-01
Stretchable electronics offers unsurpassed mechanical compliance on complex or soft surfaces like the human skin and organs. To fully exploit this great advantage, an autonomous system with a self-powered energy source has been sought for. Here, we present a new technology to pattern liquid alloys on soft substrates, targeting at fabrication of a hybrid-integrated power source in microfluidic stretchable electronics. By atomized spraying of a liquid alloy onto a soft surface with a tape transferred adhesive mask, a universal fabrication process is provided for high quality patterns of liquid conductors in a meter scale. With the developed multilayer fabrication technique, a microfluidic stretchable wireless power transfer device with an integrated LED was demonstrated, which could survive cycling between 0% and 25% strain over 1,000 times. PMID:25673261
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Fuse, Kana; Crenshaw, Edward M
2006-01-01
Sex differentials in infant mortality vary widely across nations. Because newborn girls are biologically advantaged in surviving to their first birthday, sex differentials in infant mortality typically arise from genetic factors that result in higher male infant mortality rates. Nonetheless, there are cases where mortality differentials arise from social or behavioral factors reflecting deliberate discrimination by adults in favor of boys over girls, resulting in atypical male to female infant mortality ratios. This cross-national study of 93 developed and developing countries uses such macro-social theories as modernization theory, gender perspectives, human ecology, and sociobiology/evolutionary psychology to predict gender differentials in infant mortality. We find strong evidence for modernization theory, human ecology, and the evolutionary psychology of group process, but mixed evidence for gender perspectives.
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Stability of peptides in high-temperature aqueous solutions
NASA Astrophysics Data System (ADS)
Shock, Everett L.
1992-09-01
Estimated standard molal thermodynamic properties of aqueous dipeptides and their constituent amino acids indicate that temperature increases correspond to increased stability of peptide bonds relative to hydrolysis reactions. Pressure increases cause slight decreases in peptide bond stability, which are generally offset by greater stability caused by temperature increases along geothermal gradients. These calculations suggest that peptides, polypeptides, and proteins may survive hydrothermal alteration of organic matter depending on the rates of the hydrolysis reactions. Extremely thermophilic organisms may be able to take advantage of the decreased energy required to form peptide bonds in order to maintain structural proteins and enzymes at elevated temperatures and pressures. As the rates of hydrolysis reactions increase with increasing temperature, formation of peptide bonds may become a facile process in hydrothermal systems and deep in sedimentary basins.
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Remontet, Laurent; Uhry, Zoé; Bossard, Nadine; Iwaz, Jean; Belot, Aurélien; Danieli, Coraline; Charvat, Hadrien; Roche, Laurent
2018-01-01
Cancer survival trend analyses are essential to describe accurately the way medical practices impact patients' survival according to the year of diagnosis. To this end, survival models should be able to account simultaneously for non-linear and non-proportional effects and for complex interactions between continuous variables. However, in the statistical literature, there is no consensus yet on how to build such models that should be flexible but still provide smooth estimates of survival. In this article, we tackle this challenge by smoothing the complex hypersurface (time since diagnosis, age at diagnosis, year of diagnosis, and mortality hazard) using a multidimensional penalized spline built from the tensor product of the marginal bases of time, age, and year. Considering this penalized survival model as a Poisson model, we assess the performance of this approach in estimating the net survival with a comprehensive simulation study that reflects simple and complex realistic survival trends. The bias was generally small and the root mean squared error was good and often similar to that of the true model that generated the data. This parametric approach offers many advantages and interesting prospects (such as forecasting) that make it an attractive and efficient tool for survival trend analyses.
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Experimental evolution in biofilm populations
Steenackers, Hans P.; Parijs, Ilse; Foster, Kevin R.; Vanderleyden, Jozef
2016-01-01
Biofilms are a major form of microbial life in which cells form dense surface associated communities that can persist for many generations. The long-life of biofilm communities means that they can be strongly shaped by evolutionary processes. Here, we review the experimental study of evolution in biofilm communities. We first provide an overview of the different experimental models used to study biofilm evolution and their associated advantages and disadvantages. We then illustrate the vast amount of diversification observed during biofilm evolution, and we discuss (i) potential ecological and evolutionary processes behind the observed diversification, (ii) recent insights into the genetics of adaptive diversification, (iii) the striking degree of parallelism between evolution experiments and real-life biofilms and (iv) potential consequences of diversification. In the second part, we discuss the insights provided by evolution experiments in how biofilm growth and structure can promote cooperative phenotypes. Overall, our analysis points to an important role of biofilm diversification and cooperation in bacterial survival and productivity. Deeper understanding of both processes is of key importance to design improved antimicrobial strategies and diagnostic techniques. PMID:26895713
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Friendship Dissolution Within Social Networks Modeled Through Multilevel Event History Analysis
Dean, Danielle O.; Bauer, Daniel J.; Prinstein, Mitchell J.
2018-01-01
A social network perspective can bring important insight into the processes that shape human behavior. Longitudinal social network data, measuring relations between individuals over time, has become increasingly common—as have the methods available to analyze such data. A friendship duration model utilizing discrete-time multilevel survival analysis with a multiple membership random effect structure is developed and applied here to study the processes leading to undirected friendship dissolution within a larger social network. While the modeling framework is introduced in terms of understanding friendship dissolution, it can be used to understand microlevel dynamics of a social network more generally. These models can be fit with standard generalized linear mixed-model software, after transforming the data to a pair-period data set. An empirical example highlights how the model can be applied to understand the processes leading to friendship dissolution between high school students, and a simulation study is used to test the use of the modeling framework under representative conditions that would be found in social network data. Advantages of the modeling framework are highlighted, and potential limitations and future directions are discussed. PMID:28463022
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Experimental evolution in biofilm populations.
Steenackers, Hans P; Parijs, Ilse; Dubey, Akanksha; Foster, Kevin R; Vanderleyden, Jozef
2016-05-01
Biofilms are a major form of microbial life in which cells form dense surface associated communities that can persist for many generations. The long-life of biofilm communities means that they can be strongly shaped by evolutionary processes. Here, we review the experimental study of evolution in biofilm communities. We first provide an overview of the different experimental models used to study biofilm evolution and their associated advantages and disadvantages. We then illustrate the vast amount of diversification observed during biofilm evolution, and we discuss (i) potential ecological and evolutionary processes behind the observed diversification, (ii) recent insights into the genetics of adaptive diversification, (iii) the striking degree of parallelism between evolution experiments and real-life biofilms and (iv) potential consequences of diversification. In the second part, we discuss the insights provided by evolution experiments in how biofilm growth and structure can promote cooperative phenotypes. Overall, our analysis points to an important role of biofilm diversification and cooperation in bacterial survival and productivity. Deeper understanding of both processes is of key importance to design improved antimicrobial strategies and diagnostic techniques. © FEMS 2016.
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Threat as a feature in visual semantic object memory.
Calley, Clifford S; Motes, Michael A; Chiang, H-Sheng; Buhl, Virginia; Spence, Jeffrey S; Abdi, Hervé; Anand, Raksha; Maguire, Mandy; Estevez, Leonardo; Briggs, Richard; Freeman, Thomas; Kraut, Michael A; Hart, John
2013-08-01
Threatening stimuli have been found to modulate visual processes related to perception and attention. The present functional magnetic resonance imaging (fMRI) study investigated whether threat modulates visual object recognition of man-made and naturally occurring categories of stimuli. Compared with nonthreatening pictures, threatening pictures of real items elicited larger fMRI BOLD signal changes in medial visual cortices extending inferiorly into the temporo-occipital (TO) "what" pathways. This region elicited greater signal changes for threatening items compared to nonthreatening from both the natural-occurring and man-made stimulus supraordinate categories, demonstrating a featural component to these visual processing areas. Two additional loci of signal changes within more lateral inferior TO areas (bilateral BA18 and 19 as well as the right ventral temporal lobe) were detected for a category-feature interaction, with stronger responses to man-made (category) threatening (feature) stimuli than to natural threats. The findings are discussed in terms of visual recognition of processing efficiently or rapidly groups of items that confer an advantage for survival. Copyright © 2012 Wiley Periodicals, Inc.
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Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas; Trabert, Britton; Beeghly-Fadiel, Alicia; Schildkraut, Joellen M; Moysich, Kirsten B; deFazio, Anna; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Jensen, Allan; Kjær, Susanne K; Høgdall, Estrid; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Bandera, Elisa V; Paddock, Lisa E; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M
2017-01-01
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. Methods: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). Results: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95% confidence intervals): aspirin 0.96 (0.88–1.04); non-aspirin NSAIDs 0.97 (0.89–1.05); acetaminophen 1.01 (0.93–1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0.89 (0.82–0.98)). Conclusions: Although this study did not show a clear association between analgesic use and ovarian cancer survival, further investigation with clearer definitions of use and information about post-diagnosis use is warranted. PMID:28350790
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Yan, Muxia; Xu, Ling; Jiang, Hua; Zhou, Zhenwen; Zhou, Shishui; Zhang, Li
2017-04-01
In exposure to outer pressure, microorganisms are capable of entry into the Viable But Non-Culturable (VBNC) state, and thus survive under various elimination processing. The survival microorganisms may yield negative results on culturing, and cause false negative for this golden standard methodology. In this study, a novel PMA-LAMP assay on the detection of Enterohemorrhage E. coli and shiga toxins has been developed and evaluated, with further application on a number of food borne E. coli strains. LAMP primers were designed on the target of rfbe for Enterohemorrhage E. coli and stx1with stx2 for shiga toxins. Via specific penetration through the damaged cell membrane of dead cells and intercalating into DNA, PMA could prevent DNA amplification of dead bacteria from LAMP, which enabled the differentiation of bacteria between VBNC state and dead state. The established PMA-LAMP showed significant advantage in rapidity, sensitivity and specificity, compared with regular PCR assay. The applicability had also been verified, demonstrating the PMA-LAMP was capable of detection on Enterohemorrhage E. coli and shiga toxins. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Dying scenarios improve recall as much as survival scenarios.
Burns, Daniel J; Hart, Joshua; Kramer, Melanie E
2014-01-01
Merely contemplating one's death improves retention for entirely unrelated material learned subsequently. This "dying to remember" effect seems conceptually related to the survival processing effect, whereby processing items for their relevance to being stranded in the grasslands leads to recall superior to that of other deep processing control conditions. The present experiments directly compared survival processing scenarios with "death processing" scenarios. Results showed that when the survival and dying scenarios are closely matched on key dimensions, and possible congruency effects are controlled, the dying and survival scenarios produced equivalently high recall levels. We conclude that the available evidence (cf. Bell, Roer, & Buchner, 2013; Klein, 2012), while not definitive, is consistent with the possibility of overlapping mechanisms.
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USDA-ARS?s Scientific Manuscript database
Enzyme adaptations to temperature occur constantly as temperature patterns modulate diurnally and seasonally. These adaptations entail qualitative and/or quantitative metabolic changes that often provide a competitive advantage, impact migration to new environments, and effect the survival of the s...
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ERIC Educational Resources Information Center
Frank, Helen
1976-01-01
"Feeling happy" focuses on the syndrome of self-indulgence, self-actualization or self-fulfillment as antagonistic to the survival of marital agreement. Inspite of the obvious redeeming qualities of either spouse the unhappy partner opts for divorce. The article posits the familial advantages of responsiblity and commitment and reviews the older…
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Feldman, Lisa A.; Fabre, Marie-Sophie; Grasso, Carole; Reid, Dana; Broaddus, William C.; Lanza, Gregory M.; Spiess, Bruce D.; Garbow, Joel R.; McConnell, Melanie J.
2017-01-01
Background Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy. Aim To investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2). Results PFC emulsions completely abrogated hypoxia in both subcutaneous and intracranial GL261 models and conferred a significant survival advantage orthotopically (Mantel Cox: p = 0.048) in carbogen breathing mice injected intravenously (IV) with PFC emulsions before radiation versus mice receiving radiation alone. Carbogen alone decreased hypoxia levels substantially and conferred a smaller but not statistically significant survival advantage over and above radiation alone. Conclusion IV injections of PFC emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors. PMID:28873460
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Wapstra, E; Uller, T; While, G M; Olsson, M; Shine, R
2010-03-01
The timing of birth is often correlated with offspring fitness in animals, but experimental studies that disentangle direct effects of parturition date and indirect effects mediated via variation in female traits are rare. In viviparous ectotherms, parturition date is largely driven by female thermal conditions, particularly maternal basking strategies. Our field and laboratory studies of a viviparous lizard (Niveoscincus ocellatus) show that earlier-born offspring are more likely to survive through their first winter and are larger following that winter, than are later-born conspecifics. Thus, the association between parturition date and offspring fitness is causal, rather than reflecting an underlying correlation between parturition date and maternal attributes. Survival selection on offspring confers a significant advantage for increased maternal basking in this species, mediated through fitness advantages of earlier parturition. We discuss the roles of environmentally imposed constraints and parent-offspring conflict in the evolution of maternal effects on parturition date.
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Jellyfish Patch Detecting Using Low Latitude Remote Sensing System
NASA Astrophysics Data System (ADS)
Lee, J. S.; Jo, Y. H.
2015-12-01
Jellyfish can be asexual and sexual reproduction depending on the environment, and it has excellent environmental adaptability and reproduction than other sea creatures. If the marine environment become worse, jellyfish can take advantage in the competition for survival. Marine environmental changes caused by rapid climate change, dyke construction and land reclamation will increase the amount of jellyfish and as a result can lead to a various social and economic problems. In this study, jellyfish were observed in coastal area using a low-altitude Helikite remote sensing system for the first time. Helikite is a type of helium balloon plus a kite that can get the data with optical sensors for the desired spatial resolutions by adjusting the altitudes. In addition, it has an advantage that can monitor any objects for a long time at one place as long as the electric power and helium last. In this study, we observed the jellyfish patches using a digital camera in the Chesapeake Bay and estimate populations and size of jellyfish patches through image processing. Research results suggests that we can have long-term real-time observations for not only jellyfish, but also other harmful marine creatures.
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Joint modeling of longitudinal data and discrete-time survival outcome.
Qiu, Feiyou; Stein, Catherine M; Elston, Robert C
2016-08-01
A predictive joint shared parameter model is proposed for discrete time-to-event and longitudinal data. A discrete survival model with frailty and a generalized linear mixed model for the longitudinal data are joined to predict the probability of events. This joint model focuses on predicting discrete time-to-event outcome, taking advantage of repeated measurements. We show that the probability of an event in a time window can be more precisely predicted by incorporating the longitudinal measurements. The model was investigated by comparison with a two-step model and a discrete-time survival model. Results from both a study on the occurrence of tuberculosis and simulated data show that the joint model is superior to the other models in discrimination ability, especially as the latent variables related to both survival times and the longitudinal measurements depart from 0. © The Author(s) 2013.
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Neonatal isolation impairs neurogenesis in the dentate gyrus of the guinea pig.
Rizzi, Simona; Bianchi, Patrizia; Guidi, Sandra; Ciani, Elisabetta; Bartesaghi, Renata
2007-01-01
In the current study we examined the effects of early isolation rearing on cell proliferation, survival and differentiation in the dentate gyrus of the guinea pig. Animals were assigned to either a standard (control) or an isolated environment a few days after birth (P5-P6), taking advantage of the precocious independence from maternal care of the guinea pig. On P14-P17 animals received one daily bromodeoxyuridine injection, to label dividing cells, and were sacrificed either on P18, to evaluate cell proliferation or on P45, to evaluate cell survival and differentiation. In P18 isolated animals we found a reduced cell proliferation (-35%) compared to controls and a lower expression of brain-derived neurotrophic factor (BDNF). Though in absolute terms P45 isolated animals had less surviving cells, they showed no differences in survival rate and phenotype percent distribution compared to controls. Looking at the location of the new neurons, we found that while in control animals 76% of them had migrated to the granule cell layer, in isolated animals only 55% of the new neurons had reached this layer. Examination of radial glia cells of P18 and P45 animals by vimentin immunohistochemistry showed that in isolated animals radial glia cells were reduced in density and had less and shorter processes. Granule cell count revealed that P45 isolated animals had less (-42%) granule cells than controls. Results show that isolation rearing reduces hippocampal cell proliferation, likely by reducing BDNF expression and hampers migration of the new neurons to the granule cell layer, likely by altering density/morphology of radial glia cells. The large reduction in granule cell number following isolation rearing emphasizes the role of environmental cues as relevant modulators of neurogenesis.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Deneve, Jeremiah L., E-mail: Jeremiah.Deneve@Moffitt.org; Choi, Junsung; Gonzalez, Ricardo J.
Purpose: Treatment of patients with unresectable liver metastases is challenging. Regional therapies to the liver have been developed that maximize treatment of the localized disease process without systemic toxic adverse effects. We discuss the procedural aspects of liver chemosaturation with percutaneous hepatic perfusion (CS-PHP). Methods: We present as an illustration of this technique a case report of the treatment of unresectable metastatic leiomyosarcoma of the liver. Results: A randomized phase III trial for unresectable liver metastases from melanoma was recently completed comparing CS-PHP with melphalan vs. best alternative care (BAC). When compared with BAC, CS-PHP was associated with a significantmore » improvement in hepatic progression-free survival (8.0 months CS-PHP vs. 1.6 months BAC, p < 0.0001) and overall progression-free survival (6.7 months CS-PHP vs. 1.6 months BAC, p < 0.0001), respectively. On the basis of these results, and given our experience as one of the treating institutions for this phase III trial, we appealed for compassionate use of CS-PHP in a patient with isolated bilobar unresectable hepatic metastases from leiomyosarcoma. Four target lesions were identified and monitored to assess treatment response. A total of 4 CS-PHP procedures were performed, with a 25 % reduction in size of the largest lesion observed and 16 month hepatic progression-free survival. Toxicity was mild (neutropenia) and manageable on an outpatient basis. Conclusion: CS-PHP offers several advantages for unresectable hepatic sarcoma metastases. CS-PHP is minimally invasive and repeatable, and it has a predictable and manageable systemic toxicity profile. For appropriately selected patients, CS-PHP can delay tumor progression and could potentially improve survival.« less
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Outsourcing drug discovery to India and China: from surviving to thriving.
Subramaniam, Swaminathan; Dugar, Sundeep
2012-10-01
Global pharmaceutical companies face an increasingly harsh environment for their primary business of selling medicines. They have to contend with a spiraling decline in the productivity of their R&D programs that is guaranteed to severely diminish their growth prospects. Outsourcing of drug discovery activities to low-cost locations is a growing response to this crisis. However, the upsides to outsourcing are capped by the failure of global pharmaceutical companies to take advantage of the full range of possibilities that this model provides. Companies that radically rethink and transform the way they conduct R&D, such as seeking the benefits of low-cost locations in India and China will be the ones that thrive in this environment. In this article we present our views on how the outsourcing model in drug discovery should go beyond increasing the efficiency of existing drug discovery processes to a fundamental rethink and re-engineering of these processes. Copyright © 2012. Published by Elsevier Ltd.
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M1A2 tank commander's independent thermal viewer optics: system engineering perspective
NASA Astrophysics Data System (ADS)
Ratcliff, David D.
1993-08-01
As successful as the M1A1 Abrams tank was in the Gulf War, a program has been under way for several years to improve and modernize the M1A1 to keep pace with new threats and to take advantage of new technology. This program has resulted in the M1A2 upgrade program which significantly improves the survivability and lethality of the tank. First, the point-to-point wiring and analog signal processing was replaced with digital processing and control with a modern, aircraft-style digital data bus. Additional command and control aspects of the upgrade greatly improved the situational awareness of the M1A2 commander. Finally, an additional thermal imaging system was added for the commander. This system, the M1A2 Commander's Independent Thermal Viewer (CITV) is the topic of the following paper, which details the design from a system engineering perspective, and a companion paper that presents the optical design perspective.
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Sandry, Joshua; Trafimow, David; Marks, Michael J.; Rice, Stephen
2013-01-01
Memory may have evolved to preserve information processed in terms of its fitness-relevance. Based on the assumption that the human mind comprises different fitness-relevant adaptive mechanisms contributing to survival and reproductive success, we compared alternative fitness-relevant processing scenarios with survival processing. Participants rated words for relevancy to fitness-relevant and control conditions followed by a delay and surprise recall test (Experiment 1a). Participants recalled more words processed for their relevance to a survival situation. We replicated these findings in an online study (Experiment 2) and a study using revised fitness-relevant scenarios (Experiment 3). Across all experiments, we did not find a mnemonic benefit for alternative fitness-relevant processing scenarios, questioning assumptions associated with an evolutionary account of remembering. Based on these results, fitness-relevance seems to be too wide-ranging of a construct to account for the memory findings associated with survival processing. We propose that memory may be hierarchically sensitive to fitness-relevant processing instructions. We encourage future researchers to investigate the underlying mechanisms responsible for survival processing effects and work toward developing a taxonomy of adaptive memory. PMID:23585858
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Genomics, metagenomics and proteomics in biomining microorganisms.
Valenzuela, Lissette; Chi, An; Beard, Simon; Orell, Alvaro; Guiliani, Nicolas; Shabanowitz, Jeff; Hunt, Donald F; Jerez, Carlos A
2006-01-01
The use of acidophilic, chemolithotrophic microorganisms capable of oxidizing iron and sulfur in industrial processes to recover metals from minerals containing copper, gold and uranium is a well established biotechnology with distinctive advantages over traditional mining. A consortium of different microorganisms participates in the oxidative reactions resulting in the extraction of dissolved metal values from ores. Considerable effort has been spent in the last years to understand the biochemistry of iron and sulfur compounds oxidation, bacteria-mineral interactions (chemotaxis, quorum sensing, adhesion, biofilm formation) and several adaptive responses allowing the microorganisms to survive in a bioleaching environment. All of these are considered key phenomena for understanding the process of biomining. The use of genomics, metagenomics and high throughput proteomics to study the global regulatory responses that the biomining community uses to adapt to their changing environment is just beginning to emerge in the last years. These powerful approaches are reviewed here since they offer the possibility of exciting new findings that will allow analyzing the community as a microbial system, determining the extent to which each of the individual participants contributes to the process, how they evolve in time to keep the conglomerate healthy and therefore efficient during the entire process of bioleaching.
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Against the Corporal Punishment of Children
ERIC Educational Resources Information Center
Clark, John
2004-01-01
John Wilson suggests there are six advantages for corporal punishment: cheap and easy to administer, effective deterrent, effective reform, adjustable pain, fair because of similar dislike of pain, no permanent damage. None of these survive close scrutiny. An alternative, deontological argument against corporal punishment is proposed building on…
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Socioeconomic development and girl child survival in rural North India: solution or problem?
Krishnan, Anand; Dwivedi, Purva; Gupta, Vivek; Byass, Peter; Pandav, Chandrakant S; Ng, Nawi
2013-05-01
Socioeconomic development has been considered as a solution to the problem of sex differentials at birth and under-five mortality. This paper analyses longitudinal data from the Ballabgarh Health and Demographic Surveillance System (HDSS) site in north India to check its veracity. A cohort of children born between 1 January 2006 and 31 December 2011 at Ballabgarh HDSS were followed till death, emigration, 3 years of age or end of the study. Socioeconomic status (SES) was measured by caste, parental combined years of schooling and wealth index and divided into low, mid and high strata for each of them. Sex ratio at birth (SRB) was reported as the number of girls per 1000 boys. The Kaplan-Meier survival curves were drawn and a Cox Proportional HR of girls over boys was estimated. A total of 12 517 native born children (25 797 child years) were enrolled of which 710 died (death rate of 56.7/1000-live births and 27.5/1000 child-years. Socioeconomically advantaged children had significantly lower death rates. The SRB (10-16% lower) and neonatal death rate were consistently adverse for girls in the advantaged groups by all the three indicators of SES. The first month survival rates were better for girls in the lower SES categories (significant only in caste (HR 0.58; 0.37 to 0.91). High SES categories consistently showed adverse survival rates for girls (HR of 1.22 to 1.59). Better socioeconomic situation worsened the sex differentials, especially at birth. Therefore, specific interventions targeting gender issues are required, at least as a short-term measure.
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NASA Astrophysics Data System (ADS)
Mendoza-Hernández, Pedro E.; Rosete-Rodríguez, Alejandra; Sánchez-Coronado, María E.; Orozco, Susana; Pedrero-López, Luis; Méndez, Ignacio; Orozco-Segovia, Alma
2014-07-01
Human disturbance has disrupted the dynamics of plant communities. To restore these dynamics, we could take advantage of the microclimatic conditions generated by remaining patches of vegetation and plastic mulch. These microclimatic conditions might have great importance in restoring disturbed lava fields located south of Mexico City, where the rock is exposed and the soil is shallow. We evaluated the effects of both the shade projected by vegetation patches and plastic mulch on the mean monthly soil surface temperature ( T ss) and photosynthetic photon flux density (PPFD) and on the survival and growth of Salvia mexicana throughout the year. This species was used as a phytometer of microsite quality. Shade reduced the T ss to a greater extent than mulch did. Both survival and growth were enhanced by shade and mulch, and the PPFD was related with seedling growth. During the dry season, plant biomass was lost, and there was a negative effect of PPFD on plant growth. At micro-meteorological scales, the use of shade projected by patches of vegetation and mulch significantly reduced the mortality of S. mexicana and enhanced its growth. Survival and growth of this plant depended on the environmental quality of microsites on a small scale, which was determined by the environmental heterogeneity of the patches and the landscape. For plant restoration, microsite quality must be evaluated on small scales, but on a large scale it may be enough to take advantage of landscape shade dynamics and the use of mulch to increase plant survival and growth.
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Mendoza-Hernández, Pedro E; Rosete-Rodríguez, Alejandra; Sánchez-Coronado, María E; Orozco, Susana; Pedrero-López, Luis; Méndez, Ignacio; Orozco-Segovia, Alma
2014-07-01
Human disturbance has disrupted the dynamics of plant communities. To restore these dynamics, we could take advantage of the microclimatic conditions generated by remaining patches of vegetation and plastic mulch. These microclimatic conditions might have great importance in restoring disturbed lava fields located south of Mexico City, where the rock is exposed and the soil is shallow. We evaluated the effects of both the shade projected by vegetation patches and plastic mulch on the mean monthly soil surface temperature (Tss) and photosynthetic photon flux density (PPFD) and on the survival and growth of Salvia mexicana throughout the year. This species was used as a phytometer of microsite quality. Shade reduced the T ss to a greater extent than mulch did. Both survival and growth were enhanced by shade and mulch, and the PPFD was related with seedling growth. During the dry season, plant biomass was lost, and there was a negative effect of PPFD on plant growth. At micro-meteorological scales, the use of shade projected by patches of vegetation and mulch significantly reduced the mortality of S. mexicana and enhanced its growth. Survival and growth of this plant depended on the environmental quality of microsites on a small scale, which was determined by the environmental heterogeneity of the patches and the landscape. For plant restoration, microsite quality must be evaluated on small scales, but on a large scale it may be enough to take advantage of landscape shade dynamics and the use of mulch to increase plant survival and growth.
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Larval fish assemblages across an upwelling front: Indication for active and passive retention
NASA Astrophysics Data System (ADS)
Tiedemann, Maik; Brehmer, Patrice
2017-03-01
In upwelling areas, enrichment, concentration and retention are physical processes that have major consequences for larval fish survival. While these processes generally increase larval survival, strong upwelling can also increase mortality due to an offshore transport of larvae towards unfavorable habitats. In 2013 a survey was conducted along the Senegalese coast to investigate the upwelling effect with regard to larval fish assemblages and possible larval fish retention. According to water column characteristics two distinct habitats during an upwelling event were discriminated, i.e. the inshore upwelled water and the transition area over the deepest part of the Senegalese shelf. Along the two areas 42,162 fish larvae were collected representing 133 species within 40 families. Highest larval fish abundances were observed in the inshore area and decreasing abundances towards the transition, indicating that certain fish species make use of the retentive function of the inner shelf area as spawning grounds. Two larval fish assemblages overlap both habitats, which are sharply delimited by a strong upwelling front. One assemblage inhabited the inshore/upwelling area characterized by majorly neritic and pelagic species (Sparidae spp., Sardinella aurita), that seem to take the advantage of a passive retention on the shelf. The second assemblage consisted of a mix of pelagic and mesopelagic species (Engraulis encrasicolus, Carangidae spp. and Myctophidae spp.). Some species of the second assemblage, e.g. horse mackerels (Trachurus trachurus and Trachurus trecae), large finned-lantern fish (Hygophum macrochir) and foureyed sole (Microchirus ocellatus), revealed larval peak occurrences at intermediate and deep water layers, where the near-ground upwelling layer is able to transport larvae back to the shelf. This indicates active larval retention for species that are dominant in the transition area. Diel vertical migration patterns of S. aurita, E. encrasicolus and M. ocellatus revealed that a larval fish species may adapt its behavior to the local environment and do not necessarily follow a diurnal cycle. Field observations are essential to be integrated in larval drift models, since the vertical and horizontal larval distribution will have major consequences for survival. Comprehending larval survival mechanisms is necessary for the ultimate goal to understand and predict recruitment.
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Clonal evolution models of tumor heterogeneity.
Shlush, Liran I; Hershkovitz, Dov
2015-01-01
Somatic/clonal evolution is the process of sequential acquisition of vertically transmittable genetic/epigenetic elements in multicellular organisms. Cancer is the result of somatic evolution. Understanding the processes that shape the evolution of individual tumors might help us to treat cancer more efficiently. The initiating genetic/epigenetic events occur in functional cells and provide the cell of origin a selective advantage under a changing environment. The initiating genetic events tend to be enriched in specific tissues (and are sometimes specific for those tissues), as different tissues undergo different changes in the environment that will activate selective forces on different cells of origin. For the initial clonal expansion to occur premalignant clones need to have a relative fitness advantage over their competitors. It is estimated that the premalignant phase can take several years. Once the premalignant clonal expansion is established, the premalignant cells will contribute to the changing environment and will start competing among themselves. In late stages of cancer evolution the environmental changes might be similar across different tissues, including a lack of physical space, a shortage of energy, and activation of the immune system, and more and more of the hallmarks of cancer will evolve. In this review we will explore the possible clinical relevance of the heterogeneity that evolves during this long somatic evolution. Above all, it should be stressed that the earlier the clonal expansion is recognized, the less diverse and less fit for survival the cells in the population are.
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The impact of oxygen on the final alcohol content of wine fermented by a mixed starter culture.
Morales, Pilar; Rojas, Virginia; Quirós, Manuel; Gonzalez, Ramon
2015-05-01
We have developed a wine fermentation procedure that takes advantage of the metabolic features of a previously characterized Metschnikowia pulcherrima strain in order to reduce ethanol production. It involves the use of M. pulcherrima/Saccharomyces cerevisiae mixed cultures, controlled oxygenation conditions during the first 48 h of fermentation, and anaerobic conditions thereafter. The influence of different oxygenation regimes and initial inoculum composition on yeast physiology and final ethanol content was studied. The impact of oxygenation on yeast physiology goes beyond the first aerated step and influences yields and survival rates during the anaerobic stage. The activity of M. pulcherrima in mixed oxygenated cultures resulted in a clear reduction in ethanol yield, as compared to S. cerevisiae. Despite relatively low initial cell numbers, S. cerevisiae always predominated in mixed cultures by the end of the fermentation process. Strain replacement was faster under low oxygenation levels. M. pulcherrima confers an additional advantage in terms of dissolved oxygen, which drops to zero after a few hours of culture, even under highly aerated conditions, and this holds true for mixed cultures. Alcohol reduction values about 3.7 % (v/v) were obtained for mixed cultures under high aeration, but they were associated to unacceptable volatile acidity levels. In contrast, under optimized conditions, only 0.35 g/L acetic acid was produced, for an alcohol reduction of 2.2 % (v/v), and almost null dissolved oxygen during the process.
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Transforming Higher Education in the Information Age: Presidents Respond.
ERIC Educational Resources Information Center
Breslin, Richard D.; And Others
1991-01-01
College presidents respond to an article by Richard Nolan challenging college and university presidents and chancellors to transform their campuses for survival and competitive advantage in the information age. Respondents include Richard D. Breslin, David M. Clarke, Joseph Cronin, Thomas Ehrlich, Donald N. Langenberg, Harold McAninch, and Donald…
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Pin cherry effects on Allegheny hardwood stand development
Todd E. Ristau; Stephen B. Horsley
1999-01-01
Pin cherry (Prunus pensylvanica L.) develops an early height advantage over associated species. Data from three long-term studies, extending up to 70 years after complete overstory removal, were used to evaluate the effects of pin cherry density on associates. Survival of seedling-origin stems of black cherry (Prunus serotina Ehrh...
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Facilitating Attachment between School-Aged Children and a Dying Parent
ERIC Educational Resources Information Center
Saldinger, Amy; Cain, Albert C.; Porterfield, Katherine; Lohnes, Kelly
2004-01-01
A qualitative, community study of 58 parentally bereaved children and their 35 surviving parents illustrates how families take advantage of forewarning of death to foster connections between children and dying parents and prepare for youngsters' continued attachment to dying parents after the death. Children and parents displayed strong yearnings…
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Life tables as tools of evaluation and quality control for arthropod mass production
USDA-ARS?s Scientific Manuscript database
Life tables, as a basic concept, are descriptions of survival potential at various ages or stages. Understanding critical life stages of arthropod development and their influence on the population structure is of great importance for arthropod rearing systems. Another important advantage of a life t...
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Adaptive Memory: Is Survival Processing Special?
ERIC Educational Resources Information Center
Nairne, James S.; Pandeirada, Josefa N. S.
2008-01-01
Do the operating characteristics of memory continue to bear the imprints of ancestral selection pressures? Previous work in our laboratory has shown that human memory may be specially tuned to retain information processed in terms of its survival relevance. A few seconds of survival processing in an incidental learning context can produce recall…
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Hehlmann, R; Lauseker, M; Saußele, S; Pfirrmann, M; Krause, S; Kolb, H J; Neubauer, A; Hossfeld, D K; Nerl, C; Gratwohl, A; Baerlocher, G M; Heim, D; Brümmendorf, T H; Fabarius, A; Haferlach, C; Schlegelberger, B; Müller, M C; Jeromin, S; Proetel, U; Kohlbrenner, K; Voskanyan, A; Rinaldetti, S; Seifarth, W; Spieß, B; Balleisen, L; Goebeler, M C; Hänel, M; Ho, A; Dengler, J; Falge, C; Kanz, L; Kremers, S; Burchert, A; Kneba, M; Stegelmann, F; Köhne, C A; Lindemann, H W; Waller, C F; Pfreundschuh, M; Spiekermann, K; Berdel, W E; Müller, L; Edinger, M; Mayer, J; Beelen, D W; Bentz, M; Link, H; Hertenstein, B; Fuchs, R; Wernli, M; Schlegel, F; Schlag, R; de Wit, M; Trümper, L; Hebart, H; Hahn, M; Thomalla, J; Scheid, C; Schafhausen, P; Verbeek, W; Eckart, M J; Gassmann, W; Pezzutto, A; Schenk, M; Brossart, P; Geer, T; Bildat, S; Schäfer, E; Hochhaus, A; Hasford, J
2017-11-01
Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.
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Temozolomide and other potential agents for the treatment of glioblastoma multiforme.
Nagasawa, Daniel T; Chow, Frances; Yew, Andrew; Kim, Won; Cremer, Nicole; Yang, Isaac
2012-04-01
This article provides historical and recent perspectives related to the use of temozolomide for the treatment of glioblastoma multiforme. Temozolomide has quickly become part of the standard of care for the modern treatment of stage IV glioblastoma multiforme since its approval in 2005. Yet despite its improvements from previous therapies, median survival remains approximately 15 months, with a 2-year survival rate of 8% to 26%. The mechanism of action of this chemotherapeutic agent, conferred advantages and limitations, treatment resistance and rescue, and potential targets of future research are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Perry, Russell W.; Skalski, John R.
Wetlands in the Columbia River estuary are actively being restored by reconnecting these habitats to the estuary, making more wetland habitats available to rearing and migrating juvenile salmon. Concurrently, thousands of acoustically tagged juvenile salmonids are released into the Columbia River to estimate their survival as they migrate through the estuary. Here, we develop a release-recapture model that makes use of these tagged fish to measure the success of wetland restoration projects in terms of their contribution to populations of juvenile salmon. Specifically, our model estimates the fraction of the population that enter the wetland, survival within the wetland, andmore » the mean residence time of fish within the wetland. Furthermore, survival in mainstem Columbia River downstream of the wetland can be compared between fish that remained the mainstem and entered the wetland. These conditional survival estimates provide a means of testing whether the wetland improves the subsequent survival of juvenile salmon by fostering growth or improving their condition. Implementing such a study requires little additional cost because it takes advantage of fish already released to estimate survival through the estuary. Thus, such a study extracts the maximum information at minimum cost from research projects that typically cost millions of dollars annually.« less
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Klein, Stanley B.; Robertson, Theresa E.; Delton, Andrew W.
2013-01-01
In a series of papers, Nairne and colleagues have demonstrated that tasks encouraging participants to judge words for relevance to survival led to better recall than did tasks lacking survival relevance. Klein, Robertson, and Delton (2010) presented data suggesting that the future-directed temporal orientation of the survival task (e.g., planning), rather than survival per se, accounts for the good recall found with the task. In the present studies we manipulated the amount of survival and planning processing encouraged by a set of encoding tasks. Participants performed tasks that encouraged processing stimuli for their relevance to (a) both survival and planning, (b) planning, but not survival, or (c) survival but not planning. We predicted, and found, that recall performance associated with tasks encouraging planning (i.e., survival with planning and planning without survival) should exceed tasks that encouraged survival but not planning (i.e., survival without planning). We draw several conclusions. First, planning is a necessary component of the superior recall found in the survival paradigm. Second, memory, from an evolutionary perspective, is inherently prospective—tailored by natural selection to support future decisions and judgements that cannot be known in advance with certainty. PMID:21229456
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Kalantar-Zadeh, Kamyar; Golan, Eliezer; Shohat, Tamy; Streja, Elani; Norris, Keith C.; Kopple, Joel D.
