992 resultados para controlled variable


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Abstract is not available.

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Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

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Genetic and physiological studies often comprise genotypes diverse in vigour, size and flowering time. This can make the phenotyping of complex traits challenging, particularly those associated with canopy development, biomass and yield, as the environment of one genotype can be influenced by a neighbouring genotype. Limited seed and space may encourage field assessment in single, spaced rows or in small, unbordered plots, whereas the convenience of a controlled environment or greenhouse makes pot studies tempting. However, the relevance of such growing conditions to commercial field-grown crops is unclear and often doubtful. Competition for water, light and nutrients necessary for canopy growth will be variable where immediate neighbours are genetically different, particularly under stress conditions, where competition for resources and influence on productivity is greatest. Small hills and rod-rows maximise the potential for intergenotypic competition that is not relevant to a crop’s performance in monocultures. Response to resource availability will typically vary among diverse genotypes to alter genotype ranking and reduce heritability for all growth-related traits, with the possible exception of harvest index. Validation of pot experiments to performance in canopies in the field is essential, whereas the planting of multirow plots and the simple exclusion of plot borders at harvest will increase experimental precision and confidence in genotype performance in target environments.

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We propose a family of multivariate heavy-tailed distributions that allow variable marginal amounts of tailweight. The originality comes from introducing multidimensional instead of univariate scale variables for the mixture of scaled Gaussian family of distributions. In contrast to most existing approaches, the derived distributions can account for a variety of shapes and have a simple tractable form with a closed-form probability density function whatever the dimension. We examine a number of properties of these distributions and illustrate them in the particular case of Pearson type VII and t tails. For these latter cases, we provide maximum likelihood estimation of the parameters and illustrate their modelling flexibility on simulated and real data clustering examples.

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The application of variable-number tandem repeats (VNTR) genotyping of Mycobacterium avium subsp. paratuberculosis isolates to assist in investigating incidents of bovine Johne’s disease in a low-prevalence region of Australia is described in the current study. Isolates from a response to detection of bovine Johne’s disease in Queensland were compared with strains from national and international sources. The tandem application of mycobacterial interspersed repetitive unit (MIRU) and multilocus short sequence repeats (MLSSR) genotyping identified 2 strains, 1 that infected cattle on multiple properties with trace-forward histories from a common infected property, and 1 genotypically different strain recovered from a single property. The former strain showed an identical genotype to an isolate from India. Neither strain showed a genotypic link to regions of Australia with a higher prevalence of the disease. Genotyping has indicated incursions from 2 independent sources. This intelligence has informed investigations into potential routes of entry and the soundness of ongoing control measures, and supported strategy and policy decisions regarding management of Mycobacterium avium subsp. paratuberculosis incursions for Queensland.

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Effects of large deformation and inelasticity are considered in formulating the behavior of columns of variable cross section subjected to an axial compressive load. Simple, approximate methods are used to obtain numerical results. The combined effect of the nonlinearities is shown to be of a hardening type for small column deflections

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Kontrolloidut radikaalipolymerointimenetelmät, kuten RAFT-polymerointi, ovat moderni tapa valmistaa polymeerejä säädellysti. RAFT-polymeroinnilla polymeerien ketjunpituutta, moolimassajakaumaa, mikrorakennetta (taktisuus, järjestys), koostumusta ja funktionaalisuutta kyetään hallitsemaan. Siten menetelmällä voidaan valmistaa uudenlaisia polymeeriarkkitektuureja, kuten blokki- ja tähtipolymeerejä, sekä hybridimateriaaleja ja biokonjugaatteja. Polymeeristen rakennuspalikoiden itsejärjestyminen, missä huolellisesti syntetisoidut polymeerit järjestyvät halutulla tavalla nanoskaalassa, on suosittu tutkimuskohde materiaalitieteessä. On huomattava, että blokkipolymeerien itsejärjestyminen on vielä suhteellisen nuori tutkimusaihe. Tämän hetkiset polymeeriset nanomateriaalit ovat suhteellisen yksinkertaisia luonnon luomuksiin verrattuina, tarjoten jatkuvasti uusia mahdollisuuksia seuraavan sukupolven polymeereille. Tässä työssä RAFT-polymeroinnilla syntetisoitiin amfifiilisiä di- ja triblokkikopolymeerejä sekä tutkittiin niiden järjestymistä nanorakenteiksi. Kaikissa blokkikopolymeereissä käytettiin lämpöherkkää poly(N-isopropyyliakryyliamidia). Siten polymeerit ja tutkitut materiaalit reagoivat lämpötilanmuutokseen ympäristössä eli ovat ns. ympäristöherkkiä. Työssä tutkittiin taktisuuden kontrollointia N-isopropyyliakryyliamidin RAFT-polymeroinnissa. Polymeerin taktisuutta sekä ketjunpituutta ja blokkijärjestystä säätämällä voitiin hallita polymeerin itsejärjestymistä vesiliuoksessa. Amfifiiliset polymeerit järjestyivät laimeissa vesiliuoksissa erilaisiksi misellirakenteiksi, muodostaen ns. mikrosäiliöitä. Tällaisilla polymeereillä odotetaan olevan sovelluksia esim. lääkeainevapautuksessa. Amfifiilejä käytetään myös esimerkiksi apuaineina pinnoitteissa ja kosmetiikassa. Kiinteässä tilassa tutkitut triblokkikopolymeerit muodostivat teoreettisesti ennustettuja morfologioita. Lämpöherkän materiaalin hydrogeelit toimivat suodatinmembraanina nanokokoluokassa. RAFT-polymeroinnilla syntetisoituja polymeereja voidaan sellaisenaan käyttää kultananopartikkeleiden päällystämiseen. Kultananopartikkelit ovat erittäin kiinostavia mm. niiden stabiilisuuden ja ainutlaatuisten pintaominaisuuksien vuoksi. Kun amfifiilisiä polymeerejä kiinnitettiin kultapartikkelin pinnalle, sen liuos- ja optisia ominaisuuksia voitiin säädellä pH:n ja lämpötilan avulla. Tällaisilla kultananopartikkeleilla on sovelluksia mm. diagnostiikassa, sensoreina ja solukuvauksessa.

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Climatic variability in dryland production environments (E) generates variable yield and crop production risks. Optimal combinations of genotype (G) and management (M) depend strongly on E and thus vary among sites and seasons. Traditional crop improvement seeks broadly adapted genotypes to give best average performance under a standard management regime across the entire production region, with some subsequent manipulation of management regionally in response to average local environmental conditions. This process does not search the full spectrum of potential G × M × E combinations forming the adaptation landscape. Here we examine the potential value (relative to the conventional, broad adaptation approach) of exploiting specific adaptation arising from G × M × E. We present an in-silico analysis for sorghum production in Australia using the APSIM sorghum model. Crop design (G × M) is optimised for subsets of locations within the production region (specific adaptation) and is compared with the optimum G across all environments with locally modified M (broad adaptation). We find that geographic subregions that have frequencies of major environment types substantially different from that for the entire production region show greatest advantage for specific adaptation. Although the specific adaptation approach confers yield and production risk advantages at industry scale, even greater benefits should be achievable with better predictors of environment-type likelihood than that conferred by location alone.

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Significant genotypic differences in tolerance of pollen germination and seed set to high temperatures have been shown in sorghum. However, it is unclear whether differences were associated with variation in either the threshold temperature above which reproductive processes are affected, or in the tolerance to increased temperature above that threshold. The objectives of this study were to (a) dissect known differences in heat tolerance for a range of sorghum genotypes into differences in the threshold temperature and tolerance to increased temperatures, (b) determine whether poor seed set under high temperatures can be compensated by increased seed mass, and (c) identify whether genotypic differences in heat tolerance in a controlled environment facility (CEF) can be reproduced in field conditions. Twenty genotypes were grown in a CEF under four day/night temperatures (31.9/21.0 °C, 32.8/21.0 °C, 36.1/21.0 °C, and 38.0/21.0 °C), and a subset of six genotypes was grown in the field under four different temperature regimes around anthesis. The novelty of the findings in this study related to differences in responsiveness to high temperature—genotypic differences in seed set percentage were found for both the threshold temperature and the tolerance to increased maximum temperature above that threshold. Further, the response of seed set to high temperature in the field study was well correlated to that in the CEF (R2 = 0.69), although the slope was significantly less than unity, indicating that heat stress effects may have been diluted under the variable field conditions. Poor seed set was not compensated by increased seed mass in either CEF or field environments. Grain yield was thus closely related to seed set percentage. This result demonstrates the potential for development of a low-cost field screening method to identify high-temperature tolerant varieties that could deliver sustainable yields under future warmer climates.

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A rationally designed two-step synthesis of silica vesicles is developed with the formation of vesicular structure in the first step and fine control over the entrance size by tuning the temperature in the second step. The silica vesicles have a uniform size of ≈50 nm with excellent cellular uptake performance. When the entrance size is equal to the wall thickness, silica vesicles after hydrophobic modification show the highest loading amount (563 mg/g) towards Ribonuclease A with a sustained release behavior. Consequently, the silica vesicles are excellent nano-carriers for cellular delivery applications of therapeutical biomolecules.

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Background: Falls remain the most frequent adverse event reported in hospitals, particularly geriatric rehabilitation wards. Randomised trials reducing fall injuries in hospitals have been elusive. Our previous randomised trial (n = 1206) demonstrated that multimedia education with physiotherapist falls educator support reduced falls among patients with higher cognition levels, but this benefit was offset by a potential increase in falls rates among patients with poor cognition. In the previous trial, hospital staff were blinded to the allocation of individual patients, and only delivered usual care.