143 resultados para SURROGATES


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This report is a dissertation proposal that focuses on the energy balance within an internal combustion engine with a unique coolant-based waste heat recovery system. It has been predicted by the U.S. Energy Information Administration that the transportation sector in the United States will consume approximately 15 million barrels per day in liquid fuels by the year 2025. The proposed coolant-based waste heat recovery technique has the potential to reduce the yearly usage of those liquid fuels by nearly 50 million barrels by only recovering even a modest 1% of the wasted energy within the coolant system. The proposed waste heat recovery technique implements thermoelectric generators on the outside cylinder walls of an internal combustion engine. For this research, one outside cylinder wall of a twin cylinder 26 horsepower water-cooled gasoline engine will be implemented with a thermoelectric generator surrogate material. The vertical location of these TEG surrogates along the water jacket will be varied along with the TEG surrogate thermal conductivity. The aim of this proposed dissertation is to attain empirical evidence of the impact, including energy distribution and cylinder wall temperatures, of installing TEGs in the water jacket area. The results can be used for future research on larger engines and will also assist with proper TEG selection to maximize energy recovery efficiencies.

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We used active remote sensing technology to characterize forest structure in a northern temperate forest on a landscape- and local-level in the Upper Peninsula of Michigan. Specifically, we used a form of active remote sensing called light detection and ranging (e.g., LiDAR) to aid in the depiction of current forest structural stages and total canopy gap area estimation. On a landscape-level, LiDAR data are shown not only to be a useful tool in characterizing forest structure, in both coniferous and deciduous forest cover types, but also as an effective basis for data-driven surrogates for classification of forest structure. On a local-level, LiDAR data are shown to be a benchmark reference point to evaluate field-based canopy gap area estimations, due to the highly accurate nature of such remotely sensed data. The application of LiDAR remote sensed data can help facilitate current and future sustainable forest management.

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BACKGROUND: Sedation protocols, including the use of sedation scales and regular sedation stops, help to reduce the length of mechanical ventilation and intensive care unit stay. Because clinical assessment of depth of sedation is labor-intensive, performed only intermittently, and interferes with sedation and sleep, processed electrophysiological signals from the brain have gained interest as surrogates. We hypothesized that auditory event-related potentials (ERPs), Bispectral Index (BIS), and Entropy can discriminate among clinically relevant sedation levels. METHODS: We studied 10 patients after elective thoracic or abdominal surgery with general anesthesia. Electroencephalogram, BIS, state entropy (SE), response entropy (RE), and ERPs were recorded immediately after surgery in the intensive care unit at Richmond Agitation-Sedation Scale (RASS) scores of -5 (very deep sedation), -4 (deep sedation), -3 to -1 (moderate sedation), and 0 (awake) during decreasing target-controlled sedation with propofol and remifentanil. Reference measurements for baseline levels were performed before or several days after the operation. RESULTS: At baseline, RASS -5, RASS -4, RASS -3 to -1, and RASS 0, BIS was 94 [4] (median, IQR), 47 [15], 68 [9], 75 [10], and 88 [6]; SE was 87 [3], 46 [10], 60 [22], 74 [21], and 87 [5]; and RE was 97 [4], 48 [9], 71 [25], 81 [18], and 96 [3], respectively (all P < 0.05, Friedman Test). Both BIS and Entropy had high variabilities. When ERP N100 amplitudes were considered alone, ERPs did not differ significantly among sedation levels. Nevertheless, discriminant ERP analysis including two parameters of principal component analysis revealed a prediction probability PK value of 0.89 for differentiating deep sedation, moderate sedation, and awake state. The corresponding PK for RE, SE, and BIS was 0.88, 0.89, and 0.85, respectively. CONCLUSIONS: Neither ERPs nor BIS or Entropy can replace clinical sedation assessment with standard scoring systems. Discrimination among very deep, deep to moderate, and no sedation after general anesthesia can be provided by ERPs and processed electroencephalograms, with similar P(K)s. The high inter- and intraindividual variability of Entropy and BIS precludes defining a target range of values to predict the sedation level in critically ill patients using these parameters. The variability of ERPs is unknown.

