134 resultados para SURROGATES


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The Iowa Department of Transportation (IaDOT) was interested in investigating the use of epoxy adhesive anchorages for the attachment of posts used in the BR27C combination bridge rail system. Alternative anchorage concepts were developed using a modified version of the ACI 318-11 procedures for embedded anchor design. Four design concepts were developed for review by IaDOT, including: (1) a four-bolt square anchorage, (2) a four-bolt spread anchorage, (3) a twobolt centered anchorage, and (4) a two-bolt offset anchorage. IaDOT representatives selected the four-bolt spread anchorage and the two-bolt offset anchorage as the preferred designs for evaluation. In addition to these two proposed configurations, IaDOT also requested that the researchers evaluate a third option that had been previously installed on the US-20 bridge near Hardin, IA. The proposed alternative anchorages and the original cast-in-place anchorage for the BR27C combination bridge rail were evaluated through dynamic component testing. The test of the original cast-in-place anchorage was used a baseline for comparison with the alternative designs. Test no. IBP-1 of the original cast-in-place anchorage developed a peak load of 22.9 kips (101.9 kN) at a deflection of 1.5 in. (38 mm). All three of the tested alternative anchorages provided greater load capacity than the original cast-in-place design and were deemed acceptable surrogates. Of the three alternative designs, the two-bolt offset design was deemed the best option.

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Although gene by environment interactions may play a key role in the maintenance of genetic polymorphisms, little is known about the ecological factors involved in these interactions. We investigated whether food supply and parasites can mediate covariation between the degree of adult pheomelanin-based coloration, a heritable trait, and offspring body mass in the tawny owl (Strix aluco). We swapped clutches between nests to allocate genotypes randomly among environments. Three weeks after hatching, we challenged the immune system of 80 unrelated nestlings with either a phytohemagglutinin (PHA) or a lipopolysaccharide, surrogates of alternative parasites, and then fed them ad lib. or food-restricted them during the following 6 days in the laboratory. Whatever the immune challenge, nestlings fed ad lib. converted food more efficiently into body mass when their biological mother was dark pheomelanic. In contrast, food-restricted nestlings challenged with PHA lost less body mass when their biological mother was pale pheomelanic. Nestling tawny owls born from differently melanic mothers thus show differing reaction norms relative to food availability and parasitism. This suggests that dark and pale pheomelanic owls reflect alternative adaptations to food availability and parasites, factors known to vary in space and time.

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The application of statistics to science is not a neutral act. Statistical tools have shaped and were also shaped by its objects. In the social sciences, statistical methods fundamentally changed research practice, making statistical inference its centerpiece. At the same time, textbook writers in the social sciences have transformed rivaling statistical systems into an apparently monolithic method that could be used mechanically. The idol of a universal method for scientific inference has been worshipped since the "inference revolution" of the 1950s. Because no such method has ever been found, surrogates have been created, most notably the quest for significant p values. This form of surrogate science fosters delusions and borderline cheating and has done much harm, creating, for one, a flood of irreproducible results. Proponents of the "Bayesian revolution" should be wary of chasing yet another chimera: an apparently universal inference procedure. A better path would be to promote both an understanding of the various devices in the "statistical toolbox" and informed judgment to select among these.

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BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.