2013-01-01
There are counterintuitive but consistent observations that African American maintenance dialysis patients have greater survival despite their less favorable socioeconomic status, high burden of cardiovascular risks including hypertension and diabetes, and excessively high chronic kidney disease prevalence. The fact that such individuals have a number of risk factors for lower survival and yet live longer when undergoing dialysis treatment is puzzling. Similar findings have been made among Israeli maintenance dialysis patients, in that those who are ethnically Arab have higher end-stage renal disease but exhibit greater survival than Jewish Israelis. The juxtaposition of these two situations may provide valuable insights into racial/ethnic-based mechanisms of survival in chronic diseases. Survival advantages of African American dialysis patients may be explained by differences in nutritional status, inflammatory profile, dietary intake habits, body composition, bone and mineral disorders, mental health and coping status, dialysis treatment differences, and genetic differences among other factors. Prospective studies are needed to examine similar models in other countries and to investigate the potential causes of these paradoxes in these societies. Better understanding the roots of racial/ethnic survival differences may help improve outcomes in both patients with chronic kidney disease and other individuals with chronic disease states. PMID:21175833
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Räwer, Henrik; Braun von Reinersdorff, A; Ochotta, T; Rasche, C
2011-12-01
The provision of outpatient services will be confronted by increased market concentration. Under these circumstances, individual medical practices are predicted to have a minimal chance for survival since by nature the specialized physician can only accommodate the considerably heterogeneous needs of the patients up to justifiable limits. Due to patients' higher rate of mobility in the elective process, specialty physicians in rural areas are obliged to transform their practices into professional service enterprises. While hospitals are attempting to combat a continuing economization of the health care sector, in part by applying aggressive leadership and management methods, an increasing polarization can be noted in the outpatient setting. Also in the field of urology, patients consider themselves medical treatment clients who are unwilling to be relegated to cases of the often criticized"5-minute medicine."
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Halaweish, Ihab; Nikolian, Vahagn; Georgoff, Patrick; Li, Yongqing; Alam, Hasan B
2014-01-01
Traumatic injuries and their sequela represent a major source of mortality in the United States and globally. Initial treatment for shock, traumatic brain injury, and polytrauma is limited to resuscitation fluids to replace lost volume. To date, there are no treatments with inherent pro-survival properties. Our lab has investigated the use of histone deacetylase inhibitors (HDACIs) as pharmacological agents to improve survival. This class of drugs acts through posttranslational protein modifications and is a direct regulator of chromatin structure and function, as well as the function of numerous cytoplasmic proteins. In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a significant survival advantage, even in the absence of fluid resuscitation. Positive results have also been shown in two-hit models of hemorrhage and sepsis and in hemorrhagic shock combined with traumatic brain injury. Accumulating data generated by our group and others continue to support the use of HDACIs for creation of a pro-survival phenotype. With further research and clinical trials, HDACIs have the potential to be an integral tool in treatment of trauma, especially in the pre-hospital phase. PMID:25565645
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Hard choices in assessing survival past dams — a comparison of single- and paired-release strategies
Zydlewski, Joseph D.; Stich, Daniel S.; Sigourney, Douglas B.
2017-01-01
Mark–recapture models are widely used to estimate survival of salmon smolts migrating past dams. Paired releases have been used to improve estimate accuracy by removing components of mortality not attributable to the dam. This method is accompanied by reduced precision because (i) sample size is reduced relative to a single, large release; and (ii) variance calculations inflate error. We modeled an idealized system with a single dam to assess trade-offs between accuracy and precision and compared methods using root mean squared error (RMSE). Simulations were run under predefined conditions (dam mortality, background mortality, detection probability, and sample size) to determine scenarios when the paired release was preferable to a single release. We demonstrate that a paired-release design provides a theoretical advantage over a single-release design only at large sample sizes and high probabilities of detection. At release numbers typical of many survival studies, paired release can result in overestimation of dam survival. Failures to meet model assumptions of a paired release may result in further overestimation of dam-related survival. Under most conditions, a single-release strategy was preferable.
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Corker, Jamaica
2016-01-01
Demographic research in sub-Saharan Africa (SSA) has long relied on a blunt urban/rural dichotomy that may obscure important inter-urban fertility and mortality differentials. This paper uses Demographic and Health Survey (DHS) geo-referenced data to look beyond the simple urban/rural division by spatially locating survey clusters along an urban continuum and producing estimates of fertility and child mortality by four city size categories in West Africa. Results show a gradient in urban characteristics and demographic outcomes: the largest cities are the most advantaged and smaller cities least advantaged with respect to access to urban amenities, lower fertility and under-5 survival rates. There is a difference in the patterns of fertility and under-five survival across urban categories, with fertility more linearly associated with city size while the only significant distinction for under-5 survival in urban areas is broadly between the larger and smaller cities. Notably, the small urban “satellite cities” that are adjacent to the largest cities have the most favorable outcomes of all categories. Although smaller urban areas have significantly lower fertility and child mortality than rural areas, in some cases this difference is nearly as large between the smallest and largest urban areas. These results are used to argue for the need to give greater consideration to employing an urban continuum in demographic research. PMID:28943812
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Role of capsule and O antigen in the virulence of uropathogenic Escherichia coli.
Sarkar, Sohinee; Ulett, Glen C; Totsika, Makrina; Phan, Minh-Duy; Schembri, Mark A
2014-01-01
Urinary tract infection (UTI) is one of the most common bacterial infections in humans, with uropathogenic Escherichia coli (UPEC) the leading causative organism. UPEC has a number of virulence factors that enable it to overcome host defenses within the urinary tract and establish infection. The O antigen and the capsular polysaccharide are two such factors that provide a survival advantage to UPEC. Here we describe the application of the rpsL counter selection system to construct capsule (kpsD) and O antigen (waaL) mutants and complemented derivatives of three reference UPEC strains: CFT073 (O6:K2:H1), RS218 (O18:K1:H7) and 1177 (O1:K1:H7). We observed that while the O1, O6 and O18 antigens were required for survival in human serum, the role of the capsule was less clear and linked to O antigen type. In contrast, both the K1 and K2 capsular antigens provided a survival advantage to UPEC in whole blood. In the mouse urinary tract, mutation of the O6 antigen significantly attenuated CFT073 bladder colonization. Overall, this study contrasts the role of capsule and O antigen in three common UPEC serotypes using defined mutant and complemented strains. The combined mutagenesis-complementation strategy can be applied to study other virulence factors with complex functions both in vitro and in vivo.
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Decision analysis with cumulative prospect theory.
Bayoumi, A M; Redelmeier, D A
2000-01-01
Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities: 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory.
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Bocquier, Philippe; Madise, Nyovani Janet; Zulu, Eliya Msiyaphazi
2011-05-01
Evidence of higher child mortality of rural-to-urban migrants compared with urban nonmigrants is growing. However, less attention has been paid to comparing the situation of the same families before and after they migrate with the situation of urban-to-rural migrants. We use DHS data from 18 African countries to compare child mortality rates of six groups based on their mothers' migration status: rural nonmigrants; urban nonmigrants; rural-to-urban migrants before and after they migrate; and urban-to-rural migrants before and after they migrate. The results show that rural-to-urban migrants had, on average, lower child mortality before they migrated than rural nonmigrants, and that their mortality levels dropped further after they arrived in urban areas. We found no systematic evidence of higher child mortality for rural-to-urban migrants compared with urban nonmigrants. Urban-to-rural migrants had higher mortality in the urban areas, and their move to rural areas appeared advantageous because they experienced lower or similar child mortality after living in rural areas. After we control for known demographic and socioeconomic correlates of under-5 mortality, the urban advantage is greatly reduced and sometimes reversed. The results suggest that it may not be necessarily the place of residence that matters for child survival but, rather, access to services and economic opportunities.
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NASA Technical Reports Server (NTRS)
Choi, Michael K.
2017-01-01
A thermal design concept of using propylene loop heat pipes to minimize survival heater power for NASA's Evolutionary Xenon Thruster power processing units is presented. It reduces the survival heater power from 183 W to 35 W per power processing unit. The reduction is 81%.
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Gerber, Brian D.; Kendall, William L.
2017-01-01
Monitoring animal populations can be difficult. Limited resources often force monitoring programs to rely on unadjusted or smoothed counts as an index of abundance. Smoothing counts is commonly done using a moving-average estimator to dampen sampling variation. These indices are commonly used to inform management decisions, although their reliability is often unknown. We outline a process to evaluate the biological plausibility of annual changes in population counts and indices from a typical monitoring scenario and compare results with a hierarchical Bayesian time series (HBTS) model. We evaluated spring and fall counts, fall indices, and model-based predictions for the Rocky Mountain population (RMP) of Sandhill Cranes (Antigone canadensis) by integrating juvenile recruitment, harvest, and survival into a stochastic stage-based population model. We used simulation to evaluate population indices from the HBTS model and the commonly used 3-yr moving average estimator. We found counts of the RMP to exhibit biologically unrealistic annual change, while the fall population index was largely biologically realistic. HBTS model predictions suggested that the RMP changed little over 31 yr of monitoring, but the pattern depended on assumptions about the observational process. The HBTS model fall population predictions were biologically plausible if observed crane harvest mortality was compensatory up to natural mortality, as empirical evidence suggests. Simulations indicated that the predicted mean of the HBTS model was generally a more reliable estimate of the true population than population indices derived using a moving 3-yr average estimator. Practitioners could gain considerable advantages from modeling population counts using a hierarchical Bayesian autoregressive approach. Advantages would include: (1) obtaining measures of uncertainty; (2) incorporating direct knowledge of the observational and population processes; (3) accommodating missing years of data; and (4) forecasting population size.
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Survival Outcomes After Intracranial Hemorrhage in Liver Disease.
Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac
2018-05-15
Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.
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Preference for sons and sex ratio in two non-Western societies.
Crognier, E; Baali, A; Hilali, M-K; Villena, M; Vargas, E
2006-01-01
Moroccan Berbers and the Bolivian Aymara are two unrelated peasant groups living in adverse environments with a still rather traditional agriculture. Precarious life conditions may be responsible for the importance given to male labor and hence for the cultural preference conferred on male descent. This preference, expressed in the social valorization of sons to the detriment of daughters, is more emphasized if the socioeconomic status of the family is lower. Interpreted according to the cost/benefit approach of Fisher (1958 Genetical Theory of Natural Selection, New York: Dover) of variations in the sex ratio and to its later developments (Trivers and Willard 1973 Science 179:90-91; Trivers 1985 Social Evolution, Menlo Park: Benjamin/Cummings; Hewlett 1991 J. Anthropol. Res. 47:1-37; Smith 1993 Ethol. Sociobiol. 14:39-44), these cultural characteristics could determine that parents bias the care allocated to their progeny in favor of sons, to the detriment of daughters. This could eventually affect their respective survival and finally modify the offspring tertiary sex ratio. This study compares differences in survival as indicators of parental care according to a child's sex and across three economic strata: poor, medium, and high. The Moroccan data express no other sex differences in survival than an advantage for daughters during the preweaning period in the medium and high strata. Within the same sex and across economic strata, a greater mortality between age 10-20 years is observed for boys of the poorest stratum. The Aymara data do not show sex differences by economic stratum, except for an advantage to daughters between birth and 5 years in the medium group, and no survival differences within the same sex across economic strata. These results suggest either that despite the social valorization of male progeny no differences in parental care according to sex occur, or that their magnitude is not great enough to contrast the survival of sons and daughters.
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Hamady, Zaed Z R; Lodge, J Peter A; Welsh, Fenella K; Toogood, Giles J; White, Alan; John, Timothy; Rees, Myrddin
2014-03-01
To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.
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Naunheim, Keith S; Wood, Douglas E; Mohsenifar, Zab; Sternberg, Alice L; Criner, Gerard J; DeCamp, Malcolm M; Deschamps, Claude C; Martinez, Fernando J; Sciurba, Frank C; Tonascia, James; Fishman, Alfred P
2006-08-01
The National Emphysema Treatment Trial defined subgroups of patients with severe emphysema in whom lung-volume-reduction surgery (LVRS) improved survival and function at 2 years. Two additional years of follow-up provide valuable information regarding durability. A total of 1218 patients with severe emphysema were randomized to receive LVRS or medical treatment. We present updated analyses (4.3 versus 2.4 years median follow-up), including 40% more patients with functional measures 2 years after randomization. The intention-to-treat analysis of 1218 randomized patients demonstrates an overall survival advantage for LVRS, with a 5-year risk ratio (RR) for death of 0.86 (p = 0.02). Improvement was more likely in the LVRS than in the medical group for maximal exercise through 3 years and for health-related quality of life (St. George's Respiratory Questionnaire [SGRQ]) through 4 years. Updated comparisons of survival and functional improvement were consistent with initial results for four clinical subgroups of non-high-risk patients defined by upper-lobe predominance and exercise capacity. After LVRS, the upper-lobe patients with low exercise capacity demonstrated improved survival (5-year RR, 0.67; p = 0.003), exercise throughout 3 years (p < 0.001), and symptoms (SGRQ) through 5 years (p < 0.001 years 1 to 3, p = 0.01 year 5). Upper-lobe-predominant and high-exercise-capacity LVRS patients obtained no survival advantage but were likely to improve exercise capacity (p < 0.01 years 1 to 3) and SGRQ (p < 0.01 years 1 to 4). Effects of LVRS are durable, and it can be recommended for upper-lobe-predominant emphysema patients with low exercise capacity and should be considered for palliation in patients with upper-lobe emphysema and high exercise capacity.
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Fitness of artemisinin-resistant Plasmodium falciparum in vitro.
Hott, Amanda; Tucker, Matthew S; Casandra, Debora; Sparks, Kansas; Kyle, Dennis E
2015-10-01
Drug resistance confers a fitness advantage to parasites exposed to frequent drug pressure, yet these mutations also may incur a fitness cost. We assessed fitness advantages and costs of artemisinin resistance in Plasmodium falciparum in vitro to understand how drug resistance will spread and evolve in a competitive environment. Genotyping of SNPs, drug susceptibility assays and copy number determination were used to assess the impact of artemisinin resistance on parasite fitness. An artemisinin-resistant clone (C9) selected in vitro from an isogenic parental clone (D6) was used to conduct competitive growth studies to assess fitness of artemisinin resistance. The resistant and susceptible clones were mixed or grown alone in the presence and absence of drug pressure (dihydroartemisinin or pyrimethamine) to quantify the rate at which artemisinin resistance was gained or lost. We experimentally demonstrate for the first time that artemisinin resistance provides a fitness advantage that is selected for with infrequent exposure to drug, but is lost in the absence of exposure to artemisinin drugs. The best correlations with artemisinin resistance were decreased in vitro drug susceptibility to artemisinin derivatives, increased copy number of Pf3D7_1030100 and an SNP in Pf3D7_0307600. An SNP conferring an E208K mutation in the kelch gene (Pf3D7_1343700) was not associated with resistance. Furthermore, we observed second-cycle ring-stage dormancy induced by pyrimethamine, suggesting that dormancy is a fitness trait that provides an advantage for survival from antimalarial drug stress. Artemisinin-resistant P. falciparum have a fitness advantage to survive and predominate in the population even in the face of infrequent exposure to artemisinin drugs. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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A Visual Short-Term Memory Advantage for Objects of Expertise
ERIC Educational Resources Information Center
Curby, Kim M.; Glazek, Kuba; Gauthier, Isabel
2009-01-01
Visual short-term memory (VSTM) is limited, especially for complex objects. Its capacity, however, is greater for faces than for other objects; this advantage may stem from the holistic nature of face processing. If the holistic processing explains this advantage, object expertise--which also relies on holistic processing--should endow experts…
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Rago, Adam P; Larentzakis, Andreas; Marini, John; Picard, Abby; Duggan, Michael J; Busold, Rany; Helmick, Marc; Zugates, Greg; Beagle, John; Sharma, Upma; King, David R
2015-02-01
Noncompressible abdominal hemorrhage is a significant cause of battlefield and civilian mortality. We developed a self-expanding polyurethane foam intended to provide temporary hemorrhage control and enable evacuation to a definitive surgical capability, for casualties who would otherwise die. We hypothesized that foam treatment would be efficacious over a wide range of out-of-hospital operational conditions. The foam was tested in an established lethal, closed-cavity hepatoportal injury model in four groups as follows. Group 1 involved baseline conditions, wherein foam was deployed from a pneumatically driven, first-generation delivery device at room temperature (n = 6). Group 2 involved foam deployment from a field-relevant, handheld delivery prototype (n = 12). Group 3 involved foam components that were conditioned to simulate 1-year shelf-life (n = 6). Group 4 involved foam that was conditioned to a range of temperatures (10 °C and 50 °C; n = 6 per group). In all studies, survival was monitored for up to 180 minutes and compared with an ongoing and accumulating control group with no intervention (n = 14). In Group 1 with a first-generation delivery system, foam treatment resulted in a significant survival advantage relative to the control group (p < 0.001), confirming previous results. In Group 2 with a handheld delivery system, survival was also improved, 83% at 3 hours, compared with 7% in the control group (p < 0.001). In Group 3, survival was 83% at 3 hours (p = 0.002). In Group 4 at temperature extremes, 3-hour survival was 83% (p = 0.002) and 67% (p = 0.014) in the low- and high-temperature groups, respectively. Temperature extremes did not result in hypothermia, hyperthermia, or thermal injury. In all studies, the bleeding rate in foam groups was significantly lower than in the control group (p < 0.05). Under a range of military operational conditions, foam treatment resulted in a survival advantage relative to the control group. This supports the feasibility of foam treatment as a prehospital hemostatic bridge to surgery for severely bleeding causalities.
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Adaptive plasticity in the mouse mandible.
Anderson, Philip S L; Renaud, Sabrina; Rayfield, Emily J
2014-04-18
Plasticity, i.e. non-heritable morphological variation, enables organisms to modify the shape of their skeletal tissues in response to varying environmental stimuli. Plastic variation may also allow individuals to survive in the face of new environmental conditions, enabling the evolution of heritable adaptive traits. However, it is uncertain whether such a plastic response of morphology constitutes an evolutionary adaption itself. Here we investigate whether shape differences due to plastic bone remodelling have functionally advantageous biomechanical consequences in mouse mandibles. Shape characteristics of mandibles from two groups of inbred laboratory mice fed either rodent pellets or ground pellets mixed with jelly were assessed using geometric morphometrics and mechanical advantage measurements of jaw adductor musculature. Mandibles raised on diets with differing food consistency showed significant differences in shape, which in turn altered their biomechanical profile. Mice raised on a soft food diet show a reduction in mechanical advantage relative to mice of the same inbred strain raised on a typical hard food diet. Further, the soft food eaters showed lower levels of integration between jaw regions, particularly between the molar and angular region relative to hard food eaters. Bone remodelling in mouse mandibles allows for significant shifts in biomechanical ability. Food consistency significantly influences this process in an adaptive direction, as mice raised on hard food develop jaws better suited to handle hard foods. This remodelling also affects the organisation of the mandible, as mice raised on soft food appear to be released from developmental constraints showing less overall integration than those raised on hard foods, but with a shift of integration towards the most solicited regions of the mandible facing such a food, namely the incisors. Our results illustrate how environmentally driven plasticity can lead to adaptive functional changes that increase biomechanical efficiency of food processing in the face of an increased solicitation. In contrast, decreased demand in terms of food processing seems to release developmental interactions between jaw parts involved in mastication, and may generate new patterns of co-variation, possibly opening new directions to subsequent selection. Overall, our results emphasize that mandible shape and integration evolved as parts of a complex system including mechanical loading food resource utilization and possibly foraging behaviour.
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Modeling targeted inhibition of MEK and PI3 kinase in human pancreatic cancer.
Junttila, Melissa R; Devasthali, Vidusha; Cheng, Jason H; Castillo, Joseph; Metcalfe, Ciara; Clermont, Anne C; Otter, Douglas Den; Chan, Emily; Bou-Reslan, Hani; Cao, Tim; Forrest, William; Nannini, Michelle A; French, Dorothy; Carano, Richard; Merchant, Mark; Hoeflich, Klaus P; Singh, Mallika
2015-01-01
Activating mutations in the KRAS oncogene occur in approximately 90% of pancreatic cancers, resulting in aberrant activation of the MAPK and the PI3K pathways, driving malignant progression. Significant efforts to develop targeted inhibitors of nodes within these pathways are underway and several are currently in clinical trials for patients with KRAS-mutant tumors, including patients with pancreatic cancer. To model MEK and PI3K inhibition in late-stage pancreatic cancer, we conducted preclinical trials with a mutant Kras-driven genetically engineered mouse model that faithfully recapitulates human pancreatic ductal adenocarcinoma development. Treatment of advanced disease with either a MEK (GDC-0973) or PI3K inhibitor (GDC-0941) alone showed modest tumor growth inhibition and did not significantly enhance overall survival. However, combination of the two agents resulted in a significant survival advantage as compared with control tumor-bearing mice. To model the clinical scenario, we also evaluated the combination of these targeted agents with gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer. The addition of MEK or PI3K inhibition to gemcitabine, or the triple combination regimen, incrementally enhanced overall survival as compared with gemcitabine alone. These results are reminiscent of the survival advantage conferred in this model and in patients by the combination of gemcitabine and erlotinib, an approved therapeutic regimen for advanced nonresectable pancreatic cancer. Taken together, these data indicate that inhibition of MEK and PI3K alone or in combination with chemotherapy do not confer a dramatic improvement as compared with currently available therapies for patients with pancreatic cancer. ©2014 American Association for Cancer Research.
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Wan, Xiao Chloe; Egloff, Ann Marie; Johnson, Jonas
2012-12-01
Postoperative chemoradiation (CRT) has been shown to be more effective than postoperative radiotherapy (RT) alone in high risk head and neck squamous cell carcinoma (HNSCC) patients. Multimodality therapy is associated with more treatment related-toxicity. In this study, we assessed cervical lymph node histological characteristics to detect prognostic and predictive value differences to help guide therapeutic decision making. Retrospective analysis of Cancer Registry data. HNSCC surgical patients who had tumor resection and neck dissection at our institution from 1980 to 2008 were identified (n=1510). Multivariable Cox proportional hazards regression models were developed to identify significant predictors of three outcomes: overall survival (OS), disease-specific survival (DSS), and neck disease recurrence (NDR). Hazard ratios were estimated for the number of cervical nodal metastases and presence of extracapsular spread (ECS) by adjuvant treatment after controlling for significant covariates. Increasing number of positive nodes was significantly associated with poorer outcomes in OS, DSS, and NDR models (p<0.0001, p<0.0001, p=0.0002, respectively). OS and DSS associated with adjuvant treatment (none, RT, or CRT) were modified by number of positive nodes, ECS status, and cancer site. The presence of ECS was associated with reduced OS and DSS (p=0.077, p=0.001 respectively), but not significantly associated with NDR (p=0.179). Nodal positive patients benefited from adjuvant therapy regardless of ECS status. CRT consistently conferred a survival advantage over RT across all nodal categories, although the difference was not statistically significant. We observed a consistent survival advantage with CRT over RT for patients with positive cervical nodal metastasis, although the difference was not statistically significant. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
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Gordetsky, Jennifer; Gibson, Briana; Stevens, Todd M; Ellenburg, J Luke; Grizzle, William; Rais-Bahrami, Soroush
2016-08-01
To identify occult metastases within lymph nodes (LNs) reported as negative by routine histologic evaluation. In patients with high-grade, muscle-invasive urothelial carcinoma (UC) of the bladder, pelvic lymphadenectomy during radical cystectomy demonstrates a survival advantage, increasing with the number of LNs removed, even if negative for metastatic disease. This finding may potentially be explained by the presence of occult metastases. Radical cystectomy specimens with high-grade UC invading the perivesical tissue and negative LNs (pT3N0) between 2000 and 2014 were reviewed. Five levels were cut for each LN block. Two sections were cut per level: 1 stained for hematoxylin and eosin and 1 for AE1/AE3. Micrometastases were defined as tumor deposits >0.2 mm but <2 mm. Isolated tumor cells were defined as ≤0.2 mm. Medical records and survival data were reviewed. We identified 21 cases, consisting of 370 lymph nodes. Six of 21 patients (29%) had occult metastases, including 5 occult metastatic UC and 1 occult metastatic prostate adenocarcinoma. There were 10 positive LNs; 2 macrometastases, 2 micrometastases, and 6 with ITCs. Two of 6 patients (33%) had lymphovascular invasion identified in the primary tumor. Kaplan-Meier analysis showed no significant difference in overall survival between the group of patients who remained N0 versus those upstaged due to discovery of occult metastases (P-value = .42). In patients with pT3 UC undergoing cystectomy, we demonstrated the presence of occult metastases in 29% of patients. The high percentage of occult metastases present in these cases possibly explains the proven survival advantage of removing "negative" LNs. This finding might also have implications in the histologic evaluation of LNs. Copyright © 2016 Elsevier Inc. All rights reserved.
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Spiotto, Michael T; Koshy, Matthew
2017-05-01
Although chemoradiation regimens have used various fraction sizes, it remains unclear how differences in fraction size impact outcomes. Using the National Cancer Database, we identified patients with nasopharynx or oropharynx cancers treated between 2004 and 2012 with chemoradiation using fraction sizes of 1.8Gy (n=1612), 2Gy (n=8092) or 2.12Gy (n=1660). Comparisons between fraction sizes were made in the entire cohort and in a propensity matched cohort. Median follow-up was 38.1m. Patients receiving 2.12Gy per fraction were more likely to be treated from 2007 to 2012, to be treated at an academic center, to have T3-T4 tumors and to have oropharyngeal primaries. The 3year overall survival for patients treated with 1.8Gy, 2Gy and 2.12Gy fraction sizes was 72.9%, 77.8% and 83.3%, respectively (P<0.0001). 2.12Gy fraction size was associated with improved survival in patients with nasopharynx cancer (P=0.03), base of tongue cancer (P<0.0001) and tonsil cancer (P=0.0002). On multivariate analysis, improved survival was associated with 2.12Gy fraction sizes compared to 2Gy (HR 1.23, 95% CI 1.09-1.40, P=0.001) or 1.8Gy (HR 1.36, 95% CI 1.17-1.58; P<0.0001) fractions sizes. Chemoradiation regimens using 2.12Gy fraction sizes likely have a potential advantage in select nasopharynx and oropharynx cancer patients based on age, treatment facility and radiotherapy technique. However, it remains unclear if this survival advantage reflected improved disease control due to lack of locoregional control data. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation.
Gerstein, Aleeza C; Fu, Man Shun; Mukaremera, Liliane; Li, Zhongming; Ormerod, Kate L; Fraser, James A; Berman, Judith; Nielsen, Kirsten
2015-10-13
Cryptococcus neoformans is a major life-threatening fungal pathogen. In response to the stress of the host environment, C. neoformans produces large polyploid titan cells. Titan cell production enhances the virulence of C. neoformans, yet whether the polyploid aspect of titan cells is specifically influential remains unknown. We show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters maintained an advantage over typical cells in continued exposure to stress. Although polyploid titan cells generated haploid daughter cell progeny upon in vitro replication under nutrient-replete conditions, titan cells treated with the antifungal drug fluconazole produced fluconazole-resistant diploid and aneuploid daughter cells. Interestingly, a single titan mother cell was capable of generating multiple types of aneuploid daughter cells. The increased survival and genomic diversity of titan cell progeny promote rapid adaptation to new or high-stress conditions. The ability to adapt to stress is a key element for survival of pathogenic microbes in the host and thus plays an important role in pathogenesis. Here we investigated the predominantly haploid human fungal pathogen Cryptococcus neoformans, which is capable of ploidy and cell size increases during infection through production of titan cells. The enlarged polyploid titan cells are then able to rapidly undergo ploidy reduction to generate progeny with reduced ploidy and/or aneuploidy. Under stressful conditions, titan cell progeny have a growth and survival advantage over typical cell progeny. Understanding how titan cells enhance the rate of cryptococcal adaptation under stress conditions may assist in the development of novel drugs aimed at blocking ploidy transitions. Copyright © 2015 Gerstein et al.
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Kong, Melissa H; Shaw, Linda K; O'Connor, Christopher; Califf, Robert M; Blazing, Michael A; Al-Khatib, Sana M
2010-07-01
Although no clinical trial data exist on the optimal management of atrial fibrillation (AF) in patients with diastolic heart failure, it has been hypothesized that rhythm-control is more advantageous than rate-control due to the dependence of these patients' left ventricular filling on atrial contraction. We aimed to determine whether patients with AF and heart failure with preserved ejection fraction (EF) survive longer with rhythm versus rate-control strategy. The Duke Cardiovascular Disease Database was queried to identify patients with EF > 50%, heart failure symptoms and AF between January 1,1995 and June 30, 2005. We compared baseline characteristics and survival of patients managed with rate- versus rhythm-control strategies. Using a 60-day landmark view, Kaplan-Meier curves were generated and results were adjusted for baseline differences using Cox proportional hazards modeling. Three hundred eighty-two patients met the inclusion criteria (285 treated with rate-control and 97 treated with rhythm-control). The 1-, 3-, and 5-year survival rates were 93.2%, 69.3%, and 56.8%, respectively in rate-controlled patients and 94.8%, 78.0%, and 59.9%, respectively in rhythm-controlled patients (P > 0.10). After adjustments for baseline differences, no significant difference in mortality was detected (hazard ratio for rhythm-control vs rate-control = 0.696, 95% CI 0.453-1.07, P = 0.098). Based on our observational data, rhythm-control seems to offer no survival advantage over rate-control in patients with heart failure and preserved EF. Randomized clinical trials are needed to verify these findings and examine the effect of each strategy on stroke risk, heart failure decompensation, and quality of life.
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Comparison of peritoneal dialysis and hemodialysis after kidney transplant failure.
Kang, G W; Jang, M H; Hwang, E A; Park, S B; Han, S Y
2013-10-01
Patients with a failed kidney transplant represent a unique chronic kidney disease population that is increasing in number and is at high risk of morbidity and mortality. Among transplant-naïve patients, those treated with peritoneal dialysis (PD) show an early survival advantage compared with those treated with hemodialysis (HD). But any advantage of PD after allograft failure is unknown. The aim of this study was to investigate the clinical outcomes of patients with failed allografts according to the type of dialysis modality. We reviewed medical records of patients who initiated dialysis after kidney transplant failure from November 1982 to May 2011. Demographics features, clinical data, and survival outcomes were compared between PD and HD patients who had experienced allograft failure. The 182 patients with failed allografts showed the most common cause to be chronic rejection. The median duration of function before allograft failure was 74.0 months. After allograft failure, 145 (79.7%) patients returned to HD and 37 (20.3%) to PD. Twenty-three patients (12.6%) died over the median 69.1 months duration of follow-up. During the observation period, 16 HD (11%) and 7 PD (8.9%) patients died. The survival rates of PD patients at 1 year were 91.2% and 84.4%, respectively, at 1 and 3 years, and those of HD patients 94.8% and 88.9%. There was no significant difference in the survivals of the 2 groups. The study suggests that the outcome of patients starting PD after kidney transplant failure was similar to those starting HD. Therefore, PD can be regarded to be a good treatment option for patients returning to dialysis after kidney transplant failure. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.
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Measurement of Survival Time in Brachionus Rotifers: Synchronization of Maternal Conditions.
Kaneko, Gen; Yoshinaga, Tatsuki; Gribble, Kristin E; Welch, David M; Ushio, Hideki
2016-07-22
Rotifers are microscopic cosmopolitan zooplankton used as models in ecotoxicological and aging studies due to their several advantages such as short lifespan, ease of culture, and parthenogenesis that enables clonal culture. However, caution is required when measuring their survival time as it is affected by maternal age and maternal feeding conditions. Here we provide a protocol for powerful and reproducible measurement of the survival time in Brachionus rotifers following a careful synchronization of culture conditions over several generations. Empirically, poor synchronization results in early mortality and a gradual decrease in survival rate, thus resulting in weak statistical power. Indeed, under such conditions, calorie restriction (CR) failed to significantly extend the lifespan of B. plicatilis although CR-induced longevity has been demonstrated with well-synchronized rotifer samples in past and present studies. This protocol is probably useful for other invertebrate models, including the fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans, because maternal age effects have also been reported in these species.
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Measurement of Survival Time in Brachionus Rotifers: Synchronization of Maternal Conditions
Kaneko, Gen; Yoshinaga, Tatsuki; Gribble, Kristin E.; Welch, David M.; Ushio, Hideki
2016-01-01
Rotifers are microscopic cosmopolitan zooplankton used as models in ecotoxicological and aging studies due to their several advantages such as short lifespan, ease of culture, and parthenogenesis that enables clonal culture. However, caution is required when measuring their survival time as it is affected by maternal age and maternal feeding conditions. Here we provide a protocol for powerful and reproducible measurement of the survival time in Brachionus rotifers following a careful synchronization of culture conditions over several generations. Empirically, poor synchronization results in early mortality and a gradual decrease in survival rate, thus resulting in weak statistical power. Indeed, under such conditions, calorie restriction (CR) failed to significantly extend the lifespan of B. plicatilis although CR-induced longevity has been demonstrated with well-synchronized rotifer samples in past and present studies. This protocol is probably useful for other invertebrate models, including the fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans, because maternal age effects have also been reported in these species. PMID:27500471
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Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade
Lue, Hui-wen; Podolak, Jennifer; Kolahi, Kevin; Cheng, Larry; Rao, Soumya; Garg, Devin; Xue, Chang-Hui; Rantala, Juha K.; Tyner, Jeffrey W.; Thornburg, Kent L.; Martinez-Acevedo, Ann; Liu, Jen-Jane; Amling, Christopher L.; Truillet, Charles; Louie, Sharon M.; Anderson, Kimberly E.; Evans, Michael J.; O'Donnell, Valerie B.; Nomura, Daniel K.; Drake, Justin M.; Ritz, Anna
2017-01-01
There is limited knowledge about the metabolic reprogramming induced by cancer therapies and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K–AKT–mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation. Consistent with this, we observed significantly increased lipid droplets, with subsequent mobilization to mitochondria. These changes were abrogated in cells deficient for the essential autophagy gene ATG5. Accordingly, inhibition of PLA2 significantly decreased lipid droplets, decreased oxidative phosphorylation, and increased apoptosis. Together, these results describe how treatment-induced autophagy provides nutrients for cancer cell survival and identifies novel cotreatment strategies to override this survival advantage. PMID:29138276
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Lanzetta, Gaetano; Minniti, Giuseppe
2010-01-01
Current treatment of glioblastoma in the elderly includes surgery, radiotherapy and chemotherapy, but the prognosis remains extremely poor, and its optimal management is still debated. Longer survival after extensive resection compared with biopsy only has been reported, although the survival advantage remains modest. Radiation in the form of standard (60 Gy in 30 fractions over 6 weeks) and abbreviated courses of radiotherapy (30-50 Gy in 6-20 fractions over 2-4 weeks) has been employed in elderly patients with glioblastoma, showing survival benefits compared with supportive care alone. Temozolomide is an alkylating agent recently employed in older patients with newly diagnosed glioblastoma. The addition of concomitant and/or adjuvant chemotherapy with temozolomide to radiotherapy, which is currently the standard treatment in adults with glioblastoma, is emerging as an effective therapeutic option for older patients with favorable prognostic factors. The potential benefits on survival, improvement in quality of life and toxicity of different schedules of radiotherapy plus temozolomide need to be addressed in future randomized studies.
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Stereotactic radiosurgery for multiple brain metastases
NASA Astrophysics Data System (ADS)
Lee, Anna; (Josh Yamada, Yoshiya
2017-01-01
Whole brain radiation therapy has been the traditional treatment of choice for patients with multiple brain metastases. Although stereotactic radiosurgery is widely accepted for the management to up to 4 brain metastases, its use is still controversial in cases of 5 or more brain metastases. Randomized trials have suggested that stereotactic radiosurgery alone is appropriate in up to 4 metastases without concomitant whole brain radiation. Level 1 evidence also suggests that withholding whole brain radiation may also reduce the impact of radiation on neurocognitive function and also may even offer a survival advantage. A recent analysis of a large multicentre prospective database has suggested that there are no differences in outcomes such as the likelihood of new metastasis or leptomeningeal disease in cases of 2-10 brain metastases, nor in overall survival. Hence in the era of prolonged survival with stage IV cancer, stereotactic radiosurgery is a reasonable alternative to whole brain radiation in order to minimize the impact of treatment upon quality of life without sacrificing overall survival.
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Manzini, G; Ettrich, T J; Kremer, M; Kornmann, M; Henne-Bruns, D; Eikema, D A; Schlattmann, P; de Wreede, L C
2018-02-13
Standard survival analysis fails to give insight into what happens to a patient after a first outcome event (like first relapse of a disease). Multi-state models are a useful tool for analyzing survival data when different treatments and results (intermediate events) can occur. Aim of this study was to implement a multi-state model on data of patients with rectal cancer to illustrate the advantages of multi-state analysis in comparison to standard survival analysis. We re-analyzed data from the RCT FOGT-2 study by using a multi-state model. Based on the results we defined a high and low risk reference patient. Using dynamic prediction, we estimated how the survival probability changes as more information about the clinical history of the patient becomes available. A patient with stage UICC IIIc (vs UICC II) has a higher risk to develop distant metastasis (DM) or both DM and local recurrence (LR) if he/she discontinues chemotherapy within 6 months or between 6 and 12 months, as well as after the completion of 12 months CTx with HR 3.55 (p = 0.026), 5.33 (p = 0.001) and 3.37 (p < 0.001), respectively. He/she also has a higher risk to die after the development of DM (HR 1.72, p = 0.023). Anterior resection vs. abdominoperineal amputation means 63% risk reduction to develop DM or both DM and LR (HR 0.37, p = 0.003) after discontinuation of chemotherapy between 6 and 12 months. After development of LR, a woman has a 4.62 times higher risk to die (p = 0.006). A high risk reference patient has an estimated 43% 5-year survival probability at start of CTx, whereas for a low risk patient this is 79%. After the development of DM 1 year later, the high risk patient has an estimated 5-year survival probability of 11% and the low risk patient one of 21%. Multi-state models help to gain additional insight into the complex events after start of treatment. Dynamic prediction shows how survival probabilities change by progression of the clinical history.