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Article preview View full access options BoneKEy Reports | Review Print Email Share/bookmark Finite element analysis for prediction of bone strength Philippe K Zysset, Enrico Dall'Ara, Peter Varga & Dieter H Pahr Affiliations Corresponding author BoneKEy Reports (2013) 2, Article number: 386 (2013) doi:10.1038/bonekey.2013.120 Received 03 January 2013 Accepted 25 June 2013 Published online 07 August 2013 Article tools Citation Reprints Rights & permissions Abstract Abstract• References• Author information Finite element (FE) analysis has been applied for the past 40 years to simulate the mechanical behavior of bone. Although several validation studies have been performed on specific anatomical sites and load cases, this study aims to review the predictability of human bone strength at the three major osteoporotic fracture sites quantified in recently completed in vitro studies at our former institute. Specifically, the performance of FE analysis based on clinical computer tomography (QCT) is compared with the ones of the current densitometric standards, bone mineral content, bone mineral density (BMD) and areal BMD (aBMD). Clinical fractures were produced in monotonic axial compression of the distal radii, vertebral sections and in side loading of the proximal femora. QCT-based FE models of the three bones were developed to simulate as closely as possible the boundary conditions of each experiment. For all sites, the FE methodology exhibited the lowest errors and the highest correlations in predicting the experimental bone strength. Likely due to the improved CT image resolution, the quality of the FE prediction in the peripheral skeleton using high-resolution peripheral CT was superior to that in the axial skeleton with whole-body QCT. Because of its projective and scalar nature, the performance of aBMD in predicting bone strength depended on loading mode and was significantly inferior to FE in axial compression of radial or vertebral sections but not significantly inferior to FE in side loading of the femur. Considering the cumulated evidence from the published validation studies, it is concluded that FE models provide the most reliable surrogates of bone strength at any of the three fracture sites.

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There is controversy whether determination of antibodies against myelin, myelin oligodendrocyte glycoprotein, and myelin basic protein in serum from patients with a first episode suggestive of multiple sclerosis is of prognostic value. We evaluated whether detection of antimyelin antibodies in serum indicates a worse course with earlier time to a second relapse and increased progression of disability. We conducted a prospective study at the Department of Neurology, Inselspital Bern, Switzerland from 2004 to 2008 in patients presenting with a clinically isolated syndrome (CIS) and a follow-up of at least 4 months. Antimyelin antibodies were assessed by Western blot. Results were correlated with clinical course and sex. Among 93 consecutive patients with a CIS, 74 (80%) were positive for either one or both antimyelin antibodies. A relapse occurred in 49 (53%) and the median EDSS was 2 (range 1-3.5) after a mean observation period of 20 months. Presence of antimyelin antibodies at CIS neither increased the risk for a second relapse nor for progression of disability. Stratification for gender did not reveal differences for any of the clinical surrogates. The sole determination of antimyelin antibodies in serum is of limited prognostic value for the identification of patients with different short-term course.

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Altitudinal gradients offer valuable study systems to investigate how adap- tive genetic diversity is distributed within and between natural populations and which factors promote or prevent adaptive differentiation. The environ- mental clines along altitudinal gradients tend to be steep relative to the dispersal distance of many organisms, providing an opportunity to study the joint effects of divergent natural selection and gene flow. Temperature is one variable showing consistent altitudinal changes, and altitudinal gradi- ents can therefore provide spatial surrogates for some of the changes antici- pated under climate change. Here, we investigate the extent and patterns of adaptive divergence in animal populations along altitudinal gradients by sur- veying the literature for (i) studies on phenotypic variation assessed under common garden or reciprocal transplant designs and (ii) studies looking for signatures of divergent selection at the molecular level. Phenotypic data show that significant between-population differences are common and taxo- nomically widespread, involving traits such as mass, wing size, tolerance to thermal extremes and melanization. Several lines of evidence suggest that some of the observed differences are adaptively relevant, but rigorous tests of local adaptation or the link between specific phenotypes and fitness are sorely lacking. Evidence for a role of altitudinal adaptation also exists for a number of candidate genes, most prominently haemoglobin, and for anony- mous molecular markers. Novel genomic approaches may provide valuable tools for studying adaptive diversity, also in species that are not amenable to experimentation.