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RATIONALE: Limited-channel portable monitors (PMs) are increasingly used as an alternative to polysomnography (PSG) for the diagnosis of obstructive sleep apnoea (OSA). However, recommendations for the scoring of PM recordings are still lacking. Pulse-wave amplitude (PWA) drops, considered as surrogates for EEG arousals, may increase the detection sensitivity for respiratory events in PM recordings. OBJECTIVES: To investigate the performance of four different hypopnoea scoring criteria, using 3% or 4% oxygen desaturation levels, including or not PWA drops as surrogates for EEG arousals, and to determine the impact of measured versus reported sleep time on OSA diagnosis. METHODS: Subjects drawn from a population-based cohort underwent a complete home PSG. The PSG recordings were scored using the 2012 American Academy of Sleep Medicine criteria to determine the apnoea-hypopnoea index (AHI). Recordings were then rescored using only parameters available on type 3 PM devices according to different hypopnoea criteria and patients-reported sleep duration to determine the 'portable monitor AHIs' (PM-AHIs). MAIN RESULTS: 312 subjects were included. Overall, PM-AHIs showed a good concordance with the PSG-based AHI although it tended to slightly underestimate it. The PM-AHI using 3% desaturation without PWA drops showed the best diagnostic accuracy for AHI thresholds of ≥5/h and ≥15/h (correctly classifying 94.55% and 93.27% of subjects, respectively, vs 80.13% and 87.50% with PWA drops). There was a significant but modest correlation between PWA drops and EEG arousals (r=0.20, p=0.0004). CONCLUSION: Interpretation of PM recordings using hypopnoea criteria which include 3% desaturation without PWA drops as EEG arousal surrogate showed the best diagnosis accuracy compared with full PSG.

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1. Digital elevation models (DEMs) are often used in landscape ecology to retrieve elevation or first derivative terrain attributes such as slope or aspect in the context of species distribution modelling. However, DEM-derived variables are scale-dependent and, given the increasing availability of very high-resolution (VHR) DEMs, their ecological relevancemust be assessed for different spatial resolutions. 2. In a study area located in the Swiss Western Alps, we computed VHR DEMs-derived variables related to morphometry, hydrology and solar radiation. Based on an original spatial resolution of 0.5 m, we generated DEM-derived variables at 1, 2 and 4 mspatial resolutions, applying a Gaussian Pyramid. Their associations with local climatic factors, measured by sensors (direct and ambient air temperature, air humidity and soil moisture) as well as ecological indicators derived fromspecies composition, were assessed with multivariate generalized linearmodels (GLM) andmixed models (GLMM). 3. Specific VHR DEM-derived variables showed significant associations with climatic factors. In addition to slope, aspect and curvature, the underused wetness and ruggedness indices modelledmeasured ambient humidity and soilmoisture, respectively. Remarkably, spatial resolution of VHR DEM-derived variables had a significant influence on models' strength, with coefficients of determination decreasing with coarser resolutions or showing a local optimumwith a 2 mresolution, depending on the variable considered. 4. These results support the relevance of using multi-scale DEM variables to provide surrogates for important climatic variables such as humidity, moisture and temperature, offering suitable alternatives to direct measurements for evolutionary ecology studies at a local scale.

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Skeletal tissue is constantly remodeled in a process where osteoclasts resorb old bone and osteoblasts form new bone. Balance in bone remodeling is related to age, gender and genetic factors, but also many skeletal diseases, such as osteoporosis and cancer-induced bone metastasis, cause imbalance in bone turnover and lead to decreased bone mass and increased fracture risk. Biochemical markers of bone turnover are surrogates for bone metabolism and may be used as indicators of the balance between bone resorption and formation. They are released during the remodeling process and can be conveniently and reliably measured from blood or urine by immunoassays. Most commonly used bone formation markers include N-terminal propeptides of type I collagen (PINP) and osteocalcin, whereas tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) and C-terminal cross-linked telopeptide of type I collagen (CTX) are common resorption markers. Of these, PINP has been, until recently, the only marker not commercially available for preclinical use. To date, widespread use of bone markers is still limited due to their unclear biological significance, variability, and insufficient evidence of their prognostic value to reflect long term changes. In this study, the feasibility of bone markers as predictors of drug efficacy in preclinical osteoporosis models was elucidated. A non-radioactive PINP immunoassay for preclinical use was characterized and validated. The levels of PINP, N-terminal mid-fragment of osteocalcin, TRACP 5b and CTX were studied in preclinical osteoporosis models and the results were compared with the results obtained by traditional analysis methods such as histology, densitometry and microscopy. Changes in all bone markers at early timepoints correlated strongly with the changes observed in bone mass and bone quality parameters at the end of the study. TRACP 5b correlated strongly with the osteoclast number and CTX correlated with the osteoclast activity in both in vitro and in vivo studies. The concept “resorption index” was applied to the relation of CTX/TRACP 5b to describe the mean osteoclast activity. The index showed more substantial changes than either of the markers alone in the preclinical osteoporosis models used in this study. PINP was strongly associated with bone formation whereas osteocalcin was associated with both bone formation and resorption. These results provide novel insight into the feasibility of PINP, osteocalcin, TRACP 5b and CTX as predictors of drug efficacy in preclinical osteoporosis models. The results support clinical findings which indicate that short-term changes of these markers reflect long-term responses in bone mass and quality. Furthermore, this information may be useful when considering cost-efficient and clinically predictive drug screening and development assays for mining new drug candidates for skeletal diseases.