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Understanding Artful Behavior as a Human Proclivity: Clues from a Pre-Kindergarten Classroom
ERIC Educational Resources Information Center
Blatt-Gross, Carolina
2011-01-01
Concurrent to the present reduction of arts education in mainstream American schools, many evolutionary-minded scholars are asserting that artistic behavior contributes significantly to cognition, has been advantageous for our survival, and satisfies psychological needs that are biologically embedded. Supported by long-term and wide-spread art…
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Perspective on Automation: Three Talks to Educators.
ERIC Educational Resources Information Center
Theobald, Robert; And Others
These papers take the view that automation impinges upon our socio-psychological as well as economic existence and we must take drastic measures to survive. Robert Theobald, presenting evidence that automation brings job displacement, suggests that we face the choice of trying to insure enough jobs, or of taking advantage of the new free time to…
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The American chestnut and fire: 6-year research results
Stacy L. Clark; Callie J. Schweitzer; Mike R. Saunders; Ethan P. Belair; Scott J. Torreano; Scott E. Schlarbaum
2014-01-01
American chestnut [Castanea dentata Marsh. (Borkh.)] is an iconic species with important ecological and utilitarian values, but was decimated by the mid-20th century by exotic fungal species fromAsia. Successful restoration will require sustainable silvicultural methods to maximize survival and afford chestnut a competitive advantage over natural vegetation. The study...
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Land of the Giants. Science Safari.
ERIC Educational Resources Information Center
Sheldon, Louisa; And Others
This is the fourth program in the Science Safari series produced by the Fairfax Network of the Fairfax County (Virginia) Public Schools. It focuses on large animals, their life, advantages and disadvantages of their size, and the adaptations that allow them to survive in their environments. The large animals highlighted include the Komodo dragon,…
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Selenium as an Essential Micronutrient: Roles in Cell Cycle and Apoptosis
USDA-ARS?s Scientific Manuscript database
Selenium (Se) is an anticancer nutrient, and the essential role of Se in growth of most mammalian cells is well recognized but certain cancer cells appear to have acquired a survival advantage under conditions of Se-deficiency. The objective of the present study is to understand the molecular basis ...
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Modeling the Evolution of Female Meiotic Drive in Maize
Hall, David W.; Dawe, R. Kelly
2017-01-01
Autosomal drivers violate Mendel’s law of segregation in that they are overrepresented in gametes of heterozygous parents. For drivers to be polymorphic within populations rather than fixing, their transmission advantage must be offset by deleterious effects on other fitness components. In this paper, we develop an analytical model for the evolution of autosomal drivers that is motivated by the neocentromere drive system found in maize. In particular, we model both the transmission advantage and deleterious fitness effects on seed viability, pollen viability, seed to adult survival mediated by maternal genotype, and seed to adult survival mediated by offspring genotype. We derive general, biologically intuitive conditions for the four most likely evolutionary outcomes and discuss the expected evolution of autosomal drivers given these conditions. Finally, we determine the expected equilibrium allele frequencies predicted by the model given recent estimates of fitness components for all relevant genotypes and show that the predicted equilibrium is within the range observed in maize land races for levels of drive at the low end of what has been observed. PMID:29122849
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Physiological advantages of dwarfing in surviving extinctions in high-CO2 oceans
NASA Astrophysics Data System (ADS)
Garilli, Vittorio; Rodolfo-Metalpa, Riccardo; Scuderi, Danilo; Brusca, Lorenzo; Parrinello, Daniela; Rastrick, Samuel P. S.; Foggo, Andy; Twitchett, Richard J.; Hall-Spencer, Jason M.; Milazzo, Marco
2015-07-01
Excessive CO2 in the present-day ocean-atmosphere system is causing ocean acidification, and is likely to cause a severe biodiversity decline in the future, mirroring effects in many past mass extinctions. Fossil records demonstrate that organisms surviving such events were often smaller than those before, a phenomenon called the Lilliput effect. Here, we show that two gastropod species adapted to acidified seawater at shallow-water CO2 seeps were smaller than those found in normal pH conditions and had higher mass-specific energy consumption but significantly lower whole-animal metabolic energy demand. These physiological changes allowed the animals to maintain calcification and to partially repair shell dissolution. These observations of the long-term chronic effects of increased CO2 levels forewarn of changes we can expect in marine ecosystems as CO2 emissions continue to rise unchecked, and support the hypothesis that ocean acidification contributed to past extinction events. The ability to adapt through dwarfing can confer physiological advantages as the rate of CO2 emissions continues to increase.
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Liu, George Y; Essex, Anthony; Buchanan, John T; Datta, Vivekanand; Hoffman, Hal M; Bastian, John F; Fierer, Joshua; Nizet, Victor
2005-07-18
Golden color imparted by carotenoid pigments is the eponymous feature of the human pathogen Staphylococcus aureus. Here we demonstrate a role of this hallmark phenotype in virulence. Compared with the wild-type (WT) bacterium, a S. aureus mutant with disrupted carotenoid biosynthesis is more susceptible to oxidant killing, has impaired neutrophil survival, and is less pathogenic in a mouse subcutaneous abscess model. The survival advantage of WT S. aureus over the carotenoid-deficient mutant is lost upon inhibition of neutrophil oxidative burst or in human or murine nicotinamide adenine dinucleotide phosphate oxidase-deficient hosts. Conversely, heterologous expression of the S. aureus carotenoid in the nonpigmented Streptococcus pyogenes confers enhanced oxidant and neutrophil resistance and increased animal virulence. Blocking S. aureus carotenogenesis increases oxidant sensitivity and decreases whole-blood survival, suggesting a novel target for antibiotic therapy.
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NASA Astrophysics Data System (ADS)
Shen, Yu; Wang, Ziyuan; Wen, Huaihai; Zhou, Zhi
2014-11-01
Fiber optic sensor (FOS) has received much attention in the field of Structure Health Monitoring (SHM) due to its advantages of low weight, small size, high sensitivity multiplexing ability, free of electromagnetic interference and long durability. However, in harsh environments, structures often undergo large strain where few traditional fiber optic sensors could survive. This paper report a novel material with features of light-transparent, chemically inert, thermally stable material Polydimethylsiloxane(PDMS) fabricated large axial/shearing strain sensor. The sensor was fabricated by directly coupling a conventional signal mode fiber into half cured PDMS material using a translation stage under the inspection of a microscope. Meanwhile, a laser diode and a photo detector were used in the fabrication process to make sure the sensor achieved minimum light loss. An experiment was conducted later to investigate the sensor's transmission characteristic in 1310nm infrared laser relating with the applied axial/shearing strain. The results show that the proposed sensor survived an axial strain of 6 7.79 x 106 μɛ ; a shear of 4 6.49 x 104 μɛ with good linearity and repetition. The experiment indicates that the proposed sensor can potentially be used as strain sensing elements in Structure Health Monitoring systems under earthquake or explosion.
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Malignant ascites: A review of prognostic factors, pathophysiology and therapeutic measures
Sangisetty, Suma L; Miner, Thomas J
2012-01-01
Malignant ascites indicates the presence of malignant cells in the peritoneal cavity and is a grave prognostic sign. While survival in this patient population is poor, averaging about 20 wk from time of diagnosis, quality of life can be improved through palliative procedures. Selecting the appropriate treatment modality remains a careful process, which should take into account potential risks and benefits and the life expectancy of the patient. Traditional therapies, including paracentesis, peritoneovenous shunt placement and diuretics, are successful and effective in varying degrees. After careful review of the patient’s primary tumor origin, tumor biology, tumor stage, patient performance status and comorbidities, surgical debulking and intraperitoneal chemotherapy should be considered if the benefit of therapy outweighs the risk of operation because survival curves can be extended and palliation of symptomatic malignant ascites can be achieved in select patients. In patients with peritoneal carcinomatosis who do not qualify for surgical cytoreduction but suffer from the effects of malignant ascites, intraperitoneal chemotherapy can be safely and effectively administered via laparoscopic techniques. Short operative times, short hospital stays, low complication rates and ultimately symptomatic relief are the advantages of laparoscopically administering heated intraperitoneal chemotherapy, making it not only a valuable treatment modality but also the most successful treatment modality for achieving palliative cure of malignant ascites. PMID:22590662
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Trainor, Laurel J.
2015-01-01
Whether music was an evolutionary adaptation that conferred survival advantages or a cultural creation has generated much debate. Consistent with an evolutionary hypothesis, music is unique to humans, emerges early in development and is universal across societies. However, the adaptive benefit of music is far from obvious. Music is highly flexible, generative and changes rapidly over time, consistent with a cultural creation hypothesis. In this paper, it is proposed that much of musical pitch and timing structure adapted to preexisting features of auditory processing that evolved for auditory scene analysis (ASA). Thus, music may have emerged initially as a cultural creation made possible by preexisting adaptations for ASA. However, some aspects of music, such as its emotional and social power, may have subsequently proved beneficial for survival and led to adaptations that enhanced musical behaviour. Ontogenetic and phylogenetic evidence is considered in this regard. In particular, enhanced auditory–motor pathways in humans that enable movement entrainment to music and consequent increases in social cohesion, and pathways enabling music to affect reward centres in the brain should be investigated as possible musical adaptations. It is concluded that the origins of music are complex and probably involved exaptation, cultural creation and evolutionary adaptation. PMID:25646512
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Trainor, Laurel J
2015-03-19
Whether music was an evolutionary adaptation that conferred survival advantages or a cultural creation has generated much debate. Consistent with an evolutionary hypothesis, music is unique to humans, emerges early in development and is universal across societies. However, the adaptive benefit of music is far from obvious. Music is highly flexible, generative and changes rapidly over time, consistent with a cultural creation hypothesis. In this paper, it is proposed that much of musical pitch and timing structure adapted to preexisting features of auditory processing that evolved for auditory scene analysis (ASA). Thus, music may have emerged initially as a cultural creation made possible by preexisting adaptations for ASA. However, some aspects of music, such as its emotional and social power, may have subsequently proved beneficial for survival and led to adaptations that enhanced musical behaviour. Ontogenetic and phylogenetic evidence is considered in this regard. In particular, enhanced auditory-motor pathways in humans that enable movement entrainment to music and consequent increases in social cohesion, and pathways enabling music to affect reward centres in the brain should be investigated as possible musical adaptations. It is concluded that the origins of music are complex and probably involved exaptation, cultural creation and evolutionary adaptation.
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An integrated new product development framework - an application on green and low-carbon products
NASA Astrophysics Data System (ADS)
Lin, Chun-Yu; Lee, Amy H. I.; Kang, He-Yau
2015-03-01
Companies need to be innovative to survive in today's competitive market; thus, new product development (NPD) has become very important. This research constructs an integrated NPD framework for developing new products. In stage one, customer attributes (CAs) and engineering characteristics (ECs) for developing products are collected, and fuzzy interpretive structural modelling (FISM) is applied to understand the relationships among these critical factors. Based on quality function deployment (QFD), a house of quality is then built, and fuzzy analytic network process (FANP) is adopted to calculate the relative importance of ECs. In stage two, fuzzy failure mode and effects analysis (FFMEA) is applied to understand the potential failures of the ECs and to determine the importance of ECs with respect to risk control. In stage three, a goal programming (GP) model is constructed to consider the outcome from the FANP-QFD, FFMEA and other objectives, in order to select the most important ECs. Due to pollution and global warming, environmental protection has become an important topic. With both governments and consumers developing environmental consciousness, successful green and low-carbon NPD provides an important competitive advantage, enabling the survival or renewal of firms. The proposed framework is implemented in a panel manufacturing firm for designing a green and low-carbon product.
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Shin, Jaeyong; Choi, Young; Kim, Seung Woo; Lee, Sang Gyu; Park, Eun-Cheol
2017-08-01
The literature on stroke mortality and neighborhood effect is characterized by studies that are often Western society-oriented, with a lack of racial and cultural diversity. We estimated the effect of cross-level interaction between individual and regional socioeconomic status on the survival after onset of ischemic stroke. We selected newly diagnosed ischemic stroke patients from 2002 to 2013 using stratified representative sampling data of 1,025,340 subjects. A total of 37,044 patients over the 10 years from 2004 to 2013 had newly diagnosed stroke. We calculated hazard ratios (HR) of 12- and 36-month mortality using the Cox proportional hazard model, with the reference group as stroke patients with high income in advantaged regions. For the middle income level, the patients in advantaged regions showed low HRs for overall mortality (12-month HR 1.27; 95% confidence interval [CI], 1.13-1.44; 36-month HR 1.25; 95% CI, 1.14-1.37) compared to the others in disadvantaged regions (12-month HR 1.36; 95% CI, 1.19-1.56; 36-month HR 1.30; 95% CI, 1.17-1.44). Interestingly, for the low income level, the patients in advantaged regions showed high HRs for overall mortality (12-month HR 1.27; 95% CI, 1.13-1.44; 36-month HR 1.33; 95% CI, 1.22-1.46) compared to the others in disadvantaged regions (12-month HR 1.25; 95% CI, 1.09-1.43; 36-month HR 1.30; 95% CI, 1.18-1.44). Although we need to perform further investigations to determine the exact mechanisms, regional deprivation, as well as medical factors, might be associated with survival after onset of ischemic stroke in low-income patients. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
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A visual short-term memory advantage for objects of expertise
Curby, Kim M.; Glazek, Kuba; Gauthier, Isabel
2014-01-01
Visual short-term memory (VSTM) is limited, especially for complex objects. Its capacity, however, is greater for faces than for other objects, an advantage that may stem from the holistic nature of face processing. If the holistic processing explains this advantage, then object expertise—which also relies on holistic processing—should endow experts with a VSTM advantage. We compared VSTM for cars among car experts to that among car novices. Car experts, but not car novices, demonstrated a VSTM advantage similar to that for faces; this advantage was orientation-specific and was correlated with an individual's level of car expertise. Control experiments ruled out accounts based solely on verbal- or long-term memory representations. These findings suggest that the processing advantages afforded by visual expertise result in domain-specific increases in VSTM capacity, perhaps by allowing experts to maximize the use of an inherently limited VSTM system. PMID:19170473
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Montebello, A R
1994-01-01
Wholesale political, economic, and social change is pressuring health-care organizations to reinvent themselves as they enter a new arena of managed competition. Survival is at stake. Will belt-tightening efforts, combined with structural changes and strategic alliances, achieve the necessary improvements in efficiency and help to secure an adequate patient base? It seems reasonable to expect that health-care institutions can realize the major gains in quality, productivity, efficiency, and competitive edge that organizations in the manufacturing and service industries have enjoyed for the past several years. It seems like a logical next step for health-care organizations to deploy proven methods--such as work redesign, team-based structures, and empowered workforces--that have helped to restore competitiveness to many industrial and service firms. This article describes how to organize teams at all levels and accelerate their development to achieve important organizational objectives--such as improving quality, productivity, and efficiency--while increasing employee satisfaction. Pioneering workplace innovations are reviewed to demonstrate how high-involvement teams integrating strategic planning, research, and health-care delivery processes are not only possible but highly desirable. Enhanced quality, improved productivity, greater efficiency, and employee satisfaction all translate to an undeniable competitive advantage.
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Pinto, Anabela; Almeida, José Pedro; Pinto, Susana; Pereira, João; Oliveira, António Gouveia; de Carvalho, Mamede
2010-11-01
Non-invasive ventilation (NIV) is an efficient method for treating respiratory failure in patients with amyotrophic lateral sclerosis (ALS). However, it requires a process of adaptation not always achieved due to poor compliance. The role of telemonitoring of NIV is not yet established. To test the advantage of using modem communication in NIV of ALS patients. Prospective, single blinded controlled trial. Population and methods According to their residence, 40 consecutive ventilated ALS patients were assigned to one of two groups: a control group (G1, n=20) in which compliance and ventilator parameter settings were assessed during office visits; or an intervention group (G2, n=20) in which patients received a modem device connected to the ventilator. The number of office and emergency room visits and hospital admissions during the entire span of NIV use and the number of parameter setting changes to achieve full compliance were the primary outcome measurements. Demographic and clinical features were similar between the two groups at admission. No difference in compliance was found between the groups. The incidence of changes in parameter settings throughout the survival period with NIV was lower in G2 (p<0.0001) but it was increased during the initial period needed to achieve full compliance. The number of office or emergency room visits and inhospital admissions was significantly lower in G2 (p<0.0001). Survival showed a trend favouring G2 (p=0.13). This study shows that telemonitoring reduces health care utilisation with probable favourable implications on costs, survival and functional status.
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Miller, Daniel L; Mayfield, William R; Luu, Theresa D; Helms, Gerald A; Muster, Alan R; Beckler, Vickie J; Cann, Aaron
2016-05-01
Lung cancer is the most common cause of cancer deaths in the United States. Overall survival is less than 20%, with the majority of patients presenting with advanced disease. The National Lung Screening Trial, performed mainly in academic medical centers, showed that cancer mortality can be reduced with computed tomography (CT) screening compared with chest radiography in high-risk patients. To determine whether this survival advantage can be duplicated in a community-based multidisciplinary thoracic oncology program, we initiated a CT scan screening program for lung cancer within an established health care system. In 2008, we launched a lung cancer CT screening program within the WellStar Health System (WHS) consisting of five hospitals, three health parks, 140 outpatient medical offices, and 12 imaging centers that provide care in a five-county area of approximately 1.4 million people in Metro-Atlanta. Screening criteria incorporated were the International Early Lung Cancer Action Program (2008 to 2010) and National Comprehensive Cancer Network guidelines (2011 to 2013) for moderate- and high-risk patients. A total of 1,267 persons underwent CT lung cancer screening in WHS from 2008 through 2013; 53% were men, 87% were 50 years of age or older, and 83% were current or former smokers. Noncalcified indeterminate pulmonary nodules were found in 518 patients (41%). Thirty-six patients (2.8%) underwent a diagnostic procedure for positive findings on their CT scan; 30 proved to have cancer, 28 (2.2%) primary lung cancer and 2 metastatic cancer, and 6 had benign disease. Fourteen patients (50%) had their lung cancer discovered on their initial CT scan, 11 on subsequent scans associated with indeterminate pulmonary nodules growth and 3 patients who had a new indeterminate pulmonary nodules. Only 15 (54%) of these 28 patients would have qualified as a National Lung Screening Trial high-risk patient; 75% had stage I or II disease. Overall 5-year survival was 64% and 5-year cancer specific survival was 71% in the screened patients, whereas nonscreened lung cancer patients during that time in WHS had an overall survival of only 19% (p < 0.001). A community-based multidisciplinary lung cancer screening program can improve survival of patients with lung cancer outside of a large multicenter study. This survival advantage was caused by a significant stage shift to earlier disease. Lung cancer CT screening may also benefit patients not meeting the National Lung Screening Trial criteria who are at moderate or high risk for lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Lunar mission safety and rescue: Escape/rescue analysis and plan
NASA Technical Reports Server (NTRS)
1971-01-01
The results are presented of the technical analysis of escape/rescue/survival situations, crew survival techniques, alternate escape/rescue approaches and vehicles, and the advantages and disadvantages of each for advanced lunar exploration. Candidate escape/rescue guidelines are proposed and elements of a rescue plan developed. The areas of discussions include the following: lunar arrival/departure operations, lunar orbiter operations, lunar surface operations, lunar surface base escape/rescue analysis, lander tug location operations, portable airlock, emergency pressure suit, and the effects of no orbiting lunar station, no lunar surface base, and no foreign lunar orbit/surface operations on the escape/rescue plan.
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Computer Assisted Navigation in Knee Arthroplasty
Bae, Dae Kyung
2011-01-01
Computer assisted surgery (CAS) was used to improve the positioning of implants during total knee arthroplasty (TKA). Most studies have reported that computer assisted navigation reduced the outliers of alignment and component malpositioning. However, additional sophisticated studies are necessary to determine if the improvement of alignment will improve long-term clinical results and increase the survival rate of the implant. Knowledge of CAS-TKA technology and understanding the advantages and limitations of navigation are crucial to the successful application of the CAS technique in TKA. In this article, we review the components of navigation, classification of the system, surgical method, potential error, clinical results, advantages, and disadvantages. PMID:22162787
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Diffuse intrinsic pontine glioma in children and adolescents: a single-center experience.
Vallero, Stefano Gabriele; Bertin, Daniele; Basso, Maria Eleonora; Pittana, Laura Stefania; Mussano, Anna; Fagioli, Franca
2014-06-01
Patients with diffuse intrinsic pontine glioma (DIPG) have a very poor prognosis. Only radiotherapy (XRT) has proven to be effective in delaying the disease progression. Several chemotherapy schedules have been applied so far, but none demonstrated significant improvements in progression and survival. We retrospectively analyzed the clinical data of children diagnosed with DIPG at our center (Pediatric Hospital "Regina Margherita," Turin, Italy) between 1999 and 2013. Progression-free survival (PFS) and overall survival (OS) were used to describe the outcomes. Twenty-four children were included in our report. Patients diagnosed before March 2003 (n = 12) were treated with XRT and vincristine (VCR); the remaining 12 patients received XRT and temozolomide (TMZ). Progression-free survival was 18.8 % at 1 year (SE = 7.6 %), while overall survival was 44.1 % at 1 year (SE = 9.9 %). Median PFS was 8.1 months, whereas median OS was 11.2 months. No statistically significant difference in PFS or OS was evidenced between the two treatment groups. Radiotherapy followed by VCR or TMZ allows obtaining results that are in line with previous reports, with no advantages over other similar treatment schedules. DIPGs are challenging tumors with a dismal outcome. Further research and newer therapies are urgently needed in order to achieve improvements in survival.
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Xia, Xiang; Li, Chen; Yan, Min; Liu, Bingya; Yao, Xuexin; Zhu, Zhenggang
2014-02-01
The value of noncurative resection for patients with gastric cancer with single peritoneal metastasis is still debatable. This study was undertaken to evaluate the survival benefit of resection in those patients. From 2006 to 2009, 119 patients with gastric cancer with single peritoneal metastasis were identified during surgery. Sixty-three of them had noncurative resection; the remainder had nonresection. Clinicopathological variables and survival were analyzed. Overall survival of patients in the noncurative resection group was longer than that in the nonresection group (14.869 vs 7.780 months). This survival advantage was still significantly better in the P1/P2 patients who underwent noncurative resection (mean survival time 21.164 vs 7.636 months, P = 0.001), but not in the P3 group (P = 0.489). Multivariate analysis indicated that only noncurative resection retained a significant association with better prognosis in P1/P2 patients. The perioperative mortality rate in the resection group was not significantly higher than that of the noncurative group (P = 0.747). Noncurative resection can prolong the survival of patients with gastric cancer with single P1/P2 peritoneal metastasis. This surgical approach should not be taken into account for those patients with P3 gastric cancer.
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Weisenburger, Dennis D; Savage, Kerry J; Harris, Nancy Lee; Gascoyne, Randy D; Jaffe, Elaine S; MacLennan, Kenneth A; Rüdiger, Thomas; Pileri, Stefano; Nakamura, Shigeo; Nathwani, Bharat; Campo, Elias; Berger, Francoise; Coiffier, Bertrand; Kim, Won-Seog; Holte, Harald; Federico, Massimo; Au, Wing Y; Tobinai, Kensei; Armitage, James O; Vose, Julie M
2011-03-24
The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.
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Gender, social norms, and survival in maritime disasters
Elinder, Mikael; Erixson, Oscar
2012-01-01
Since the sinking of the Titanic, there has been a widespread belief that the social norm of “women and children first” (WCF) gives women a survival advantage over men in maritime disasters, and that captains and crew members give priority to passengers. We analyze a database of 18 maritime disasters spanning three centuries, covering the fate of over 15,000 individuals of more than 30 nationalities. Our results provide a unique picture of maritime disasters. Women have a distinct survival disadvantage compared with men. Captains and crew survive at a significantly higher rate than passengers. We also find that: the captain has the power to enforce normative behavior; there seems to be no association between duration of a disaster and the impact of social norms; women fare no better when they constitute a small share of the ship’s complement; the length of the voyage before the disaster appears to have no impact on women’s relative survival rate; the sex gap in survival rates has declined since World War I; and women have a larger disadvantage in British shipwrecks. Taken together, our findings show that human behavior in life-and-death situations is best captured by the expression “every man for himself.” PMID:22847426
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Serum albumin predicts survival in patients with hilar cholangiocarcinoma
Waghray, Abhijeet; Sobotka, Anastasia; Marrero, Carlos Romero; Estfan, Bassam; Aucejo, Federico
2017-01-01
Background and aims: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. Methods: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. Results: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19‐9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14–0.70) with a survival benefit of 44 weeks. Conclusion: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. PMID:27389416
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Fuchs, Claudia; Trazzi, Stefania; Torricella, Roberta; Viggiano, Rocchina; De Franceschi, Marianna; Amendola, Elena; Gross, Cornelius; Calzà, Laura; Bartesaghi, Renata; Ciani, Elisabetta
2014-01-01
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a neurodevelopmental disorder characterized by early-onset intractable seizures, severe developmental delay, intellectual disability, and Rett's syndrome-like features. Since the physiological functions of CDKL5 still need to be elucidated, in the current study we took advantage of a new Cdkl5 knockout (KO) mouse model in order to shed light on the role of this gene in brain development. We mainly focused on the hippocampal dentate gyrus, a region that largely develops postnatally and plays a key role in learning and memory. Looking at the process of neurogenesis, we found a higher proliferation rate of neural precursors in Cdkl5 KO mice in comparison with wild type mice. However, there was an increase in apoptotic cell death of postmitotic granule neuron precursors, with a reduction in total number of granule cells. Looking at dendritic development, we found that in Cdkl5 KO mice the newly-generated granule cells exhibited a severe dendritic hypotrophy. In parallel, these neurodevelopmental defects were associated with impairment of hippocampus-dependent memory. Looking at the mechanisms whereby CDKL5 exerts its functions, we identified a central role of the AKT/GSK-3β signaling pathway. Overall our findings highlight a critical role of CDKL5 in the fundamental processes of brain development, namely neuronal precursor proliferation, survival and maturation. This evidence lays the basis for a better understanding of the neurological phenotype in patients carrying mutations in the CDKL5 gene. PMID:24952363
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Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?
Yeh, Albert C; Ramaswamy, Sridhar
2015-12-01
Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. ©2015 American Association for Cancer Research.
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Mechanisms of Cancer Cell Dormancy – Another Hallmark of Cancer?
Yeh, Albert C.; Ramaswamy, Sridhar
2015-01-01
Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biological level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biological insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately down-regulate the Ras/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. PMID:26354021
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Di Venosa, Gabriela; Perotti, Christian; Batlle, Alcira; Casas, Adriana
2015-08-01
It is known that Photodynamic Therapy (PDT) induces changes in the cytoskeleton, the cell shape, and the adhesion properties of tumour cells. In addition, these targets have also been demonstrated to be involved in the development of PDT resistance. The reversal of PDT resistance by manipulating the cell adhesion process to substrata has been out of reach. Even though the existence of cell adhesion-mediated PDT resistance has not been reported so far, it cannot be ruled out. In addition to its impact on the apoptotic response to photodamage, the cytoskeleton alterations are thought to be associated with the processes of metastasis and invasion after PDT. In this review, we will address the impact of photodamage on the microfilament and microtubule cytoskeleton components and its regulators on PDT-treated cells as well as on cell adhesion. We will also summarise the impact of PDT on the surviving and resistant cells and their metastatic potential. Possible strategies aimed at taking advantage of the changes induced by PDT on actin, tubulin and cell adhesion proteins by targeting these molecules will also be discussed.
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Burns, Patricia; Alard, Jeanne; Hrdỳ, Jiri; Boutillier, Denise; Páez, Roxana; Reinheimer, Jorge; Pot, Bruno; Vinderola, Gabriel; Grangette, Corinne
2017-01-01
Gut microbiota dysbiosis plays a central role in the development and perpetuation of chronic inflammation in inflammatory bowel disease (IBD) and therefore is key target for interventions with high quality and functional probiotics. The local production of stable probiotic formulations at limited cost is considered an advantage as it reduces transportation cost and time, thereby increasing the effective period at the consumer side. In the present study, we compared the anti-inflammatory capacities of the Bifidobacterium animalis subsp. lactis (B. lactis) INL1, a probiotic strain isolated in Argentina from human breast milk, with the commercial strain B. animalis subsp. lactis BB12. The impact of spray-drying, a low-cost alternative of bacterial dehydration, on the functionality of both bifidobacteria was also investigated. We showed for both bacteria that the spray-drying process did not impact on bacterial survival nor on their protective capacities against acute and chronic colitis in mice, opening future perspectives for the use of strain INL1 in populations with IBD. PMID:28233848
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Bioluminescence lights the way to food safety
NASA Astrophysics Data System (ADS)
Brovko, Lubov Y.; Griffiths, Mansel W.
2003-07-01
The food industry is increasingly adopting food safety and quality management systems that are more proactive and preventive than those used in the past which have tended to rely on end product testing and visual inspection. The regulatory agencies in many countries are promoting one such management tool, Hazard Analysis Critical Control Point (HACCP), as a way to achieve a safer food supply and as a basis for harmonization of trading standards. Verification that the process is safe must involve microbiological testing but the results need not be generated in real-time. Of all the rapid microbiological tests currently available, the only ones that come close to offering real-time results are bioluminescence-based methods. Recent developments in application of bioluminescence for food safety issues are presented in the paper. These include the use of genetically engineered microorganisms with bioluminescent and fluorescent phenotypes as a real time indicator of physiological state and survival of food-borne pathogens in food and food processing environments as well as novel bioluminescent-based methods for rapid detection of pathogens in food and environmental samples. Advantages and pitfalls of the methods are discussed.
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Ibrahim, Leena A.; Mesik, Lukas; Ji, Xu-ying; Fang, Qi; Li, Hai-fu; Li, Ya-tang; Zingg, Brian; Zhang, Li I.; Tao, Huizhong Whit
2016-01-01
Summary Cross-modality interaction in sensory perception is advantageous for animals’ survival. How cortical sensory processing is cross-modally modulated and what are the underlying neural circuits remain poorly understood. In mouse primary visual cortex (V1), we discovered that orientation selectivity of layer (L)2/3 but not L4 excitatory neurons was sharpened in the presence of sound or optogenetic activation of projections from primary auditory cortex (A1) to V1. The effect was manifested by decreased average visual responses yet increased responses at the preferred orientation. It was more pronounced at lower visual contrast, and was diminished by suppressing L1 activity. L1 neurons were strongly innervated by A1-V1 axons and excited by sound, while visual responses of L2/3 vasoactive intestinal peptide (VIP) neurons were suppressed by sound, both preferentially at the cell's preferred orientation. These results suggest that the cross-modality modulation is achieved primarily through L1 neuron and L2/3 VIP-cell mediated inhibitory and disinhibitory circuits. PMID:26898778
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Rumor Processes in Random Environment on and on Galton-Watson Trees
NASA Astrophysics Data System (ADS)
Bertacchi, Daniela; Zucca, Fabio
2013-11-01
The aim of this paper is to study rumor processes in random environment. In a rumor process a signal starts from the stations of a fixed vertex (the root) and travels on a graph from vertex to vertex. We consider two rumor processes. In the firework process each station, when reached by the signal, transmits it up to a random distance. In the reverse firework process, on the other hand, stations do not send any signal but they “listen” for it up to a random distance. The first random environment that we consider is the deterministic 1-dimensional tree with a random number of stations on each vertex; in this case the root is the origin of . We give conditions for the survival/extinction on almost every realization of the sequence of stations. Later on, we study the processes on Galton-Watson trees with random number of stations on each vertex. We show that if the probability of survival is positive, then there is survival on almost every realization of the infinite tree such that there is at least one station at the root. We characterize the survival of the process in some cases and we give sufficient conditions for survival/extinction.
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Challenges in the estimation of Net SURvival: The CENSUR working survival group.
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 to provide useful information for cancer control and cancer policy. A "team science" approach is necessary to address new challenges concerning the estimation of net survival. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Rozo, Zayda Lorena Corredor; Márquez-Ortiz, Ricaurte Alejandro; Castro, Betsy Esperanza; Gómez, Natasha Vanegas; Escobar-Pérez, Javier
2017-07-01
Staphylococcus aureus pandemic clone USA300 has, in addition to its constitutive arginine catabolism (arc) gene cluster, an arginine catabolism mobile element (ACME) carrying another such cluster, which gives this clone advantages in colonisation and infection. Gene arcR, which encodes an oxygen-sensitive transcriptional regulator, is inside ACME and downstream of the constitutive arc gene cluster, and this situation may have an impact on its activation. Different relative expression behaviours are proven here for arcRACME and the arcACME operon compared to the constitutive ones. We also show that the artificially expressed recombinant ArcRACME protein binds to the promoter region of the arcACME operon; this mechanism can be related to a positive feedback model, which may be responsible for increased anaerobic survival of the USA300 clone during infection-related processes.
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Similarity network fusion for aggregating data types on a genomic scale.
Wang, Bo; Mezlini, Aziz M; Demir, Feyyaz; Fiume, Marc; Tu, Zhuowen; Brudno, Michael; Haibe-Kains, Benjamin; Goldenberg, Anna
2014-03-01
Recent technologies have made it cost-effective to collect diverse types of genome-wide data. Computational methods are needed to combine these data to create a comprehensive view of a given disease or a biological process. Similarity network fusion (SNF) solves this problem by constructing networks of samples (e.g., patients) for each available data type and then efficiently fusing these into one network that represents the full spectrum of underlying data. For example, to create a comprehensive view of a disease given a cohort of patients, SNF computes and fuses patient similarity networks obtained from each of their data types separately, taking advantage of the complementarity in the data. We used SNF to combine mRNA expression, DNA methylation and microRNA (miRNA) expression data for five cancer data sets. SNF substantially outperforms single data type analysis and established integrative approaches when identifying cancer subtypes and is effective for predicting survival.
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Health care: development of data for a marketing approach.
Stitt, V J
1985-06-01
Marketing in health care is a relatively new process. It is a business tool that can serve a very useful purpose. Health care management has become aware of the usefulness of marketing in long-range planning. Through a well-thought-out marketing plan, the provider will not be leaving the future to chance. A well-conceived, patient-oriented, competitor-aware marketing plan should place the medical practice at a strategic advantage as the health care industry joins other industries in the competitive marketplace for the consumer's dollar.The ever-increasing political and regulatory environment that the health care field is undergoing emphasizes the need for the inclusion of marketing skills, such as cost containment, in the medical curriculum. It should be the obligation of the training facilities as well as medical societies to respond to this need by providing the education that will enable black providers to survive in this competitive environment.
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Visual Search Efficiency is Greater for Human Faces Compared to Animal Faces
Simpson, Elizabeth A.; Mertins, Haley L.; Yee, Krysten; Fullerton, Alison; Jakobsen, Krisztina V.
2015-01-01
The Animate Monitoring Hypothesis proposes that humans and animals were the most important categories of visual stimuli for ancestral humans to monitor, as they presented important challenges and opportunities for survival and reproduction; however, it remains unknown whether animal faces are located as efficiently as human faces. We tested this hypothesis by examining whether human, primate, and mammal faces elicit similarly efficient searches, or whether human faces are privileged. In the first three experiments, participants located a target (human, primate, or mammal face) among distractors (non-face objects). We found fixations on human faces were faster and more accurate than primate faces, even when controlling for search category specificity. A final experiment revealed that, even when task-irrelevant, human faces slowed searches for non-faces, suggesting some bottom-up processing may be responsible for the human face search efficiency advantage. PMID:24962122
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2012-05-15
CAPE CANAVERAL, Fla. – The prototype rover Artemis Jr. for NASA’s Regolith and Environment Science and Oxygen and Lunar Volatile Extraction, or RESOLVE, project rests atop the prototype lander, prepared for further processing in a test facility behind the Operations and Checkout Building at NASA’s Kennedy Space Center in Florida. RESOLVE consists of a rover and drill provided by the Canadian Space Agency to support a NASA payload that is designed to prospect for water, ice and other lunar resources. RESOLVE also will demonstrate how future explorers can take advantage of resources at potential landing sites by manufacturing oxygen from soil. NASA will conduct field tests in July outside of Hilo, Hawaii, with equipment and concept vehicles that demonstrate how explorers might prospect for resources and make their own oxygen for survival while on other planetary bodies. For more information, visit http://www.nasa.gov/exploration/analogs/index.html. Photo credit: NASA/Dimitri Gerondidakis
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Health Care: Development of Data for a Marketing Approach
Stitt, Van J.
1985-01-01
Marketing in health care is a relatively new process. It is a business tool that can serve a very useful purpose. Health care management has become aware of the usefulness of marketing in long-range planning. Through a well-thought-out marketing plan, the provider will not be leaving the future to chance. A well-conceived, patient-oriented, competitor-aware marketing plan should place the medical practice at a strategic advantage as the health care industry joins other industries in the competitive marketplace for the consumer's dollar. The ever-increasing political and regulatory environment that the health care field is undergoing emphasizes the need for the inclusion of marketing skills, such as cost containment, in the medical curriculum. It should be the obligation of the training facilities as well as medical societies to respond to this need by providing the education that will enable black providers to survive in this competitive environment. PMID:4020892
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Pivot tables for mortality analysis, or who needs life tables anyway?