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An often-cited reason for studying the process of invasion by alien species is that the understanding sought can be used to mitigate the impacts of the invaders. Here, we present an analysis of the correlates of local impacts of established alien bird and mammal species in Europe, using a recently described metric to quantify impact. Large-bodied, habitat generalist bird and mammal species that are widespread in their native range, have the greatest impacts in their alien European ranges, supporting our hypothesis that surrogates for the breadth and the amount of resources a species uses are good indicators of its impact. However, not all surrogates are equally suitable. Impacts are generally greater for mammal species giving birth to larger litters, but in contrast are greater for bird species laying smaller clutches. There is no effect of diet breadth on impacts in birds or mammals. On average, mammals have higher impacts than birds. However, the relationships between impact and several traits show common slopes for birds and mammals, and relationships between impact and body mass and latitude do not differ between birds and mammals. These results may help to anticipate which species would have large impacts if introduced, and so direct efforts to prevent such introductions.

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A cross-sectional study on the use of three pesticides and their presence in drinking water sources was conducted in Githunguri/Kiaria community between January 1994-March 1995. The main objective of the study was to determine the extent to which some of the pesticides used by the Githunguri/Kiaria agricultural community were polluting their drinking water sources. Due to monetary and physical limitations, only DDT, its isomers and metabolites, carbofuran and carbaryl pesticides were identified and used as surrogates of pollution for the other pesticides.^ The study area was divided into high and low lying geographic surface areas. Thirty-four and 38 water sampling sites were randomly selected respectively. During wet and dry seasons, a total of 144 water samples were collected and analyzed at the Kenya Bureau of Standards Laboratory in Nairobi. Gas chromatography was used to analyze samples for possible presence of DDT, its isomers and metabolites, while high pressure liquid chromatography was used to analyze samples for carbofuran and carbaryl pesticides.^ Six sites testing positively for DDT, its isomers and metabolites represented 19.4% of the total sampled sites, with a mean concentration of 0.00310 ppb in the dry season and 0.0130 ppb in the wet season. All the six sites testing positively for the same pesticide exceeded the European maximum contaminant limit (MCL) in the wet season, and only one site exceeded the European MCL in the dry season.^ Those sites testing positively for carbofuran and carbaryl represented 5.6% of the total sampled sites. The mean concentration for the carbofuran at the sites was 2.500 ppb and 1.590 ppb in the dry and wet seasons respectively. Similarly, the mean concentration for carbaryl at the sites was 0.281 ppb in the dry season and 0.326 ppb in the wet season.^ One site testing positively for carbofuran exceeded the European MCL and WHO set limit in the wet season, while one site testing positively for the same pesticide exceeded the USA, Canada, European and WHO MCLs in the dry season. Similarly, one site which tested positively for carbaryl pesticide exceeded the European MCL in both seasons.^ Out of the 2,587 community members in the study area, 333 (13%) were exposed through their drinking water sources to the three pesticides investigated by this study. As a public health measure, integrated pest management approaches (IPM), protection of the wells and education of the community is necessary to minimize the pollution of the environment and safeguard the drinking water sources from pollution by the pesticides. ^

