849 resultados para Integración of methods
Resumo:
The proteasome has been validated as a therapeutic target, with proteasome inhibitors showing particular efficacy in the treatment of Multiple Myeloma. A wide range of methods have been developed to profile proteasome activity. These include the current method of choice fluorogenic peptide substrates, as well as bioluminescent imaging, immunological methods, and more recently, site-specific fluorescent probes. The aim of this review is to evaluate the currently available methods for profiling proteasome activity and their suitability for use in translational studies. Ongoing development of techniques for profiling proteasome activity will facilitate future research into proteasome-related pathologies, thus accelerating the development of more specific drug regimes. (C) 2010 Elsevier Ltd. All rights reserved.
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Background: Postal and electronic questionnaires are widely used for data collection in epidemiological studies but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of health research. Objectives: To identify effective strategies to increase response to postal and electronic questionnaires. Search strategy: We searched 14 electronic databases to February 2008 and manually searched the reference lists of relevant trials and reviews, and all issues of two journals. We contacted the authors of all trials or reviews to ask about unpublished trials. Where necessary, we also contacted authors to confirm methods of allocation used and to clarify results presented. We assessed the eligibility of each trial using pre-defined criteria. Selection criteria: Randomised controlled trials of methods to increase response to postal or electronic questionnaires. Data collection and analysis: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity among trial odds ratios using a Chi 2 test and the degree of inconsistency between trial results was quantified using the I 2 statistic. Main results: Postal We found 481 eligible trials.The trials evaluated 110 different ways of increasing response to postal questionnaires.We found substantial heterogeneity among trial results in half of the strategies. The odds of response were at least doubled using monetary incentives (odds ratio 1.87; 95% CI 1.73 to 2.04; heterogeneity P < 0.00001, I 2 = 84%), recorded delivery (1.76; 95% CI 1.43 to 2.18; P = 0.0001, I 2 = 71%), a teaser on the envelope - e.g. a comment suggesting to participants that they may benefit if they open it (3.08; 95% CI 1.27 to 7.44) and a more interesting questionnaire topic (2.00; 95% CI 1.32 to 3.04; P = 0.06, I 2 = 80%). The odds of response were substantially higher with pre-notification (1.45; 95% CI 1.29 to 1.63; P < 0.00001, I 2 = 89%), follow-up contact (1.35; 95% CI 1.18 to 1.55; P < 0.00001, I 2 = 76%), unconditional incentives (1.61; 1.36 to 1.89; P < 0.00001, I 2 = 88%), shorter questionnaires (1.64; 95%CI 1.43 to 1.87; P < 0.00001, I 2 = 91%), providing a second copy of the questionnaire at follow up (1.46; 95% CI 1.13 to 1.90; P < 0.00001, I 2 = 82%), mentioning an obligation to respond (1.61; 95% CI 1.16 to 2.22; P = 0.98, I 2 = 0%) and university sponsorship (1.32; 95% CI 1.13 to 1.54; P < 0.00001, I 2 = 83%). The odds of response were also increased with non-monetary incentives (1.15; 95% CI 1.08 to 1.22; P < 0.00001, I 2 = 79%), personalised questionnaires (1.14; 95% CI 1.07 to 1.22; P < 0.00001, I 2 = 63%), use of hand-written addresses (1.25; 95% CI 1.08 to 1.45; P = 0.32, I 2 = 14%), use of stamped return envelopes as opposed to franked return envelopes (1.24; 95% CI 1.14 to 1.35; P < 0.00001, I 2 = 69%), an assurance of confidentiality (1.33; 95% CI 1.24 to 1.42) and first class outward mailing (1.11; 95% CI 1.02 to 1.21; P = 0.78, I 2 = 0%). The odds of response were reduced when the questionnaire included questions of a sensitive nature (0.94; 95% CI 0.88 to 1.00; P = 0.51, I 2 = 0%). Electronic: We found 32 eligible trials. The trials evaluated 27 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were increased by more than a half using non-monetary incentives (1.72; 95% CI 1.09 to 2.72; heterogeneity P < 0.00001, I 2 = 95%), shorter e-questionnaires (1.73; 1.40 to 2.13; P = 0.08, I 2 = 68%), including a statement that others had responded (1.52; 95% CI 1.36 to 1.70), and a more interesting topic (1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third using a lottery with immediate notification of results (1.37; 95% CI 1.13 to 1.65), an offer of survey results (1.36; 95% CI 1.15 to 1.61), and using a white background (1.31; 95% CI 1.10 to 1.56). The odds of response were also increased with personalised e-questionnaires (1.24; 95% CI 1.17 to 1.32; P = 0.07, I 2 = 41%), using a simple header (1.23; 95% CI 1.03 to 1.48), using textual representation of response categories (1.19; 95% CI 1.05 to 1.36), and giving a deadline (1.18; 95% CI 1.03 to 1.34). The odds of response tripled when a picture was included in an e-mail (3.05; 95% CI 1.84 to 5.06; P = 0.27, I 2 = 19%). The odds of response were reduced when "Survey" was mentioned in the e-mail subject line (0.81; 95% CI 0.67 to 0.97; P = 0.33, I 2 = 0%), and when the e-mail included a male signature (0.55; 95% CI 0.38 to 0.80; P = 0.96, I 2 = 0%). Authors' conclusions: Health researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this systematic review. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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The development of methods providing reliable estimates of demographic parameters (e. g., survival rates, fecundity) for wild populations is essential to better understand the ecology and conservation requirements of individual species. A number of methods exist for estimating the demographics of stage-structured populations, but inherent mathematical complexity often limits their uptake by conservation practitioners. Estimating survival rates for pond-breeding amphibians is further complicated by their complex migratory and reproductive behaviours, often resulting in nonobservable states and successive cohorts of eggs and tadpoles. Here we used comprehensive data on 11 distinct breeding toad populations (Bufo calamita) to clarify and assess the suitability of a relatively simple method [the Kiritani-Nakasuji-Manly (KNM) method] to estimate the survival rates of stage-structured populations with overlapping life stages. The study shows that the KNM method is robust and provides realistic estimates of amphibian egg and larval survival rates for species in which breeding can occur as a single pulse or over a period of several weeks. The study also provides estimates of fecundity for seven distinct toad populations and indicates that it is essential to use reliable estimates of fecundity to limit the risk of under- or overestimating the survival rates when using the KNM method. Survival and fecundity rates for B. calamita populations were then used to define population matrices and make a limited exploration of their growth and viability. The findings of the study recently led to the implementation of practical conservation measures at the sites where populations were most vulnerable to extinction. © 2010 The Society of Population Ecology and Springer.
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Research Findings: Under the United Nations Convention on the Rights of the Child (UNCRC), children have the right to express their views on all matters affecting them and to have those views given due weight. This right applies in the context of research; however, examples of young children being engaged as co-researchers remain rare. Practice or Policy: This article examines the implications of adopting an explicit UNCRC-informed approach to engaging children as co-researchers. It draws on a research project that sought to ascertain young children's views on after-school programs and that involved a university-based research team working along with 2 groups of co-researchers; each composed of 4 children aged 4 to 5. The article discusses the contribution made by children to the development of the research questions and choice of methods and their involvement in the interpretation of the data and dissemination of the findings. It suggests that, although there are limits to what young children can and will want to do in the context of adult-led research studies, an explicit UNCRC-informed approach requires the adoption of supportive strategies that can assist children to engage in a meaningful way, with consequent benefits for the research findings and outputs
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STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.
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Methods for rapid and simple analysis of lipopolysaccharide (LPS) from bacterial whole-cell lysates or membrane preparations have contributed to advancing our knowledge of the genetics of the LPS biogenesis. LPS, a major constituent of the outer membranes in Gram-negative bacteria, has a complex mechanism of synthesis and assembly that requires the coordinated participation of many genes and gene products. This chapter describes a collection of methods routinely used in our laboratory for the characterization of LPS in Escherichia coli and other bacteria.
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Computer-aided drug design becomes an important part of G-protein coupled receptors (GPCR) drug discovery process that is applied for improving the efficiency of derivation and optimization of novel ligands. It represents the combination of methods that-use-structural information of a receptor binding site of known ligands to design new ligands. In this report, we give a brief description of ligand binding sites in cholecystokinin and gastrin receptors (CK1R and CCK2R) which were delineated using experimental and computational methods, and then, we show how the validated ligand binding sites can be used to design and improve novel ligands. The translation of the knowledge of ligand-binding sites of different GPCRs to computer-aided design of novel ligands is summarized.
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Diffuse contaminants can make their way into rivers via a number of different pathways, including overland flow, interflow, and shallow and deep groundwater. Identification of the key pathway(s) delivering contaminants to a receptor is important for implementing effective water management strategies. The ‘Pathways Project’, funded by the Irish Environmental Protection Agency, is developing a catchment management tool that will enable practitioners to identify the critical source areas for diffuse contaminants, and the key pathways of interest in assessing contaminant problems on a catchment and sub-catchment scale.
One of the aims of the project is to quantify the flow and contaminant loadings being delivered to the stream via each of the main pathways. Chemical separation of stream event hydrographs is being used to supplement more traditional physical hydrograph separation methods. Distinct, stable chemical signatures are derived for each of the pathway end members, and the proportion of flow from each during a rainfall event can be determined using a simple mass balance approach.
Event sampling was carried out in a test catchment underlain by poorly permeable soils and bedrock, which is predominantly used for grazing with a number of one-off rural residential houses. Results show that artificial field drainage, which includes subterranean land drains and collector drains around the perimeters of the 1 to 10 ha fields, plays an important role in the delivery of flow and nutrients to the streams in these types of hydrogeological settings.
Nitrate infiltrates with recharge and is delivered to the stream primarily via the artificial drains and the shallow groundwater pathway. Longitudinal stream profiles show that the nitrate load input is relatively uniform over the 8 km length of the stream at high flows, suggesting widespread diffuse contaminant input. In contrast, phosphorus is adsorbed in the clay-rich soil and is transported mainly via the overland flow pathway and the artificial drains. Longitudinal stream profiles for phosphorus suggest a pattern of more discrete points of phosphorus inputs, which may be related to point sources of contamination.
These techniques have application elsewhere within a toolkit of methods for determining the key pathways delivering contaminants to surface water receptors.
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The importance of accurately measuring gas diffusivity in porous materials has led to a number of methods being developed. In this study the Temporal Analysis of Products (TAP) reactor and Flux Response Technology (FRT) have been used to examine the diffusivity in the washcoat supported on cordierite monoliths. Herein, the molecular diffusion of propane within four monoliths with differently prepared alumina/CeZrOx washcoats was investigated as a function of temperature. Moment-based analysis of the observed TAP responses led to the calculation of the apparent intermediate gas constant, Kp, that characterises adsorption into the mesoporous network and apparent time delay, tapp, that characterises residence time in the mesoporous network. Additionally, FRT has been successfully adapted as an extensive in situ perturbation technique in measuring intraphase diffusion coefficients in the washcoats of the same four monolith samples. The diffusion coefficients obtained by moment-based analysis of TAP responses are larger than the coefficients determined by zero length column (ZLC) analysis of flux response profiles with measured values of the same monolith samples between 20 and 100 °C ranging from 2–5×10-9 m2 s-1 to 4–8×10-10 m2 s-1, respectively. The TAP and FRT data, therefore, provide a range of the lower and upper limits of diffusivity, respectively. The reported activation energies and diffusivities clearly correlate with the difference in the washcoat structure of different monolith samples.
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The paper describes the development and application of a multiple linear regression model to identify how the key elements of waste and recycling infrastructure, namely container capacity and frequency of collection affect the yield from municipal kerbside recycling programmes. The overall aim of the research was to gain an understanding of the factors affecting the yield from municipal kerbside recycling programmes in Scotland. The study isolates the principal kerbside collection service offered by 32 councils across Scotland, eliminating those recycling programmes associated with flatted properties or multi occupancies. The results of a regression analysis model has identified three principal factors which explain 80% of the variability in the average yield of the principal dry recyclate services: weekly residual waste capacity, number of materials collected and the weekly recycling capacity. The use of the model has been evaluated and recommendations made on ongoing methodological development and the use of the results in informing the design of kerbside recycling programmes. The authors hope that the research can provide insights for the ongoing development of methods to optimise the design and operation of kerbside recycling programmes.
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The ecological footprint is now a widely accepted indicator of sustainable
development. Footprinting translates resource consumption into the land area
required to sustain it, and allows for an average per capita footprint for a region
or nation to be compared with the global average. This paper reports on a project
in which footprints were calculated for two Irish cities, namely Belfast in
Northern Ireland and Limerick in the Republic of Ireland for the year 2001. As
is frequently the case at sub-national scale, data quality and availability were
often problematic, and in general data gaps were filled by means of population
proxies or national averages. A range of methods was applied to convert
resource flows to land areas. Both footprints suggest that the lifestyles of citizens
of the cities use several times more land than their global share, as has been
found for other cities.