Wesley, David; Cox, Hugh F
2007-01-01
Actuarial life-table analysis has long been used by life insurance medical directors for mortality abstraction from clinical studies. Ironically, today's life actuary instead uses pivot tables to analyze mortality. Pivot tables (a feature/function in MS Excel) collapse various dimensions of data that were previously arranged in an "experience study" format. Summary statistics such as actual deaths, actual and expected mortality (usually measured in dollars), and calculated results such as actual to expected ratios, are then displayed in a 2-dimensional grid. The same analytic process, excluding the dollar focus, can be used for clinical mortality studies. For raw survival data, especially large datasets, this combination of experience study data and pivot tables has clear advantages over life-table analysis in both accuracy and flexibility. Using the SEER breast cancer data, we compare the results of life-table analysis and pivot-table analysis.
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ERIC Educational Resources Information Center
Suddendorf, T.; Busby, J.
2005-01-01
Mechanisms that produce behavior which increase future survival chances provide an adaptive advantage. The flexibility of human behavior is at least partly the result of one such mechanism, our ability to travel mentally in time and entertain potential future scenarios. We can study mental time travel in children using language. Current results…
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Tan, Jia-Yi; Yin, Wai-Fong; Chan, Kok-Gan
2014-01-01
Hafnia alvei is an opportunistic pathogen involved in various types of nosocomical infections. The species has been found to inhabit food and mammalian guts. However, its status as an enteropathogen, and whether the food-inhabiting strains could be a source of gastrointestinal infection remains obscure. In this report we present a draft genome of H. alvei strain FB1 isolated from fish paste meatball, a food popular among Malaysian and Chinese populations. The data was generated on the Illumina MiSeq platform. A comparative study was carried out on FB1 against two other previously sequenced H. alvei genomes. Several gene clusters putatively involved in survival and pathogenesis of H. alvei FB1 in food and gut environment were characterised in this study. These include the widespread colonisation island (WCI), the tad locus that is known to play an essential role in biofilm formation, a eut operon that might contribute to advantage in nutrient acquisition in gut environment, and genes responsible for siderophore production This features enable the bacteria to successful colonise in the host gut environment. With the whole genome data of H. alvei FB1 presented in this study, we hope to provide an insight into future studies on this candidate of enteropathogen by looking into the possible mechanisms employed to survive stresses and gain advantage in competitions, which eventually leads to successful colonisation and pathogenesis. This is to serve as the basis for more effective clinical diagnosis and treatment.
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Minimalist breast conserving surgical approaches for inferiorly sited cancers.
Tan, Mona P
2017-08-01
Contemporary data suggests that breast conservation treatment (BCT) may confer a survival advantage when compared to mastectomy. Hence, it would be logical to adopt strategies which increase eligibility of successful BCT without compromising oncologic principles or cosmetic outcome. With respect to achieving good aesthetics, inferiorly sited breast cancers pose a particular technical challenge. A vast array of techniques, collectively referred to as oncoplastic breast surgery (OBS) have been developed to minimise post treatment distortion. The purported advantages of these approaches are the acquisition of wider margins and reduced re-excision rates. However, to date, there is a lack of data demonstrating significant reduction in local recurrence and overall survival when compared with less extensive procedures. In this review, "minimalist" procedures are described where strict oncologic criteria of clear margins are fulfilled and acceptable cosmesis are simultaneously achieved. These techniques offer less tissue loss, less extensive parenchymal mobilisation and shorter operating times without compromising margin status and aesthetics. They involve the combination of innovative incision designs and certain parenchymal resection patterns. Incision designs include the boomerang, golf-tee, anchor and arrowhead incisions which have been previously described but not widely used. Parenchymal resection patterns follow the "sick lobe hypothesis". These techniques, termed "reductionist", or "minimalist" comprising approaches where breast conserving surgery is condensed to its irreducible elements, offer alternatives which align with contemporary objectives of surgery where optimal survival outcomes are achieved through individualised procedures resulting in reduced iatrogenic impact. This logically allows scope for de-escalation of surgical therapy for breast cancer.
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Luo, Qiuping; Wang, Ziwei; Li, Shengjie; Zhou, Jianying
2015-01-01
Second-line chemotherapy has been proved to be effective on patients with relapsed or refractory small cell lung cancer (SCLC). Although topotecan has been approved by many countries for the monotherapy with an acknowledged efficacy, its efficacy of low response rate and short median survival time is disappointing. Considering the optimal regimen of second-line therapy is yet uncertain, we conducted this meta-analysis to provide theoretical basis for making clinical decisions. A comprehensive electronic search was performed to identify eligible studies. The ending points included response, overall survival (OS), and adverse events. Odds ratios and 95% confidence interval were calculated to compare the effects. Six trials with 1369 patients were included. With regard to response rate, only amrubicin showed a significant improvement compared with topotecan. Irinotecan and etoposide did not show any advantages. When targeted on OS, neither of these monotherapy regimens exhibited any advantage when compared to topotecan. When aimed at toxicity, amrubicin showed a better effect on reducing hematologic toxicity, but a worse outcome on increasing the nonhematologic toxicity, whereas others showed equal efficacy. There is no strong evidence that any advantage for second-line treatment of SCLC when compared with topotecan, except amrubicin. And amrubicin seems to be superior to topotecan in terms of response rates, with a lower toxicity than topotecan, which is of high value in clinical application, and may be the direction of second-line monotherapy in the future. PMID:26770633
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High tie versus low tie of the inferior mesenteric artery in colorectal cancer: A meta-analysis.
Yang, Yafan; Wang, Guiying; He, Jingli; Zhang, Jianfeng; Xi, Jinchuan; Wang, Feifei
2018-04-01
Colorectal cancer surgery includes "high tie" and "low tie"of the inferior mesenteric artery(IMA). However, different ligation level is closely related to the blood supply of anastomosis, which may increase the leakage rate, and it is unclear which technique confers a lower anastomotic leakage rate(AL) and survival advantage. To compare the effectiveness and impact of inferior mesenteric artery (IMA) high ligation versus IMA low ligation on anastomotic leakage, lymph nodes yield rates and 5-year survival. A list of these studies, published in English from 1990 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect and Web of Science. Anastomotic leakage rate, the yield of lymph nodes and 5-year survival were compared using Review Manager 5.3. There was no significant difference in anastomotic leakage, number of lymph nodes retrieved and 5-year survival rate for both techniques. Neither the high tie nor the low tie strategy has an evidence in terms of anastomotic leakage rate, harvested lymph nodes, and the 5-year survival rate. Further RCT is needed. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
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Chishti, Uzma; Aziz, Aliya B.; Akhtar, Munazza; Sheikh, Sana
2015-01-01
Objective: To compare perioperative morbidity and survival data between patients with early-stage endometrial cancer who did or did not undergo selective lymphadenectomy. Methods: Retrospective analysis of 180 patients with early-stage endometrial carcinoma treated between 1999 and 2008 was performed in Aga Khan University Hospital, Karachi, Pakistan. Results: Data from 180 patients were analysed. The selective lymphadenectomy group contained 108 women (60%) and the no lymphadenectomy group contained 72 women (40%). The median number of lymph nodes removed was 9. The mean age and extent of disease, as assessed by staging, tumour size, myometrial invasion, and lymphovascular invasion were comparable between groups. Upstaging of the disease to stage 3 and 4 occurred in 11% of patients in the lymphadenectomy group. There were no significant differences in the medical or surgical complications between groups. At a median follow-up of 26 months, both groups had comparable survival (lymphadenectomy versus no lymphadenectomy: 34 versus 32 months). Similar survival was noted for patients who underwent the removal of more or less than 5 pelvic lymph nodes. Conclusion: Selective lymphadenectomy offers the advantage of improved surgical staging but no therapeutic benefit in terms of overall survival. PMID:26430436
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The path forward in prostate cancer therapeutics
Aragon-Ching, Jeanny B; Madan, Ravi A
2018-01-01
The last decade has seen remarkable advances in the treatment of prostate cancer. Until 2010, only docetaxel had demonstrated the ability to improve the survival in metastatic castration-resistant prostate cancer (mCRPC).1 While effective, many men were reluctant to get treatment with docetaxel because of the perceived toxicity, thereby further limiting the benefit of the one available and effective therapy. Remarkably, within the last 8 years, the field has seen a multitude of therapies that demonstrate an ability to extend survival for men with prostate cancer. Abiraterone and enzalutamide demonstrated the importance of the androgen axis in propelling prostate cancer growth.23 Sipuleucel-T was immunotherapy's entry into the evolving prostate cancer armamentarium, as the therapeutic cancer vaccine established an ability to extend survival despite an apparent lack of short-term effect on progression-free survival and prostate-specific antigen (PSA).4 Radium-223 built on the palliative success of previous radiopharmaceuticals, but this alpha-emitting agent importantly had limited hematologic-related toxicity and was associated with a survival advantage, unlike its in-class predecessors.5 Cabazitaxel also emerged as a second-line chemotherapy option in patients who had already progressed on docetaxel.6 PMID:29536949
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Adaptive memory: young children show enhanced retention of fitness-related information.
Aslan, Alp; Bäuml, Karl-Heinz T
2012-01-01
Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on reproductive adults, but also on pre-reproductive children, the present study examined whether young children show superior memory for information that is processed in terms of its survival value. In two experiments, we found such survival processing to enhance retention in 4- to 10-year-old children, relative to various control conditions that also required deep, meaningful processing but were not related to survival. These results suggest that, already in very young children, survival processing is a special and extraordinarily effective form of memory encoding. The results support the functional-evolutionary proposal that young children's memory is "tuned" to process and retain fitness-related information. Copyright © 2011 Elsevier B.V. All rights reserved.
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The survival strategy of the soil microbial biomass
NASA Astrophysics Data System (ADS)
Brookes, Philip; Kemmitt, Sarah; Dungait, Jennifer; Xu, Jianming
2014-05-01
The soil microbial biomass (biomass) is defined as the sum of the masses of all soil microorganisms > 5000 µm3 (e.g. fungi, bacteria, protozoa, yeasts, actinomycetes and algae). Typically comprising about 1 to 3 % of total soil organic matter (SOM), the biomass might be though to live in a highly substrate-rich environment. However, the SOM is, normally, only exceedingly slowly available to the biomass. However the biomass can survive for months or even years on this meagre energy source. Not surprisingly, therefore, the biomass exhibits many features typical of a dormant or resting population. These include a very low rate of basal and specific respiration, a slow rate of cell division (about once every six months on average) and slow turnover rate. These are clearly adaptations to existing in an environment where substrate availability is very low. Yet, paradoxically, the biomass, in soils worldwide, has an adenosine triphosphate (ATP) concentration (around 10 to 12 µmol ATP g-1 biomass C), and an Adenylate Energy Charge (AEC = [(ATP) + (0.5 ADP)]/[(ATP)+(ADP) + (AMP)]) which are typical of microorganisms growing exponentially in a chemostat. This sets us several questions. Firstly, under the condition of extremely limited substrate availability in soil, why does the biomass not mainly exist as spores, becoming active, by increasing both its ATP concentration and AEC, when substrate (plant and animal residues) becomes available? We surmise that a spore strategy may put organisms at a competitive disadvantage, compared to others which are prepared to invest energy, maintaining high ATP and ATP, to take advantage of a 'food event' as soon as it becomes available. Secondly, since SOM is available (although only very slowly) to the biomass, why have some groups not evolved the ability to mineralize it faster, obtain more energy, and so gain a competitive advantage? We believe that the reason why organisms do not use this strategy is, simply, that they cannot. Our explanation is that the rate of mineralization of humified SOM is not, as usually believed, regulated by microbial activity but by abiotic processes which are outside of the control of the biomass. We do not yet know what these processes are. They could involve diffusion from soil aggregates, oxidation processes, free radical reactions, other mechanisms, or none of these. We will present experimental evidence in support of our hypothesis - termed "The Regulatory Gate Hypothesis". If correct this hypothesis will have serious implication for our understanding of soil organic matter dynamics, CO2 evolution from soil and climate change.
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Sea ice microorganisms: environmental constraints and extracellular responses.
Ewert, Marcela; Deming, Jody W
2013-03-28
Inherent to sea ice, like other high latitude environments, is the strong seasonality driven by changes in insolation throughout the year. Sea-ice organisms are exposed to shifting, sometimes limiting, conditions of temperature and salinity. An array of adaptations to survive these and other challenges has been acquired by those organisms that inhabit the ice. One key adaptive response is the production of extracellular polymeric substances (EPS), which play multiple roles in the entrapment, retention and survival of microorganisms in sea ice. In this concept paper we consider two main areas of sea-ice microbiology: the physico-chemical properties that define sea ice as a microbial habitat, imparting particular advantages and limits; and extracellular responses elicited in microbial inhabitants as they exploit or survive these conditions. Emphasis is placed on protective strategies used in the face of fluctuating and extreme environmental conditions in sea ice. Gaps in knowledge and testable hypotheses are identified for future research.
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Sea Ice Microorganisms: Environmental Constraints and Extracellular Responses
Ewert, Marcela; Deming, Jody W.
2013-01-01
Inherent to sea ice, like other high latitude environments, is the strong seasonality driven by changes in insolation throughout the year. Sea-ice organisms are exposed to shifting, sometimes limiting, conditions of temperature and salinity. An array of adaptations to survive these and other challenges has been acquired by those organisms that inhabit the ice. One key adaptive response is the production of extracellular polymeric substances (EPS), which play multiple roles in the entrapment, retention and survival of microorganisms in sea ice. In this concept paper we consider two main areas of sea-ice microbiology: the physico-chemical properties that define sea ice as a microbial habitat, imparting particular advantages and limits; and extracellular responses elicited in microbial inhabitants as they exploit or survive these conditions. Emphasis is placed on protective strategies used in the face of fluctuating and extreme environmental conditions in sea ice. Gaps in knowledge and testable hypotheses are identified for future research. PMID:24832800
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Suknuntha, Kran; Ishii, Yuki; Tao, Lihong; Hu, Kejin; McIntosh, Brian E.; Yang, David; Swanson, Scott; Stewart, Ron; Wang, Jean Y.J.; Thomson, James; Slukvin, Igor
2016-01-01
A definitive cure for chronic myeloid leukemia (CML) requires identifying novel therapeutic targets to eradicate leukemia stem cells (LSCs). However, the rarity of LSCs within the primitive hematopoietic cell compartment remains a major limiting factor for their study in humans. Here we show that primitive hematopoietic cells with typical LSC features, including adhesion defect, increased long-term survival and proliferation, and innate resistance to tyrosine kinase inhibitor (TKI) imatinib, can be generated de novo from reprogrammed primary CML cells. Using CML iPSC-derived primitive leukemia cells, we discovered olfactomedin 4 (OLFM4) as a novel factor that contributes to survival and growth of somatic lin−CD34+ cells from bone marrow of patients with CML in chronic phase, but not primitive hematopoietic cells from normal bone marrow. Overall, this study shows the feasibility and advantages of using reprogramming technology to develop strategies for targeting primitive leukemia cells. PMID:26561938
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Fiber sensors for control and health monitoring system for mining machinery
NASA Astrophysics Data System (ADS)
Claus, Richard O.; Gunther, Michael F.; Greene, Jonathan A.; Tran, Tuan A.; Murphy, Kent A.
1994-05-01
This paper describes initial results of a fiber optic-based sensor during on-site testing performed by FEORC and Fiber and Sensor Technologies at Ingersol-Rand. Advantages of the fiber optic sensor are a demonstrated enhanced survivability, higher sensitivity, smaller size, electromagnetic interference immunity, and reduced risk of explosion. The conventional wire strain gages typically survive only a few minutes attached to the drill steel and drive chain, while the fiber sensors described here have survived over 400 hours and are currently still functioning properly. The tests described include the demonstration of strain energy measurements on the drive chain and drill steel, and displacement measurements of the piston within the drifter. All of the sensors tested can be used as both a laboratory evaluation and testing tools, as well as being an integral part of a proposed control and health monitoring system.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nelson, John W.; Ghafoori, A. Paiman; Willett, Christopher G.
Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treatedmore » neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age {<=}60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic therapy.« less
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Innovative Bioreactor Development for Methanotrophic Biodegradation of Trichloroethylene
1994-01-01
biodegradation ot TCE for system optimization and process scaleup; 4. To determine the advantage of pulsed flow over steady-state operation through computer...TCE to nonhazardous products. The process is co-metabolic, i.e., the microorganisms do not derive any energetic advantage from degradation of the TCE...proces-. aleup; 4. To determine the advantage of pulsed flow over steady-state operation through computer process simulation using the empirical Alvarez
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The evolution of contralateral control of the body by the brain: is it a protective mechanism?
Whitehead, Lorne; Banihani, Saleh
2014-01-01
Contralateral control, the arrangement whereby most of the human motor and sensory fibres cross the midline in order to provide control for contralateral portions of the body, presents a puzzle from an evolutionary perspective. What caused such a counterintuitive and complex arrangement to become dominant? In this paper we offer a new perspective on this question by showing that in a complex interactive control system there could be a significant net survival advantage with contralateral control, associated with the effect of injuries of intermediate severity. In such cases an advantage could arise from a combination of non-linear system response combined with correlations between injuries on the same side of the head and body. We show that a simple mathematical model of these ideas emulates such an advantage. Based on this model, we conclude that effects of this kind are a plausible driving force for the evolution of contralateral control.
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Enhanced visual short-term memory in action video game players.
Blacker, Kara J; Curby, Kim M
2013-08-01
Visual short-term memory (VSTM) is critical for acquiring visual knowledge and shows marked individual variability. Previous work has illustrated a VSTM advantage among action video game players (Boot et al. Acta Psychologica 129:387-398, 2008). A growing body of literature has suggested that action video game playing can bolster visual cognitive abilities in a domain-general manner, including abilities related to visual attention and the speed of processing, providing some potential bases for this VSTM advantage. In the present study, we investigated the VSTM advantage among video game players and assessed whether enhanced processing speed can account for this advantage. Experiment 1, using simple colored stimuli, revealed that action video game players demonstrate a similar VSTM advantage over nongamers, regardless of whether they are given limited or ample time to encode items into memory. Experiment 2, using complex shapes as the stimuli to increase the processing demands of the task, replicated this VSTM advantage, irrespective of encoding duration. These findings are inconsistent with a speed-of-processing account of this advantage. An alternative, attentional account, grounded in the existing literature on the visuo-cognitive consequences of video game play, is discussed.
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The deprivation syndrome is the driving force of phylogeny, ontogeny and oncogeny.
Heininger, K
2001-01-01
Energy is the motor of life. Energy ensures the organism's survival and competitive advantage for reproductive success. For almost 3 billion years, unicellular organisms were the only life form on earth. Competition for limited energy resources and raw materials exerted an incessant selective pressure on organisms. In the adverse environment and due to their 'feast and famine' life style, hardiness to a variety of stressors, particularly to nutrient deprivation, was the selection principle. Both resistance and mutagenic adaptation to stressors were established as survival strategies by means of context-specific processes creating stability or variability of DNA sequence. The conservation of transduction pathways and functional homology of effector molecules clearly bear witness that the principles of life established during prokaryotic and eukaryotic unicellular evolution, although later diversified, have been unshakably cast to persist during metazoan phylogenesis. A wealth of evidence suggests that unicellular organisms evolved the phenomena of differentiation and apoptosis, sexual reproduction, and even aging, as responses to environmental challenges. These evolutionary accomplishments were elaborated from the dichotomous resistance/mutagenesis response and sophisticated the capacity of cells to tune their genetic information to changing environmental conditions. Notably, the social deprivation responses, differentiation and apoptosis, evolved as intercellularly coordinated events: a multitude of differentiation processes were elaborated from sporulation, the prototypic stress resistance response, while apoptosis, contrary to current concepts, is no altruistic cell suicide but was programmed as a mutagenic survival response; this response, however, is socially thwarted leading into mutagenic error catastrophe. In the hybrid differentiation-apoptosis process, cytocide and cannibalism of apoptotic cells thus serve the purpose of fueling the survival of the selfish genes in the differentiating cells. However, successful mutagenesis, although repressed, persisted in the asocial stress response of carcinogenesis as a regression to primitive unicellular behavior following failure of intercellular communication. While somatic mutagenesis was largely prevented, Metazoa elaborated germ cell mutagenesis as an evolutionary vehicle. Genetic competence, a primitive, stress-induced mating behavior, evolved into sexual reproduction which harnessed mutagenesis by subjecting highly mutable germ cells to a rigid viability selection. These processes were programmatically fixed as life- and cell-cycle events but retained their deprivation response phenotypes. Thus, the differentiation-apoptosis tandem evolved as the 'clay' to mold the specialized structures and functions of a multicellular organism while sexual reproduction elaborated the principle of quality-checked mutagenesis to create the immense diversity of Metazoa following the Cambrian explosion. Throughout these events, reactive oxygen and nitrogen species, which are regulated by energy homeostasis, shape the genetic information in a regulated but random, uncoded process providing the fitness-related feedback of phenotype to genotype. The interplay of genes and environment establishes a dynamic stimulus-response feedback cycle which, in animate nature, may be the organizing principle to contrive the reciprocal duality of energy and matter.
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Evaluation of Revascularization Subtypes in Octogenarians Undergoing Coronary Artery Bypass Grafting
Aziz, Abdulhameed; Lee, Anson M.; Pasque, Michael K.; Lawton, Jennifer S.; Moazami, Nader; Damiano, Ralph J.; Moon, Marc R.
2009-01-01
Background Recent data suggest that octogenarians’ long-term survival after complete CABG revascularization is superior to incomplete revascularization. Discriminating between variable definitions of “complete” complicates interpretation of survival data. We aimed to clarify octogenarian long-term survival rates by stratifying revascularization subtypes. Methods and Results From 1986 to 2007, 580 patients 80 to 94 years of age underwent CABG. Functional complete revascularization was defined as at least one graft to all diseased coronary vessels with greater than 50% stenosis. Traditional complete revascularization was defined as one graft to each major arterial system with at least 50% stenosis. Incomplete revascularization was defined as leaving diseased, ungrafted regions. Revascularization was functional in 279 (48%), traditional in 181 (31%), and incomplete in 120 (21%). Long-term survival was evaluated by Kaplan-Meier analysis. Of 537 operative survivors, there were 402 late deaths. Cumulative long-term survival totaled 2,890 patient-years. Late survival (Kaplan-Meier) was similar between functional (6.8 years, mean) and traditional (6.7 years) groups (p=0.51), but diminished with incomplete (4.2 years) revascularization (p=0.007). Survival by group at 5 years was: 59±3% functional, 57±4% traditional, and 45±5% incomplete. Survival at 8 years was: 40±3% functional, 37±4% traditional, and 26±5% incomplete. To minimize selection bias in patients with limited life expectancy, Kaplan-Meier analysis was repeated including only patients with survival greater than 12 months. Survival was again impaired with incomplete revascularization (p=0.04), and there was no difference between functional and traditional complete revascularization (p=0.73). Conclusions Bypassing all diseased arterial vessels after revascularization does not afford significant long-term survival advantage compared to a traditional approach. Incomplete revascularization, related to more extensive disease, is associated with an 18% decline in survival. These data suggest that it is important to avoid incomplete revascularization in octogenarians, but the supplementary endeavor required to perform functional complete revascularization does not improve survival. PMID:19752388
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Cost unit accounting based on a clinical pathway: a practical tool for DRG implementation.
Feyrer, R; Rösch, J; Weyand, M; Kunzmann, U
2005-10-01
Setting up a reliable cost unit accounting system in a hospital is a fundamental necessity for economic survival, given the current general conditions in the healthcare system. Definition of a suitable cost unit is a crucial factor for success. We present here the development and use of a clinical pathway as a cost unit as an alternative to the DRG. Elective coronary artery bypass grafting was selected as an example. Development of the clinical pathway was conducted according to a modular concept that mirrored all the treatment processes across various levels and modules. Using service records and analyses the process algorithms of the clinical pathway were developed and visualized with CorelTM iGrafix Process 2003. A detailed process cost record constituted the basis of the pathway costing, in which financial evaluation of the treatment processes was performed. The result of this study was a structured clinical pathway for coronary artery bypass grafting together with a cost calculation in the form of cost unit accounting. The use of a clinical pathway as a cost unit offers considerable advantages compared to the DRG or clinical case. The variance in the diagnoses and procedures within a pathway is minimal, so the consumption of resources is homogeneous. This leads to a considerable improvement in the value of cost unit accounting as a strategic control instrument in hospitals.
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Garside, R; Pitt, M; Anderson, R; Rogers, G; Dyer, M; Mealing, S; Somerville, M; Price, A; Stein, K
2007-11-01
To assess the clinical and cost-effectiveness of adjuvant carmustine wafers (BCNU-W) and also of adjuvant and concomitant temozolomide (TMZ), compared with surgery with radiotherapy. Electronic databases were searched up to August 2005. Included trials were critically appraised for key elements of internal and external validity. Relevant data were extracted and a narrative synthesis of the evidence produced. Where possible, data on absolute survival at a fixed time point were meta-analysed using a random effects model. A Markov (state transition) model was developed to assess the cost-utility of the two interventions. The model compared BCNU-W or TMZ separately with current standard treatment with surgery and radiotherapy. The simulated cohort had a mean age of 55 years and was modelled over 5 years. Two randomised controlled trials (RCTs) (n = 32, n = 240) and two observational studies of BCNU-W compared with placebo wafers as adjuvant therapy to surgery and radiotherapy for newly diagnosed high-grade glioma were identified. All the studies were in adults and provided data on 193 patients who had received BCNU-W. The RCT findings excluded under 65-year-olds and those with a Karnofsky Performance Status of less than 60. The largest multi-centre RCT suggested a possible survival advantage with BCNU-W among a cohort of patients with grade III and IV tumours, adding a median of 2.3 months [95% confidence interval (CI) -0.5 to 5.1]. However, analysis using per-protocol, unstratified methods shows this difference to be not statistically significant (HR 0.77, 95% CI 0.57 to 1.03, p = 0.08). Long-term follow-up suggests a significant survival advantage using unstratified analysis. No difference in progression-free survival (PFS) was demonstrated. Subgroup analysis of those with grade IV tumours also showed no significant survival advantage with BCNU-W [hazard ratio (HR) 0.82, 95% CI 0.55 to 1.11, p = 0.20, unstratified analysis]. It is estimated that the cost of surgery and radiotherapy, with follow-up, treatment of adverse effects and end of life care is around 17,000 pounds per patient. Treatment with BCNU-W adds an additional 6600 pounds. Across the modelled cohort of 1000 patients, use of BCNU-W costs an additional 6.6 million pounds and confers an additional 122 quality-adjusted life-years (QALYs). On average, that is 6600 pounds per patient for 0.122 QALYs (6.3 quality-adjusted life-weeks). The base-case incremental cost-effectiveness ratio (ICER) is 54,500 pounds/QALY. In probabilistic sensitivity analyses, BCNU-W was not cost-effective in 89% of the simulations assuming a willingness to pay threshold of 30,000 pounds/QALY. In 15% of simulations, BCNU-W was dominated (i.e. did more harm than good, conferring fewer QALYs at greater cost). The cost-effectiveness acceptability curve (CEAC) suggests that it is very unlikely to be the most cost-effective option at normal levels of willingness to pay (11% probability at 30,000 pounds/QALY), only becoming likely to be the most cost-effective option at much higher levels of willingness to pay (50% probability at 55,000 pounds/QALY). Two RCTs (n = 130, n = 573) and two observational studies were included, giving evidence for 429 adult patients receiving TMZ. Currently, TMZ is licensed for use in those with newly diagnosed grade IV gliomas only. The RCTs excluded those with lower performance status and, in the larger RCT, those older than 70 years. TMZ provides a small but statistically significant median survival benefit of 2.5 months (95% CI 2.0 to 3.8), giving an HR of 0.63 (95% CI 0.52 to 0.75, p < 0.001). At 2 years, 26.5% of patients treated with TMZ were alive compared with 10.4% of those in the control arm. Median PFS is also enhanced with TMZ, giving a median 1.9 months' advantage (95% CI 1.4 to 2.7, p < 0.001). No analysis of the subgroup of patients with confirmed grade IV tumours was undertaken. Subgroup analysis of patients by O6-methylguanine-DNA methyltransferase (MGMT) activity showed a significant treatment advantage for those with reduced MGMT activity but not for those with normal activity, although this analysis was based on a selected sample of patients and the test used has proved difficult to replicate. A median gain of 6.4 (95% CI 4.4 to 9.5) more life-months is seen with TMZ among those with reduced MGMT, giving an HR of 0.51 (p < 0.007). PFS is increased by a median of 4.4 months (95% CI 1.2 to 6.3), giving an HR of 0.48 (p = 0.001). The model shows a cost per patient for being treated with surgery, radiotherapy and including adverse effects of treatment and end of life care of around 17,000 pounds per patient. TMZ in the adjuvant and concomitant phase adds an additional cost of around 7800 pounds. Across the modelled cohort of 1000 patients, use of TMZ costs an additional 7.8 million pounds and confers an additional 217 QALYs. For the average patient this is 7800 pounds for an additional 0.217 QALYs (11 quality-adjusted life-weeks). The base-case ICER is 36,000 pounds/QALY. Probabilistic sensitivity analyses shows that TMZ was not cost-effective in 77% of the simulations. The CEAC suggests that there is a 23% chance that TMZ is the most cost-effective option at a willingness to pay level of 30,000 pounds/QALY, rising to be more cost-effective than no TMZ at slightly higher levels (50% probability at 35,000 pounds/QALY). BCNU-W has not been proven to confer a significant advantage in survival for patients with grade III tumours when treated with the drug, compared with placebo. There does not appear to be a survival advantage for patients with grade IV tumours. No increase in PFS has been shown. Limited evidence suggests a small but significant advantage in both overall survival and PFS with TMZ among a mixed population with grade IV and grade III (7-8%) tumours. However, it remains unclear whether this is true in grade IV tumours alone. On the basis of best available evidence, the authors consider that neither BCNU-W nor TMZ is likely to be considered cost-effective by NHS decision-makers. However, data for the model were drawn from limited evidence of variable quality. Tumour type is clearly important in assessing patient prognosis with different treatments. Grade IV tumours are commonest and appear to have least chance of response. There were too few grade III tumours included to carry out a formal assessment, but they appear to respond better and drive results for both drugs. Future use of genetic and biomarkers may help identify subtypes which will respond, but current licensing indications do not specify these. Further research is suggested into the effectiveness of these drugs, and also into areas such as genetic markers, chemotherapy regimens, patient and carer quality of life, and patient views on survival advantages vs treatment disadvantages.
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Vishniac, H S
1995-11-01
Microcosms containing an air-dried autoclaved loamy sand (Eufala A) with low salt and organic content were inoculated with a representative (obligately aerobic, encapsulated) soil yeast, Cryptococcus albidus var. albidus (T) ATCC 10666, singly (for growth rate and survival determinations) and together with the bacterial biota native to Eufala A. The yeast competed successfully with the more rapidly growing bacteria in the presence of added water from 1% (5.7% of field capacity) to 14% (80% of field capacity) but grew for shorter times than when grown alone; times correlated with the lag phase of the bacterial biota. When well-watered (10 and 14%) competition cultures were allowed to dry and used as inoculum for subcultures, the yeast made significant growth only at 1% added water but survived at the higher moisture concentrations. The competitive ability of Cr. albidus confirms the previously reported advantages of the cryptococcal capsule in hydration and desiccation and, together with lengthy survival, suggests that the importance of such yeasts in the biogeochemistry of arid soils has been seriously underestimated.
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Bria, Emilio; Massari, Francesco; Maines, Francesca; Pilotto, Sara; Bonomi, Maria; Porta, Camillo; Bracarda, Sergio; Heng, Daniel; Santini, Daniele; Sperduti, Isabella; Giannarelli, Diana; Cognetti, Francesco; Tortora, Giampaolo; Milella, Michele
2015-01-01
A correlation, power and benchmarking analysis between progression-free and overall survival (PFS, OS) of randomized trials with targeted agents or immunotherapy for advanced renal cell carcinoma (RCC) was performed to provide a practical tool for clinical trial design. For 1st-line of treatment, a significant correlation was observed between 6-month PFS and 12-month OS, between 3-month PFS and 9-month OS and between the distributions of the cumulative PFS and OS estimates. According to the regression equation derived for 1st-line targeted agents, 7859, 2873, 712, and 190 patients would be required to determine a 3%, 5%, 10% and 20% PFS advantage at 6 months, corresponding to an absolute increase in 12-month OS rates of 2%, 3%, 6% and 11%, respectively. These data support PFS as a reliable endpoint for advanced RCC receiving up-front therapies. Benchmarking and power analyses, on the basis of the updated survival expectations, may represent practical tools for future trial' design. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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The protective effect of marriage for survival: a review and update.
Rendall, Michael S; Weden, Margaret M; Favreault, Melissa M; Waldron, Hilary
2011-05-01
The theory that marriage has protective effects for survival has itself lived for more than 100 years since Durkheim's groundbreaking study of suicide (Durkheim 1951 [1897]). Investigations of differences in this protective effect by gender, by age, and in contrast to different unmarried statuses, however, have yielded inconsistent conclusions. These investigations typically either use data in which marital status and other covariates are observed in cross-sectional surveys up to 10 years before mortality exposure, or use data from panel surveys with much smaller sample sizes. Their conclusions are usually not based on formal statistical tests of contrasts between men and women or between never-married, divorced/separated, and widowed statuses. Using large-scale pooled panel survey data linked to death registrations and earnings histories for U.S. men and women aged 25 and older, and with appropriate contrast tests, we find a consistent survival advantage for married over unmarried men and women, and an additional survival "premium" for married men. We find little evidence of mortality differences between never-married, divorced/separated, and widowed statuses.
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2013-01-01
Background The objective of this study was to evaluate the effect on outcomes of intraoperative recombinant human interleukin-2 injection after surgical resection of peripheral nerve sheath tumours. In this double-blind trial, 40 patients due to undergo surgical excision (<5 mm margins) of presumed peripheral nerve sheath tumours were randomized to receive intraoperative injection of interleukin-2 or placebo into the wound bed. Results There were no significant differences in any variable investigated or in median survival between the two groups. The median recurrence free interval was 874 days (range 48–2141 days), The recurrence-free interval and overall survival time were significantly longer in dogs that undergone the primary surgery by a specialist-certified surgeon compared to a referring veterinarian regardless of whether additional adjunct therapy was given. Conclusion Overall, marginal excision of peripheral nerve sheath tumours in dogs resulted in a long survival time, but adjuvant treatment with recombinant human interleukin-2 (rhIL-2) did not provide a survival advantage. PMID:23927575
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Hanna, Adrian; Birla, Rodica; Iosif, Cristina; Boeriu, Marius; Constantinoiu, Silviu
2016-01-01
The purpose of this paper is to present the advantages and disadvantages of neoadjuvant RCT in multimodal therapyof ESC. Between 1998-2014 221 patients were treated with ESC, 85 of whom received neoadjuvant RCT. For these we have made imaging and pathologic assessment of response using RECIST and MANDARD criteria and statistical data were interpreted in terms of the factors that influence the response. Also, they were evaluated statistical correlations between RCT and resectability, postoperative morbidity, mortality and long-term survival. 45 patients were imagistic responders and 34 underwent surgery, 40 non-responders of which 14 underwent surgery. Of the 48 surgical patients with preoperative RCT, histopathological evaluation showed that 32 were pathological responders and 16 non responders. There were performed statistical analyzes of correlations between RCT and resectability, stage, location of ESC, morbidity, mortality and survival. RCT increase resectability, improves survival and maximum duration of survival, more in responders than in nonresponders and does not affect postoperative complications and postoperative mortality, nor among the responders or nonresponders. Imaging evaluation result of the response to RCT overestimate responders. Celsius.
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Zanchi, Caroline; Johnston, Paul R; Rolff, Jens
2017-10-01
The simultaneous expression of costly immune effectors such as multiple antimicrobial peptides is a hallmark of innate immunity of multicellular organisms, yet the adaptive advantage remains unresolved. Here, we test current hypotheses on the evolution of such defence cocktails. We use RNAi gene knock-down to explore, the effects of three highly expressed antimicrobial peptides, displaying different degrees of activity in vitro against Staphylococcus aureus, during an infection in the beetle Tenebrio molitor. We find that a defensin confers no survival benefit but reduces bacterial loads. A coleoptericin contributes to host survival without affecting bacterial loads. An attacin has no individual effect. Simultaneous knock-down of the defensin with the other AMPs results in increased mortality and elevated bacterial loads. Contrary to common expectations, the effects on host survival and bacterial load can be independent. The expression of multiple AMPs increases host survival and contributes to the control of persisting infections and tolerance. This is an emerging property that explains the adaptive benefit of defence cocktails. © 2017 John Wiley & Sons Ltd.
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Beckmann, Kerri R; Bennett, Alice; Young, Graeme P; Cole, Stephen R; Joshi, Rohit; Adams, Jacqui; Singhal, Nimit; Karapetis, Christos; Wattchow, David; Roder, David
2016-01-20
Inequalities in survival from colorectal cancer (CRC) across socioeconomic groups and by area of residence have been described in various health care settings. Few population-wide datasets which include clinical and treatment information are available in Australia to investigate disparities. This study examines socio-demographic differences in survival for CRC patients in South Australia (SA), using a population-wide database derived via linkage of administrative and surveillance datasets. The study population comprised all cases of CRC diagnosed in 2003-2008 among SA residents aged 50-79 yrs in the SA Central Cancer Registry. Measures of socioeconomic status (area level), geographical remoteness, clinical characteristics, comorbid conditions, treatments and outcomes were derived through record linkage of central cancer registry, hospital-based clinical registries, hospital separations, and radiotherapy services data sources. Socio-demographic disparities in CRC survival were examined using competing risk regression analysis. Four thousand six hundred and forty one eligible cases were followed for an average of 4.7 yrs, during which time 1525 died from CRC and 416 died from other causes. Results of competing risk regression indicated higher risk of CRC death with higher grade (HR high v low =2.25, 95% CI 1.32-3.84), later stage (HR C v A = 7.74, 95% CI 5.75-10.4), severe comorbidity (HR severe v none =1.21, 95% CI 1.02-1.44) and receiving radiotherapy (HR = 1.41, 95% CI 1.18-1.68). Patients from the most socioeconomically advantaged areas had significantly better outcomes than those from the least advantaged areas (HR =0.75, 95% 0.62-0.91). Patients residing in remote locations had significantly worse outcomes than metropolitan residents, though this was only evident for stages A-C (HR = 1.35, 95 % CI 1.01-1.80). These disparities were not explained by differences in stage at diagnosis between socioeconomic groups or area of residence. Nor were they explained by differences in patient factors, other tumour characteristics, comorbidity, or treatment modalities. Socio-economic and regional disparities in survival following CRC are evident in SA, despite having a universal health care system. Of particular concern is the poorer survival for patients from remote areas with potentially curable CRC. Reasons for these disparities require further exploration to identify factors that can be addressed to improve outcomes.
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Elsheshtawi, Mohamed; Elkhaky, Maged T; Sayed, Shaban R; Bahkali, Ali H; Mohammed, Arif A; Gambhir, Dikshit; Mansour, Aref S; Elgorban, Abdallah M
2017-02-01
This study was conducted to determine the compatibility of Contans® ( Coniothyrium minitans ) with fungicides against Sclerotinia sclerotiorum . Results showed that both Contans® and Topsin® significantly reduced the disease incidence caused by S. sclerotiorum by 90% and 95% survival plants, respectively when they were individually applied and compared to control. While, soil application of Contans® and Sumisclex mixture was the most effective in suppressing the white rot disease incidence that produced 100% survival plants, application of C. minitans combined with the reduced doses of fungicides would be advantageous in saving labor cost, thus increasing production efficiency of bean.
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Army Science Board 2001 AD HOC Study Knowledge Management
2001-11-01
dissemination, Army, Army culture, information dominance , knowledge dominance, information sharing, situational awareness, network-centric, infosphere...proposed effort and the emerging Army ICT for Information Dominance are all excellent foundation efforts for KM and Information Assurance. The panel’s...level is critical to survivability and lethality. – Unreliable information will quickly reverse the advantages of “ Information Dominance ” essential to
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Antisense Oligonucleotide Therapy for Patients with Advanced Cancer | Center for Cancer Research
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the U.S. Improvements in therapy have increased the survival of patients with CRC from 10 months to two years, but for patients who stop responding to treatments, such as irinotecan, options for additional therapy are limited. Antisense oligonucleotides (ASOs) may offer advantages over traditional
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ERIC Educational Resources Information Center
Orgill, Anna A.
This brief paper suggests that Attention Deficit Disorder (ADD) may result from a specific "novelty seeking" gene which has been associated over the history of man's evolution with a biological advantage in situations where energy, risk taking, and creativity are essentials. It reviews research on the genetics of ADD which suggest that novelty…
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Drug-targeting strategies in cancer therapy.
Huang, P S; Oliff, A
2001-02-01
Genetic changes in cell-cycle, apoptotic, and survival pathways cause tumorigenesis, leading to significant phenotypic changes in transformed cells. These changes in the tumor environment - elevated expression of surface proteases, increased angiogenesis and glucuronidase activity - can be taken advantage of to improve the therapeutic index of existing cancer therapies. Targeting cytotoxics to tumor cells by enzymatic activation is a promising strategy for improving chemotherapeutics.
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Deterrence in Oligopolistic Competition.
1987-03-01
maneuvering for advantage in an oligopolistic market . Competitive battles for entry into a market , and subsequently for market shares or continued survival...on institutional features peculiar to market competition among firms, the available case studies and sta- tistical evidence are not described here...that might enter the market in competition with the present incumbents, which is usually detrimental to the incumbents. Each firm can affect its market
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1976-07-01
relatively normal except fungi frequent. 5.5-6.0 Eastern brook trout (Salvelinus fontinalis) survive at over pit 5.5. Rainbow trout (Salmo gairdneri...salt or ester of a thio acid, made from corn or wheat starch. These material3 have the advantage of being non-toxic natural substances and potentially
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RNA viruses and microRNAs: challenging discoveries for the 21st century
Swaminathan, Gokul; Martin-Garcia, Julio
2013-01-01
RNA viruses represent the predominant cause of many clinically relevant viral diseases in humans. Among several evolutionary advantages acquired by RNA viruses, the ability to usurp host cellular machinery and evade antiviral immune responses is imperative. During the past decade, RNA interference mechanisms, especially microRNA (miRNA)-mediated regulation of cellular protein expression, have revolutionized our understanding of host-viral interactions. Although it is well established that several DNA viruses express miRNAs that play crucial roles in their pathogenesis, expression of miRNAs by RNA viruses remains controversial. However, modulation of the miRNA machinery by RNA viruses may confer multiple benefits for enhanced viral replication and survival in host cells. In this review, we discuss the current literature on RNA viruses that may encode miRNAs and the varied advantages of engineering RNA viruses to express miRNAs as potential vectors for gene therapy. In addition, we review how different families of RNA viruses can alter miRNA machinery for productive replication, evasion of antiviral immune responses, and prolonged survival. We underscore the need to further explore the complex interactions of RNA viruses with host miRNAs to augment our understanding of host-virus interplay. PMID:24046280
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Bacteria and game theory: the rise and fall of cooperation in spatially heterogeneous environments.
Lambert, Guillaume; Vyawahare, Saurabh; Austin, Robert H
2014-08-06
One of the predictions of game theory is that cooperative behaviours are vulnerable to exploitation by selfish individuals, but this result seemingly contradicts the survival of cooperation observed in nature. In this review, we will introduce game theoretical concepts that lead to this conclusion and show how the spatial competition dynamics between microorganisms can be used to model the survival and maintenance of cooperation. In particular, we focus on how Escherichia coli bacteria with a growth advantage in stationary phase (GASP) phenotype maintain a proliferative phenotype when faced with overcrowding to gain a fitness advantage over wild-type populations. We review recent experimental approaches studying the growth dynamics of competing GASP and wild-type strains of E. coli inside interconnected microfabricated habitats and use a game theoretical approach to analyse the observed inter-species interactions. We describe how the use of evolutionary game theory and the ideal free distribution accurately models the spatial distribution of cooperative and selfish individuals in spatially heterogeneous environments. Using bacteria as a model system of cooperative and selfish behaviours may lead to a better understanding of the competition dynamics of other organisms-including tumour-host interactions during cancer development and metastasis.
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Tesson, Stephanie; Richards, Imogen; Porter, David; Phillips, Kelly-Anne; Rankin, Nicole; Musiello, Toni; Marven, Michelle; Butow, Phyllis
2016-05-01
Most women diagnosed with unilateral breast cancer without BRCA1 or BRCA2 mutations are at low risk of contralateral breast cancer. Contralateral Prophylactic Mastectomy (CPM) decreases the relative risk of contralateral breast cancer, but may not increase life expectancy; yet international uptake is increasing. This study applied protection motivation theory (PMT) to determine factors associated with women's intentions to undergo CPM. Three hundred eighty-eight women previously diagnosed with unilateral breast cancer and of negative or unknown BRCA1 or BRCA2 status were recruited from an advocacy group's research database. Participants completed measures of PMT constructs based on a common hypothetical CPM decision-making scenario. PMT constructs explained 16% of variance in intentions to undergo CPM. Response efficacy (CPM's advantages) and response costs (CPM's disadvantages) were unique individual predictors of intentions. Decision-making appears driven by considerations of the psychological, cosmetic and emotional advantages and disadvantages of CPM. Overestimations of threat to life from contralateral breast cancer and survival benefit from CPM also appear influential factors. Patients require balanced and medically accurate information regarding the pros and cons of CPM, survival rates, and recurrence risks to ensure realistic and informed decision-making.
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Gorey, Kevin M.; Luginaah, Isaac N.; Hamm, Caroline; Fung, Karen Y.; Holowaty, Eric J.
2010-01-01
This study examined the differential effect of extreme impoverishment on breast cancer care in urban Canada and the United States. Ontario and California registry-based samples diagnosed between 1998 and 2000 were followed until 2006. Extremely poor and affluent neighborhoods were compared. Poverty was associated with non-localized disease, surgical and radiation therapy (RT) waits, nonreceipt of breast conserving surgery, RT and hormonal therapy, and shorter survival in California, but not in Ontario. Extremely poor Ontario women were consistently advantaged on care indices over their California counterparts. More inclusive health insurance coverage in Canada seems the most plausible explanation for such Canadian breast cancer care advantages. PMID:19840902
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Marital Status and Survival in Patients with Carcinoid Tumors.
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 < 0.0001). Even after controlling for other prognostic factors, married patients have a survival advantage after diagnosis of any carcinoid tumor, potentially reflecting better social support and financial means than patients without partners.
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Habib, Robert H.; Dimitrova, Kamellia R.; Badour, Sanaa A.; Yammine, Maroun B.; El-Hage-Sleiman, Abdul-Karim M.; Hoffman, Darryl M.; Geller, Charles M.; Schwann, Thomas A.; Tranbaugh, Robert F.
2017-01-01
BACKGROUND Treatment of multivessel coronary artery disease with traditional single-arterial coronary artery bypass graft (SA-CABG) has been associated with superior intermediate-term survival and reintervention compared with percutaneous coronary intervention (PCI) using either bare-metal stents (BMS) or drug-eluting stents (DES). OBJECTIVES This study sought to investigate longer-term outcomes including the potential added advantage of multiarterial coronary artery bypass graft (MA-CABG). METHODS We studied 8,402 single-institution, primary revascularization, multivessel coronary artery disease patients: 2,207 BMS-PCI (age 66.6 ± 11.9 years); 2,381 DES-PCI (age 65.9 ± 11.7 years); 2,289 SA-CABG (age 69.3 ± 9.0 years); and 1,525 MA-CABG (age 58.3 ± 8.7 years). Patients with myocardial infarction within 24 h, shock, or left main stents were excluded. Kaplan-Meier analysis and Cox regression were used to separately compare 9-year all-cause mortality and unplanned reintervention for BMS-PCI and DES-PCI to respective propensity-matched SA-CABG and MA-CABG cohorts. RESULTS BMS-PCI was associated with worse survival than SA-CABG, especially from 0 to 7 years (p = 0.015) and to a greater extent than MA-CABG was (9-year follow-up: 76.3% vs. 86.9%; p < 0.001). The surgery-to-BMS-PCI hazard ratios (HR) were as follows: versus SA-CABG, HR: 0.87; and versus MA-CABG, HR: 0.38. DES-PCI showed similar survival to SA-CABG except for a modest 0 to 3 years surgery advantage (HR: 1.06; p = 0.615). Compared with MA-CABG, DES-PCI exhibited worse survival at 5 (86.3% vs. 95.6%) and 9 (82.8% vs. 89.8%) years (HR: 0.45; p <0.001). Reintervention was substantially worse with PCI for all comparisons (all p <0.001). CONCLUSIONS Multiarterial surgical revascularization, compared with either BMS-PCI or DES-PCI, resulted in substantially enhanced death and reintervention-free survival. Accordingly, MA-CABG represents the optimal therapy for multivessel coronary artery disease and should be enthusiastically adopted by multidisciplinary heart teams as the best evidence-based therapy. PMID:26403338
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Modeling time-to-event (survival) data using classification tree analysis.
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.
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Serum albumin predicts survival in patients with hilar cholangiocarcinoma.
Waghray, Abhijeet; Sobotka, Anastasia; Marrero, Carlos Romero; Estfan, Bassam; Aucejo, Federico; Narayanan Menon, K V
2017-02-01
Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma. All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation. A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19-9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14-0.70) with a survival benefit of 44 weeks. This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.
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Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma
Larson, Erik W; Peterson, Halloran E; Lamoreaux, Wayne T; MacKay, Alexander R; Fairbanks, Robert K; Call, Jason A; Carlson, Jonathan D; Ling, Benjamin C; Demakas, John J; Cooke, Barton S; Lee, Christopher M
2014-01-01
Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed. PMID:24829861
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78 FR 35826 - Unfair Competitive Advantages; Enhancement of the Formal Complaint Process
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-14
... Postal Service to the time and expense of the discovery process. The Commission anticipates that allowing.... 1739] Unfair Competitive Advantages; Enhancement of the Formal Complaint Process AGENCY: Postal... enhance the formal complaint process in cases involving alleged violations of a law that prohibits the...
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Cancer and beyond: the question of survivorship.
Breaden, K
1997-11-01
Today, more people are surviving cancer as a result of improved treatment and early diagnosis. In Australia, the 5-year survival rate for persons diagnosed with cancer is now approaching 50%. Although there is a growing population of cancer survivors, little is known about what surviving entails. Traditionally, a survivor has been defined as one who has been disease-free for more than 5 years. However, this definition does not take into account the experience nor the process of survival and the aim of this article is to document the process of surviving cancer as reflected in the experiences of cancer survivors. Using a method of hermeneutic phenomenology (as described by van Manen), the study draws on the stories of six women, who by their definition, are surviving cancer. A discussion of themes has been structured according to the everyday experiences of living in a body and living in time. The women describe a survival process that includes: 'feeling whole again'; 'the body as the house of suspicion'; 'the future in question'; 'changes in time'; 'lucky to be alive'; and 'sharing the journey'.
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Dynamic frailty models based on compound birth-death processes.
Putter, Hein; van Houwelingen, Hans C
2015-07-01
Frailty models are used in survival analysis to model unobserved heterogeneity. They accommodate such heterogeneity by the inclusion of a random term, the frailty, which is assumed to multiply the hazard of a subject (individual frailty) or the hazards of all subjects in a cluster (shared frailty). Typically, the frailty term is assumed to be constant over time. This is a restrictive assumption and extensions to allow for time-varying or dynamic frailties are of interest. In this paper, we extend the auto-correlated frailty models of Henderson and Shimakura and of Fiocco, Putter and van Houwelingen, developed for longitudinal count data and discrete survival data, to continuous survival data. We present a rigorous construction of the frailty processes in continuous time based on compound birth-death processes. When the frailty processes are used as mixtures in models for survival data, we derive the marginal hazards and survival functions and the marginal bivariate survival functions and cross-ratio function. We derive distributional properties of the processes, conditional on observed data, and show how to obtain the maximum likelihood estimators of the parameters of the model using a (stochastic) expectation-maximization algorithm. The methods are applied to a publicly available data set. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Rogers, Nina Trivedy; Demakakos, Panayotes; Taylor, Mark Steven; Steptoe, Andrew; Hamer, Mark; Shankar, Aparna
2018-01-01
Background 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. Methods 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, whilst controlling for selected confounders. To investigate effect modification by disability, the analyses were repeated in participants with and without self-reported functional disabilities. Results Volunteering was associated with a reduced probability of death from all-causes in univariate analyses (HR = 0.65, CI 0.58–0.73, P < 0.0001), but adjustment for covariates rendered this association non-significant (HR = 0.90, CI 0.79–1.01, P = 0.07). Able-bodied volunteers had significantly increased survival compared to able-bodied non-volunteers (HR = 0.81, 95% CI: 0.69 – 0.95, P = 0.009). There was no significant survival advantage among disabled volunteers, compared to disabled non-volunteers (HR = 1.06, CI 0.88–1.29, P = 0.53). Conclusion Volunteering is associated with reduced mortality in older adults in England, but this effect appears to be limited to volunteers who report no disabilities. PMID:26811548
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Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M
2017-06-07
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.
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Kemna, Mariska; Albers, Erin; Bradford, Miranda C; Law, Sabrina; Permut, Lester; McMullan, D Mike; Law, Yuk
2016-03-01
The effect of donor-recipient sex matching on long-term survival in pediatric heart transplantation is not well known. Adult data have shown worse survival when male recipients receive a sex-mismatched heart, with conflicting results in female recipients. We analyzed 5795 heart transplant recipients ≤ 18 yr in the Scientific Registry of Transplant Recipients (1990-2012). Recipients were stratified based on donor and recipient sex, creating four groups: MM (N = 1888), FM (N = 1384), FF (N = 1082), and MF (N = 1441). Males receiving sex-matched donor hearts had increased unadjusted allograft survival at five yr (73.2 vs. 71%, p = 0.01). However, this survival advantage disappeared with longer follow-up and when adjusted for additional risk factors by multivariable Cox regression analysis. In contrast, for females, receiving a sex-mismatched heart was associated with an 18% higher risk of allograft loss over time compared to receiving a sex-matched heart (HR 1.18, 95% CI: 1.00-1.38) and a 26% higher risk compared to sex-matched male recipients (HR 1.26, 95% CI: 1.10-1.45). Females who receive a heart from a male donor appear to have a distinct long-term survival disadvantage compared to all other groups. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Trinidad, Eva M.; García, Dolores; Soler, Gloria; Ortuño, Francisco J.; Zapata, Agustín G.; Alonso, Luis M.
2016-01-01
A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-α activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of α4 and αL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival. PMID:27374180
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Familiarity with breeding habitat improves daily survival in colonial cliff swallows
BROWN, CHARLES R.; BROWN, MARY BOMBERGER; BRAZEAL, KATHLEEN R.
2008-01-01
One probable cost of dispersing to a new breeding habitat is unfamiliarity with local conditions such as the whereabouts of food or the habits of local predators, and consequently immigrants may have lower probabilities of survival than more experienced residents. Within a breeding season, estimated daily survival probabilities of cliff swallows (Petrochelidon pyrrhonota) at colonies in southwestern Nebraska were highest for birds that had always nested at the same site, followed by those for birds that had nested there in some (but not all) past years. Daily survival probabilities were lowest for birds that were naïve immigrants to a colony site and for yearling birds that were nesting for the first time. Birds with past experience at a colony site had monthly survival 8.6% greater than that of naïve immigrants. All colonies where experienced residents did better than immigrants were smaller than 750 nests in size, and in colonies greater than 750 nests, naïve immigrants paid no survival costs relative to experienced residents. Removal of nest ectoparasites by fumigation resulted in higher survival probabilities for all birds, on average, and diminished the differences between immigrants and past residents, probably by improving bird condition to the extent that effects of past experience were relatively less important and harder to detect. The greater survival of experienced residents could not be explained by condition or territory quality, suggesting that familiarity with a local area confers survival advantages during the breeding season for cliff swallows. Colonial nesting may help to moderate the cost of unfamiliarity with an area, likely through social transfer of information about food sources and enhanced vigilance in large groups. PMID:19802326
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Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.
Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles
2016-03-01
Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.
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Ten-year survival after epithelial ovarian cancer is not associated with BRCA mutation status.
Kotsopoulos, Joanne; Rosen, Barry; Fan, Isabel; Moody, Joel; McLaughlin, John R; Risch, Harvey; May, Taymaa; Sun, Ping; Narod, Steven A
2016-01-01
After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12 years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors. We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10 years for a range of factors including BRCA mutation status and extent of residual disease post-surgery. Of the 1421 patients, 109 (7.7%) had BRCA1 mutations and 68 (4.8%) had BRCA2 mutations. A status of no residual disease was achieved by 39% of non-carriers and 19% of mutation carriers (P<0.0001). By 10-years of follow-up, 43% of non-carriers, 57% of BRCA1 mutation carriers and 69% of BRCA2 mutation carriers had died from ovarian cancer. Among women with stage III/IV serous cancers and no residual disease, the 10-year actuarial survival was 42% for non-carriers and 29% for mutation carriers (P=0.40). The initial survival advantage among women with BRCA mutations may reflect a higher initial sensitivity of BRCA carriers to chemotherapy, but this response does not predict long-term survival. The strongest predictor of long-term survival is status of no residual disease at resection. Copyright © 2015. Published by Elsevier Inc.
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Turner, Hailey; Séguin, Bernard; Worley, Deanna R; Ehrhart, Nicole P; Lafferty, Mary H; Withrow, Stephen J; Selmic, Laura E
2017-12-01
OBJECTIVE To determine survival times of selected dogs with metastatic (stage III) osteosarcoma, whether disease-free interval (DFI) was associated with survival time after diagnosis of stage III disease (ie, stage III survival time), and whether a survival benefit of metastasectomy existed. DESIGN Retrospective case series with nested cohort study. ANIMALS 194 client-owned dogs treated for histologically confirmed appendicular osteosarcoma from 1997 through 2009. PROCEDURES Dogs were included if they had stage I or II osteosarcoma at the time of initial evaluation, had amputation of the affected appendage and ≥ 1 dose of chemotherapy afterward, and developed metastasis within the follow-up period or prior to death. Data collected from the medical records included signalment, primary tumor location, clinical and laboratory findings, whether metastasectomy was performed, and outcome. Various factors were examined for associations with outcome. RESULTS Dogs that received no treatment for the metastasis had a median survival time between 49 and 57 days after diagnosis of stage III osteosarcoma. Duration of the preceding DFI had no association with this period. Metastasectomy alone was associated with a longer median stage III survival time (232 days) than no metastasectomy (49 days). Among all dogs identified as qualifying for pulmonary metastasectomy on the basis of < 3 pulmonary nodules visible on thoracic radiographs and a DFI > 275 days (n = 21), a survival advantage was also identified for those that actually received pulmonary metastasectomy (6). CONCLUSIONS AND CLINICAL RELEVANCE Preceding DFI had no influence on survival time of dogs with stage III osteosarcoma. Metastasectomy was associated with an increase in survival time for selected dogs.
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Training in peroral endoscopic myotomy (POEM) for esophageal achalasia
Eleftheriadis, Nicholas; Inoue, Haruhiro; Ikeda, Haruo; Onimaru, Manabu; Yoshida, Akira; Hosoya, Toshihisa; Maselli, Roberta; Kudo, Shin-ei
2012-01-01
Peroral endoscopic myotomy (POEM) has been developed in the context of natural orifice transluminal endoscopic surgery (NOTES) as a minimally invasive endoscopic treatment for symptomatic esophageal achalasia, which is a chronic progressive benign disease with severe morbidity and difficult management. Since September 2008, POEM has been successfully performed in more than 200 consecutive patients with symptomatic achalasia at the Digestive Disease Center of Showa University, Northern Yokohama Hospital, Yokohama, Japan, with excellent short- and long-term results and absence of serious complications. International experience of POEM within clinical studies is also promising. According to these results, POEM is considered as a safe procedure that can be applied to all achalasia patients. However, the low incidence of achalasia (0.3%–1% per 100,000 population), in combination with the potential serious complications related to the technically demanding POEM procedure, has made training difficult. There is therefore an urgent need for an animal model for training to decrease the learning curve. Further, there are other ethical and training issues to address. The pig is the most appropriate animal model for training in POEM due to its anatomy being similar to that of humans. The porcine esophagus has the advantage of easy mobilization due to absence of tight junctions to surrounding organs. A non-survival porcine model would be a simple, inexpensive, and reproducible animal model for training in POEM, without the need for concern about complications. A possible training process might first involve observation of POEM performed by specialists, then training on non-survival and survival porcine models, followed by training in humans under specialist guidance and finally, performance of POEM in humans. PMID:22888256
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NASA Technical Reports Server (NTRS)
Jones, Steven M.; Paik, Jong-Ah
2013-01-01
A method has been developed for creating aerogel using normal pressure and ambient temperatures. All spacecraft, satellites, and landers require the use of thermal insulation due to the extreme environments encountered in space and on extraterrestrial bodies. Ambient dried aerogels introduce the possibility of using aerogel as thermal insulation in a wide variety of instances where supercritically dried aerogels cannot be used. More specifically, thermoelectric devices can use ambient dried aerogel, where the advantages are in situ production using the cast-in ability of an aerogel. Previously, aerogels required supercritical conditions (high temperature and high pressure) to be dried. Ambient dried aerogels can be dried at room temperature and pressure. This allows many materials, such as plastics and certain metal alloys that cannot survive supercritical conditions, to be directly immersed in liquid aerogel precursor and then encapsulated in the final, dried aerogel. Additionally, the metalized Mylar films that could not survive the previous methods of making aerogels can survive the ambient drying technique, thus making multilayer insulation (MLI) materials possible. This results in lighter insulation material as well. Because this innovation does not require high-temperature or high-pressure drying, ambient dried aerogels are much less expensive to produce. The equipment needed to conduct supercritical drying costs many tens of thousands of dollars, and has associated running expenses for power, pressurized gasses, and maintenance. The ambient drying process also expands the size of the pieces of aerogel that can be made because a high-temperature, high-pressure system typically has internal dimensions of up to 30 cm in diameter and 60 cm in height. In the case of this innovation, the only limitation on the size of the aerogels produced would be in the ability of the solvent in the wet gel to escape from the gel network.
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Denti, Licia; Artoni, Andrea; Scoditti, Umberto; Gatti, Elisa; Bussolati, Chiara; Ceda, Gian Paolo
2016-06-01
Pre-hospital delay in acute stroke is critical to the administration of thrombolysis and affects patients' clinical outcome. In this study, the impact of pre-hospital delay on the outcome of ischemic stroke was investigated in an Italian cohort of patients who did not receive thrombolysis. Data from a cohort of 1847 patients, suffering from first-ever ischemic stroke and referred to an in-hospital clinical pathway were analyzed retrospectively. The relationship between pre-hospital delay and 1-month mortality was assessed with adjustment for demographics, premorbid disability, and stroke severity, which was graded according to the Scandinavian Stroke Scale, with higher scores indicating less severity. Five hundred and twelve patients (27.7%) arrived at hospital within 2 hours of symptom onset. A significant correlation was found between early arrival and a reduced risk of 1-month mortality (hazard ratio .65; 95% confidence interval .48-.89; P = .02). There was a significant interaction (P = .01) between pre-hospital delay and the neurological score on mortality in the multivariate model, and the survival advantage of early admission was significant only for patients with scores on the Scandinavian Stroke Scale less than 18 (hazard ratio .54; 95% confidence interval .34-.85; P = .008). Our study suggests that reducing pre-hospital delay can increase the probability of survival in patients with ischemic stroke, especially those who are most severely affected. Even if the patients cannot benefit from thrombolysis, survival rates can be increased provided that they are managed according to standardized care processes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
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Carbon ion irradiation of the human prostate cancer cell line PC3: A whole genome microarray study
SUETENS, ANNELIES; MOREELS, MARJAN; QUINTENS, ROEL; CHIRIOTTI, SABINA; TABURY, KEVIN; MICHAUX, ARLETTE; GRÉGOIRE, VINCENT; BAATOUT, SARAH
2014-01-01
Hadrontherapy is a form of external radiation therapy, which uses beams of charged particles such as carbon ions. Compared to conventional radiotherapy with photons, the main advantage of carbon ion therapy is the precise dose localization along with an increased biological effectiveness. The first results obtained from prostate cancer patients treated with carbon ion therapy showed good local tumor control and survival rates. In view of this advanced treatment modality we investigated the effects of irradiation with different beam qualities on gene expression changes in the PC3 prostate adenocarcinoma cell line. For this purpose, PC3 cells were irradiated with various doses (0.0, 0.5 and 2.0 Gy) of carbon ions (LET=33.7 keV/μm) at the beam of the Grand Accélérateur National d’Ions Lourds (Caen, France). Comparative experiments with X-rays were performed at the Belgian Nuclear Research Centre. Genome-wide gene expression was analyzed using microarrays. Our results show a downregulation in many genes involved in cell cycle and cell organization processes after 2.0 Gy irradiation. This effect was more pronounced after carbon ion irradiation compared with X-rays. Furthermore, we found a significant downregulation of many genes related to cell motility. Several of these changes were confirmed using qPCR. In addition, recurrence-free survival analysis of prostate cancer patients based on one of these motility genes (FN1) revealed that patients with low expression levels had a prolonged recurrence-free survival time, indicating that this gene may be a potential prognostic biomarker for prostate cancer. Understanding how different radiation qualities affect the cellular behavior of prostate cancer cells is important to improve the clinical outcome of cancer radiation therapy. PMID:24504141
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Yuo, Theodore H; Chaer, Rabih A; Dillavou, Ellen D; Leers, Steven A; Makaroun, Michel S
2015-12-01
Current guidelines suggest that arteriovenous fistula (AVF) is associated with survival advantage over arteriovenous graft (AVG). However, AVFs often require months to become functional, increasing tunneled dialysis catheter (TDC) use, which can erode the benefit of an AVF. We sought to compare survival in patients with end-stage renal disease after creation of an AVF or AVG in patients starting hemodialysis (HD) with a TDC and to identify patient populations that may benefit from preferential use of AVG over AVF. Using U.S. Renal Data System databases, we identified incident HD patients in 2005 through 2008 and observed them through 2008. Initial access type and clinical variables including albumin levels were assessed using U.S. Renal Data System data collection forms. Attempts at AVF and AVG creation in patients who started HD through a TDC were identified by Current Procedural Terminology codes. We accounted for the effect of changes in access type by truncating follow-up when an additional AVF or AVG was performed. Survival curves were then constructed, and log-rank tests were used for pairwise survival comparisons, stratified by age. Multivariate analysis was performed with Cox proportional hazards regressions; variables were chosen using stepwise elimination. An interaction of access type and albumin level was detected, and Cox models using differing thresholds for albumin level were constructed. The primary outcome was survival. Among the 138,245 patients who started with a TDC and had complete records amenable for analysis, 22.8% underwent AVF creation (mean age ± standard deviation, 68.9 ± 12.5 years; 27.8% mortality at 1 year) and 7.6% underwent AVG placement (70.2 ± 12.0 years; 28.2% mortality) within 3 months of HD initiation; 69.6% remained with a TDC (63.2 ± 15.4 years; 33.8% mortality). In adjusted Cox proportional hazards regression, AVF creation is equivalent to AVG placement in terms of survival (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.93-1.02; P = .349). AVG placement is superior to continued TDC use (HR, 1.54; 95% CI, 1.48-1.61; P < .001). In patients older than 80 years with albumin levels >4.0 g/dL, AVF creation is associated with higher mortality hazard compared with AVG creation (HR, 1.22; 95% CI, 1.04-1.43; P = .013). For patients who start HD through a TDC, placement of an AVF and AVG is associated with similar mortality hazard. Further study is necessary to determine the ideal access for patients in whom the survival advantage of an AVF over an AVG is uncertain. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
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An Own-Race Advantage for Components as Well as Configurations in Face Recognition
ERIC Educational Resources Information Center
Hayward, William G.; Rhodes, Gillian; Schwaninger, Adrian
2008-01-01
The own-race advantage in face recognition has been hypothesized as being due to a superiority in the processing of configural information for own-race faces. Here we examined the contributions of both configural and component processing to the own-race advantage. We recruited 48 Caucasian participants in Australia and 48 Chinese participants in…
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Mahoney, John R; Aghamohammadi, Cina; Crutchfield, James P
2016-02-15
A stochastic process' statistical complexity stands out as a fundamental property: the minimum information required to synchronize one process generator to another. How much information is required, though, when synchronizing over a quantum channel? Recent work demonstrated that representing causal similarity as quantum state-indistinguishability provides a quantum advantage. We generalize this to synchronization and offer a sequence of constructions that exploit extended causal structures, finding substantial increase of the quantum advantage. We demonstrate that maximum compression is determined by the process' cryptic order--a classical, topological property closely allied to Markov order, itself a measure of historical dependence. We introduce an efficient algorithm that computes the quantum advantage and close noting that the advantage comes at a cost-one trades off prediction for generation complexity.
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Brand, Matthias; Schiebener, Johannes; Pertl, Marie-Theres; Delazer, Margarete
2014-01-01
Recent models on decision making under risk conditions have suggested that numerical abilities are important ingredients of advantageous decision-making performance, but empirical evidence is still limited. The results of our first study show that logical reasoning and basic mental calculation capacities predict ratio processing and that ratio processing predicts decision making under risk. In the second study, logical reasoning together with executive functions predicted probability processing (numeracy and probability knowledge), and probability processing predicted decision making under risk. These findings suggest that increasing an individual's understanding of ratios and probabilities should lead to more advantageous decisions under risk conditions.
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2014-01-01
Background Hafnia alvei is an opportunistic pathogen involved in various types of nosocomical infections. The species has been found to inhabit food and mammalian guts. However, its status as an enteropathogen, and whether the food-inhabiting strains could be a source of gastrointestinal infection remains obscure. In this report we present a draft genome of H. alvei strain FB1 isolated from fish paste meatball, a food popular among Malaysian and Chinese populations. The data was generated on the Illumina MiSeq platform. Results A comparative study was carried out on FB1 against two other previously sequenced H. alvei genomes. Several gene clusters putatively involved in survival and pathogenesis of H. alvei FB1 in food and gut environment were characterised in this study. These include the widespread colonisation island (WCI), the tad locus that is known to play an essential role in biofilm formation, a eut operon that might contribute to advantage in nutrient acquisition in gut environment, and genes responsible for siderophore production This features enable the bacteria to successful colonise in the host gut environment. Conclusion With the whole genome data of H. alvei FB1 presented in this study, we hope to provide an insight into future studies on this candidate of enteropathogen by looking into the possible mechanisms employed to survive stresses and gain advantage in competitions, which eventually leads to successful colonisation and pathogenesis. This is to serve as the basis for more effective clinical diagnosis and treatment. PMID:25075225
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Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease☆
Darabian, Sirous; Rattanasompattikul, Manoch; Hatamizadeh, Parta; Bunnapradist, Suphamai; Budoff, Matthew J.; Kovesdy, Csaba P.; Kalantar-Zadeh, Kamyar
2012-01-01
Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic–hematologic, (6) inflammatory–oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 μg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway. PMID:26889405
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An Approach to Addressing Selection Bias in Survival Analysis
Carlin, Caroline S.; Solid, Craig A.
2014-01-01
This work proposes a frailty model that accounts for non-random treatment assignment in survival analysis. Using Monte Carlo simulation, we found that estimated treatment parameters from our proposed endogenous selection survival model (esSurv) closely parallel the consistent two-stage residual inclusion (2SRI) results, while offering computational and interpretive advantages. The esSurv method greatly enhances computational speed relative to 2SRI by eliminating the need for bootstrapped standard errors, and generally results in smaller standard errors than those estimated by 2SRI. In addition, esSurv explicitly estimates the correlation of unobservable factors contributing to both treatment assignment and the outcome of interest, providing an interpretive advantage over the residual parameter estimate in the 2SRI method. Comparisons with commonly used propensity score methods and with a model that does not account for non-random treatment assignment show clear bias in these methods that is not mitigated by increased sample size. We illustrate using actual dialysis patient data comparing mortality of patients with mature arteriovenous grafts for venous access to mortality of patients with grafts placed but not yet ready for use at the initiation of dialysis. We find strong evidence of endogeneity (with estimate of correlation in unobserved factors ρ̂ = 0.55), and estimate a mature-graft hazard ratio of 0.197 in our proposed method, with a similar 0.173 hazard ratio using 2SRI. The 0.630 hazard ratio from a frailty model without a correction for the non-random nature of treatment assignment illustrates the importance of accounting for endogeneity. PMID:24845211
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Minimalist breast conserving surgical approaches for inferiorly sited cancers
2017-01-01
Contemporary data suggests that breast conservation treatment (BCT) may confer a survival advantage when compared to mastectomy. Hence, it would be logical to adopt strategies which increase eligibility of successful BCT without compromising oncologic principles or cosmetic outcome. With respect to achieving good aesthetics, inferiorly sited breast cancers pose a particular technical challenge. A vast array of techniques, collectively referred to as oncoplastic breast surgery (OBS) have been developed to minimise post treatment distortion. The purported advantages of these approaches are the acquisition of wider margins and reduced re-excision rates. However, to date, there is a lack of data demonstrating significant reduction in local recurrence and overall survival when compared with less extensive procedures. In this review, “minimalist” procedures are described where strict oncologic criteria of clear margins are fulfilled and acceptable cosmesis are simultaneously achieved. These techniques offer less tissue loss, less extensive parenchymal mobilisation and shorter operating times without compromising margin status and aesthetics. They involve the combination of innovative incision designs and certain parenchymal resection patterns. Incision designs include the boomerang, golf-tee, anchor and arrowhead incisions which have been previously described but not widely used. Parenchymal resection patterns follow the “sick lobe hypothesis”. These techniques, termed “reductionist”, or “minimalist” comprising approaches where breast conserving surgery is condensed to its irreducible elements, offer alternatives which align with contemporary objectives of surgery where optimal survival outcomes are achieved through individualised procedures resulting in reduced iatrogenic impact. This logically allows scope for de-escalation of surgical therapy for breast cancer. PMID:28861382
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Berney, Michael; Greening, Chris; Conrad, Ralf; Jacobs, William R; Cook, Gregory M
2014-08-05
Oxygen availability is a major factor and evolutionary force determining the metabolic strategy of bacteria colonizing an environmental niche. In the soil, conditions can switch rapidly between oxia and anoxia, forcing soil bacteria to remodel their energy metabolism accordingly. Mycobacterium is a dominant genus in the soil, and all its species are obligate aerobes. Here we show that an obligate aerobe, the soil actinomycete Mycobacterium smegmatis, adopts an anaerobe-type strategy by activating fermentative hydrogen production to adapt to hypoxia. This process is controlled by the two-component system DosR-DosS/DosT, an oxygen and redox sensor that is well conserved in mycobacteria. We show that DosR tightly regulates the two [NiFe]-hydrogenases: Hyd3 (MSMEG_3931-3928) and Hyd2 (MSMEG_2719-2718). Using genetic manipulation and high-sensitivity GC, we demonstrate that Hyd3 facilitates the evolution of H2 when oxygen is depleted. Combined activity of Hyd2 and Hyd3 was necessary to maintain an optimal NAD(+)/NADH ratio and enhanced adaptation to and survival of hypoxia. We demonstrate that fermentatively-produced hydrogen can be recycled when fumarate or oxygen become available, suggesting Mycobacterium smegmatis can switch between fermentation, anaerobic respiration, and aerobic respiration. Hydrogen metabolism enables this obligate aerobe to rapidly meet its energetic needs when switching between microoxic and anoxic conditions and provides a competitive advantage in low oxygen environments.
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PSHREG: A SAS macro for proportional and nonproportional subdistribution hazards regression
Kohl, Maria; Plischke, Max; Leffondré, Karen; Heinze, Georg
2015-01-01
We present a new SAS macro %pshreg that can be used to fit a proportional subdistribution hazards model for survival data subject to competing risks. Our macro first modifies the input data set appropriately and then applies SAS's standard Cox regression procedure, PROC PHREG, using weights and counting-process style of specifying survival times to the modified data set. The modified data set can also be used to estimate cumulative incidence curves for the event of interest. The application of PROC PHREG has several advantages, e.g., it directly enables the user to apply the Firth correction, which has been proposed as a solution to the problem of undefined (infinite) maximum likelihood estimates in Cox regression, frequently encountered in small sample analyses. Deviation from proportional subdistribution hazards can be detected by both inspecting Schoenfeld-type residuals and testing correlation of these residuals with time, or by including interactions of covariates with functions of time. We illustrate application of these extended methods for competing risk regression using our macro, which is freely available at: http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/statistical-software/pshreg, by means of analysis of a real chronic kidney disease study. We discuss differences in features and capabilities of %pshreg and the recent (January 2014) SAS PROC PHREG implementation of proportional subdistribution hazards modelling. PMID:25572709
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Chai, Hua; Li, Zi-Na; Meng, De-Yu; Xia, Liang-Yong; Liang, Yong
2017-10-12
Gene selection is an attractive and important task in cancer survival analysis. Most existing supervised learning methods can only use the labeled biological data, while the censored data (weakly labeled data) far more than the labeled data are ignored in model building. Trying to utilize such information in the censored data, a semi-supervised learning framework (Cox-AFT model) combined with Cox proportional hazard (Cox) and accelerated failure time (AFT) model was used in cancer research, which has better performance than the single Cox or AFT model. This method, however, is easily affected by noise. To alleviate this problem, in this paper we combine the Cox-AFT model with self-paced learning (SPL) method to more effectively employ the information in the censored data in a self-learning way. SPL is a kind of reliable and stable learning mechanism, which is recently proposed for simulating the human learning process to help the AFT model automatically identify and include samples of high confidence into training, minimizing interference from high noise. Utilizing the SPL method produces two direct advantages: (1) The utilization of censored data is further promoted; (2) the noise delivered to the model is greatly decreased. The experimental results demonstrate the effectiveness of the proposed model compared to the traditional Cox-AFT model.
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Exploitation of the host cell ubiquitin machinery by microbial effector proteins.
Lin, Yi-Han; Machner, Matthias P
2017-06-15
Pathogenic bacteria are in a constant battle for survival with their host. In order to gain a competitive edge, they employ a variety of sophisticated strategies that allow them to modify conserved host cell processes in ways that favor bacterial survival and growth. Ubiquitylation, the covalent attachment of the small modifier ubiquitin to target proteins, is such a pathway. Ubiquitylation profoundly alters the fate of a myriad of cellular proteins by inducing changes in their stability or function, subcellular localization or interaction with other proteins. Given the importance of ubiquitylation in cell development, protein homeostasis and innate immunity, it is not surprising that this post-translational modification is exploited by a variety of effector proteins from microbial pathogens. Here, we highlight recent advances in our understanding of the many ways microbes take advantage of host ubiquitylation, along with some surprising deviations from the canonical theme. The lessons learned from the in-depth analyses of these host-pathogen interactions provide a fresh perspective on an ancient post-translational modification that we thought was well understood.This article is part of a Minifocus on Ubiquitin Regulation and Function. For further reading, please see related articles: 'Mechanisms of regulation and diversification of deubiquitylating enzyme function' by Pawel Leznicki and Yogesh Kulathu ( J. Cell Sci. 130 , 1997-2006). 'Cell scientist to watch - Mads Gyrd-Hansen' ( J. Cell Sci. 130 , 1981-1983). © 2017. Published by The Company of Biologists Ltd.
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Protein Intake and Breast Cancer Survival in the Nurses' Health Study.
Holmes, Michelle D; Wang, Jun; Hankinson, Susan E; Tamimi, Rulla M; Chen, Wendy E
2017-01-20
Purpose Greater protein intake has been associated with better breast cancer survival in several prospective studies, including among 1,982 women in the Nurses' Health Study. We proposed to extend this previous finding. We hypothesized that protein, essential amino acid, branched-chain amino acid, and leucine intakes are associated with improved survival and that these associations are stronger in tumors expressing insulin receptor (IR). Patients and Methods We included 6,348 women diagnosed with stage I to III breast cancer between 1976 and 2004. There were 1,046 distant recurrences. Relative risks (RRs) and 95% CIs were calculated according to quintiles of updated postdiagnostic diet using adjusted Cox proportional hazards models based on follow-up until 2010. Results There was an inverse association between energy-adjusted protein intake and recurrence. Multivariable RRs for increasing quintiles of intake compared with the lowest were 0.95 (95% CI, 0.79 to 1.15), 0.92 (95% CI, 0.76 to 1.11), 0.75 (95% CI, 0.61 to 0.91), and 0.84 (95% CI, 0.69 to 1.03; trend P = .02). For animal protein intake, the RRs were 0.88 (95% CI, 0.73 to 1.06), 0.85 (95% CI, 0.70 to 1.02), 0.75 (95% CI, 0.62 to 0.92), and 0.78 (95% CI, 0.63 to 0.95; trend P = .003). Neither essential amino acids, branched-chain amino acids, nor any individual amino acid stood out as being the source of the association. The association also did not differ by IR status. There was no clear association with any protein-containing foods. Conclusion We found a modest survival advantage with higher intake of protein, regardless of IR status. There was no clear mechanism for this association, although it is consistent with prior studies. Our data suggest that there is likely no advantage for women with a history of breast cancer in restricting protein intake or protein-containing foods.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, Youngrok
2013-05-15
Heterogeneity exists on a data set when samples from di erent classes are merged into the data set. Finite mixture models can be used to represent a survival time distribution on heterogeneous patient group by the proportions of each class and by the survival time distribution within each class as well. The heterogeneous data set cannot be explicitly decomposed to homogeneous subgroups unless all the samples are precisely labeled by their origin classes; such impossibility of decomposition is a barrier to overcome for estimating nite mixture models. The expectation-maximization (EM) algorithm has been used to obtain maximum likelihood estimates ofmore » nite mixture models by soft-decomposition of heterogeneous samples without labels for a subset or the entire set of data. In medical surveillance databases we can find partially labeled data, that is, while not completely unlabeled there is only imprecise information about class values. In this study we propose new EM algorithms that take advantages of using such partial labels, and thus incorporate more information than traditional EM algorithms. We particularly propose four variants of the EM algorithm named EM-OCML, EM-PCML, EM-HCML and EM-CPCML, each of which assumes a specific mechanism of missing class values. We conducted a simulation study on exponential survival trees with five classes and showed that the advantages of incorporating substantial amount of partially labeled data can be highly signi cant. We also showed model selection based on AIC values fairly works to select the best proposed algorithm on each specific data set. A case study on a real-world data set of gastric cancer provided by Surveillance, Epidemiology and End Results (SEER) program showed a superiority of EM-CPCML to not only the other proposed EM algorithms but also conventional supervised, unsupervised and semi-supervised learning algorithms.« less
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Castro, Jorge
2006-12-01
The date of emergence may have far-reaching implications for seedling performance. Seedlings emerging early in the growing season often have a greater rate of survival or grow better if early emergence provides advantages with respect to an environmental cue. As a result, the benefits of early emergence may be lost if the environmental stress creating the differences among cohorts disappears. The experimental manipulation under field conditions of the factors that constitute the main sources of stress for seedling establishment is thus a straightforward method to evaluate the impact of date of emergence on seedling establishment under realistic conditions. Two field experiments were performed to analyse the effect of emergence date on survival and first-year growth of Scots pine seedlings in natural mountain forests in south-east Spain. Two main environmental factors that determine seedling success in these mountains were considered: (1) microhabitat type (monitoring the effect of date of emergence in the three most common microhabitats where seedlings recruit); (2) summer drought (monitored by an irrigation treatment with control and watered sampling points). Overall, early emergence resulted in a higher probability of survival and better growth in the two experiments and across microhabitats. However, the reduction in summer drought did not diminish the differences observed among cohorts: all cohorts increased their survival and growth, but early cohorts still had a clear advantage. Date of emergence determines establishment success of Pinus sylvestris seedlings, even if cohorts are separated by only a few days, irrespective of the intensity of summer drought. The experimental design, covering a gradient of light intensity and soil moisture that simulates conditions of the regeneration niche of Scots pine across its geographical range, allows the results to be extrapolated to other areas of the species. Date of emergence is thus likely to have a large impact on the demography of Scots pine across its geographical range.
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Yang, Hao; Feng, Cong; Cai, Bo-Ning; Yang, Jun; Liu, Hai-Xia; Ma, Lin
2017-02-01
The aim of this study was to evaluate the effectiveness and toxicities of three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) in patients with cervical esophageal cancer. Specifically, we asked whether technological advances conferred an advantage with respect to the clinical curative effect. Seventy-eight patients with cervical esophageal cancer treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2007 and 2014 were enrolled in the study: 26 received 3DCRT, 30 were treated with IMRT, and 22 underwent VMAT. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze overall survival (OS) and failure-free survival (FFS). Treatment-related toxicity was also assessed. For all patients, the 2-year OS and FFS rates were 56.2 and 53.9%, respectively. The 2-year OS for the 3DCRT, IMRT, and VMAT groups was 53.6, 55.6, and 60.6%, respectively (P = 0.965). The corresponding 2-year FFS rates were 49.5, 56.7, and 60.1% (P = 0.998). A univariate analysis of the complete response to treatment showed an advantage of treatment modality with respect to OS (P < 0.001). The development of acute hematologic toxicity was not significantly different among the three groups. The survival rates of patients treated with IMRT and VMAT were comparable to the survival of patients administered 3DCRT, while lower lung mean dose, V20, maximum dose of brachial plexus and spinal cord. Grade 1 radiation pneumonitis occurred significantly less in patients treated with IMRT and VMAT than with 3DCRT (P = 0.011). A complete response was the most important prognostic factor of the patients with cervical esophageal cancer. © 2016 International Society for Diseases of the Esophagus.
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Linton, Anthony; Soeberg, Matthew; Broome, Richard; Kao, Steven; van Zandwijk, Nico
2017-07-01
Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM. We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed. We identified 910 patients (67% residing in major cities; 92% <50 km from MDT). Median overall survival was 10.0 months. On multivariate analysis, age >70 (hazard ratio (HR) = 1.39), male gender (HR =1.36), non-epithelioid histological subtype (HR = 2.18) and IRSAD status by decreasing quintile (HR = 1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6 months vs 8.8 months; P = 0.162) or within 50 km of MDT (10.3 months vs 7.8 months; P = 0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P = 0.001). This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW. © 2017 Asian Pacific Society of Respirology.
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Santana-Davila, Rafael; Devisetty, Kiran; Szabo, Aniko; Sparapani, Rodney; Arce-Lara, Carlos; Gore, Elizabeth M.; Moran, Amy; Williams, Christina D.; Kelley, Michael J.; Whittle, Jeffrey
2015-01-01
Purpose The optimal chemotherapy regimen to use with radiotherapy in stage III non–small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP). Methods We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data. Results A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). In an instrumental variables analysis, there was no survival advantage for patients treated in centers where EP was used more than 50% of the time as compared with centers where EP was used in less than 10% of the patients (HR, 1.07; 95% CI, 0.90 to 1.26). Patients treated with EP, compared with patients treated with CP, had more hospitalizations (2.4 v 1.7 hospitalizations, respectively; P < .001), outpatient visits (17.6 v 12.6 visits, respectively; P < .001), infectious complications (47.3% v 39.4%, respectively; P = .0022), acute kidney disease/dehydration (30.5% v 21.2%, respectively; P < .001), and mucositis/esophagitis (18.6% v 14.4%, respectively; P = .0246). Conclusion After accounting for prognostic variables, patients treated with EP versus CP had similar overall survival, but EP was associated with increased morbidity. PMID:25422491
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"The Gaze Heuristic:" Biography of an Adaptively Rational Decision Process.
Hamlin, Robert P
2017-04-01
This article is a case study that describes the natural and human history of the gaze heuristic. The gaze heuristic is an interception heuristic that utilizes a single input (deviation from a constant angle of approach) repeatedly as a task is performed. Its architecture, advantages, and limitations are described in detail. A history of the gaze heuristic is then presented. In natural history, the gaze heuristic is the only known technique used by predators to intercept prey. In human history the gaze heuristic was discovered accidentally by Royal Air Force (RAF) fighter command just prior to World War II. As it was never discovered by the Luftwaffe, the technique conferred a decisive advantage upon the RAF throughout the war. After the end of the war in America, German technology was combined with the British heuristic to create the Sidewinder AIM9 missile, the most successful autonomous weapon ever built. There are no plans to withdraw it or replace its guiding gaze heuristic. The case study demonstrates that the gaze heuristic is a specific heuristic type that takes a single best input at the best time (take the best 2 ). Its use is an adaptively rational response to specific, rapidly evolving decision environments that has allowed those animals/humans/machines who use it to survive, prosper, and multiply relative to those who do not. Copyright © 2017 Cognitive Science Society, Inc.
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Reducing the cost of health care capital.
Silberman, R
1984-08-01
Although one may ask four financial experts their opinion on the future of the hospital capital market and receive five answers, the blatant need for financial strategic planning is evident. Clearly, the hospital or system with sound financial management will be better positioned to gain and/or maintain an edge in the competitive environment of the health care sector. The trends of the future include hospitals attempting to: Maximize the efficiency of invested capital. Use the expertise of Board members. Use alternative capital sources. Maximize rate of return on investments. Increase productivity. Adjust to changes in reimbursements. Restructure to use optimal financing for capital needs, i.e., using short-term to build up debt capacity if long-term financing is needed in the future. Take advantage of arbitrage (obtain capital and reinvest it until the funds are needed). Delay actual underwriting until funds are to be used. Better management of accounts receivable and accounts payable to avoid short-term financing for cash flow shortfalls. Use for-profit subsidiaries to obtain venture capital by issuing stock. Use product line management. Use leasing to obtain balance sheet advantages. These trends indicate a need for hospital executives to possess a thorough understanding of the capital formation process. In essence, the bottom line is that the short-term viability and long-term survival of a health care organization will greatly depend on the financial expertise of its decision-makers.
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Silicon web process development
NASA Technical Reports Server (NTRS)
Duncan, C. S.; Seidensticker, R. G.; Mchugh, J. P.; Skutch, M. E.; Driggers, J. M.; Hopkins, R. H.
1981-01-01
The silicon web process takes advantage of natural crystallographic stabilizing forces to grow long, thin single crystal ribbons directly from liquid silicon. The ribbon, or web, is formed by the solidification of a liquid film supported by surface tension between two silicon filaments, called dendrites, which border the edges of the growing strip. The ribbon can be propagated indefinitely by replenishing the liquid silicon as it is transformed to crystal. The dendritic web process has several advantages for achieving low cost, high efficiency solar cells. These advantages are discussed.
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Strasberg, Steven M; Gao, Feng; Sanford, Dominic; Linehan, David C; Hawkins, William G; Fields, Ryan; Carpenter, Danielle H; Brunt, Elizabeth M; Phillips, Carolyn
2014-01-01
Objectives: Jaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours. Methods: Thirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P-value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection. Results: Preoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five-year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage. Conclusions: Preoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect. PMID:23600768
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Boronat-García, Alejandra; Palomero-Rivero, Marcela; Guerra-Crespo, Magdalena; Millán-Aldaco, Diana; Drucker-Colín, René
2016-01-01
Cell replacement therapy in Parkinson’s disease (PD) aims at re-establishing dopamine neurotransmission in the striatum by grafting dopamine-releasing cells. Chromaffin cell (CC) grafts produce some transitory improvements of functional motor deficits in PD animal models, and have the advantage of allowing autologous transplantation. However, CC grafts have exhibited low survival, poor functional effects and dopamine release compared to other cell types. Recently, chromaffin progenitor-like cells were isolated from bovine and human adult adrenal medulla. Under low-attachment conditions, these cells aggregate and grow as spheres, named chromospheres. Here, we found that bovine-derived chromosphere-cell cultures exhibit a greater fraction of cells with a dopaminergic phenotype and higher dopamine release than CC. Chromospheres grafted in a rat model of PD survived in 57% of the total grafted animals. Behavioral tests showed that surviving chromosphere cells induce a reduction in motor alterations for at least 3 months after grafting. Finally, we found that compared with CC, chromosphere grafts survive more and produce more robust and consistent motor improvements. However, further experiments would be necessary to determine whether the functional benefits induced by chromosphere grafts can be improved, and also to elucidate the mechanisms underlying the functional effects of the grafts. PMID:27525967
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Survival of Norway spruce remains higher in mixed stands under a dryer and warmer climate.
Neuner, Susanne; Albrecht, Axel; Cullmann, Dominik; Engels, Friedrich; Griess, Verena C; Hahn, W Andreas; Hanewinkel, Marc; Härtl, Fabian; Kölling, Christian; Staupendahl, Kai; Knoke, Thomas
2015-02-01
Shifts in tree species distributions caused by climatic change are expected to cause severe losses in the economic value of European forestland. However, this projection disregards potential adaptation options such as tree species conversion, shorter production periods, or establishment of mixed species forests. The effect of tree species mixture has, as yet, not been quantitatively investigated for its potential to mitigate future increases in production risks. For the first time, we use survival time analysis to assess the effects of climate, species mixture and soil condition on survival probabilities for Norway spruce and European beech. Accelerated Failure Time (AFT) models based on an extensive dataset of almost 65,000 trees from the European Forest Damage Survey (FDS)--part of the European-wide Level I monitoring network--predicted a 24% decrease in survival probability for Norway spruce in pure stands at age 120 when unfavorable changes in climate conditions were assumed. Increasing species admixture greatly reduced the negative effects of unfavorable climate conditions, resulting in a decline in survival probabilities of only 7%. We conclude that future studies of forest management under climate change as well as forest policy measures need to take this, as yet unconsidered, strongly advantageous effect of tree species mixture into account. © 2014 John Wiley & Sons Ltd.
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Treasure, Tom; Monson, Kathryn; Fiorentino, Francesca; Russell, Christopher
2014-01-01
Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit? Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative. Setting 58 hospitals in the UK. Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms. Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered. Primary outcome measure Survival. Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival. Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years. Trial registration number ISRCTN76694943. PMID:24823671
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Abdul-Rahman, H; Berawi, M A
Knowledge Management (KM) addresses the critical issues of organizational adoption, survival and competence in the face of an increasingly changing environment. KM embodies organizational processes that seek a synergistic combination of the data and information processing capabilities of information and communication technologies (ICT), and the creative and innovative capacity of human beings to improve ICT In that role, knowledge management will improve quality management and avoid or minimize losses and weakness that usually come from poor performance as well as increase the competitive level of the company and its ability to survive in the global marketplace. To achieve quality, all parties including the clients, company consultants, contractors, entrepreneurs, suppliers, and the governing bodies (i.e., all involved stake-holders) need to collaborate and commit to achieving quality. The design based organizations in major business and construction companies have to be quality driven to support healthy growth in today's competitive market. In the march towards vision 2020 and globalization (i.e., the one world community) of many companies, their design based organizations need to have superior quality management and knowledge management to anticipate changes. The implementation of a quality system such as the ISO 9000 Standards, Total Quality Management, or Quality Function Deployment (QFD) focuses the company's resources towards achieving faster and better results in the global market with less cost. To anticipate the needs of the marketplace and clients as the world and technology change, a new system, which we call Power Quality System (PQS), has been designed. PQS is a combination of information and communication technologies (ICT) and the creative and innovative capacity of human beings to meet the challenges of the new world business and to develop high quality products.
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Fuchs, Claudia; Trazzi, Stefania; Torricella, Roberta; Viggiano, Rocchina; De Franceschi, Marianna; Amendola, Elena; Gross, Cornelius; Calzà, Laura; Bartesaghi, Renata; Ciani, Elisabetta
2014-10-01
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in a neurodevelopmental disorder characterized by early-onset intractable seizures, severe developmental delay, intellectual disability, and Rett's syndrome-like features. Since the physiological functions of CDKL5 still need to be elucidated, in the current study we took advantage of a new Cdkl5 knockout (KO) mouse model in order to shed light on the role of this gene in brain development. We mainly focused on the hippocampal dentate gyrus, a region that largely develops postnatally and plays a key role in learning and memory. Looking at the process of neurogenesis, we found a higher proliferation rate of neural precursors in Cdkl5 KO mice in comparison with wild type mice. However, there was an increase in apoptotic cell death of postmitotic granule neuron precursors, with a reduction in total number of granule cells. Looking at dendritic development, we found that in Cdkl5 KO mice the newly-generated granule cells exhibited a severe dendritic hypotrophy. In parallel, these neurodevelopmental defects were associated with impairment of hippocampus-dependent memory. Looking at the mechanisms whereby CDKL5 exerts its functions, we identified a central role of the AKT/GSK-3β signaling pathway. Overall our findings highlight a critical role of CDKL5 in the fundamental processes of brain development, namely neuronal precursor proliferation, survival and maturation. This evidence lays the basis for a better understanding of the neurological phenotype in patients carrying mutations in the CDKL5 gene. Copyright © 2014. Published by Elsevier Inc.
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Spatial structure increases the waiting time for cancer
Martens, Erik A.; Kostadinov, Rumen; Maley, Carlo C.; Hallatschek, Oskar
2012-01-01
Cancer results from a sequence of genetic and epigenetic changes which lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells, and thus, to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been experiencing increasing interest in recent years. Many efforts have been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones, decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help to predict the onset of cancers with pronounced spatial structure and to interpret spatially-sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer, and possibly other cancers where spatial structure matters. PMID:22707911
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Spatial structure increases the waiting time for cancer
NASA Astrophysics Data System (ADS)
Martens, Erik A.; Kostadinov, Rumen; Maley, Carlo C.; Hallatschek, Oskar
2011-11-01
Cancer results from a sequence of genetic and epigenetic changes that lead to a variety of abnormal phenotypes including increased proliferation and survival of somatic cells and thus to a selective advantage of pre-cancerous cells. The notion of cancer progression as an evolutionary process has been attracting increasing interest in recent years. A great deal of effort has been made to better understand and predict the progression to cancer using mathematical models; these mostly consider the evolution of a well-mixed cell population, even though pre-cancerous cells often evolve in highly structured epithelial tissues. In this study, we propose a novel model of cancer progression that considers a spatially structured cell population where clones expand via adaptive waves. This model is used to assess two different paradigms of asexual evolution that have been suggested to delineate the process of cancer progression. The standard scenario of periodic selection assumes that driver mutations are accumulated strictly sequentially over time. However, when the mutation supply is sufficiently high, clones may arise simultaneously on distinct genetic backgrounds, and clonal adaptation waves interfere with each other. We find that in the presence of clonal interference, spatial structure increases the waiting time for cancer, leads to a patchwork structure of non-uniformly sized clones and decreases the survival probability of virtually neutral (passenger) mutations, and that genetic distance begins to increase over a characteristic length scale Lc. These characteristic features of clonal interference may help us to predict the onset of cancers with pronounced spatial structure and to interpret spatially sampled genetic data obtained from biopsies. Our estimates suggest that clonal interference likely occurs in the progression of colon cancer and possibly other cancers where spatial structure matters.
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Hedlund, Mathilde; Ronne-Engstrom, Elisabeth; Ekselius, Lisa; Carlsson, Marianne
2008-02-01
The aims of this study were: (1) to describe nurses' views of the physical and supportive needs of patients who have suffered a subarachnoid haemorrhage (SAH), (2) to describe nurses' views of changes in social circumstances and (3) changes in the mental condition of patients after SAH. As patients with SAH are generally younger and predominantly female compared with other stroke groups they may have different needs of nursing support to facilitate adaptation. Caring for persons surviving stroke involves advanced nursing skills such as monitoring neurological functions in neurointensive care and providing physical care during rehabilitation. Explorative descriptive design. Semi-structured interviews were performed with 18 nurses in neurointensive and rehabilitation care. A qualitative latent content analysis was conducted. Nurses viewed patients' need for support as a process ranging from highly advanced technological care to 'softer' more emotional care. However, shortages in the communication between neurointesive and rehabilitation nurses regarding this support were acknowledged. Changes in social circumstances and mental conditions were viewed both as obstacles and advantages regarding return to everyday life. Nurses also viewed that the characteristics of the group with SAH was not particularly different from the group with other types of stroke. Support to patients with SAH is viewed as a process carried out by nurses at neurointensive care units and rehabilitation units. Shortages in communication, regarding this support, were acknowledged. Obstacles and advantages with respect to returning to everyday life could apply to any stroke group, which could make it more difficult for nurses to detect the specific needs of patients with SAH. The communication between neurointensive nurses and rehabilitation nurses regarding support to patients with SAH is not satisfactory. Occasionally the specific needs of patients with SAH are not recognized.
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Schmutz, Joel A.; Thomson, David L.; Cooch, Evan G.; Conroy, Michael J.
2009-01-01
Stochastic variation in survival rates is expected to decrease long-term population growth rates. This expectation influences both life-history theory and the conservation of species. From this expectation, Pfister (1998) developed the important life-history prediction that natural selection will have minimized variability in those elements of the annual life cycle (such as adult survival rate) with high sensitivity. This prediction has not been rigorously evaluated for bird populations, in part due to statistical difficulties related to variance estimation. I here overcome these difficulties, and in an analysis of 62 populations, I confirm her prediction by showing a negative relationship between the proportional sensitivity (elasticity) of adult survival and the proportional variance (CV) of adult survival. However, several species deviated significantly from this expectation, with more process variance in survival than predicted. For instance, projecting the magnitude of process variance in annual survival for American redstarts (Setophaga ruticilla) for 25 years resulted in a 44% decline in abundance without assuming any change in mean survival rate. For most of these species with high process variance, recent changes in harvest, habitats, or changes in climate patterns are the likely sources of environmental variability causing this variability in survival. Because of climate change, environmental variability is increasing on regional and global scales, which is expected to increase stochasticity in vital rates of species. Increased stochasticity in survival will depress population growth rates, and this result will magnify the conservation challenges we face.
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ERIC Educational Resources Information Center
Kaun, Karla R.; Hendel, Thomas; Gerber, Bertram; Sokolowski, Marla B.
2007-01-01
Animals must be able to find and evaluate food to ensure survival. The ability to associate a cue with the presence of food is advantageous because it allows an animal to quickly identify a situation associated with a good, bad, or even harmful food. Identifying genes underlying these natural learned responses is essential to understanding this…
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Aircraft Survivability. Summer 2011
2011-01-01
airbag systems and the DEA, offer unique advantages for improving rotorcraft crashworthiness, either as stand-alone systems or in conjunction with a...deployment methods were studied with the goal of achieving equivalent deployment times as external airbag systems. Since 2006, experimental evaluation of...Y., Gansman B., and Bradney C., “Rotorcraft External Airbag Protection System,” Proceedings of the AHS 62nd Annual Forum, Phoenix AZ, May 2006. 5
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Barrows, F.T.; Lellis, W.A.
2006-01-01
Two methods were developed for the production of larval fish diets. The first method, microextrusion marumerization (MEM), has been tested in laboratory feeding trials for many years and produces particles that are palatable and water stable. The second method, particle-assisted rotational agglomeration (PARA), produced diets that have lower density than diets produced by MEM. Each method was used to produce diets in the 250- to 400- and 400- to 700-??m range and compared with a reference diet (Fry Feed Kyowa* [FFK]) for feeding larval walleye in two experiments. The effect of substituting 4% of the fish meal with freeze-dried artemia fines was also investigated. In the first experiment, 30-d survival was greater (P < 0.05) for fish fed a diet produced by PARA without Artemia (49.1.0%) than for fish fed the same diet produced by MEM (27.6%). The addition of Artemia to a diet produced by MEM did not increase survival of larval walleye. Fish fed the reference diet had 24.4% survival. In the second experiment, there was an effect of both processing method and Artemia supplementation, and an interaction of these effects, on survival. Fish fed a diet produced by PARA without Artemia supplementation had 48.4% survival, and fish fed the same diet produced by MEM had only 19.6% survival. Inclusion of 4% freeze-dried Artemia improved (P < 0.04) survival of fish fed MEM particles but not those fed PARA particles. Fish fed FFK had greater weight gain than fish fed other diets in both experiments. Data indicate that the PARA method of diet processing produces smaller, lower density particles than the MEM process and that diets produced by the PARA process support higher survival of larval walleye with low capital and operating costs. ?? Copyright by the World Aquaculture Society 2006.
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Leite, F C B; Leite, D V da R; Pereira, L F; de Barros Pita, W; de Morais, M A
2016-09-01
Dekkera bruxellensis hit the spotlight in the past decade mostly due to its rather high ability to adapt to several different fermentation processes. This yeast relies on different genetic and physiological aspects to achieve and preserve its high industrial fitness and some of these traits are shared with Saccharomyces cerevisiae. We have previously described that D. bruxellensis is unable to make use of accumulating trehalose as a strategy for cell adaptation and survival in the industrial scenario, as opposed to S. cerevisiae. Since trehalose is often involved in mechanisms related to cell protection, we aimed to investigate both cause and effect of the absence of this metabolite in the cell adaptive capacity in the industrial environment. Our results indicate that the major cause for the nonaccumulation of trehalose is the high constitutive activity of neutral trehalase. Therefore, the rate of trehalose degradation could be higher than its rate of synthesis, preventing accumulation. Altogether, our data elucidate the mechanisms involved in the lack of trehalose accumulation in D. bruxellensis as well as evaluates the implications of this feature. Dekkera bruxellensis can successfully take advantage of its peculiar physiological and genetic traits in order to adapt and survive in fermentation processes. So far, tolerance to stress has been credited to trehalose synthesis. The data presented in this work provided information on the underlying mechanism that prevents trehalose accumulation and corroborated the recent information that trehalose itself is not implicated in yeast stress tolerance. Second, it showed that D. bruxellensis responds differently to Saccharomyces cerevisiae to excess of sugar, which may explain its preference for respiration (oxidative metabolism) over fermentation (reductive metabolism) even at limited oxygen supply. These findings help to understand the drop on ethanol production in processes overtaken by this yeast. © 2016 The Society for Applied Microbiology.
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Gene duplications in prokaryotes can be associated with environmental adaptation
2010-01-01
Background Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes. Results Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis. Conclusions Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive advantage to the organism. Paralogs and singletons dominate different categories of functional classification, where paralogs in particular seem to be associated with processes involving interaction with the environment. PMID:20961426
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Gene duplications in prokaryotes can be associated with environmental adaptation.
Bratlie, Marit S; Johansen, Jostein; Sherman, Brad T; Huang, Da Wei; Lempicki, Richard A; Drabløs, Finn
2010-10-20
Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes. Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis. Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive advantage to the organism. Paralogs and singletons dominate different categories of functional classification, where paralogs in particular seem to be associated with processes involving interaction with the environment.
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Modeling the survival responses of a multi-component biofilm to environmental stress
NASA Astrophysics Data System (ADS)
Carles Brangarí, Albert; Manzoni, Stefano; Sanchez-Vila, Xavier; Fernàndez-Garcia, Daniel
2017-04-01
Biofilms are consortia of microorganisms embedded in self-produced matrices of biopolymers. The survival of such communities depends on their capacity to improve the environmental conditions of their habitat by mitigating, or even benefitting from some adverse external factors. The mechanisms by which the microbial habitat is regulated remain mostly unknown. However, many studies have reported physiological responses to environmental stresses that include the release of extracellular polymeric substances (EPS) and the induction of a dormancy state. A sound understanding of these capacities is required to enhance the knowledge of the microbial dynamics in soils and its potential role in the carbon cycle, with significant implications for the degradation of contaminants and the emission of greenhouse gases, among others. We present a numerical analysis of the dynamics of soil microbes and their responses to environmental stresses. The conceptual model considers a multi-component heterotrophic biofilm made up of active cells, dormant cells, EPS, and extracellular enzymes. Biofilm distribution and properties are defined at the pore-scale and used to determine nutrient availability and water saturation via feedbacks of biofilm on soil hydraulic properties. The pore space micro-habitat is modeled as a simplified pore-network of cylindrical tubes in which biofilms proliferate. Microbial compartments and most of the carbon fluxes are defined at the bulk level. Microbial processes include the synthesis, decay and detachment of biomass, the activation/deactivation of cells, and the release and reutilization of EPS. Results suggest that the release of EPS and the capacity to enter a dormant state offer clear evolutionary advantages in scenarios characterized by environmental stress. On the contrary, when the conditions are favorable, the diversion of carbon into the production of the aforementioned survival mechanisms does not confer any additional benefit and the population of active cells decline. The proposed model (including complex relations between active biomass and biofilm) has been proved useful to capture the most relevant processes involved in biofilm proliferation and its adaptation to environmental conditions. These aspects are largely neglected in biogeochemical models, but could be relevant in soils where strong feedbacks of microbial activity on hydraulic properties emerge.
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NASA Astrophysics Data System (ADS)
Dagan, Shai; Hua, Yimin; Boday, Dylan J.; Somogyi, Arpad; Wysocki, Ronald J.; Wysocki, Vicki H.
2009-06-01
The use of silicon nanoparticles for laser desorption/ionization (LDI) is a new appealing matrix-less approach for the selective and sensitive mass spectrometry of small molecules in MALDI instruments. Chemically modified silicon nanoparticles (30 nm) were previously found to require very low laser fluence in order to induce efficient LDI, which raised the question of internal energy deposition processes in that system. Here we report a comparative study of internal energy deposition from silicon nanoparticles to previously explored benzylpyridinium (BP) model compounds during LDI experiments. The internal energy deposition in silicon nanoparticle-assisted laser desorption/ionization (SPALDI) with different fluorinated linear chain modifiers (decyl, hexyl and propyl) was compared to LDI from untreated silicon nanoparticles and from the organic matrix, [alpha]-cyano-4-hydroxycinnamic acid (CHCA). The energy deposition to internal vibrational modes was evaluated by molecular ion survival curves and indicated that the ions produced by SPALDI have an internal energy threshold of 2.8-3.7 eV. This is slightly lower than the internal energy induced using the organic CHCA matrix, with similar molecular survival curves as previously reported for LDI off silicon nanowires. However, the internal energy associated with desorption/ionization from the silicon nanoparticles is significantly lower than that reported for desorption/ionization on silicon (DIOS). The measured survival yields in SPALDI gradually decrease with increasing laser fluence, contrary to reported results for silicon nanowires. The effect of modification of the silicon particle surface with semifluorinated linear chain silanes, including fluorinated decyl (C10), fluorinated hexyl (C6) and fluorinated propyl (C3) was explored too. The internal energy deposited increased with a decrease in the length of the modifier alkyl chain. Unmodified silicon particles exhibited the highest analyte internal energy deposition. These findings may suggest a role of the modifier as a moderator in the energy dissipation and relaxation process. The relatively low internal energy content of SPALDI-produced ions indicates that this is a "soft" desorption technique, with potential advantages in the analysis of labile compounds.
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When semantics aids phonology: A processing advantage for iconic word forms in aphasia.
Meteyard, Lotte; Stoppard, Emily; Snudden, Dee; Cappa, Stefano F; Vigliocco, Gabriella
2015-09-01
Iconicity is the non-arbitrary relation between properties of a phonological form and semantic content (e.g. "moo", "splash"). It is a common feature of both spoken and signed languages, and recent evidence shows that iconic forms confer an advantage during word learning. We explored whether iconic forms conferred a processing advantage for 13 individuals with aphasia following left-hemisphere stroke. Iconic and control words were compared in four different tasks: repetition, reading aloud, auditory lexical decision and visual lexical decision. An advantage for iconic words was seen for some individuals in all tasks, with consistent group effects emerging in reading aloud and auditory lexical decision. Both these tasks rely on mapping between semantics and phonology. We conclude that iconicity aids spoken word processing for individuals with aphasia. This advantage is due to a stronger connection between semantic information and phonological forms. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Peters, Brian M.; Luna-Tapia, Arturo; Tournu, Hélène; Rybak, Jeffrey M.; Rogers, P. David
2017-01-01
ABSTRACT We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro, it does not seem to affect azole susceptibility in vivo. PMID:28348159
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Peters, Brian M; Luna-Tapia, Arturo; Tournu, Hélène; Rybak, Jeffrey M; Rogers, P David; Palmer, Glen E
2017-06-01
We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21 Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro , it does not seem to affect azole susceptibility in vivo . Copyright © 2017 American Society for Microbiology.
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High-Fat and Ketogenic Diets in Amyotrophic Lateral Sclerosis
Paganoni, Sabrina; Wills, Anne-Marie
2015-01-01
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials. PMID:23666040
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Transients control in Raman fiber amplifiers
NASA Astrophysics Data System (ADS)
Freitas, Marcio; Givigi, Sidney N., Jr.; Klein, Jackson; Calmon, Luiz C.; de Almeida, Ailson R.
2004-11-01
Raman fiber amplifiers (RFA) are being used in optical transmission communication systems in the recent years due to their advantages in comparison to erbium-doped fiber amplifiers (EDFA). Recently the analysis of RFAs dynamic response and transients control has become important in order to predict the system response to add/drop of channels or cable cuts in optical systems, and avoid impairments caused by the power transients. Fast signal power transients in the surviving channels are caused by the cross-gain saturation effect in RFA and the slope of the gain saturation characteristics determines the steady-state surviving channel power excursion. We are presenting the modeling and analysis of power transients and its control using a pump control method for a single and multi-pump scheme.
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Relative yield of two transferrin phenotypes in coho salmon
McIntyre, John D.; Johnson, A. Kenneth
1977-01-01
Experimental groups of coho salmon (Oncorhynchus kisutch) of transferring types AA and AC were compared to determine relative growth and survival before release, yields from the fishery, and returns of fish to the hatchery as 2- and 3-yr-olds. In the hatchery, growth was faster and survival higher in the AA than in the AC types. However, yields of AA and AC types were equal, although the yield of AC types as 3-yr-olds was greater than that of AA types because more of the AA males matured in 2 years. We concluded that it would be futile to attempt to increase the yield of coho salmon by maximizing the frequency of biochemical phenotypes that display only a temporary advantage over other types.
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Robotic surgery for lung resections—total port approach: advantages and disadvantages
Ramadan, Omar I.; Cerfolio, Robert J.
2017-01-01
Minimally invasive thoracic surgery, when compared with open thoracotomy, has been shown to have improved perioperative outcomes as well as comparable long-term survival. Robotic surgery represents a powerful advancement of minimally invasive surgery, with vastly improved visualization and instrument maneuverability, and is increasingly popular for thoracic surgery. However, there remains debate over the best robotic approaches for lung resection, with several different techniques evidenced and described in the literature. We delineate our method for total port approach with four robotic arms and discuss how its advantages outweigh its disadvantages. We conclude that it is preferred to other robotic approaches, such as the robotic assisted approach, due to its enhanced visualization, improved instrument range of motion, and reduced potential for injury. PMID:29078585
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Robotic surgery for lung resections-total port approach: advantages and disadvantages.
Ramadan, Omar I; Wei, Benjamin; Cerfolio, Robert J
2017-01-01
Minimally invasive thoracic surgery, when compared with open thoracotomy, has been shown to have improved perioperative outcomes as well as comparable long-term survival. Robotic surgery represents a powerful advancement of minimally invasive surgery, with vastly improved visualization and instrument maneuverability, and is increasingly popular for thoracic surgery. However, there remains debate over the best robotic approaches for lung resection, with several different techniques evidenced and described in the literature. We delineate our method for total port approach with four robotic arms and discuss how its advantages outweigh its disadvantages. We conclude that it is preferred to other robotic approaches, such as the robotic assisted approach, due to its enhanced visualization, improved instrument range of motion, and reduced potential for injury.
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Lübke, Katrin T; Pause, Bettina M
2015-02-01
This article is part of a Special Issue "Chemosignals and Reproduction" Across phyla, chemosensory communication is crucial for mediating a variety of social behaviors, which form the basis for ontogenetic and phylogenetic survival. In the present paper, evidence on chemosensory communication in humans, with special reference to reproduction and survival, will be presented. First, the impact of chemosignals on human reproduction will be reviewed. Work will be presented, showing how chemosensory signals are involved in mate choice and partnership formation by communicating attractiveness and facilitating a partner selection, which is of evolutionary advantage, and furthermore providing information about the level of sexual hormones. In addition to direct effects on phylogenetic survival, chemosignals indirectly aid reproductive success by fostering harm protection. Results will be presented, showing that chemosensory communication aids the emotional bond between mother and child, which in turn motivates parental caretaking and protection, leading to infant survival. Moreover, the likelihood of group survival can be increased through the use of stress-related chemosignals. Stress-related chemosignals induce a stress-related physiology in the perceiver, thereby priming a fight-flight-response, which is necessary for an optimum adaption to environmental harm. Finally, effects of sexual orientation on chemosensory communication will be discussed in terms of their putative role in stabilizing social groups, which might indirectly provide harm protection and foster survival. An integrative model of the presented data will be introduced. In conclusion, an outlook, focusing on the involvement of chemosensory communication in human social behavior and illustrating a novel approach to the significance of chemosensory signals in human survival, will be given. Copyright © 2014 Elsevier Inc. All rights reserved.
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Survival predictability of lean and fat mass in men and women undergoing maintenance hemodialysis.
Noori, Nazanin; Kovesdy, Csaba P; Dukkipati, Ramanath; Kim, Youngmee; Duong, Uyen; Bross, Rachelle; Oreopoulos, Antigone; Luna, Amanda; Benner, Debbie; Kopple, Joel D; Kalantar-Zadeh, Kamyar
2010-11-01
Larger body size is associated with greater survival in maintenance hemodialysis (MHD) patients. It is not clear how lean body mass (LBM) and fat mass (FM) compare in their associations with survival across sex in these patients. We examined the hypothesis that higher FM and LBM are associated with greater survival in MHD patents irrespective of sex. In 742 MHD patients, including 31% African Americans with a mean (± SD) age of 54 ± 15 y, we categorized men (n = 391) and women (n = 351) separately into 4 quartiles of near-infrared interactance-measured LBM and FM. Cox proportional hazards models estimated death hazard ratios (HRs) (and 95% CIs), and cubic spline models were used to examine associations with mortality over 5 y (2001-2006). After adjustment for case-mix and inflammatory markers, the highest quartiles of FM and LBM were associated with greater survival in women: HRs of 0.38 (95% CI: 0.20, 0.71) and 0.34 (95% CI: 0.17, 0.67), respectively (reference: first quartile). In men, the highest quartiles of FM and percentage FM (FM%) but not of LBM were associated with greater survival: HRs of 0.51 (95% CI: 0.27, 0.96), 0.45 (95% CI: 0.23, 0.88), and 1.17 (95% CI: 0.60, 2.27), respectively. Cubic spline analyses showed greater survival with higher FM% and higher "FM minus LBM percentiles" in both sexes, whereas a higher LBM was protective in women. In MHD patients, higher FM in both sexes and higher LBM in women appear to be protective. The survival advantage of FM appears to be superior to that of LBM. Clinical trials to examine the outcomes of interventions that modify body composition in MHD patients are indicated.
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Koshy, Matthew; Malik, Renuka; Spiotto, Michael; Mahmood, Usama; Rusthoven, Chad G; Sher, David J
2017-06-01
To determine the effect of radiotherapy (RT) technique on treatment compliance and overall survival (OS) in patients with stage III non-small lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT). This study included patients with stage III NSCLC in the National Cancer Database treated between 2003 and 2011 with definitive CRT to 60-63 Gray (Gy). Radiation treatment interruption (RTI) was defined as a break of ≥4 days. Treatment technique was dichotomized as intensity modulated (IMRT) or non-IMRT techniques. Out of the cohort of 7492, 35% had a RTI and 10% received IMRT. With a median follow-up of surviving patients of 32 months, the median survival for those with non-IMRT vs. IMRT was 18.2 months vs. 20 months (p<0.0001). Median survival for those with and without an RTI≥4 days was 16.1 months vs. 19.8 months (p<0.0001). Use of IMRT predicted for a decreased likelihood of RTI (odds ratio, 0.84, p=0.04). On multivariable analysis for OS, IMRT had a HR of 0.89 (95% CI: 0.80-0.98, p=0.01) and RTI had a HR of 1.2 (95% confidence interval (CI): 1.14-1.27, p=0.001). IMRT was associated with small but significant survival advantage for patients with stage III NSCLC treated with CRT. A RTI led to inferior survival, and both IMRT and RTI were independently associated with OS. Additional research should investigate whether improved tolerability, reduced normal tissue exposure, or superior coverage drives the association between IMRT and improved survival. Copyright © 2017 Elsevier B.V. All rights reserved.
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Shi, Xiao; Zhang, Ting-Ting; Hu, Wei-Ping; Ji, Qing-Hai
2017-04-25
The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187-1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266-1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role.
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Shi, Xiao; Zhang, Ting-ting; Hu, Wei-ping; Ji, Qing-hai
2017-01-01
Background The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Results Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187–1.339, P < 0.001) and OS (HR: 1.328, 95% CI: 1.266–1.392, P < 0.001). Multivariate logistic regression showed married patients were more likely to be diagnosed at earlier stage (P < 0.001) and receive surgery (P < 0.001). Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). Materials and Methods 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Conclusions Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role. PMID:28415710
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Sedinger, J.S.; Chelgren, N.D.
2007-01-01
We examined the relationship between mass late in the first summer and survival and return to the natal breeding colony for 12 cohorts (1986-1997) of female Black Brant (Branta bernicla nigricans). We used Cormack-Jolly-Seber methods and the program MARK to analyze capture-recapture data. Models included two kinds of residuals from regressions of mass on days after peak of hatch when goslings were measured; one based on the entire sample (12 cohorts) and the other based only on individuals in the same cohort. Some models contained date of peak of hatch (a group covariate related to lateness of nesting in that year) and mean cohort residual mass. Finally, models allowed survival to vary among cohorts. The best model of encounter probability included an effect of residual mass on encounter probability and allowed encounter probability to vary among age classes and across years. All competitive models contained an effect of one of the estimates of residual mass; relatively larger goslings survived their first year at higher rates. Goslings in cohorts from later years in the analysis tended to have lower first-year survival, after controlling for residual mass, which reflected the generally smaller mean masses for these cohorts but was potentially also a result of population-density effects additional to those on growth. Variation among cohorts in mean mass accounted for 56% of variation among cohorts in first-year survival. Encounter probabilities, which were correlated with breeding probability, increased with relative mass, which suggests that larger goslings not only survived at higher rates but also bred at higher rates. Although our findings support the well-established linkage between gosling mass and fitness, they suggest that additional environmental factors also influence first-year survival.
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Bourke, Stephen C; Tomlinson, Mark; Williams, Tim L; Bullock, Robert E; Shaw, Pamela J; Gibson, G John
2006-02-01
Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured. NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit. In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.
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Clarke, John R; Ragone, Andrew V; Greenwald, Lloyd
2005-09-01
We conducted a comparison of methods for predicting survival using survival risk ratios (SRRs), including new comparisons based on International Classification of Diseases, Ninth Revision (ICD-9) versus Abbreviated Injury Scale (AIS) six-digit codes. From the Pennsylvania trauma center's registry, all direct trauma admissions were collected through June 22, 1999. Patients with no comorbid medical diagnoses and both ICD-9 and AIS injury codes were used for comparisons based on a single set of data. SRRs for ICD-9 and then for AIS diagnostic codes were each calculated two ways: from the survival rate of patients with each diagnosis and when each diagnosis was an isolated diagnosis. Probabilities of survival for the cohort were calculated using each set of SRRs by the multiplicative ICISS method and, where appropriate, the minimum SRR method. These prediction sets were then internally validated against actual survival by the Hosmer-Lemeshow goodness-of-fit statistic. The 41,364 patients had 1,224 different ICD-9 injury diagnoses in 32,261 combinations and 1,263 corresponding AIS injury diagnoses in 31,755 combinations, ranging from 1 to 27 injuries per patient. All conventional ICD-9-based combinations of SRRs and methods had better Hosmer-Lemeshow goodness-of-fit statistic fits than their AIS-based counterparts. The minimum SRR method produced better calibration than the multiplicative methods, presumably because it did not magnify inaccuracies in the SRRs that might occur with multiplication. Predictions of survival based on anatomic injury alone can be performed using ICD-9 codes, with no advantage from extra coding of AIS diagnoses. Predictions based on the single worst SRR were closer to actual outcomes than those based on multiplying SRRs.
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Inactivation of Salmonella and Listeria in ground chicken breast meat during thermal processing.
Murphy, R Y; Marks, B P; Johnson, E R; Johnson, M G
1999-09-01
Thermal inactivation of six Salmonella spp. and Listeria innocua was evaluated in ground chicken breast and liquid medium. Survival of Salmonella and Listeria was affected by the medium composition. Under the same thermal process condition, significantly more Salmonella and Listeria survived in chicken breast meat than in 0.1% peptone-agar solution. The thermal lethality of six tested Salmonella spp. was additive in chicken meat. Survival of Listeria in chicken meat during thermal processing was not affected by the presence of the six Salmonella spp. Sample size and shape affected the inactivation of Salmonella and Listeria in chicken meat during thermal processing.
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Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis.
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.
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NASA Technical Reports Server (NTRS)
Hopkins, William D.; Washburn, David A.; Rumbaugh, Duane M.
1990-01-01
Visual forms were unilaterally presented using a video-task paradigm to ten humans, chimpanzees, and two rhesus monkeys to determine whether hemispheric advantages existed in the processing of these stimuli. Both accuracy and reaction time served as dependent measures. For the chimpanzees, a significant right hemisphere advantage was found within the first three test sessions. The humans and monkeys failed to show a hemispheric advantage as determined by accuracy scores. Analysis of reaction time data revealed a significant left hemisphere advantage for the monkeys. A visual half-field x block interaction was found for the chimpanzees, with a significant left visual field advantage in block two, whereas a right visual field advantage was found in block four. In the human subjects, a left visual field advantage was found in block three when they used their right hands to respond. The results are discussed in relation to recent reports of hemispheric advantages for nonhuman primates.
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Clinical significance of acquired somatic mutations in aplastic anaemia.
Marsh, J C W; Mufti, G J
2016-08-01
Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.
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Surveillance imaging in mantle cell lymphoma in first remission lacks clinical utility.
Guidot, Daniel M; Switchenko, Jeffrey M; Nastoupil, Loretta J; Koff, Jean L; Blum, Kristie A; Maly, Joseph; Flowers, Christopher R; Cohen, Jonathon B
2018-04-01
Mantle cell lymphoma (MCL) is a heterogeneous disease with high relapse rates. Limited data guide the use of surveillance imaging following treatment. We constructed a retrospective cohort from two academic institutions of patients with MCL who completed first-line therapy and underwent follow-up for relapse, analyzing the effect of surveillance imaging on survival. Of 217 patients, 102 had documented relapse, with 38 (37%) diagnosed by surveillance imaging and 64 (63%) by other methods. Relapse diagnosis by surveillance imaging had no significant advantage in overall survival from diagnosis date (hazard ratio [HR] = 0.80, p = .39) or relapse date (HR = 0.72, p = .22). Of 801 surveillance images, PET/CT had a positive predictive value (PPV) of 24% and number needed-to-scan/treat (NNT) of 51 to detect one relapse, and CT had a PPV of 49% and NNT of 24. For MCL after first-line therapy, relapse detection by surveillance imaging was not associated with improved survival and lacks clinical benefit.
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Huang, Wei; Siemann, Evan; Yang, Xuefang; Wheeler, Gregory S; Ding, Jianqing
2013-09-22
To date, it remains unclear how herbivore-induced changes in plant primary and secondary metabolites impact above-ground and below-ground herbivore interactions. Here, we report effects of above-ground (adult) and below-ground (larval) feeding by Bikasha collaris on nitrogen and secondary chemicals in shoots and roots of Triadica sebifera to explain reciprocal above-ground and below-ground insect interactions. Plants increased root tannins with below-ground herbivory, but above-ground herbivory prevented this increase and larval survival doubled. Above-ground herbivory elevated root nitrogen, probably contributing to increased larval survival. However, plants increased foliar tannins with above-ground herbivory and below-ground herbivory amplified this increase, and adult survival decreased. As either foliar or root tannins increased, foliar flavonoids decreased, suggesting a trade-off between these chemicals. Together, these results show that plant chemicals mediate contrasting effects of conspecific larval and adult insects, whereas insects may take advantage of plant responses to facilitate their offspring performance, which may influence population dynamics.
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Alexander, Greg R; Wingate, Martha S; Bader, Deren; Kogan, Michael D
2008-01-01
We examined trends in birthweight-gestational age distributions and related infant mortality for African American and white women and calculated the estimated excess annual number of African American infant deaths. Live births to US-resident mothers with a maternal race of white or African American were selected from the National Center for Health Statistics' linked live birth-infant death cohort files (1985-1988 and 1995-2000). The racial disparity in infant mortality widened despite an increasing rate of white low-birthweight infants. White preterm infants had relatively greater gains in survival and the white advantage in survival at term increased. Annually, African American women experience approximately 3300 more infant deaths than would be expected. The increasing US racial disparity in infant mortality is largely influenced by changes in birthweight-gestational age-specific mortality, rather than the birthweight-gestational age distribution. Improvement in the survival of white preterm and low-birthweight infants, probably reflecting advances in and changing access to medical technology, contributed appreciably to this trend.
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Mondoñedo, Jarred R; Suki, Béla
2017-02-01
Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.
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Fan, Yun; Bergmann, Andreas
2014-01-01
Although apoptosis is mechanistically well understood, a comprehensive understanding of how cells modulate their susceptibility towards apoptosis in a developing tissue is lacking. Here, we reveal striking dynamics in the apoptotic susceptibilities of different cell types in the Drosophila retina over a period of only 24 hours. Mitotic cells are extremely susceptible to apoptotic signals, while post-mitotic cells have developed several strategies to promote survival. For example, photoreceptor neurons accumulate the inhibitor of apoptosis, Diap1. In unspecified cells, Cullin-3-mediated degradation keeps Diap1 levels low. These cells depend on EGFR signaling for survival. As development proceeds, developmentally older photoreceptors degrade Diap1 resulting in increased apoptosis susceptibility. Finally, R8 photoreceptors have very efficient survival mechanisms independently of EGFR or Diap1. These examples illustrate how complex cellular susceptibility towards apoptosis is regulated in a developing organ. Similar complexities may regulate apoptosis susceptibilities in mammalian development and tumor cells may take advantage of it. PMID:24981611
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Mondoñedo, Jarred R.
2017-01-01
Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. PMID:28182686
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Mazack, Jane E.; Kranzfelder, Petra; Anderson, Alyssa M.; Bouchard, William; Perry, James; Vondracek, Bruce C.; Ferrington, Leonard C.
2014-01-01
Diamesa mendotae Muttkowski, 1915 is a winter-active species common in groundwater-buffered streams of Minnesota and Wisconsin. This species is capable of surviving under snow cover for at least 28 days. Field collections of adult D. mendotae were used to determine survivorship under long-term exposure to controlled sub-freezing conditions. Specimens were placed into a controlled temperature chamber at −5 °C, batches removed at weekly intervals, and subsequently held at 6 °C to determine survivorship and longevity. Our results indicate that overall survivorship is negatively related to treatment duration of sub-freezing treatment, individuals can survive sub-freezing temperatures for at least 70 days, with total longevity of 92 days. Additionally, males had a significantly higher rate of survivorship than females within treatments. Total longevity increased with treatment time, suggesting adult D. mendotae may survive long periods of below-freezing temperatures under natural conditions before mating, which may convey population-level advantages.
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Controlling hormone signaling is a plant and pathogen challenge for growth and survival.
López, Miguel Angel; Bannenberg, Gerard; Castresana, Carmen
2008-08-01
Plants and pathogens have continuously confronted each other during evolution in a battle for growth and survival. New advances in the field have provided fascinating insights into the mechanisms that have co-evolved to gain a competitive advantage in this battle. When plants encounter an invading pathogen, not only responses signaled by defense hormones are activated to restrict pathogen invasion, but also the modulation of additional hormone pathways is required to serve other purposes, which are equally important for plant survival, such as re-allocation of resources, control of cell death, regulation of water stress, and modification of plant architecture. Notably, pathogens can counteract both types of responses as a strategy to enhance virulence. Pathogens regulate production and signaling responses of plant hormones during infection, and also produce phytohormones themselves to modulate plant responses. These results indicate that hormone signaling is a relevant component in plant-pathogen interactions, and that the ability to dictate hormonal directionality is critical to the outcome of an interaction.
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Aging in the colonial chordate, Botryllus schlosseri.
Munday, Roma; Rodriguez, Delany; Di Maio, Alessandro; Kassmer, Susannah; Braden, Brian; Taketa, Daryl A; Langenbacher, Adam; De Tomaso, Anthony
2015-01-30
What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research.
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The prisoner's dilemma as a cancer model.
West, Jeffrey; Hasnain, Zaki; Mason, Jeremy; Newton, Paul K
2016-09-01
Tumor development is an evolutionary process in which a heterogeneous population of cells with different growth capabilities compete for resources in order to gain a proliferative advantage. What are the minimal ingredients needed to recreate some of the emergent features of such a developing complex ecosystem? What is a tumor doing before we can detect it? We outline a mathematical model, driven by a stochastic Moran process, in which cancer cells and healthy cells compete for dominance in the population. Each are assigned payoffs according to a Prisoner's Dilemma evolutionary game where the healthy cells are the cooperators and the cancer cells are the defectors. With point mutational dynamics, heredity, and a fitness landscape controlling birth and death rates, natural selection acts on the cell population and simulated 'cancer-like' features emerge, such as Gompertzian tumor growth driven by heterogeneity, the log-kill law which (linearly) relates therapeutic dose density to the (log) probability of cancer cell survival, and the Norton-Simon hypothesis which (linearly) relates tumor regression rates to tumor growth rates. We highlight the utility, clarity, and power that such models provide, despite (and because of) their simplicity and built-in assumptions.
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de Alteriis, Elisabetta; Cartenì, Fabrizio; Parascandola, Palma; Serpa, Jacinta; Mazzoleni, Stefano
2018-01-01
ABSTRACT The mechanisms behind the Warburg effect in mammalian cells, as well as for the similar Crabtree effect in the yeast Saccharomyces cerevisiae, are still a matter of debate: why do cells shift from the energy-efficient respiration to the energy-inefficient fermentation at high sugar concentration? This review reports on the strong similarities of these phenomena in both cell types, discusses the current ideas, and provides a novel interpretation of their common functional mechanism in a dynamic perspective. This is achieved by analysing another phenomenon, the sugar-induced-cell-death (SICD) occurring in yeast at high sugar concentration, to highlight the link between ATP depletion and cell death. The integration between SICD and the dynamic functioning of the glycolytic process, suggests that the Crabtree/Warburg effect may be interpreted as the avoidance of ATP depletion in those conditions where glucose uptake is higher than the downstream processing capability of the second phase of glycolysis. It follows that the down-regulation of respiration is strategic for cell survival allowing the allocation of more resources to the fermentation pathway, thus maintaining the cell energetic homeostasis. PMID:29509056
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Lipids in host-pathogen interactions: pathogens exploit the complexity of the host cell lipidome.
van der Meer-Janssen, Ynske P M; van Galen, Josse; Batenburg, Joseph J; Helms, J Bernd
2010-01-01
Lipids were long believed to have a structural role in biomembranes and a role in energy storage utilizing cellular lipid droplets and plasma lipoproteins. Research over the last decades has identified an additional role of lipids in cellular signaling, membrane microdomain organization and dynamics, and membrane trafficking. These properties make lipids an attractive target for pathogens to modulate host cell processes in order to allow their survival and replication. In this review we will summarize the often ingenious strategies of pathogens to modify the lipid homeostasis of host cells, allowing them to divert cellular processes. To this end pathogens take full advantage of the complexity of the lipidome. The examples are categorized in generalized and emerging principles describing the involvement of lipids in host-pathogen interactions. Several pathogens are described that simultaneously induce multiple changes in the host cell signaling and trafficking mechanisms. Elucidation of these pathogen-induced changes may have important implications for drug development. The emergence of high-throughput lipidomic techniques will allow the description of changes of the host cell lipidome at the level of individual molecular lipid species and the identification of lipid biomarkers.
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A transgenic rat with ubiquitous expression of firefly luciferase gene
NASA Astrophysics Data System (ADS)
Hakamata, Yoji; Murakami, Takashi; Kobayashi, Eiji
2006-02-01
In vivo imaging strategies provide cellular and molecular events in real time that helps us to understand biological processes in living animals. The development of molecular tags such as green fluorescent proteins and luciferase from the firefly Photinus pyralis has lead to a revolution in the visualization of complex biochemical processes. We developed a novel inbred transgenic rat strain containing firefly luciferase based on the transgenic (Tg) technique in rats. This Tg rat expressed the luciferase gene ubiquitously under control of the ROSA26 promoter. Cellular immune responsiveness against the luciferase protein was evaluated using conventional skin grafting and resulted in the long-term acceptance of Tg rat skin on wild-type rats. Strikingly, organ transplant with heart and small bowel demonstrated organ viability and graft survival, suggesting that cells from luciferase-Tg are transplantable to track their fate. Taking advantage of the less immunogenic luciferase, we also tested the role of hepatocyte-infusion in a liver injury model, and bone marrow-derived cells in a skin defect model. Employed in conjunction with modern advances in optical imaging, this luciferase-Tg rat system provides an innovative animal tool and a new means of facilitating biomedical research such as in the case of regeneration medicine.
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Spugnini, Enrico; Fais, Stefano
2017-04-01
One of the unsolved mysteries in oncology includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to the development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. In the last decades a primordial role for proton exchangers has been supported as a key tumor advantage in facing off the acidic milieu. Proton exchangers do not allow intracellular acidification through a continuous elimination of H+ either outside the cells or within the internal vacuoles. This article wants to comment a translational process through that led to the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed powerful chemosensitizers as well. In this process we achieved the clinical proof of concept that PPI may well be included in new anti-cancer strategies with a solid background and rationale. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Frizzled Receptors in Development and Disease
Wang, Yanshu; Chang, Hao; Rattner, Amir; Nathans, Jeremy
2016-01-01
Frizzled proteins are the principal receptors for the Wnt family of ligands. They mediate canonical Wnt signaling together with Lrp5 and Lrp6 coreceptors. In conjunction with Celsr, Vangl, and a small number of additional membrane and membrane-associated proteins, they also play a central role in tissue polarity/planar cell polarity (PCP) signaling. Targeted mutations in 9 of the 10 mammalian Frizzled genes have revealed their roles in an extraordinarily diverse set of developmental and homeostatic processes, including morphogenetic movements responsible for palate, ventricular septum, ocular furrow, and neural tube closure; survival of thalamic neurons; bone formation; central nervous system (CNS) angiogenesis and blood–brain barrier formation and maintenance; and a wide variety of processes that orient subcellular, cellular, and multicellular structures relative to the body axes. The last group likely reflects the mammalian equivalent of tissue polarity/PCP signaling, as defined in Drosophila, and it includes CNS axon guidance, hair follicle and tongue papilla orientation, and inner ear sensory hair bundle orientation. Frizzled receptors are ubiquitous among multicellular animals and, with other signaling molecules, they very likely evolved to permit the development of the complex tissue architectures that provide multicellular animals with their enormous selective advantage. PMID:26969975
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Wlodarski, Rafael; Pearce, Eiluned
2016-06-01
It has previously been suggested that the historically and geographically widespread persistence of religious beliefs occurs because it is a by-product of normal cognitive processes, ones which first evolved to confer survival advantages in the social domain. If this theory holds, then it is likely that inter-individual variation in the same biases may predict corresponding variation in religious thoughts and behaviors. Using an online questionnaire, 298 participants answered questions regarding their tendency to detect agency, the degree to which they displayed schizotypal traits, their ability to understand the emotions and motivations of others ("mentalizing"), and their religious beliefs and behaviors. Path analysis suggests that mentalizing, agency detection, and schizotypal thinking were each independently related to religiosity. Furthermore, schizotypal thinking and agency detection were highly interrelated with one another, whereas mentalizing was not. Although the degree to which an individual engages with religious or spiritual beliefs will be influenced by their cultural and historical context, this paper helps to elucidate the interplay between various cognitive processes that might predispose some individuals but not others toward holding such beliefs in the first place.
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Aging in the colonial chordate, Botryllus schlosseri
Munday, Roma; Rodriguez, Delany; Di Maio, Alessandro; Kassmer, Susannah; Braden, Brian; Taketa, Daryl A.; Langenbacher, Adam; De Tomaso, Anthony
2015-01-01
What mechanisms underlie aging? One theory, the wear-and-tear model, attributes aging to progressive deterioration in the molecular and cellular machinery which eventually lead to death through the disruption of physiological homeostasis. The second suggests that life span is genetically programmed, and aging may be derived from intrinsic processes which enforce a non-random, terminal time interval for the survivability of the organism. We are studying an organism that demonstrates both properties: the colonial ascidian, Botryllus schlosseri. Botryllus is a member of the Tunicata, the sister group to the vertebrates, and has a number of life history traits which make it an excellent model for studies on aging. First, Botryllus has a colonial life history, and grows by a process of asexual reproduction during which entire bodies, including all somatic and germline lineages, regenerate every week, resulting in a colony of genetically identical individuals. Second, previous studies of lifespan in genetically distinct Botryllus lineages suggest that a direct, heritable basis underlying mortality exists that is unlinked to reproductive effort and other life history traits. Here we will review recent efforts to take advantage of the unique life history traits of B. schlosseri and develop it into a robust model for aging research. PMID:26136620
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Survival of Parents and Siblings of Supercentenarians
Perls, Thomas; Kohler, Iliana V.; Andersen, Stacy; Schoenhofen, Emily; Pennington, JaeMi; Young, Robert; Terry, Dellara; Elo, Irma T.
2011-01-01
Background Given previous evidence of familial predisposition for longevity, we hypothesized that siblings and parents of supercentenarians (age ≥ 110 years) were predisposed to survival to very old age and that, relative to their birth cohorts, their relative survival probabilities (RSPs) are even higher than what has been observed for the siblings of centenarians. Methods Mean age at death conditional upon survival to ages 20 and 50 and survival probabilities from ages 20 and 50 to higher ages were determined for 50 male and 56 female siblings and 54 parents of 29 supercentenarians. These estimates were contrasted with comparable estimates based on birth cohort-specific mortality experience for the United States and Sweden. Results Conditional on survival to age 20 years, mean age at death of supercentenarians’ siblings was ~81 years for men and women. Compared with respective Swedish and U.S. birth cohorts, these estimates were 17%–20% (12–14 years) higher for the brothers and 11%–14% (8–10 years) higher for the sisters. Sisters had a 2.9 times greater probability and brothers had a 4.3 times greater probability of survival from age 20 to age 90. Mothers of supercentenarians had a 5.8 times greater probability of surviving from age 50 to age 90. Fathers also experienced an increased survival probability from age 50 to age 90 of 2.7, but it failed to attain statistical significance. Conclusions The RSPs of siblings and mothers of supercentenarians revealed a substantial survival advantage and were most pronounced at the oldest ages. The RSP to age 90 for siblings of supercentenarians was approximately the same as that reported for siblings of centenarians. It is possible that greater RSPs are observed for reaching even higher ages such as 100 years, but a larger sample of supercentenarians and their siblings and parents is needed to investigate this possibility. PMID:17895443
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Survival of parents and siblings of supercentenarians.
Perls, Thomas; Kohler, Iliana V; Andersen, Stacy; Schoenhofen, Emily; Pennington, JaeMi; Young, Robert; Terry, Dellara; Elo, Irma T
2007-09-01
Given previous evidence of familial predisposition for longevity, we hypothesized that siblings and parents of supercentenarians (age >or= 110 years) were predisposed to survival to very old age and that, relative to their birth cohorts, their relative survival probabilities (RSPs) are even higher than what has been observed for the siblings of centenarians. Mean age at death conditional upon survival to ages 20 and 50 and survival probabilities from ages 20 and 50 to higher ages were determined for 50 male and 56 female siblings and 54 parents of 29 supercentenarians. These estimates were contrasted with comparable estimates based on birth cohort-specific mortality experience for the United States and Sweden. Conditional on survival to age 20 years, mean age at death of supercentenarians' siblings was approximately 81 years for men and women. Compared with respective Swedish and U.S. birth cohorts, these estimates were 17%-20% (12-14 years) higher for the brothers and 11%-14% (8-10 years) higher for the sisters. Sisters had a 2.9 times greater probability and brothers had a 4.3 times greater probability of survival from age 20 to age 90. Mothers of supercentenarians had a 5.8 times greater probability of surviving from age 50 to age 90. Fathers also experienced an increased survival probability from age 50 to age 90 of 2.7, but it failed to attain statistical significance. The RSPs of siblings and mothers of supercentenarians revealed a substantial survival advantage and were most pronounced at the oldest ages. The RSP to age 90 for siblings of supercentenarians was approximately the same as that reported for siblings of centenarians. It is possible that greater RSPs are observed for reaching even higher ages such as 100 years, but a larger sample of supercentenarians and their siblings and parents is needed to investigate this possibility.
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New agreement measures based on survival processes
Guo, Ying; Li, Ruosha; Peng, Limin; Manatunga, Amita K.
2013-01-01
Summary The need to assess agreement arises in many scenarios in biomedical sciences when measurements were taken by different methods on the same subjects. When the endpoints are survival outcomes, the study of agreement becomes more challenging given the special characteristics of time-to-event data. In this paper, we propose a new framework for assessing agreement based on survival processes that can be viewed as a natural representation of time-to-event outcomes. Our new agreement measure is formulated as the chance-corrected concordance between survival processes. It provides a new perspective for studying the relationship between correlated survival outcomes and offers an appealing interpretation as the agreement between survival times on the absolute distance scale. We provide a multivariate extension of the proposed agreement measure for multiple methods. Furthermore, the new framework enables a natural extension to evaluate time-dependent agreement structure. We develop nonparametric estimation of the proposed new agreement measures. Our estimators are shown to be strongly consistent and asymptotically normal. We evaluate the performance of the proposed estimators through simulation studies and then illustrate the methods using a prostate cancer data example. PMID:23844617
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Koyama, Kento; Hokunan, Hidekazu; Hasegawa, Mayumi; Kawamura, Shuso
2016-01-01
ABSTRACT Despite effective inactivation procedures, small numbers of bacterial cells may still remain in food samples. The risk that bacteria will survive these procedures has not been estimated precisely because deterministic models cannot be used to describe the uncertain behavior of bacterial populations. We used the Poisson distribution as a representative probability distribution to estimate the variability in bacterial numbers during the inactivation process. Strains of four serotypes of Salmonella enterica, three serotypes of enterohemorrhagic Escherichia coli, and one serotype of Listeria monocytogenes were evaluated for survival. We prepared bacterial cell numbers following a Poisson distribution (indicated by the parameter λ, which was equal to 2) and plated the cells in 96-well microplates, which were stored in a desiccated environment at 10% to 20% relative humidity and at 5, 15, and 25°C. The survival or death of the bacterial cells in each well was confirmed by adding tryptic soy broth as an enrichment culture. Changes in the Poisson distribution parameter during the inactivation process, which represent the variability in the numbers of surviving bacteria, were described by nonlinear regression with an exponential function based on a Weibull distribution. We also examined random changes in the number of surviving bacteria using a random number generator and computer simulations to determine whether the number of surviving bacteria followed a Poisson distribution during the bacterial death process by use of the Poisson process. For small initial cell numbers, more than 80% of the simulated distributions (λ = 2 or 10) followed a Poisson distribution. The results demonstrate that variability in the number of surviving bacteria can be described as a Poisson distribution by use of the model developed by use of the Poisson process. IMPORTANCE We developed a model to enable the quantitative assessment of bacterial survivors of inactivation procedures because the presence of even one bacterium can cause foodborne disease. The results demonstrate that the variability in the numbers of surviving bacteria was described as a Poisson distribution by use of the model developed by use of the Poisson process. Description of the number of surviving bacteria as a probability distribution rather than as the point estimates used in a deterministic approach can provide a more realistic estimation of risk. The probability model should be useful for estimating the quantitative risk of bacterial survival during inactivation. PMID:27940547
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Koyama, Kento; Hokunan, Hidekazu; Hasegawa, Mayumi; Kawamura, Shuso; Koseki, Shigenobu
2017-02-15
Despite effective inactivation procedures, small numbers of bacterial cells may still remain in food samples. The risk that bacteria will survive these procedures has not been estimated precisely because deterministic models cannot be used to describe the uncertain behavior of bacterial populations. We used the Poisson distribution as a representative probability distribution to estimate the variability in bacterial numbers during the inactivation process. Strains of four serotypes of Salmonella enterica, three serotypes of enterohemorrhagic Escherichia coli, and one serotype of Listeria monocytogenes were evaluated for survival. We prepared bacterial cell numbers following a Poisson distribution (indicated by the parameter λ, which was equal to 2) and plated the cells in 96-well microplates, which were stored in a desiccated environment at 10% to 20% relative humidity and at 5, 15, and 25°C. The survival or death of the bacterial cells in each well was confirmed by adding tryptic soy broth as an enrichment culture. Changes in the Poisson distribution parameter during the inactivation process, which represent the variability in the numbers of surviving bacteria, were described by nonlinear regression with an exponential function based on a Weibull distribution. We also examined random changes in the number of surviving bacteria using a random number generator and computer simulations to determine whether the number of surviving bacteria followed a Poisson distribution during the bacterial death process by use of the Poisson process. For small initial cell numbers, more than 80% of the simulated distributions (λ = 2 or 10) followed a Poisson distribution. The results demonstrate that variability in the number of surviving bacteria can be described as a Poisson distribution by use of the model developed by use of the Poisson process. We developed a model to enable the quantitative assessment of bacterial survivors of inactivation procedures because the presence of even one bacterium can cause foodborne disease. The results demonstrate that the variability in the numbers of surviving bacteria was described as a Poisson distribution by use of the model developed by use of the Poisson process. Description of the number of surviving bacteria as a probability distribution rather than as the point estimates used in a deterministic approach can provide a more realistic estimation of risk. The probability model should be useful for estimating the quantitative risk of bacterial survival during inactivation. Copyright © 2017 Koyama et al.
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Gill, Sharlene; Sargent, Daniel
2006-06-01
The intent of adjuvant therapy is to eradicate micro-metastatic residual disease following curative resection with the goal of preventing or delaying recurrence. The time-honored standard for demonstrating efficacy of new adjuvant therapies is an improvement in overall survival (OS). This typically requires phase III trials of large sample size with lengthy follow-up. With the intent of reducing the cost and time of completing such trials, there is considerable interest in developing alternative or surrogate end points. A surrogate end point may be employed as a substitute to directly assess the effects of an intervention on an already accepted clinical end point such as mortality. When used judiciously, surrogate end points can accelerate the evaluation of new therapies, resulting in the more timely dissemination of effective therapies to patients. The current review provides a perspective on the suitability and validity of disease-free survival (DFS) as an alternative end point for OS. Criteria for establishing surrogacy and the advantages and limitations associated with the use of DFS as a primary end point in adjuvant clinical trials and as the basis for approval of new adjuvant therapies are discussed.
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The genetic basis for survivorship in coronary artery disease
Dungan, Jennifer R.; Hauser, Elizabeth R.; Qin, Xuejun; Kraus, William E.
2013-01-01
Survivorship is a trait characterized by endurance and virility in the face of hardship. It is largely considered a psychosocial attribute developed during fatal conditions, rather than a biological trait for robustness in the context of complex, age-dependent diseases like coronary artery disease (CAD). The purpose of this paper is to present the novel phenotype, survivorship in CAD as an observed survival advantage concurrent with clinically significant CAD. We present a model for characterizing survivorship in CAD and its relationships with overlapping time- and clinically-related phenotypes. We offer an optimal measurement interval for investigating survivorship in CAD. We hypothesize genetic contributions to this construct and review the literature for evidence of genetic contribution to overlapping phenotypes in support of our hypothesis. We also present preliminary evidence of genetic effects on survival in people with clinically significant CAD from a primary case-control study of symptomatic coronary disease. Identifying gene variants that confer improved survival in the context of clinically appreciable CAD may improve our understanding of cardioprotective mechanisms acting at the gene level and potentially impact patients clinically in the future. Further, characterizing other survival-variant genetic effects may improve signal-to-noise ratio in detecting gene associations for CAD. PMID:24143143
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Xue, Cong; Hong, Shaodong; Li, Ning; Feng, Weineng; Jia, Jun; Peng, Jiewen; Lin, Daren; Cao, Xiaolong; Wang, Siyang; Zhang, Weimin; Zhang, Hongyu; Dong, Wei; Zhang, Li
2015-01-01
There is no consensus on the optimal treatment for patients with advanced non-small-cell lung cancer (NSCLC) and stable disease (SD) after gefitinib therapy. This randomized, open-label, multicenter study aimed to explore whether dose-escalation of gefitinib would improve response and survival in NSCLC patients who achieved SD after one-month of standard gefitinib dosage. Between May 2009 and January 2012, 466 patients were enrolled and 100 eligible patients were randomized (1:1) to receive either a higher dose (500 mg/d; H group) or to continue standard dose (250 mg/d; S group) of gefitinib. Objective response rate (ORR) was similar between the two groups (12.5% vs 12.5%, p = 1.000). There were no significant differences regarding progression-free survival (PFS) and overall survival (OS) between both arms (H group vs S group: median PFS, 5.30 months vs 6.23 months, p = 0.167; median OS, 13.70 months vs 18.87 months, p = 0.156). Therefore, dose-escalation of gefitinib does not confer a response or survival advantage in patients who achieve SD with one month of standard-dose gefitinib treatment. PMID:26216071
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Intracellular ice formation in insects: unresolved after 50 years?
Sinclair, Brent J; Renault, David
2010-01-01
Many insects survive internal ice formation. The general model of freeze tolerance is of extracellular ice formation (EIF) whereby ice formation in the haemocoel leads to osmotic dehydration of the cells, whose contents remain unfrozen. However, survivable intracellular ice formation (IIF) has been reported in fat body and certain other cells of some insects. Although the cellular location of ice has been determined only in vitro, several lines of evidence suggest that IIF occurs in vivo. Both cell-to-cell propagation of intracellular ice and inoculation from the haemocoel may be important, although the route of ice into the cell is unclear. It is unclear why some cells survive IIF and others do not, but it is suggested that the shape, size, and low water content of fat body cells may predispose them towards surviving ice formation. We speculate that IIF may reduce water loss in some freeze tolerant species, but there are too few data to build a strong conceptual model of the advantages of IIF. We suggest that new developments in microscopy and other forms of imaging may allow investigation of the cellular location of ice in freeze tolerant insects in vivo.
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Han, Yi J; Baskin, Jerry M; Tan, Dun Y; Baskin, Carol C; Wu, Ming Y
2018-02-19
Seed predation by insects is common in seeds of Fabaceae (legume) species with physical dormancy (PY). However, the consequences of insect seed predation on the life history of legumes with PY have been little studied. In the largest genus of seed plants, Astragalus (Fabaceae), only one study has tested the effects of insect predation on germination, and none has tested it directly on seedling survival. Thus, we tested the effects of insect predation on seed germination and seedling growth and survival of Astragalus lehmannianus, a central Asian sand-desert endemic. Under laboratory conditions, seeds lightly predated in the natural habitat of this perennial legume germinated to a much higher percentage than intact seeds, and seedlings from predated and nonpredated seeds survived and grew about equally well. Further, in contrast to our prediction seedlings from predated seeds that germinated "out-of-season" under near-natural conditions in NW China survived over winter. The implication of our results is that individual plants from predated seeds that germinate early (in our case autumn) potentially have a fitness advantage over those from nonpredated seeds, which delay germination until spring of a subsequent year.
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Li, Ting; Yang, Yang Claire; Zhang, Yanlong
2018-05-01
This study examined the patterns of social-network types and their relative survival benefits among Chinese older adults. We examined how macro-level social factors such as cultural norms and unbalanced regional economic development shaped older people's network behaviors, and whether these factors could moderate the association between network types and mortality. Using data from the Chinese Longitudinal Healthy Longevity Survey (2008-2014), we identified four network types-diverse, friend-focused, family-focused, and restricted-based on individuals' social network measures. Multinomial logistic analyses revealed that older people situated in an area with a deeply rooted family culture or a more advanced economy tend to be less likely to enroll in a diverse network than a family-focused one. This prevents them from achieving the best adaptive survival, as Cox regression analyses showed that the family-focused network type was less beneficial than the diverse one for the survival of older adults. Furthermore, while the survival advantage of the diverse-network type over the family-focused type did not change with cultural contexts, economic development attenuated the deleterious effects of the friend-focused network type. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Liver, kidney, and thoracic organ transplantation under FK 506.
Todo, S; Fung, J J; Starzl, T E; Tzakis, A; Demetris, A J; Kormos, R; Jain, A; Alessiani, M; Takaya, S; Shapiro, R
1990-01-01
The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93.3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cyclosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index. PMID:1697743
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The prognostic significance of lymphatics in colorectal liver metastases.
Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher
2014-01-01
Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.
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Using integration technology as a strategic advantage.
Fry, P A
1993-08-01
The underlying premise of the Managed Competition Act previously cited is that through managed competition providers will be forced to lower care costs while increasing the level of positive care outcomes. Because it may also be that tomorrow's hospitals will find a severe rationing of technology, what can they do to prepare? Most of the systems in place today already have built within them all the necessary potential to address this premise and technology requirement with no change, no conversion, no expense for new equipment and software, and no disruption in day-to-day operations, just a little re-engineering. Today, however, these systems are similar to a 20-mule team pulling in different directions: all the power is there, but the wagon remains motionless and totally unable to reach its objective. It takes a skilled wagonmaster to bring them together, to make the mules work as a cohesive unit, to make the power of 20 mules greater than the sum of 20 mules. So it is and will be for the hospital of tomorrow. System integration is no longer a question of whether but of when. Those hospitals that use it today as a strategic advantage will be in a better position tomorrow to use it as a competitive strategic advantage in an environment that will reward low cost and high positive care outcomes and will penalize those that cannot compete. The technology is already here and economically within reach of nearly every hospital, just waiting to be used. The question that must nag all of us who want to make the health care system of America better is, Why not make the when now? Rich Helppie, president of Superior Consultant Company, summarized the solution well: The old ways will not give way to the new overnight. The re-engineering process in healthcare must evolve. Compared to the last 20 years, however, such evolution may appear to be a massive, forthright, complete, comprehensive, drastic and rapid revolution. Survival is the name of the game, and for healthcare organizations to survive, they must join the re-engineering revolution. When that happens, the "Americanized" health care system might look like the community network shown in Figure 7, which is a networked integration of all the systems used in the community working together and exchanging information, with hospitals exchanging information with other hospitals and sharing it with physicians, clinics, laboratories, radiology centers, universities, employers, payors, and governmental agencies.(ABSTRACT TRUNCATED AT 400 WORDS)
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Wang, Yujuan; Gupta, Shubham; Hua, Vi; Ramos-Garcia, Raquel; Shevrin, Daniel; Jovanovic, Borko D.; Nelson, Joel B
2009-01-01
BACKGROUND We have previously reported that finasteride administration in intermittent androgen deprivation therapy (IADT) can improve survival of nude mice bearing LNCaP xenograft tumors when the duration of off-cycle in IADT was fixed. A recent retrospective study showed that addition of finasteride doubled the duration of the off-cycle, without changing progression to castration resistance. In view of the above difference, we attempted to investigate the relationship of 5α-reductase inhibition with the off-cycle interval and overall survival in a murine model. METHODS Subcutaneous LNCaP tumors were established in nude mice (Balb/C-Nu). After the tumors reached a size of 0.5 cm in diameter, the mice were castrated and followed up for 2 weeks after which they were randomized to continuous androgen deprivation (CAD), CAD plus finasteride, IADT, and IADT plus finasteride. The off-cycle was discontinued when the tumor volume was doubled. Subsequent cycles were carried out similarly. RESULTS Use of finasteride during the off-cycle of IADT doubled the first off-cycle duration. However, prolongation of the off-cycle by finasteride did not translate into an increase in overall survival. CONCLUSIONS The survival advantage of IADT+F over IADT that we previously reported was lost when the off-cycle prolongation by finasteride was allowed. Maximum possible lengthening of the off-cycle by 5α-reductase inhibition is not associated with survival improvement in this animal model. PMID:19739129
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Fellner, Marie-Christin; Bäuml, Karl-Heinz T; Hanslmayr, Simon
2013-10-01
Memory crucially depends on the way information is processed during encoding. Differences in processes during encoding not only lead to differences in memory performance but also rely on different brain networks. Although these assumptions are corroborated by several previous fMRI and ERP studies, little is known about how brain oscillations dissociate between different memory encoding tasks. The present study therefore compared encoding related brain oscillatory activity elicited by two very efficient encoding tasks: a typical deep semantic item feature judgment task and a more elaborative survival encoding task. Subjects were asked to judge words either for survival relevance or for animacy, as indicated by a cue presented prior to the item. This allowed dissociating pre-item activity from item-related activity for both tasks. Replicating prior studies, survival processing led to higher recognition performance than semantic processing. Successful encoding in the semantic condition was reflected by a strong decrease in alpha and beta power, whereas successful encoding in the survival condition was related to increased alpha and beta long-range phase synchrony. Moreover, a pre-item subsequent memory effect in theta power was found which did not vary with encoding condition. These results show that measures of local synchrony (power) and global long range-synchrony (phase synchronization) dissociate between memory encoding processes. Whereas semantic encoding was reflected in decreases in local synchrony, increases in global long range synchrony were related to elaborative survival encoding, presumably reflecting the involvement of a more widespread cortical network in this task. Copyright © 2013 Elsevier Inc. All rights reserved.
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Business Process Reengineering for Quality Improvement.
1995-07-01
17 1.7.3. UNDERSTANDING BUSINESS VALUE...44 3.1.1. UNDERSTANDING BUSINESS PROCESS...targets which will promote the survival and growth of the business. 1.7.3. UNDERSTANDING BUSINESS VALUE Many businesses that have survived the test of time
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Zheng, Lei; Wolfgang, Christopher L
2015-01-01
Pancreatic cancer has a dismal prognosis. A technically perfect surgical operation may still not provide a survival advantage for patients with technically resectable pancreatic cancer. Appropriate selection of patients for surgical resections is an imminent issue. Recent studies have provided an important clue on what serum biomarkers may be used to select out the patients who would unlikely benefit from the surgical resection.
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The Long and Complicated Relationship between Epstein-Barr Virus and Epithelial Cells.
Hutt-Fletcher, Lindsey M
2017-01-01
The roles of epithelial cells in infection and persistence of the Epstein-Barr virus (EBV) have long been difficult to resolve. However, recent developments have reinforced the conclusion that these cells are a major site of virus replication and raised the possibility that, like papillomaviruses, EBV has evolved to take advantage of epithelial differentiation to ensure survival, persistence, and spread. Copyright © 2016 American Society for Microbiology.
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Defending Our Satellites: The Need for Electronic Warfare Education and Training
2015-12-01
intercept Allied bombers attacking at night.9 As a result of the electronic warfare advantage that systems like Window and Airborne Cigar be- stowed...74 | Air & Space Power Journal Defending Our Satellites The Need for Electronic Warfare Education and Training Lt Col E. Lincoln Bonner, USAF...expanding education and training in the use of electronic warfare to defend US satellites and improve their survivability. The following discussion
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Antisense Oligonucleotide Therapy for Patients with Advanced Cancer | Center for Cancer Research
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the U.S. Improvements in therapy have increased the survival of patients with CRC from 10 months to two years, but for patients who stop responding to treatments, such as irinotecan, options for additional therapy are limited. Antisense oligonucleotides (ASOs) may offer advantages over traditional therapies if an appropriate target can be identified.
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Hemoglobin Function in Stored Blood.
1974-08-01
States during 1973. Several advantages over ACA) are important. Blood stored in CPD maintains higher ./ levels of 2,3-DPG (2,3- diphosphoglycerate ) and a...survival and ATP levels in stored blood is explained by the several functions of ATP which are necessary for cell viability. However, ATP levels do...not correlate with oxygen affinity during storage. Levels of 2,3-DPG determine oxygen affinity and thus hemoglobin function. (12,13) When normal levels
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ERIC Educational Resources Information Center
Chen, Y.; Norton, D. J.; McBain, R.; Gold, J.; Frazier, J. A.; Coyle, J. T.
2012-01-01
An important issue for understanding visual perception in autism concerns whether individuals with this neurodevelopmental disorder possess an advantage in processing local visual information, and if so, what is the nature of this advantage. Perception of movement speed is a visual process that relies on computation of local spatiotemporal signals…
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Ishizuka, Wataru; Goto, Susumu
2012-04-01
Intraspecific adaptation in Abies sachalinensis was examined using models based on long-term monitoring data gathered during a reciprocal transplant experiment with eight seed source populations and six transplantation sites along an altitudinal gradient. The consequence of local adaptation was evaluated by testing the home-site advantage for upslope and downslope transplants at five ages. The populations' fitness-linked trait was set as their productivity (tree height × survival rate) at each age. The effects of global warming were evaluated on the basis of the 36-year performance of downslope transplants. Evidence was found for adaptive genetic variation affecting both height and survival from an early age. Increasing the distance between seed source and planting site significantly reduced productivity for both upslope and downslope transplantation, demonstrating the existence of a significant home-site advantage. The decrease in productivity was most distinct for upslope transplantations, indicating strong local adaptation to high altitudes. Global warming is predicted to increase the productivity of high-altitude populations. However, owing to their existing local adaptation, all tested populations exhibited lower productivity under warming than demes that were optimal for the new climate. These negative predictions should be considered when planning the management of locally adapted plant species such as A. sachalinensis.
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Cedra, Susan; Wiegand, Susanne; Kolb, Marlen; Dietz, Andreas; Wichmann, Gunnar
2017-01-01
Targeting of αVβ3 and αVβ5 integrins by cilengitide may reduce growth of solid tumors including head and neck squamous cell carcinoma (HNSCC). Preclinical investigations suggest increased activity of cilengitide in combination with other treatment modalities. The only published trial in HNSCC (ADVANTAGE) investigated cisplatin, 5-fluorouracil, and cetuximab (PFE) without or with once (PFE+CIL1W) or twice weekly cilengitide (PFE+CIL2W) in recurrent/metastatic HNSCC. ADVANTAGE showed good tolerability of the cilengitide arms and even lower adverse events (AEs) compared to PFE but not the benefit in overall survival expected based on preclinical data. As we found in the FLAVINO assay, a short-time ex vivo assay for prediction of chemosensitivity, only a subgroup of HNSCC had an increased suppressive effect of cilengitide containing combination therapies on colony formation of epithelial cells (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines, whereas other HNSCC failed to respond. Response to αVβ3 and αVβ5 integrin targeting by cilengitide classifies HNSCC regarding outcome. We present FLAVINO data arguing for further development of cilengitide plus cetuximab in treatment of a subgroup of HNSCC potentially identified by the FLAVINO assay using a set of biomarkers for response evaluation. PMID:28872582
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Jun, Wang; Wei, Wen; Weibing, Wu; Jing, Xu; Fuxi, Zhen; Xiaoxiang, Xi; Bihong, Lu; Tong, Zhou; Liang, Chen; Jinhua, Luo
2017-05-01
For esophageal carcinoma patients with early gastrectomy, individualized surgical plans-including selection of replacement conduit and operation route based on patient's new lesion and surgical history-can achieve the desired therapeutic effect and improve postoperative life quality. We investigated the outcomes at our institution. The clinical data of 42 esophageal carcinoma patients with early gastrectomy were analyzed retrospectively. Esophagectomy was performed combining replacement with remnant stomach in 16 patients, jejunum in 17, and colon in 9. Esophagectomy combining replacement with gastric remnant got advantages of shorter operation time and less bleeding over that of replacement with jejunum or colon. Gastric remnant group scored higher on the QLQ-C30 questionnaire than jejunum or colon group with respect to overall quality of life, physical function, and social relationships. In QLQ-OES18 questionnaire, the scores of appetite recovery and reflux mitigation were more favorable in remnant stomach group than those in jejunum or colon group. Survival analysis showed no significant difference in survival rate among the patients undergoing replacement with gastric remnant, jejunum, or colon. For esophageal carcinoma patients with early gastrectomy, esophagus-gastric remnant anastomosis possesses advantages of shorter operation time, less surgical trauma, and greater life quality after surgery. © 2017 Wiley Periodicals, Inc.
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Electrophysiological explorations of the bilingual advantage: evidence from a Stroop task.
Coderre, Emily L; van Heuven, Walter J B
2014-01-01
Bilinguals have been shown to exhibit a performance advantage on executive control tasks, outperforming their monolingual counterparts. Although a wealth of research has investigated this 'bilingual advantage' behaviourally, electrophysiological correlates are lacking. Using EEG with a Stroop task that manipulated the stimulus onset asynchrony (SOA) of word and colour presentation, the current study addressed two facets of the bilingual advantage. The possibility that bilinguals experience superior conflict processing relative to monolinguals (a 'conflict-specific advantage') was investigated by comparing behavioural interference effects as well as the amplitude of the Ninc, a conflict-related ERP component occurring from approximately 300-500 ms after the onset of conflict. In contrast, the hypothesis that bilinguals experience domain-general, conflict-independent enhancements in executive processing (a 'non-conflict-specific advantage') was evaluated by comparing the control condition (symbol strings) between groups. There was some significant, but inconsistent, evidence for a conflict-specific bilingual advantage. In contrast, strong evidence emerged for a non-conflict-specific advantage, with bilinguals demonstrating faster RTs and reduced ERP amplitudes on control trials compared to monolinguals. Importantly, when the control stimulus was presented before the colour, ERPs to control trials revealed group differences before the onset of conflict, suggesting differences in the ability to ignore or suppress distracting irrelevant information. This indicates that bilinguals experience superior executive processing even in the absence of conflict and semantic salience, and suggests that the advantage extends to more efficient proactive management of the environment.
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Back to Basics: A Bilingual Advantage in Infant Visual Habituation
ERIC Educational Resources Information Center
Singh, Leher; Fu, Charlene S. L.; Rahman, Aishah A.; Hameed, Waseem B.; Sanmugam, Shamini; Agarwal, Pratibha; Jiang, Binyan; Chong, Yap Seng; Meaney, Michael J.; Rifkin-Graboi, Anne
2015-01-01
Comparisons of cognitive processing in monolinguals and bilinguals have revealed a bilingual advantage in inhibitory control. Recent studies have demonstrated advantages associated with exposure to two languages in infancy. However, the domain specificity and scope of the infant bilingual advantage in infancy remains unclear. In the present study,…
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Unconscious Affective Responses to Food.
Sato, Wataru; Sawada, Reiko; Kubota, Yasutaka; Toichi, Motomi; Fushiki, Tohru
2016-01-01
Affective or hedonic responses to food are crucial for humans, both advantageously (e.g., enhancing survival) and disadvantageously (e.g., promoting overeating and lifestyle-related disease). Although previous psychological studies have reported evidence of unconscious cognitive and behavioral processing related to food, it remains unknown whether affective reactions to food can be triggered unconsciously and its relationship with daily eating behaviors. We investigated these issues by using the subliminal affective priming paradigm. Photographs of food or corresponding mosaic images were presented in the peripheral visual field for 33 ms. Target photos of faces with emotionally neutral expressions were then presented, and participants rated their preferences for the faces. Eating behaviors were also assessed using questionnaires. The food images, relative to the mosaics, increased participants' preference for subsequent target faces. Furthermore, the difference in the preference induced by food versus mosaic images was positively correlated with the tendency to engage in external eating. These results suggest that unconscious affective reactions are elicited by the sight of food and that these responses contribute to daily eating behaviors related to overeating.
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Dorsal Raphe Serotonergic Neurons Control Intertemporal Choice under Trade-off.
Xu, Sangyu; Das, Gishnu; Hueske, Emily; Tonegawa, Susumu
2017-10-23
Appropriate choice about delayed reward is fundamental to the survival of animals. Although animals tend to prefer immediate reward, delaying gratification is often advantageous. The dorsal raphe (DR) serotonergic neurons have long been implicated in the processing of delayed reward, but it has been unclear whether or when their activity causally directs choice. Here, we transiently augmented or reduced the activity of DR serotonergic neurons, while mice decided between differently delayed rewards as they performed a novel odor-guided intertemporal choice task. We found that these manipulations, precisely targeted at the decision point, were sufficient to bidirectionally influence impulsive choice. The manipulation specifically affected choices with more difficult trade-off. Similar effects were observed when we manipulated the serotonergic projections to the nucleus accumbens (NAc). We propose that DR serotonergic neurons preempt reward delays at the decision point and play a critical role in suppressing impulsive choice by regulating decision trade-off. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A.
King, Cason R; Zhang, Ali; Tessier, Tanner M; Gameiro, Steven F; Mymryk, Joe S
2018-05-01
As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected "hub" proteins to "hack" the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function. Copyright © 2018 King et al.
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Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A
King, Cason R.; Zhang, Ali; Tessier, Tanner M.; Gameiro, Steven F.
2018-01-01
ABSTRACT As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected “hub” proteins to “hack” the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function. PMID:29717008
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Survival Advantage of Neonatal CNS Gene Transfer for Late Infantile Neuronal Ceroid Lipofuscinosis
Sondhi, Dolan; Peterson, Daniel A.; Edelstein, Andrew M.; del Fierro, Katrina; Hackett, Neil R.; Crystal, Ronald G.
2009-01-01
Summary Late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal autosomal recessive neurodegenerative lysosomal storage disorder of childhood, is caused by mutations in the CLN2 gene, resulting in deficiency of the protein tripeptidyl peptidase I (TPP-I). We have previously shown that direct CNS administration of AAVrh.10hCLN2 to adult CLN2 knockout mice, a serotype rh.10 adeno-associated virus expressing the wild type CLN2 cDNA, will partially improve neurological function and survival. In this study, we explore the hypothesis that administration of AAVrh.10hCLN2 to the neonatal brain will significantly improve the results of AAVrh.10hCLN2 therapy. To assess this concept, AAVrh.10hCLN2 vector was administered directly to the CNS of CLN2 knockout mice at 2 days, 3 wk and 7 wk of age. While all treatment groups show a marked increase in total TPP-I activity over wild-type mice, neonatally treated mice displayed high levels of TPP-I activity in the CNS 1 yr after administration which was spread throughout the brain. Using behavioral markers, 2 day treated mice demonstrate marked improvement over 3 wk, 7 wk or untreated mice. Finally, neonatal administration of AAVrh.10hCLN2 was associated with markedly enhanced survival, with a median time of death 376 days for neonatal treated mice, 277 days for 3 wk treated mice, 168 days for 7 wk treated mice, and 121 days for untreated mice. These data suggest that neonatal treatment offers many unique advantages, and that early detection and treatment may be essential for maximal gene therapy for childhood lysosomal storage disorders affecting the CNS. PMID:18639872
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Surgical advantages of reduced-port laparoscopic gastrectomy in gastric cancer.
Kunisaki, Chikara; Makino, Hirochika; Yamaguchi, Naotaka; Izumisawa, Yusuke; Miyamato, Hiroshi; Sato, Kei; Hayashi, Tsutomu; Sugano, Nobuhiro; Suzuki, Yoshihiro; Ota, Mitsuyoshi; Tsuburaya, Akira; Kimura, Jun; Takagawa, Ryo; Kosaka, Takashi; Ono, Hidetaka Andrew; Akiyama, Hirotoshi; Endo, Itaru
2016-12-01
Although a few studies have reported the use of reduced-port laparoscopic gastrectomy (RPG) in gastric cancer patients, the feasibility of routinely using this technique remains unclear. It is therefore important to evaluate the surgical advantages of this technique in this patient group. Between August 2010 and July 2015, 165 patients underwent RPGs at our hospital, performed by a single surgeon. Of these patients, 88 underwent reduced-port laparoscopic distal gastrectomy (RPLDG) and 77 underwent reduced-port laparoscopic total gastrectomy (RPLTG). In addition to short-term surgical outcomes after RPG, survival times and the surgical learning curve were also evaluated. Blood losses during lymph node dissection in the RPLDG and RPLTG groups were not significantly different (p = 0.160). Conversion to open surgery was necessary in only two patients. Postoperative morbidities were observed in 14.8 % of the RPLDG group and 14.3 % of the RPLTG group, but there were no deaths. Most patients expressed high cosmetic satisfaction in both groups. In the RPLDG group, operation time during reconstruction decreased over the first 50 cases and then plateaued, as the surgeon's experience of the technique increased. In contrast, in the RPLTG group, operation times dropped with surgical experience for both lymph node dissection, plateauing after 40 cases, and for reconstruction, plateauing after 30 cases. Only three patients died of gastric cancer in the follow-up period and three patients died of other diseases. Five-year overall survival and 5-year disease-specific survival were 95.6 and 98.0 %, respectively. We have shown that reduced-port gastrectomy (RPG) could be an acceptable and satisfactory procedure for treating gastric cancer for an experienced laparoscopic gastric surgeon who has sufficient previous experience of conventional laparoscopic gastrectomies.
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Stannard, S R; Johnson, N A
2004-01-01
Elevated intramyocellular triglyceride (IMTG) is strongly associated with insulin resistance, though a cause and effect relationship has not been fully described. Insulin sensitivity and IMTG content are both dynamic and can alter rapidly in response to dietary variation, physical activity and thermoregulatory response. Physically active humans (athletes) display elevated IMTG content, but in contrast to obese persons, are insulin sensitive. This paradox has created confusion surrounding the role of IMTG in the development of insulin resistance. In this review we consider the modern athlete as the physiological archetype of the Late Palaeolithic hunter–gatherer to whom the selection pressures of food availability, predation and fluctuating environmental conditions applied and to whom the genotype of modern man is virtually identical. As food procurement by the hunter–gatherer required physical activity, ‘thrifty’ genes that encouraged immediate energy storage upon refeeding after food deprivation (Neel, 1962) must have been of secondary importance in survival to genes that preserved physical capacity during food deprivation. Similarly genes that enabled survival during cold exposure whilst starved would be of primary importance. In this context, we discuss the advantage afforded by an elevated IMTG content, and how under these conditions, a concomitant muscle resistance to insulin-mediated glucose uptake would also be advantageous. In sedentary modern man, adiposity is high and skeletal muscle appears to respond as if a state of starvation exists. In this situation, elevated plasma lipids serve to accrue lipid and induce insulin resistance in skeletal muscle. Reversal of this physiological state is primarily dependant on adequate contractile activity, however, in modern Western society, physical inactivity combined with abundant food and warmth has rendered IMTG a redundant muscle substrate. PMID:14608009
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The Rate of Seasonal Changes in Temperature Alters Acclimation of Performance under Climate Change.
Nilsson-Örtman, Viktor; Johansson, Frank
2017-12-01
How the ability to acclimate will impact individual performance and ecological interactions under climate change remains poorly understood. Theory predicts that the benefit an organism can gain from acclimating depends on the rate at which temperatures change relative to the time it takes to induce beneficial acclimation. Here, we present a conceptual model showing how slower seasonal changes under climate change can alter species' relative performance when they differ in acclimation rate and magnitude. To test predictions from theory, we performed a microcosm experiment where we reared a mid- and a high-latitude damselfly species alone or together under the rapid seasonality currently experienced at 62°N and the slower seasonality predicted for this latitude under climate change and measured larval growth and survival. To separate acclimation effects from fixed thermal responses, we simulated growth trajectories based on species' growth rates at constant temperatures and quantified how much and how fast species needed to acclimate to match the observed growth trajectories. Consistent with our predictions, the results showed that the midlatitude species had a greater capacity for acclimation than the high-latitude species. Furthermore, since acclimation occurred at a slower rate than seasonal temperature changes, the midlatitude species had a small growth advantage over the high-latitude species under the current seasonality but a greater growth advantage under the slower seasonality predicted for this latitude under climate change. In addition, the two species did not differ in survival under the current seasonality, but the midlatitude species had higher survival under the predicted climate change scenario, possibly because rates of cannibalism were lower when smaller heterospecifics were present. These findings highlight the need to incorporate acclimation rates in ecological models.
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Factors Mediating Environmental Biofilm Formation by Legionella pneumophila.
Abu Khweek, Arwa; Amer, Amal O
2018-01-01
Legionella pneumophila ( L. pneumophila ) is an opportunistic waterborne pathogen and the causative agent for Legionnaires' disease, which is transmitted to humans via inhalation of contaminated water droplets. The bacterium is able to colonize a variety of man-made water systems such as cooling towers, spas, and dental lines and is widely distributed in multiple niches, including several species of protozoa In addition to survival in planktonic phase, L. pneumophila is able to survive and persist within multi-species biofilms that cover surfaces within water systems. Biofilm formation by L. pneumophila is advantageous for the pathogen as it leads to persistence, spread, resistance to treatments and an increase in virulence of this bacterium. Furthermore, Legionellosis outbreaks have been associated with the presence of L. pneumophila in biofilms, even after the extensive chemical and physical treatments. In the microbial consortium-containing L. pneumophila among other organisms, several factors either positively or negatively regulate the presence and persistence of L. pneumophila in this bacterial community. Biofilm-forming L. pneumophila is of a major importance to public health and have impact on the medical and industrial sectors. Indeed, prevention and removal protocols of L. pneumophila as well as diagnosis and hospitalization of patients infected with this bacteria cost governments billions of dollars. Therefore, understanding the biological and environmental factors that contribute to persistence and physiological adaptation in biofilms can be detrimental to eradicate and prevent the transmission of L. pneumophila . In this review, we focus on various factors that contribute to persistence of L. pneumophila within the biofilm consortium, the advantages that the bacteria gain from surviving in biofilms, genes and gene regulation during biofilm formation and finally challenges related to biofilm resistance to biocides and anti-Legionella treatments.
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2014-01-01
The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195
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ERIC Educational Resources Information Center
Funk, Robert N.
Until recently, the name commonly given to the relationship between the college and its students was in loco parentis, a concept that today is completely outdated. Due process of law has replaced it and many feel that its advantages are great. There are many disadvantages, however. (1) The literal adoption of legal processes from "the outside…
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The Combined Effect of Individual and Neighborhood Socioeconomic Status on Cancer Survival Rates
Lai, Ning-Sheng; Huang, Kuang-Yung; Chien, Sou-Hsin; Chang, Yu-Han; Lian, Wei-Cheng; Hsu, Ta-Wen; Lee, Ching-Chih
2012-01-01
Background This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and mortality rates for major cancers in Taiwan. Methods A population-based follow-up study was conducted with 20,488 cancer patients diagnosed in 2002. Each patient was traced to death or for 5 years. The individual income-related insurance payment amount was used as a proxy measure of individual SES for patients. Neighborhood SES was defined by income, and neighborhoods were grouped as living in advantaged or disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rates between the different SES groups after adjusting for possible confounding and risk factors. Results After adjusting for patient characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and area of residence), tumor extent, treatment modalities (operation and adjuvant therapy), and hospital characteristics (ownership and teaching level), colorectal cancer, and head and neck cancer patients under 65 years old with low individual SES in disadvantaged neighborhoods conferred a 1.5 to 2-fold higher risk of mortality, compared with patients with high individual SES in advantaged neighborhoods. A cross-level interaction effect was found in lung cancer and breast cancer. Lung cancer and breast cancer patients less than 65 years old with low SES in advantaged neighborhoods carried the highest risk of mortality. Prostate cancer patients aged 65 and above with low SES in disadvantaged neighborhoods incurred the highest risk of mortality. There was no association between SES and mortality for cervical cancer and pancreatic cancer. Conclusions Our findings indicate that cancer patients with low individual SES have the highest risk of mortality even under a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group. PMID:22957007
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Staying alive: Vibrio cholerae’s cycle of environmental survival, transmission, and dissemination
Jones, Christopher J.; Yildiz, Fitnat H.
2015-01-01
Infectious diseases kill nearly 9 million people annually. Bacterial pathogens are responsible for a large proportion of these diseases and the bacterial agents of pneumonia, diarrhea, and tuberculosis are leading causes of death and disability worldwide (1). Increasingly, the crucial role of non-host environments in the life cycle of bacterial pathogens is being recognized. Heightened scrutiny has been given to the biological processes impacting pathogen dissemination and survival in the natural environment, as these processes are essential for the transmission of pathogenic bacteria to new hosts. This chapter focuses on the model environmental pathogen, Vibrio cholerae, to describe recent advances in our understanding of how pathogens survive between hosts and highlight the processes necessary to support the cycle of environmental survival, transmission, and dissemination. We describe the physiological and molecular responses of V. cholerae to changing environmental conditions, focusing on its survival in aquatic reservoirs between hosts and its entry and exit from human hosts. PMID:27227302
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Ellison, Laura E; O'Shea, Thomas J; Wimsatt, Jeffrey; Pearce, Roger D; Neubaum, Daniel J; Neubaum, Melissa A; Bowen, Richard A
2006-10-01
Blood was collected from wild big brown bats (Eptesicus fuscus) with and without anesthesia in Fort Collins, Colorado in 2004 to assess the impacts of these procedures on short-term survival and 1-yr return rates. Short-term survival and 1-yr return rates after release were passively monitored using PIT tag detection hoops placed at selected buildings. Comparison of 14-day maximum likelihood survival estimates from bats not bled (142 adult females, 62 volant juveniles), and bats sampled for blood with anesthesia (96 adult females, 23 volant juveniles) and without anesthesia (112 adult females, 22 volant juveniles) indicated no adverse effects of either treatment (juveniles: chi(2) = 53.38, df = 41, P = 0.09; adults: chi(2) = 39.09, df = 44, P = 0.68). Return rates of bats one year after sampling were similar among adult female controls (75.4%, n = 142, 95% CI = 67.4-82.2%), females sampled for blood with anesthesia (83.0%, n = 112, 95% CI = 74.8-89.5%), and females sampled without anesthesia (87.5%, n = 96, 95% CI = 79.2-93.4%). Lack of an effect was also noted in 1-yr return rates of juvenile females. These data suggest that the use of anesthesia during sampling of blood has no advantages in terms of enhancement of survival in big brown bats.
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Appin, Christina L; Gao, Jingjing; Chisolm, Candace; Torian, Mike; Alexis, Dianne; Vincentelli, Cristina; Schniederjan, Matthew J; Hadjipanayis, Costas; Olson, Jeffrey J; Hunter, Stephen; Hao, Chunhai; Brat, Daniel J
2013-07-01
Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics. © 2013 The Authors; Brain Pathology © 2013 International Society of Neuropathology.
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Browne, William J; Steele, Fiona; Golalizadeh, Mousa; Green, Martin J
2009-06-01
We consider the application of Markov chain Monte Carlo (MCMC) estimation methods to random-effects models and in particular the family of discrete time survival models. Survival models can be used in many situations in the medical and social sciences and we illustrate their use through two examples that differ in terms of both substantive area and data structure. A multilevel discrete time survival analysis involves expanding the data set so that the model can be cast as a standard multilevel binary response model. For such models it has been shown that MCMC methods have advantages in terms of reducing estimate bias. However, the data expansion results in very large data sets for which MCMC estimation is often slow and can produce chains that exhibit poor mixing. Any way of improving the mixing will result in both speeding up the methods and more confidence in the estimates that are produced. The MCMC methodological literature is full of alternative algorithms designed to improve mixing of chains and we describe three reparameterization techniques that are easy to implement in available software. We consider two examples of multilevel survival analysis: incidence of mastitis in dairy cattle and contraceptive use dynamics in Indonesia. For each application we show where the reparameterization techniques can be used and assess their performance.