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Aim The global spread of woody plants into grasslands is predicted to increase over the coming century. While there is general agreement regarding the anthropogenic causes of this phenomenon, its ecological consequences are less certain. We analysed how woody vegetation of differing cover affects plant diversity (richness and evenness) and the surrogates of multiple ecosystem processes (multifunctionality) in global drylands, and how these change with aridity. Location Two hundred and twenty-four dryland sites from all continents except Antarctica, widely differing in their environmental conditions (from arid to dry-subhumid sites) and relative woody cover (from 0 to 100). Methods Using a standardized field survey, we measured the cover, richness and evenness of perennial vegetation. At each site, we measured 14 soil variables related to fertility and the build-up of nutrient pools. These variables are critical for maintaining ecosystem functioning in drylands. Results Species richness and ecosystem multifunctionality were strongly related to woody vegetation, with both variables peaking at a relative woody cover (RWC) of 41–60. This relationship shifted with aridity. We observed linear positive effects of RWC in dry-subhumid sites. These positive trends shifted to hump-shaped RWC–diversity and multifunctionality relationships under semi-arid environments. Finally, hump-shaped (richness, evenness) or linear negative (multifunctionality) effects of RWC were found under the most arid conditions. Main conclusions Plant diversity and multifunctionality peaked at intermediate levels of woody cover, although this relationship became increasingly positive in wetter environments. This comprehensive study accounts for multiple ecosystem attributes across a range of levels of woody cover and environmental conditions. Our results help us to reconcile contrasting views of woody encroachment found in the current literature and can be used to improve predictions of the likely effects of encroachment on biodiversity and ecosystem services.

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Most existing studies addressing the effects of invasive species on biodiversity focus on species richness ignoring better indicators of biodiversity and better predictors of ecosystem functioning such as the diversity of evolutionary histories (phylodiversity). Moreover, no previous study has separated the direct effect of alien plants on multiple ecosystem functions simultaneously (multifunctionality) from those indirect ones mediated by the decrease on biodiversity caused by alien plants. We aimed to analyze direct and indirect effects, mediated or not by its effect on biodiversity, of the invasive tree Ailanthus altissima on ecosystem multifunctionality of riparian habitats under Mediterranean climate. We measured vegetation attributes (species richness and phylodiversity) and several surrogates of ecosystem functioning (understory plant biomass, soil enzyme activities, available phosphorous and organic matter) in plots infested by A. altissima and in control (non-invaded) ones. We used structural equation modelling to tease apart the direct and indirect effects of A. altissima on ecosystem multifunctionality. Our results suggest that lower plant species richness, phylodiversity and multifunctionality were associated to the presence of A. altissima. When analyzing each function separately, we found that biodiversity has the opposite effect of the alien plant on all the different functions measured, therefore reducing the strength of the effect (either positive or negative) of A. altissima on them. This is one of the few existing studies addressing the effect of invasive species on phylodiversity and also studying the effect of invasive species on multiple ecosystem functions simultaneously.

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This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co-active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose-finding and long-term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit.

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DNA duplexes containing unnatural base-pair surrogates are attractive biomolecular nanomaterials with potentially beneficial photophysical or electronic properties. Herein we report the first X-ray structure of a duplex containing a phen-pair in the center of the double helix in a zipper like stacking arrangement.

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Pencil beam scanned (PBS) proton therapy has many advantages over conventional radiotherapy, but its effectiveness for treating mobile tumours remains questionable. Gating dose delivery to the breathing pattern is a well-developed method in conventional radiotherapy for mitigating tumour-motion, but its clinical efficiency for PBS proton therapy is not yet well documented. In this study, the dosimetric benefits and the treatment efficiency of beam gating for PBS proton therapy has been comprehensively evaluated. A series of dedicated 4D dose calculations (4DDC) have been performed on 9 different 4DCT(MRI) liver data sets, which give realistic 4DCT extracting motion information from 4DMRI. The value of 4DCT(MRI) is its capability of providing not only patient geometries and deformable breathing characteristics, but also includes variations in the breathing patterns between breathing cycles. In order to monitor target motion and derive a gating signal, we simulate time-resolved beams' eye view (BEV) x-ray images as an online motion surrogate. 4DDCs have been performed using three amplitude-based gating window sizes (10/5/3 mm) with motion surrogates derived from either pre-implanted fiducial markers or the diaphragm. In addition, gating has also been simulated in combination with up to 19 times rescanning using either volumetric or layered approaches. The quality of the resulting 4DDC plans has been quantified in terms of the plan homogeneity index (HI), total treatment time and duty cycle. Results show that neither beam gating nor rescanning alone can fully retrieve the plan homogeneity of the static reference plan. Especially for variable breathing patterns, reductions of the effective duty cycle to as low as 10% have been observed with the smallest gating rescanning window (3 mm), implying that gating on its own for such cases would result in much longer treatment times. In addition, when rescanning is applied on its own, large differences between volumetric and layered rescanning have been observed as a function of increasing number of re-scans. However, once gating and rescanning is combined, HI to within 2% of the static plan could be achieved in the clinical target volume, with only moderately prolonged treatment times, irrespective of the rescanning strategy used. Moreover, these results are independent of the motion surrogate used. In conclusion, our results suggest image guided beam gating, combined with rescanning, is a feasible, effective and efficient motion mitigation approach for PBS-based liver tumour treatments.