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Biosignal measurement and processing is increasingly being deployed in ambulatory situations particularly in connected health applications. Such an environment dramatically increases the likelihood of artifacts which can occlude features of interest and reduce the quality of information available in the signal. If multichannel recordings are available for a given signal source, then there are currently a considerable range of methods which can suppress or in some cases remove the distorting effect of such artifacts. There are, however, considerably fewer techniques available if only a single-channel measurement is available and yet single-channel measurements are important where minimal instrumentation complexity is required. This paper describes a novel artifact removal technique for use in such a context. The technique known as ensemble empirical mode decomposition with canonical correlation analysis (EEMD-CCA) is capable of operating on single-channel measurements. The EEMD technique is first used to decompose the single-channel signal into a multidimensional signal. The CCA technique is then employed to isolate the artifact components from the underlying signal using second-order statistics. The new technique is tested against the currently available wavelet denoising and EEMD-ICA techniques using both electroencephalography and functional near-infrared spectroscopy data and is shown to produce significantly improved results. © 1964-2012 IEEE.
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Objective assessment of animal personality is typically time consuming, requiring the repeated measure of behavioural responses. By contrast, subjective assessment of personality allows information to be collected quickly by experienced caregivers. However, subjective assessment must predict behaviour to be valid. Comparisons of subjective assessments and behaviour have been made but often with methodological weaknesses and thus, limited success. Here we test the validity of a subjective assessment against a battery of behaviour tests in 146 horses (Equus caballus). Our first aim was to determine if subjective personality assessment could predict behaviour during behaviour testing. We made specific a priori predictions for how subjectively measured personality should relate to behaviour testing. We found that Extroversion predicted time to complete a handling test and refusal behaviour during this test. It also predicted minimum distance to a novel object. Neuroticism predicted how reactive an individual was to a sudden visual stimulus but not how quickly it recovered from this. Agreeableness did not predict any behaviour during testing. There were several unpredicted correlations between subjective measures and behaviour tests which we explore further. Our second aim was to combine data from the subjective assessment and behaviour tests to gain a more comprehensive understanding of personality. We found that the combination of methods provides new insights into horse behaviour. Furthermore, our data are consistent with the idea of horses showing different coping styles, a novel finding for this species. © 2013 Elsevier B.V.
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There is a growing body of knowledge that uses innovative qualitative methods to support and facilitate the involvement of young children, aged 7 years and under, in the research process. Across several fields of study the recent growth in research that engages with young children stands in sharp contrast with the situation just a few years ago where there was a dearth of activity and knowledge in this area. Designed to seek their views, experiences and perspectives the range of methods is now burgeoning. This chapter explores reasons for the growth in the use of innovative qualitative methods, the underlying principles through which the engagement of young children has been achieved and the different types of method with detailed case examples. For each method the main critical issues regarding their effectiveness are identified and discussed in further detail. The latter sections of the chapter focus on contemporary issues regarding the use of innovative methods. Highlighted, in particular, are some of the common concerns and criticisms with regards to the trustworthiness, reliability, validity and generalizability of the data that is collated using innovative qualitative methods.
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Despite considerable advances in reducing the production of dioxin-like toxicants in recent years, contamination of the food chain still occasionally occurs resulting in huge losses to the agri-food sector and risk to human health through exposure. Dioxin-like toxicity is exhibited by a range of stable and bioaccumulative compounds including polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), produced by certain types of combustion, and man-made coplanar polychlorinated biphenyls (PCBs), as found in electrical transformer oils. While dioxinergic compounds act by a common mode of action making exposure detection biomarker based techniques a potentially useful tool, the influence of co-contaminating toxicants on such approaches needs to be considered. To assess the impact of possible interactions, the biological responses of H4IIE cells to challenge by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in combination with PCB-52 and benzo-a-pyrene (BaP) were evaluated by a number of methods in this study. Ethoxyresorufin-O-deethylase (EROD) induction in TCDD exposed cells was suppressed by increasing concentrations of PCB-52, PCB-153, or BaP up to 10 mu M. BaP levels below 1 mu M suppressed TCDD stimulated EROD induction, but at higher concentrations, EROD induction was greater than the maximum observed when cells were treated with TCDD alone. A similar biphasic interaction of BaP with TCDD co-exposure was noted in the AlamarBlue assay and to a lesser extent with PCB-52. Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) profiling of peptidomic responses of cells exposed to compound combinations was compared. Cells co-exposed to TCDD in the presence of BaP or PCB-52 produced the most differentiated spectra with a substantial number of non-additive interactions observed. These findings suggest that interactions between dioxin and other toxicants create novel, additive, and non-additive effects, which may be more indicative of the types of responses seen in exposed animals than those of single exposures to the individual compounds.