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A simple and low cost method to determine volatile contaminants in post-consumer recycled PET flakes was developed and validated by Headspace Dynamic Concentration and Gas Chromatography-Flame Ionization Detection (HDC-GC-FID). The analytical parameters evaluated by using surrogates include: correlation coefficient, detection limit, quantification limit, accuracy, intra-assay precision, and inter-assay precision. In order to compare the efficiency of the proposed method to recognized automated techniques, post-consumer PET packaging samples collected in Brazil were used. GC-MS was used to confirm the identity of the substances identified in the PET packaging. Some of the identified contaminants were estimated in the post-consumer material at concentrations higher than 220 ng.g-1. The findings in this work corroborate data available in the scientific literature pointing out the suitability of the proposed analytical method.

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This annotated bibliography provides an account of the research that has been done on engineering resilience, ecological resilience, and social-ecological resilience. Undertaken as part of the WEPGN research project titled “Applying resilience analysis to a transboundary river system: Developing surrogates for institutions and governance”, this annotated bibliography investigates factors that lead to greater resilience, with a focus on institutions and governance. Citations for key scholarly publications related to three types of resilience – engineering, ecological, and social-ecological – are listed in the first three sections along with a brief summary of each work. The fourth and final section of the document provides additional resources on resilience.

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Une stratégie de synthèse efficace de différents composés de type azabicyclo[X.Y.0]alkanone fonctionnalisés a été développée. La stratégie synthétique implique la préparation de dipeptides par couplage avec des motifs vinyl-, allyl-, homoallyl- et homohomoallylglycine suivi d’une réaction de fermeture de cycle par métathèse permettant d’obtenir des lactames macrocycliques de 8, 9 et 10 membres, qui subissent une iodolactamisation transannulaire menant à l’obtention de mimes peptidiques bicycliques portant un groupement iode. Des couplages croisés catalysés par des métaux de transition ont été développés pour la synthèse d’acides aminés ω-insaturés énantiomériquement purs à partir de l’iodoanaline. L’étude du mécanisme suggère que l’iodure subit une attaque du coté le moins stériquement encombré de la lactame macrocyclique insaturée pour mener à l’obtention d’un intermédiaire iodonium. La cyclisation se produit ensuite par une route minimisant les interactions diaxiales et la tension allylique. L’iodolactamisation des différentes lactames macrocycliques insaturées a mené à l’obtention regio- et diastéréosélective d’acides aminés 5,5- et 6,6-iodobicycicliques. De plus, une imidate azabicyclo[4.3.1]alkane pontée de type anti-Bredt fut synthétisée à partir d’une lactame macrocyclique insaturé à neuf membres. Les analyses cristallographiques et spectroscopiques des macrocycles à 8, 9 et 10 membres, du composé iodobicyclique 5,5 ainsi que de l’imidate pontée, montrent bien le potentiel de ces dipeptides rigidifiés de servir en tant que mimes des résidus centraux de tours β de type I, II’, II et VI.