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Intracavitary brachytherapy (ICB) combined with external beam irradiation for treatment of cervical cancer is highly successful in achieving local control. The M.D. Anderson Cancer Center employs Fletcher Suit Delclos (FSD) applicators. FSD applicators contain shields to limit dose to critical structures. Dosimetric evaluation of ICB implants is limited to assessing dose at reference points. These points serve as surrogates for treatment intensity and critical structure dose. Several studies have mentioned that the ICRU38 reference points inadequately characterize the dose distribution. Also, the ovoid shields are rarely considered in dosimetry. ^ The goal of this dissertation was to ascertain the influence of the ovoid shields on patient dose distributions. Monte Carlo dosimetry (MCD) was applied to patient computed tomography(CT) scans. These data were analyzed to determine the effect of the shields on dose to standard reference points and the bladder and rectum. The hypothesis of this work is that the ICRU38 bladder and rectal points computed conventionally are not clinically acceptable surrogates for the maximum dose points as determined by MCD. ^ MCD was applied to the tandem and ovoids. The FSD ovoids and tandem were modeled in a single input file that allowed dose to be calculated for any patient. Dose difference surface histograms(DDSH) were computed for the bladder and rectum. Reference point doses were compared between shielded and unshielded ovoids, and a commercial treatment planning system. ^ The results of this work showed the tandem tip screw caused a 33% reduction in dose. The ovoid shields reduced the dose by a maximum of 48.9%. DDSHs revealed on average 5% of the bladder surface area was spared 53 cGy and 5% of the rectal surface area was spared 195 cGy. The ovoid shields on average reduced the dose by 18% for the bladder point and 25% for the rectal point. The Student's t-test revealed the ICRU38 bladder and rectal points do not predict the maximum dose for these organs. ^ It is concluded that modeling the tandem and ovoid internal structures is necessary for accurate dose calculations, the bladder shielding segments may not be necessary, and that the ICRU38 bladder point is irrelevant. ^

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Despite extensive research, the etiology of adult glioma remains largely unknown. We sought to further explore the role of immune and genetic factors in glioma etiology using data from the Harris County Brain Tumor Study and the first U.S. genome-wide association study of glioma. First, using a case-control study design, we examined the association between adult glioma risk and surrogates of the timing and frequency of common early childhood infections, birth order and sibship size, respectively. We found that each one-unit increase in birth order was associated with a 12% decreased risk of glioma development in adulthood (OR=0.88, 95% CI=0.81-0.96); however, sibship size was not associated with adult glioma risk (OR=0.96, 95% CI=0.91-1.02). Second, we used a multi-strategic approach to explore the relationships between glioma risk, history of asthma/allergies, and 23 functional SNPs in 11 inflammation genes. We found three inflammation gene SNPs to be significantly associated with glioma risk (COX2/PTGS2 rs20417 [OR=1.41]; IL10 rs1800896 [OR=1.57]; and IL13 rs20541 [OR=0.39]). Joint effects analysis of the risk-conferring alleles of these three SNPs revealed a trend of increasing risk with increasing number of adverse alleles among those without asthma/allergies (p<0.0001). Finally, we conducted a case-only study to explore pairwise SNP-SNP interactions in immune-related pathways among a population of 1304 non-Hispanic white glioma cases. After correction for multiple comparisons, we found 279 significant SNP-SNP interactions among polymorphisms of immune-related genes, many of which have not been previously examined. Our results, cumulatively, suggest an important role for immune and genetic factors in glioma etiology and provide several new hypotheses for future studies.^