976 resultados para Clinical evolution


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Texture evolution in a low cost beta titanium alloy was studied for different modes of rolling and heat treatments. The alloy was cold rolled by unidirectional and multi-step cross rolling. The cold rolled material was either aged directly or recrystallized and then aged. The evolution of texture in alpha and beta phases were studied. The rolling texture of beta phase that is characterized by the gamma fiber is stronger for MSCR than UDR; while the trend is reversed on recrystallization. The mode of rolling affects alpha transformation texture on aging with smaller alpha lath size and stronger alpha texture in UDR than in MSCR. The defect structure in beta phase influences the evolution of a texture on aging. A stronger defect structure in beta phase leads to variant selection with the rolled samples showing fewer variants than the recrystallized samples.

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Oded Schramm, the inventor of the stochastic Loewner evolution (SLE), died on 1 September 2008 in a tragic hiking accident in the Cascades Mountains. He was forty-six. He is survived by his wife and two children.

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Phenotypic convergence is thought to be driven by parallel substitutions coupled with natural selection at the sequence level. Multiple independent evolutionary transitions of mammals to an aquatic environment offer an opportunity to test this thesis. Here, whole genome alignment of coding sequences identified widespread parallel amino acid substitutions in marine mammals; however, the majority of these changes were not unique to these animals. Conversely, we report that candidate aquatic adaptation genes, identified by signatures of likelihood convergence and/or elevated ratio of nonsynonymous to synonymous nucleotide substitution rate, are characterized by very few parallel substitutions and exhibit distinct sequence changes in each group. Moreover, no significant positive correlation was found between likelihood convergence and positive selection in all three marine lineages. These results suggest that convergence in protein coding genes associated with aquatic lifestyle is mainly characterized by independent substitutions and relaxed negative selection.

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Graphitic carbon nitride (g-C3N4), as a promising metal-free catalyst for photo-catalytic and electrochemical water splitting, has recently attracted tremendous research interest. However, the underlying catalytic mechanism for the hydrogen evolution reaction (HER) is not fully understood. By using density functional theory calculations, here we have established that the binding free energy of hydrogen atom (ΔGH∗0) on g-C3N4 is very sensitive to mechanical strain, leading to substantial tuning of the HER performance of g-C3N4 at different coverages. The experimentally-observed high HER activity in N-doped graphene supported g-C3N4 (Zheng et al., 2014) is actually attributed to electron-transfer induced strain. A more practical strategy to induce mechanical strain in g-C3N4 is also proposed by doping a bridge carbon atom in g-C3N4 with an isoelectronic silicon atom. The calculated ΔGH∗0 on the Si-doped g-C3N4 is ideal for HER. Our results indicate that g-C3N4 would be an excellent metal-free mechano-catalyst for HER and this finding is expected to guide future experiments to efficiently split water into hydrogen based on the g-C3N4 materials.

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A numerical model of the entire casting process starting from the mould filling stage to complete solidification is presented. The model takes into consideration any phase change taking place during the filling process. A volume of fluid method is used for tracking the metal–air interface during filling and an enthalpy based macro-scale solidification model is used for the phase change process. The model is demonstrated for the case of filling and solidification of Pb–15 wt%Sn alloy in a side-cooled two-dimensional rectangular cavity, and the resulting evolution of a mushy region and macrosegregation are studied. The effects of process parameters related to filling, namely degree of melt superheat and filling velocity on macrosegregation in the cavity, are also investigated. Results show significant differences in the progress of the mushy zone and macrosegregation pattern between this analysis and conventional analysis without the filling effect.

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The development of a new consumer product and its release to market is typically an expensive and risky process. It is estimated that up to 80% of all new products fail in the marketplace (Savoia, 2014). The consequences of failure can be ruinous for a manufacturer both financially and in terms of brand reputation. So even small improvements in success prediction have the potential to save money, effort and brand reputation. This paper proposes an approach where the history and evolution of a product is mapped and analyzed. The results of the analysis can then be used to inform design decisions. This paper will also demonstrate the similarities between biological evolution and the evolution of consumer products. Using the existing structure and terminology of biological evolution allows us to focus on the aspects of innovations that have led to success and those that have led to failure. This paper uses the case study of the wristwatch and its development over 100 years. The analysis of this leads to recommendations for contemporary “smartwatches.”

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The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 ± 0.2) and stunted (mean s.d. height = - 2.2 ± 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium - mean % expected for age = 58 ± 5%, n = 15). Mean ad libitum nutrient intake was 63 ± 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight >-1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight <-1.0) was 38% (P<0.003). Declining nutritional status during the waiting period also adversely affected outcome. We conclude that malnutrition and/or declining nutritional status is a major factor adversely affecting survival in children awaiting OLTP. In transplant units where waiting time is greater than 40 days, earlier referral, prioritization of cases and the use of adult donor livers may reduce this risk and efforts to maintain or improve nutritional status deserve further study.

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Introduction Two symposia on “cardiovascular diseases and vulnerable plaques” Cardiovascular disease (CVD) is the leading cause of death worldwide. Huge effort has been made in many disciplines including medical imaging, computational modeling, bio- mechanics, bioengineering, medical devices, animal and clinical studies, population studies as well as genomic, molecular, cellular and organ-level studies seeking improved methods for early detection, diagnosis, prevention and treatment of these diseases [1-14]. However, the mechanisms governing the initiation, progression and the occurrence of final acute clinical CVD events are still poorly understood. A large number of victims of these dis- eases who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs [8,9]. Most cardiovascular diseases are associated with vulnerable plaques. A grand challenge here is to develop new imaging techniques, predictive methods and patient screening tools to identify vulnerable plaques and patients who are more vulnerable to plaque rupture and associated clinical events such as stroke and heart attack, and recommend proper treatment plans to prevent those clinical events from happening. Articles in this special issue came from two symposia held recently focusing on “Cardio-vascular Diseases and Vulnerable Plaques: Data, Modeling, Predictions and Clinical Applications.” One was held at Worcester Polytechnic Institute (WPI), Worcester, MA, USA, July 13-14, 2014, right after the 7th World Congress of Biomechanics. This symposium was endorsed by the World Council of Biomechanics, and partially supported by a grant from NIH-National Institute of Biomedical Image and Bioengineering. The other was held at Southeast University (SEU), Nanjing, China, April 18-20, 2014.

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Animals often behave in a profligate fashion and decimate the populations of plants and animals they depend upon. They may, however, evolve prudent behaviour under special conditions, namely when such prudence greatly enhances the success of populations that are not too prone to invasions by profligate individuals. Cultural evolution in human societies can also lead to the adoption of prudent practices under similar conditions. These are more likely to be realized in stable environments in which the human populations tend to grow close to the carrying capacity, when the human groups are closed, and when the technology is stagnant. These conditions probably prevailed in the hunter—gatherer societies of the tropics and subtropics, and led to the adoption of a number of socially imposed restraints on the use of plant and animal resources. Such practices were rationalized in the form of Nature-worship. The Indian caste society became so organized as to fulfill these conditions, and gave rise to two religions, Buddhism and Jainism, which emphasize compassion towards all forms of life. The pastoral nomads of the middle east, on the other hand, lived in an environment which militated against prudence, and these societies gave rise to religions like Christianity, which declared war on nature. As the ruling elite and state have grown in power, they have tried to wrest control of natural resources from the local communities. This has sometimes resulted in conservation and prudent use under guidance from the state, but has often led to conflicts with local populations to the detriment of prudent behaviour. Modern technological progress has also often removed the need for conservation, as when availability of coal permitted the deforestation of England. While modern scientific understanding has led to a better appreciation of the need for prudence, the prevailing social and economic conditions often militate against any implementation of the understanding, as is seen from the history of whaling. However, the imperative for survival of the poor from the Third-World countries may finally bring about conditions in which ecological prudence may once again come to dominate human cultures as it might once have done with stable societies of hunter—gatherers.

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This study investigates the use of unsupervised features derived from word embedding approaches and novel sequence representation approaches for improving clinical information extraction systems. Our results corroborate previous findings that indicate that the use of word embeddings significantly improve the effectiveness of concept extraction models; however, we further determine the influence that the corpora used to generate such features have. We also demonstrate the promise of sequence-based unsupervised features for further improving concept extraction.

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The goal of this article is to provide a new design framework and its corresponding estimation for phase I trials. Existing phase I designs assign each subject to one dose level based on responses from previous subjects. Yet it is possible that subjects with neither toxicity nor efficacy responses can be treated at higher dose levels, and their subsequent responses to higher doses will provide more information. In addition, for some trials, it might be possible to obtain multiple responses (repeated measures) from a subject at different dose levels. In this article, a nonparametric estimation method is developed for such studies. We also explore how the designs of multiple doses per subject can be implemented to improve design efficiency. The gain of efficiency from "single dose per subject" to "multiple doses per subject" is evaluated for several scenarios. Our numerical study shows that using "multiple doses per subject" and the proposed estimation method together increases the efficiency substantially.

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A decision-theoretic framework is proposed for designing sequential dose-finding trials with multiple outcomes. The optimal strategy is solvable theoretically via backward induction. However, for dose-finding studies involving k doses, the computational complexity is the same as the bandit problem with k-dependent arms, which is computationally prohibitive. We therefore provide two computationally compromised strategies, which is of practical interest as the computational complexity is greatly reduced: one is closely related to the continual reassessment method (CRM), and the other improves CRM and approximates to the optimal strategy better. In particular, we present the framework for phase I/II trials with multiple outcomes. Applications to a pediatric HIV trial and a cancer chemotherapy trial are given to illustrate the proposed approach. Simulation results for the two trials show that the computationally compromised strategy can perform well and appear to be ethical for allocating patients. The proposed framework can provide better approximation to the optimal strategy if more extensive computing is available.

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Prostate cancer is a leading contributor to male cancer-related deaths worldwide. Kallikrein-related peptidases (KLKs) are serine proteases that exhibit deregulated expression in prostate cancer, with KLK3, or prostate specific antigen (PSA), being the widely-employed clinical biomarker for prostate cancer. Other KLKs, such as KLK2, show promise as prostate cancer biomarkers and, additionally, their altered expression has been utilised for the design of KLK-targeted therapies. There is also a large body of in vitro and in vivo evidence supporting their role in cancer-related processes. Here, we review the literature on studies to date investigating the potential of other KLKs, in addition to PSA, as biomarkers and in therapeutic options, as well as their current known functional roles in cancer progression. Increased knowledge of these KLK-mediated functions, including degradation of the extracellular matrix, local invasion, cancer cell proliferation, interactions with fibroblasts, angiogenesis, migration, bone metastasis and tumour growth in vivo, may help define new roles as prognostic biomarkers and novel therapeutic targets for this cancer.

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Quasi-two-dimensional oxides of the La,+,Sr,+,Mn04 system, possessing the KZNiF4 structure, show no evidence for ferromagnetic ordering in contrast to the corresponding three-dimensional La,+.Sr,MnO~ perovskites. Instead, there is an increasing tendency toward antiferromagnetic ordering with mcreasmg x m La,+,Sr,,, MnOp. Furthermore, these oxides are relatively high-resistivity materials over the entire compositional range. Substitution of Ba for Sr in La&r,.5Mn04 decreases the ferromagnetic interaction. Increasing the number of perovskite layers in SrO (La,-,Sr,MnO& causes an increase in electrical conductivity as well as ferromagnetic interaction. The oxide becomes a highly conducting ferromagnet when n 2 2.