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Introducción: Ingresar a la UCI no es una experiencia exclusiva del paciente; implica e involucra directamente a la familia, en aspectos generadores de estrés, estrategias de afrontamiento, temores, actitudes y expectativas, la participación de la familia en el cuidado y el rol del psicólogo. Objetivo: Revisar de los antecedentes teóricos y empíricos sobre la experiencia de la familia en UCI. Metodología: Se revisaron 62 artículos indexados en bases de datos. Resultados: la UCI es algo desconocido tanto para el paciente como para la familia, por esto este entorno acentúa la aparición de síntomas ansiosos, depresivos y en algunos casos estrés post traumático. La muerte es uno de los principales temores que debe enfrentar la familia. Con el propósito de ajustarse a las demandas de la UCI, los familiares exhiben estrategias de afrontamiento enfocadas principalmente en la comunicación, el soporte espiritual y religioso y la toma de decisiones. El cuidado centrado en la familia permite una mejor comunicación, relación con el paciente y personal médico. El papel del psicólogo es poco explorado en el espacio de la UCI, pero este puede promover estrategias de prevención y de rehabilitación en el paciente y su grupo familiar. Discusión: es importante tener en cuenta que la muerte en UCI es una posibilidad, algunos síntomas como ansiedad, depresión pueden aparecer y mantenerse en el tiempo, centrar el cuidado en la familia permite tomar las decisiones basados en el diagnóstico y pronóstico y promueve expectativas realistas. Conclusiones: temores, expectativas, actitudes, estrategias de afrontamiento, factores generadores de estrés permiten explicar y comprender la experiencia de la familia del paciente en UCI.

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Man-made wetlands are often created to compensate for the loss or degradation of natural wetlands, but little is known about the processes taking place in these artificial environments, especially at the community level. Throughout this thesis, we have assessed the phenomena of primary succession over different time (short-, mid- and long-term) and spatial scales (local, regional, interregional levels), applying different approaches (taxonomic and functional) and subject groups (invertebrates and amphibians). Our main findings regarding time scales show a 3-phase successional pattern in Mediterranean man-made wetlands’ communities, where at the short term (1 year) colonization processes dominate; at mid term perspectives (2 to 7 years) succession signs begin to be conspicuous, and later on (≥ 10 years) parameters such as species richness reach an asymptote. At that moment, some biological strategies dominate, and biodiversity surrogates indicate that communities are indistinct between man-made and natural wetlands. Regarding spatial effects, we corroborated that both local and regional factors affect the establishing communities. Particularly, the low hydrological stability of the Mediterranean region has enhanced biological traits favoring resilience and resistance to disturbances when comparing Mediterranean and cold temperate aquatic communities. Even within the Mediterranean region, low levels of hydrological stability have significant effects on the successional dynamics. In these cases, local communities are highly nested within regional natural ones, and so are not able to make net contributions to regional richness. We also showed the influence of the regional pool of recruiters over local communities, both in the case of invertebrates and amphibians. Especially for the latter group, man-made Mediterranean temporary ponds (MTPs) can play an important role in their conservation.

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Following on from the companion study (Johnson et al., 2006), a photochemical trajectory model (PTM) has been used to simulate the chemical composition of organic aerosol for selected events during the 2003 TORCH (Tropospheric Organic Chemistry Experiment) field campaign. The PTM incorporates the speciated emissions of 124 nonmethane anthropogenic volatile organic compounds (VOC) and three representative biogenic VOC, a highly-detailed representation of the atmospheric degradation of these VOC, the emission of primary organic aerosol (POA) material and the formation of secondary organic aerosol (SOA) material. SOA formation was represented by the transfer of semi and non-volatile oxidation products from the gas-phase to a condensed organic aerosol-phase, according to estimated thermodynamic equilibrium phase-partitioning characteristics for around 2000 reaction products. After significantly scaling all phase-partitioning coefficients, and assuming a persistent background organic aerosol (both required in order to match the observed organic aerosol loadings), the detailed chemical composition of the simulated SOA has been investigated in terms of intermediate oxygenated species in the Master Chemical Mechanism, version 3.1 ( MCM v3.1). For the various case studies considered, 90% of the simulated SOA mass comprises between ca. 70 and 100 multifunctional oxygenated species derived, in varying amounts, from the photooxidation of VOC of anthropogenic and biogenic origin. The anthropogenic contribution is dominated by aromatic hydrocarbons and the biogenic contribution by alpha-and beta-pinene (which also constitute surrogates for other emitted monoterpene species). Sensitivity in the simulated mass of SOA to changes in the emission rates of anthropogenic and biogenic VOC has also been investigated for 11 case study events, and the results have been compared to the detailed chemical composition data. The role of accretion chemistry in SOA formation, and its implications for the results of the present investigation, is discussed.

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1. Species-based indices are frequently employed as surrogates for wider biodiversity health and measures of environmental condition. Species selection is crucial in determining an indicators metric value and hence the validity of the interpretation of ecosystem condition and function it provides, yet an objective process to identify appropriate indicator species is frequently lacking. 2. An effective indicator needs to (i) be representative, reflecting the status of wider biodiversity; (ii) be reactive, acting as early-warning systems for detrimental changes in environmental conditions; (iii) respond to change in a predictable way. We present an objective, niche-based approach for species' selection, founded on a coarse categorisation of species' niche space and key resource requirements, which ensures the resultant indicator has these key attributes. 3. We use UK farmland birds as a case study to demonstrate this approach, identifying an optimal indicator set containing 12 species. In contrast to the 19 species included in the farmland bird index (FBI), a key UK biodiversity indicator that contributes to one of the UK Government's headline indicators of sustainability, the niche space occupied by these species fully encompasses that occupied by the wider community of 62 species. 4. We demonstrate that the response of these 12 species to land-use change is a strong correlate to that of the wider farmland bird community. Furthermore, the temporal dynamics of the index based on their population trends closely matches the population dynamics of the wider community. However, in both analyses, the magnitude of the change in our indicator was significantly greater, allowing this indicator to act as an early-warning system. 5. Ecological indicators are embedded in environmental management, sustainable development and biodiversity conservation policy and practice where they act as metrics against which progress towards national, regional and global targets can be measured. Adopting this niche-based approach for objective selection of indicator species will facilitate the development of sensitive and representative indices for a range of taxonomic groups, habitats and spatial scales.

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Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-mediated vasodilation (FMD)) that plateaued after 2 weeks. Subsequently, in a randomised, controlled, double-masked, parallel-group dietary intervention trial (Clinicaltrials.gov: NCT01799005), 100 healthy, middle-aged (35–60 years) men and women consumed either the CF-containing drink (450 mg) or a nutrient-matched CF-free control bi-daily for 1 month. The primary end point was FMD. Secondary end points included plasma lipids and blood pressure, thus enabling the calculation of Framingham Risk Scores and pulse wave velocity. At 1 month, CF increased FMD over control by 1·2 % (95 % CI 1·0, 1·4 %). CF decreased systolic and diastolic blood pressure by 4·4 mmHg (95 % CI 7·9, 0·9 mmHg) and 3·9 mmHg (95 % CI 6·7, 0·9 mmHg), pulse wave velocity by 0·4 m/s (95 % CI 0·8, 0·04 m/s), total cholesterol by 0·20 mmol/l (95 % CI 0·39, 0·01 mmol/l) and LDL-cholesterol by 0·17 mmol/l (95 % CI 0·32, 0·02 mmol/l), whereas HDL-cholesterol increased by 0·10 mmol/l (95 % CI 0·04, 0·17 mmol/l). By applying the Framingham Risk Score, CF predicted a significant lowering of 10-year risk for CHD, myocardial infarction, CVD, death from CHD and CVD. In healthy individuals, regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk, demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects.